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Case Report of a 63-Year-Old Patient With Alzheimer Disease and a Novel Presenilin 2 Mutation

Wells, Jennie L. BSc, MSc, MD, FACP, FRCPC, CCRP *,† ; Pasternak, Stephen H. MD, PhD, FRCPC †,‡,§

* Department of Medicine, Division of Geriatric Medicine, Schulich School of Medicine and Dentistry, Western University

† St. Joseph’s Health Care London—Parkwood Institute

‡ Molecular Medicine Research Group, Robarts Research Institute

§ Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada

The authors declare no conflicts of interest.

Reprints: Jennie L. Wells, BSc, MSc, MD, FACP, FRCPC, CCRP, Department of Medicine, Division of Geriatric Medicine, St. Joseph’s Health Care London—Parkwood Institute, Room A2-129, P.O. Box 5777 STN B, London, ON, Canada N6A 4V2 (e-mail: [email protected] ).

This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0/

Early onset Alzheimer disease (EOAD) is a neurodegenerative dementing disorder that is relatively rare (<1% of all Alzheimer cases). Various genetic mutations of the presenilin 1 ( PSEN1 ) and presenilin 2 ( PSEN2 ) as well as the amyloid precursor protein (APP) gene have been implicated. Mutations of PSEN1 and PSEN2 alter γ-secretase enzyme that cleaves APP resulting in increase in the relative amount of the more amyloidogenic Aβ42 that is produced. 1

PSEN2 has been less studied than PSEN1 and fewer mutations are known. Here, we report a case of a 63-year-old woman (at the time of death) with the clinical history consistent with Alzheimer D, an autopsy with brain histopathology supporting Alzheimer disease (AD), congophylic angiopathy, and Lewy Body pathology, and whose medical genetic testing reveals a novel PSEN2 mutation of adenosine replacing cytosine at codon 222, nucleotide position 665 (lysine replacing threonine) that has never been previously reported. This suggests that genetic testing may be useful in older patients with mixed pathology.

CASE REPORT

The patient was referred to our specialty memory clinic at the age of 58 with a 2-year history of repetitiveness, memory loss, and executive function loss. Magnetic resonance imaging scan at age 58 revealed mild generalized cortical atrophy. She is white with 2 years of postsecondary education. Retirement at age 48 from employment as a manager in telecommunications company was because family finances allowed and not because of cognitive challenges with work. Progressive cognitive decline was evident by the report of deficits in instrumental activities of daily living performance over the past 9 months before her initial consultation in the memory clinic. Word finding and literacy skills were noted to have deteriorated in the preceding 6 months according to her spouse. Examples of functional losses were being slower in processing and carrying out instructions, not knowing how to turn off the stove, and becoming unable to assist in boat docking which was the couple’s pastime. She stopped driving a motor vehicle about 6 months before her memory clinic consultation. Her past medical history was relevant for hypercholesterolemia and vitamin D deficiency. She had no surgical history. She had no history of smoking, alcohol, or other drug misuse. Laboratory screening was normal. There was no first-degree family history of presenile dementia. Neurocognitive assessment at the first clinic visit revealed a Mini Mental State Examination (MMSE) score of 14/30; poor verbal fluency (patient was able to produce only 5 animal names and 1 F-word in 1 min) as well as poor visuospatial and executive skills ( Fig. 1 ). She had fluent speech without semantic deficits. Her neurological examination was pertinent for normal muscle tone and power, mild ideomotor apraxia on performing commands for motor tasks with no suggestion of cerebellar dysfunction, normal gait, no frontal release signs. Her speech was fluent with obvious word finding difficulties but with no phonemic or semantic paraphrasic errors. Her general physical examination was unremarkable without evidence of presenile cataracts. She had normal hearing. There was no evidence of depression or psychotic symptoms.

At the time of the initial assessment, her mother was deceased at age 79 after a hip fracture with a history long-term smoking and idiopathic pulmonary fibrosis. Her family believes that there is possible German and Danish descent on her father’s side. Her father was alive and well at age 80 at the time of her presentation with a history coronary artery disease. He is still alive and well with no functional or cognitive concerns at age 87 at the time of writing this report. Her paternal grandfather died at approximately age 33 of appendicitis with her paternal grandmother living with mild memory loss but without known dementia or motor symptoms until age 76, dying after complications of abdominal surgery. Her paternal uncle was diagnosed with Parkinson disease in his 40s and died at age 58. Her maternal grandmother was reported to be functionally intact, but mildly forgetful at the time of her death at age 89. The maternal grandfather had multiple myocardial infarctions and died of congestive heart failure at age 75. She was the eldest of 4 siblings (ages 44 to 56 at the time of presentation); none had cognitive problems. She had no children.

Because of her young age and clinical presentation with no personality changes, language or motor change, nor fluctuations, EOAD was the most likely clinical diagnosis. As visuospatial challenges were marked at her first visit and poor depth perception developing over time, posterior cortical variant of AD was also on the differential as was atypical presentation of frontotemporal dementias. Without fluctuations, Parkinsonism, falls, hallucinations, or altered attention, Lewy Body dementia was deemed unlikely. After treatment with a cholinesterase inhibitor, her MMSE improved to 18/30, tested 15 months later with stability in function. Verbal fluency improved marginally with 7 animals and 3 F-words. After an additional 18 months, function and cognition declined (MMSE=13/30) so memantine was added. The stabilizing response to the cholinesterase inhibitor added some degree of confidence to the EOAD diagnosis. In the subsequent 4 years, she continued to decline in cognition and function such that admission to a care facility was required with associated total dependence for basic activities of daily living. Noted by family before transfer to the long-term care facility were episodic possible hallucinations. It was challenging to know if what was described was misinterpretation of objects in view or a true hallucination. During this time, she developed muscle rigidity, motor apraxias, worsening perceptual, and language skills and became dependent for all activities of daily livings. At the fourth year of treatment, occasional myoclonus was noted. She was a 1 person assist for walking because of increased risk of falls. After 1 year in the care home, she was admitted to the acute care hospital in respiratory distress. CT brain imaging during that admission revealed marked generalized global cortical atrophy and marked hippocampal atrophy ( Fig. 2 ). She died at age 63 of pneumonia. An autopsy was performed confirming the cause of death and her diagnosis of AD, showing numerous plaques and tangles with congophilic amyloid angiopathy. In addition, there was prominent Lewy Body pathology noted in the amygdala.

Three years before her death informed consent was obtained from the patient and family to perform medical genetic testing for EOAD. The standard panel offered by the laboratory was selected and included PSEN1 , PSEN2 , APP, and apoE analysis. Tests related to genes related to frontotemporal dementia were not requested based on clinical presentation and clinical judgement. This was carried out with blood samples and not cerebrospinal fluid because of patient, family, and health provider preference. The results revealed a novel PSEN2 mutation with an adenosine replacing cytosine at nucleotide position 665, codon 222 [amino acid substation of lysine for threonine at position 221 (L221T)]. This PSEN2 variant was noted to be novel to the laboratory’s database, noting that models predicted that this variant is likely pathogenic. The other notable potentially significant genetic finding is the apoliprotein E genotype was Є 3/4 .

β-amyloid (Aβ) is a 38 to 43 amino acid peptide that aggregates in AD forming toxic soluble oligomers and insoluble amyloid fibrils which form plaques. Aβ is produced by the cleavage of the APP first by an α-secretase, which produces a 99 amino acid C-terminal fragment of APP, and then at a variable “gamma” position by the γ-secretase which releases the Aβ peptide itself. It is this second γ-cleavage which determines the length and therefore the pathogenicity of the Aβ peptides, with 42 amino acid form of Aβ having a high propensity to aggregate and being more toxic.

The γ-secretase is composed of at least 4 proteins, mAph1, PEN2, nicastrin, and presenilin . Of these proteins, presenilin has 2 distinct isoforms ( PSEN1 and PSEN2 ), which contain the catalytic site responsible for the γ-cleavage. PSEN mutants are the most common genetic cause of AD with 247 mutations described in PSEN1 and 48 mutations described in PSEN2 (Alzgene database; www.alzforum.org/mutations ). PSEN2 mutations are reported to be associated with AD of both early onset and variable age onset as well as with other neurodegenerative disorders such as Lewy Body dementia, frontotemporal dementia, Parkinson dementia, and posterior cortical atrophy. 2–4 In addition, PSEN2 has associations with breast cancer and dilated cardiomyopathy. 3

PSEN2 mutants are believed to alter the γ-secretase cleavage of APP increasing the relative amount of the more toxic Aβ42. The mean age of onset in PSEN2 mutations, is 55.3 years but the range of onset is surprisingly wide, spanning 39 to 83 years. Over 52% of cases are over 60 years. All cases have extensive amyloid plaque and neurofibrillary tangles, and many have extensive alpha-synuclein pathology as well. 5

In considering the novelty of this reported PSEN2 mutation, a literature search of Medline, the Alzgene genetic database of PSEN2 and the Alzheimer Disease and Frontotemporal Dementia Mutation Databases (AD&FTMD) were completed ( www.molgen.vib-ua.be/ADMutations ). The mutation presented here (L221T) has never been described before.

Although this mutation has not been described, we believe that it is highly likely to be pathogenic. This mutation is not conservative, as it replaces a lysine residue which is positively charged with threonine which is an uncharged polar, hydrophilic amino acid. The mutation itself occurs in a small cytoplasmic loop between transmembrane domain 4 and 5, which is conserved in the PSEN1 gene, and in PSEN2 is highly conserved across vertebrates, including birds and zebrafish all the way to Caenorhabditis elegans , but differs in Drosophila melanogaster (fruit fly) ( Fig. 3 ). We examined this mutation using several computer algorithms which examine the likelihood that a mutation will not be tolerated. Both SIFT ( http://sift.bii.a-star.edu.sg ) and PolyPhen-2.2.2 (HumVar) ( www.bork.embl-heidelberg.de/PolyPhen ) predicts that this variant is pathogenic. Interestingly, it is noted that PSEN1 mutations after amino acid 200 develop amyloid angiopathy. 5,7

This patient also had an additional risk factor for AD, being a heterozygote for the apoЄ4 allele. Among other mechanisms, its presence reduces clearance of Aβ42 from the brain and increases glial activation. 8 Although the apoЄ4 allele is known to lower the age of onset of dementia in late onset AD, it has not been clearly shown to influence age of onset of EOAD in a limited case series. 9 It should be noted that heterozygote state may have contributed to an acceleration of her course given the known metabolism of apoЄ4 and its association with accelerated cerebral amyloid and known reduction in age of onset. 10

Given that there is no definite family history of autosomal dominant early onset dementia, it is likely that her PSEN2 mutation was a new random event. With the unusually wide age of onset it is conceivable that one of her parents could still harbor this PSEN2 mutation. The patient’s father, however, is currently 87 and living independently at the time of writing this manuscript, making him highly unlikely to be an EOAD carrier. Nonpaternity is an alternate explanation for the lack of known first-degree relative with EOAD; however, this is deemed unlikely by the family member who provided the supplemental history. Her mother died at age 79, so she could conceivably carry our mutation but we do not have access to this genetic material. Without extensive testing of many family members it would be impossible to speculate about autosomal recessive form of gene expression. In addition, the genetic testing requested was limited to presenilins , APP, and apoE mutations. Danish heritage may add Familial Danish dementia as a remote consideration; however, Familial Danish dementia has a much different clinical presentation with long tract signs, cerebellar dysfunction, onset in the fourth decade as well as hearing loss and cataracts at a young age. 11 This disease has high autosomal dominant penetration which also makes it less likely in the patient’s context. This specific gene (chromosome 13) was not tested. The autopsy findings do not support this possibility. There are reports of Familial AD pedigrees in Germany, including a Volga pedigree with PSEN141I mutation in exon 5, but this is clearly separate from our mutation which is in exon 7. Our mutation was also not observed in a recent cohort of 23 German individuals with EOAD which underwent whole genome sequencing, but did find 2 carriers of the Volga pedigree. It is also possible that both the PSEN2 mutation and the ApoE genotype contributed to her disease and early onset presentation. This case illustrates the multiple pathology types which occur in individuals bearing PSEN2 mutations, and highlights the later ages in which patients can present with PSEN2 mutations. 12

ACKNOWLEDGMENT

The authors acknowledge Gwyneth Duhn, RN, BNSc, MSc, for her support of this paper.

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Case studies

These three case studies help you to consider different situations that people with dementia face. They are:

• Raj , a 52 year old with a job and family, who has early onset dementia
• Bob and Edith , an older married couple who both have dementia and are struggling to cope, along with their family
• Joan , an older woman, who lives alone and has just been diagnosed with dementia

Each case study contains:

• A vignette setting out the situation
• An ecogram showing who is involved
• An assessment which gives essential information about what is happening and the social worker’s conclusion
• A care and support plan which says what actions will be taken to achieve outcomes

You can use the practice guidance to think about how you would respond in these situations.

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• Understanding Alzheimer's Disease

Understanding Alzheimer's Disease

What is Alzheimer's disease?

Alzheimer's disease is a brain disease that slowly destroys memory and thinking skills. It is a progressive disease, which means it gets worse over time.

Alzheimer's disease is irreversible. People with Alzheimer's eventually lose the ability to carry out the simplest of tasks.

Alzheimer's is the most common cause of dementia among people aged 65 and older. Dementia is loss of the ability to think and remember things that is severe enough that a person has trouble doing day-to-day activities.

About 5.8 million people in the United States have Alzheimer's disease.

Rarely, people younger than 65 can have Alzheimer's. This is called early-onset Alzheimer's disease . Around one of every 20 people with Alzheimer's have early-onset Alzheimer's disease.

You're more likely to get Alzheimer's if one or more of your close family members – parents, brothers, or sisters – has it.

Common early symptoms of Alzheimer's disease

The most common early symptom of Alzheimer's disease is trouble remembering recent events.

Other early symptoms may include

• Having trouble completing daily tasks, and
• Getting lost when driving on a route the person used to know well

These symptoms are not the same as normal forgetfulness, which can happen to all of us as we get older. For example, if you sometimes forget about an appointment, forget a person's name, or misplace your keys, it doesn't mean you have Alzheimer's.

Symptoms of mild Alzheimer's disease

A person with mild Alzheimer's disease may

• Need help with usual tasks (like managing finances, planning meals, and keeping appointments)
• Have trouble sleeping, and
• Become anxious or depressed.

Symptoms of moderate Alzheimer's disease – When Alzheimer's disease worsens

As symptoms of Alzheimer's disease get worse, a person may

• Have some trouble recognizing family members and friends.
• Need help with daily activities like getting dressed.
• Become fearful or suspicious of other people.
• Believe they are seeing or hearing things that aren't real.

Symptoms of severe Alzheimer's disease – When Alzheimer's disease becomes severe

When Alzheimer's disease becomes severe , a person loses much of their ability to communicate and needs full-time help to take care of themselves.

What causes Alzheimer's disease?

Doctors don't fully understand what causes Alzheimer's disease in most people.

Most people with Alzheimer's disease are older, but just getting older doesn't cause the disease. Many people live well into their 90s without getting Alzheimer's disease.

What causes Alzheimer's disease? – Genes associated with Alzheimer's disease

Carrying a variant of a gene known as APOE increases a person's risk for Alzheimer's disease, especially the late-onset form of the disease. But not everyone who has this gene gets the disease, and people who don't have the gene can still get the disease.  

Early-onset Alzheimer's disease can also be caused by an inherited change in one of three other genes, yet these genes are very uncommon.

What causes Alzheimer's disease? – Conditions that may increase risk for Alzheimer's disease

Other conditions that may increase risk for Alzheimer's disease include

• High blood pressure
• An unhealthy diet

What happens in the brain in Alzheimer's disease?

Doctors now know that changes begin happening in the brain 10-20 years or more before a person with Alzheimer's disease shows any symptoms.

Neurons are brain cells that send and receive signals to and from the brain. Everything we do as living beings – walking, thinking, forming memories – happens because of these signals. A healthy adult brain contains about 100 billion neurons.

When a person has Alzheimer's disease, tiny pieces of a protein called beta amyloid build up in between neurons, forming clusters, or plaques .

Another protein, called tau , builds up inside neurons, forming dense, thread-like tangles .

Together, these plaques and tangles block neurons from sending and receiving signals .

Because of these and other abnormal changes in the brain, neurons start to die. The first place this happens is in the parts of the brain where memories are formed.

As more neurons die, the brain starts to shrink. As Alzheimer's gets worse over time, the brain may shrink to about a third of its normal size.

What is mixed dementia?

Mixed dementia is dementia that's caused by brain changes due to Alzheimer's disease and one or more other brain diseases.

For example, a person may have dementia that's caused by both Alzheimer's disease and Parkinson's disease.

What is vascular dementia?

A person may also have both Alzheimer's disease and vascular dementia . This type of dementia occurs when the brain gets less blood than it needs. This can happen after a person has had a series of small strokes.

Can Alzheimer's disease be prevented?

Studies show there are steps you can take to reduce your risk for Alzheimer's disease.

• Don't smoke.
• Keep your body and your mind active.
• Stay in touch with family and friends.
• Eat a healthy diet.
• Maintain a healthy weight.
• Control high blood pressure.
• Drink alcohol in moderation.
• Drink coffee in moderation.

Recent studies suggest that getting vaccinated against pneumonia and the flu can also help lower your risk for Alzheimer's disease.

• National Institute on Aging. Alzheimer's Disease Fact Sheet. https://www.nia.nih.gov/health/alzheimers-disease-fact-sheet. Reviewed 5/22/2019.
• National Institute of Neurological Disorders and Stroke. Alzheimer's Disease Information Page. Definition. https://www.ninds.nih.gov/Disorders/All-Disorders/Alzheimers-Disease-Information-Page. Last modified 3/27/2019.
• Alzheimer's Association. 2020 Alzheimer's Disease Facts and Figures. https://www.alz.org/media/Documents/alzheimers-facts-and-figures.pdf.
• Zhu XC, Tan L, Wang HF, et al. Rate of early onset Alzheimer's disease: a systematic review and meta-analysis. Ann Transl Med 2015;3:38.
• National Institute on Aging. Alzheimer's and Hallucinations, Delusions, and Paranoia. https://www.nia.nih.gov/health/alzheimers-and-hallucinations-delusions-and-paranoia. Reviewed 5/17/2017.
• National Institute on Aging. Alzheimer's Disease Genetics Fact Sheet. https://www.nia.nih.gov/health/alzheimers-disease-genetics-fact-sheet. Reviewed 12/24/2019.
• Dementia Care Central. Normal Brain vs. Alzheimer's. https://www.dementiacarecentral.com/video/video-brain-changes/.
• National Institute on Aging. What Do We Know About Diet and Prevention of Alzheimer's Disease? https://www.nia.nih.gov/health/what-do-we-know-about-diet-and-prevention-alzheimers-disease. Reviewed 11/27/2019.
• Livingston G, Sommerlad A, Orgeta V, et al. Dementia prevention, intervention, and care. Lancet. 2017;390(10113):2673-2734. doi:10.1016/S0140-6736(17)31363-6
• The SPRINT MIND Investigators for the SPRINT Research Group. Effect of Intensive vs Standard Blood Pressure Control on Probable Dementia: A Randomized Clinical Trial. JAMA. 2019;321(6):553–561. doi:10.1001/jama.2018.21442
• Neafsey EJ, Collins MA. Moderate alcohol consumption and cognitive risk. Neuropsychiatr Dis Treat. 2011;7:465-484. doi:10.2147/NDT.S23159
• Driscoll I, Shumaker SA, Snively BM, et al. Relationships Between Caffeine Intake and Risk for Probable Dementia or Global Cognitive Impairment: The Women's Health Initiative Memory Study. J Gerontol A Biol Sci Med Sci. 2016;71(12):1596-1602. doi:10.1093/gerona/glw078
• Alzheimer's Association. Flu, Pneumonia Vaccinations Tied to Lower Risk of Alzheimer's Dementia [press release]. 2020 July 27. https://www.alz.org/aaic/releases_2020/vaccines-dementia-risk.asp

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Case Study 1: A 55-Year-Old Woman With Progressive Cognitive, Perceptual, and Motor Impairments

Information & authors, metrics & citations, view options, case presentation, what are diagnostic considerations based on the history how might a clinical examination help to narrow the differential diagnosis.

How Does the Examination Contribute to Our Understanding of Diagnostic Considerations? What Additional Tests or Studies Are Indicated?

Considering This Additional Data, What Would Be an Appropriate Diagnostic Formulation?

Does information about the longitudinal course of her illness alter the formulation about the most likely underlying neuropathological process, neuropathology.

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• Posterior Cortical Atrophy
• Corticobasal Syndrome
• Atypical Alzheimer Disease
• Network Degeneration

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Dementia case study with questions and answers

Dementia case study with questions and answers

Common dementia exam questions for medical finals, OSCEs and MRCP PACES

The case below illustrates the key features in the assessment of a patient with dementia or undiagnosed memory decline. It works through history, examination and investigations – click on the plus symbols to see the answers to each question

Part 1: Mavis

• Mavis is an 84-year old lady, referred to you in the memory clinic for assessment of memory impairment. She attends in the company of her son and daughter-in-law.
• On the pre-clinic questionnaire her son has reported a severe deterioration in all aspects of her cognition over the past 12 months.
• The patient herself acknowledges that there have been memory problems, but feels it is just her short term memory that is an issue.

Question 1.

• To begin the history, start broadly. Build rapport and establish both the patient’s view on memory impairment (if any) and the family’s (or other collateral history).
• Patient’s (and collateral) view of memory decline
• Biographical history
• Objective view of memory decline (e.g. knowledge of current affairs)
• Impact of memory decline on day-to-day living and hobbies
• Social history, including safety and driving
• General medical history (especially medications)
• See below for details on these…

Question 2.

• Is it for everything or are specific details missed out/glossed over?
• Try to pin down specific details (e.g. names of people/places).
• At what time in chronological order do things start to get hazy?

Question 3.

• If under 12 years this will lead to additional point being awarded on some cognitive tests
• Ask about long term memories, e.g. wedding day or different jobs
• Then move on to more recent memories, e.g. last holiday

Question 4.

• If your patient watches the news/read newspapers on a regular basis, ask them to recount the headlines from the past few days.
• Be sure to look for specifics to prevent your patient masking memory deficiencies with broad statements. For example: “The government are incompetent, aren’t they?!” should be clarified by pinning down exactly why they are incompetent, for example: “Jeremy Hunt”.
• If they like to read, can they recall plotlines from current books or items from magazines?
• If they watch TV, can they recount recent plot lines from soaps, or formats of quiz shows?

Question 5.

• Ask about hobbies and other daily activities, and whether or not these have declined recently.
• If your patient no longer participates in a particular hobby, find out why: is it as a result of a physical impairment (e.g. arthritis making cooking difficult), or as the result of a loss of interest/ability to complete tasks (e.g. no longer able to complete crosswords/puzzles).
• Once you have a good idea of the memory decline itself, begin to ask about other features. Including a social and general medical history.

Question 6.

• Review their social history and current set-up, and also subjective assessments from both patient and family over whether or not the current arrangements are safe and sustainable as they are.
• Previous and ongoing alcohol intake
• Smoking history
• Still driving (and if so, how safe that is considered to be from collateral history)
• Who else is at home
• Any package of care
• Upstairs/downstairs living
• Meal arrangements (and whether weight is being sustained).
• Of all these issues, that of driving is perhaps one of the most important, as any ultimate diagnosis of dementia must be informed (by law) to both the DVLA and also the patient’s insurers. If you feel they are still safe to drive despite the diagnosis, you may be asked to provide a report to the DVLA to support this viewpoint.

Now perform a more generalised history, to include past medical history and – more importantly – a drug history.

Question 7.

• Oxybutynin, commonly used in primary care for overactive bladder (anticholinergic side effects)
• Also see how the medications are given (e.g. Dossett box)
• Are lots of full packets found around the house?

Part 2: The History

On taking a history you have found:

• Mavis was able to give a moderately detailed biographical history, but struggled with details extending as far back as the location of her wedding, and also her main jobs throughout her life.
• After prompting from her family, she was able to supply more information, but it was not always entirely accurate.
• Her main hobby was knitting, and it was noted that she had been able to successfully knit a bobble hat for her great-grand child as recently as last month, although it had taken her considerably longer to complete than it might have done a few years previously, and it was a comparatively basic design compared to what she has been able to create previously.
• She has a few children living in the area, who would frequently pop in with shopping, but there had been times when they arrived to find that she was packed and in her coat, stating that she was “just getting ready to go home again”.
• She had been helping occasionally with the school run, but then a couple of weekends ago she had called up one of her sons – just before she was due to drive over for Sunday lunch – and said that she could not remember how to drive to his house.
• Ever since then, they had confiscated her keys to make sure she couldn’t drive. Although she liked to read the paper every day, she could not recall any recent major news events.  Before proceeding to examine her, you note that the GP referral letter has stated that her dementia screen investigations have been completed.

Question 8.

• Raised WCC suggests infection as a cause of acute confusion
• Uraemia and other electrolyte disturbances can cause a persistent confusion.
• Again, to help rule out acute infection/inflammatory conditions
• Liver failure can cause hyperammonaemia, which can cause a persistent confusion.
• Hyper- or hypothyroidism can cause confusion.
• B12 deficiency is an easily missed and reversible cause of dementia.
• This looks for space occupying lesions/hydrocephalus which may cause confusion.
• This can also help to determine the degree of any vascular component of an ultimately diagnosed dementia.

Part 3: Examination

• With the exception of age-related involutional changes on the CT head (noted to have minimal white matter changes/small vessel disease), all the dementia screen bloods are reassuring.
• You next decide to perform a physical examination of Mavis.

Question 9.

• Important physical findings that are of particular relevance to dementia, are looking for other diseases that may have an effect on cognition.
• To look for evidence of stroke – unlikely in this case given the CT head
• Gait (shuffling) and limb movements (tremor, rigidity, bradykinesia)
• Affect is also important here and may also point to underlying depression
• Pay attention to vertical gaze palsy, as in the context of Parkinsonism this may represent a Parkinson plus condition (e.g. progressive supranuclear palsy).
• It is also useful to look at observations including blood pressure (may be overmedicated and at risk of falls from syncope) and postural blood pressure (again, may indicate overmedication but is also associated with Parkinson plus syndromes e.g. MSA)

Part 4: Cognitive Testing

• On examination she is alert and well, mobilising independently around the clinic waiting room area.  A neurological examination was normal throughout, and there were no other major pathologies found on a general examination.
• You now proceed to cognitive testing:

Question 10.

• Click here for details on the MOCA
• Click here for details on the MMSE
• Click here for details on the CLOX test

Part 5: Diagnosis

• Mavis scores 14/30 on a MOCA, losing marks throughout multiple domains of cognition.

Question 11.

• Given the progressive nature of symptoms described by the family, the impairment over multiple domains on cognitive testing, and the impact on daily living that this is starting to have (e.g. packing and getting ready to leave her own home, mistakenly believing she is somewhere else), coupled with the results from her dementia screen, this is most likely an Alzheimer’s type dementia .

Question 12.

• You should proceed by establishing whether or not Mavis would like to be given a formal diagnosis, and if so, explain the above.
• You should review her lying and standing BP and ECG, and – if these give no contraindications – suggest a trial of treatment with an acetylcholinesterase inhibitor, such as donepezil.
• It is important to note the potential side effects – the most distressing of which are related to issues of incontinence.
• If available, put her in touch with support groups
• Given the history of forgetting routes before even getting into the care, advise the patient that she should stop driving and that they need to inform the DVLA of this (for now, we will skip over the depravation of liberty issues that the premature confiscation of keys performed by the family has caused…)
• The GP should be informed of the new diagnosis, and if there are concerns over safety, review by social services for potential support should be arranged.
• Follow-up is advisable over the next few months to see whether the trial of treatment has been beneficial, and whether side effects have been well-tolerated.

Now click here to learn more about dementia

Perfect revision for medical students, finals, osces and mrcp paces, …or  click here to learn about the diagnosis and management of delirium.

• Research article
• Open access
• Published: 25 June 2019

A collective case study of the features of impactful dementia training for care home staff

• Claire A. Surr   ORCID: orcid.org/0000-0002-4312-6661 1 ,
• Cara Sass 1 ,
• Michelle Drury 2 ,
• Natasha Burnley 1 ,
• Alison Dennison 2 ,
• Sarah Burden 1 &
• Jan Oyebode 2  

BMC Geriatrics volume  19 , Article number:  175 ( 2019 ) Cite this article

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Metrics details

Up to 80% of care home residents have dementia. Ensuring this workforce is appropriately trained is of international concern. Research indicates variable impact of training on a range of resident and staff outcomes. Little is still known about the most effective approaches to the design, delivery and implementation of dementia training. This study aimed to investigate the features and contextual factors associated with an effective approach to care home staff training on dementia.

An embedded, collective case study was undertaken in three care home provider organisations who had responded to a national training audit. Data collected included individual or small group interviews with training leads, facilitators, staff attending training, managers, residents and their relatives. Observations of care practice were undertaken using Dementia Care Mapping. Training delivery was observed and training materials audited. A within case analysis of each site, followed by cross case analysis using convergence coding was undertaken.

All sites provided bespoke, tailored training, delivered largely using face-to-face, interactive methods, which staff and managers indicated were valuable and effective. Self-study booklets and on-line learning where were used, were poorly completed and disliked by staff. Training was said to improve empathy, knowledge about the lived experience of dementia and the importance of considering and meeting individual needs. Opportunities to continually reflect on learning and support to implement training in practice were valued and felt to be an essential component of good training. Practice developments as a result of training included improved communication, increased activity, less task-focussed care and increased resident well-being. However, observations indicated positive well-being and engagement was not a consistent experience across all residents in all sites. Barriers to training attendance and implementation were staff time, lack of dedicated training space and challenges in gaining feedback on training and its impact. Facilitators included a supportive organisational ethos and skilled training facilitation.

Conclusions

Effective training is tailored to learners’, delivered face-to-face by an experienced facilitator, is interactive and is embedded within a supportive organisational culture/ethos. Further research is needed on the practical aspects of sustainable and impactful dementia training delivery and implementation in care home settings.

Peer Review reports

Care homes provide care to 19–38% of people with dementia in Western countries [ 1 , 2 ] and up to 80% of people living in care homes are thought to have dementia [ 2 , 3 ]. In order to be able to deliver high quality person-centred care for this group, care home staff need to be provided with appropriate training that supports them to have the right knowledge, skills and attitudes [ 4 , 5 ]. In England, there have been a range of initiatives, led by government over the last ten years to ensure the health and social care workforce receives appropriate dementia training [ 6 , 7 , 8 , 9 , 10 , 11 ]. However, in addition to ensuring the availability of training, there is a need to ensure that training is of high quality to provide the best chance of effecting practice change. A number of systematic reviews have examined research on the effectiveness of dementia training for the care home workforce in relation to a range of outcomes including the general benefits of training [ 12 ], impact on resident functional ability and quality of life [ 13 ], improving staff communication skills [ 14 ] and for supporting complex resident behaviours [ 15 , 16 ]. The studies report variable impact of staff training on these outcomes. Training appears to most consistently support improvement of general care home staff skills [ 12 ], communication [ 14 ] and support for residents in activities of daily living [ 13 ]. However, there are inconsistent findings in relation to the impact of training programmes on resident outcomes such as behaviours (e.g. agitation, anxiety, neuropsychiatric symptoms) [ 13 , 14 , 15 , 16 ] and quality of life [ 13 ]. The reviews generally conclude that there is limited robust evidence for training efficacy due to methodological weaknesses in study designs and lack of follow-up over time. Where studies have included longer follow-up any positive results observed are generally not sustained. Few reviews consider features of effective training. One systematic review examining the challenges to and strategies for implementation of training in practice [ 5 ] identified the key challenges to include low staff attendance, lack of organizational support, and financial limitations. Therefore, there is limited available evidence on the most effective approaches to the design, delivery and implementation of impactful dementia training in care home settings.

The What Works in dementia education and training? (What Works?) study aimed to investigate the elements of an effective approach to dementia training and education for the health and social care workforce. This was achieved through conducting: 1) a systematic literature review of current evidence (see [ 17 ]); 2) a national audit of health and social care providers, commissioners and training providers on currently available dementia training; 3) a survey of staff who had completed programmes reported in the audit to assess their dementia knowledge, attitudes and confidence; 4) multiple case studies [ 18 ] in health and social care settings (general hospitals n  = 3, mental health/community services n  = 3, social care n = 3, general practitioner practices n  = 1) who responded to the audit and whose training met good practice criteria identified from the literature review. In order to ensure enough data could be collected at each site to provide an in-depth picture [ 19 ], we aimed to recruit three case study sites from each setting type. This was deemed feasible within the project resources and timescales but was sufficiently large to permit cross-case comparison.

The study was underpinned by two theoretical models for the evaluation of training. Richards and DeVries’ [ 20 ] Conceptual Model for Dynamic Evaluation of Learning Activities, explores training design and facilitation processes. Kirkpatrick’s [ 21 , 22 ] four-level model for evaluation of training interventions examines 1) learner reaction to training, 2) extent of learning in terms of knowledge, attitudes and confidence, 3) staff behaviour change, and 4) practice results or outcomes.

This paper reports a collective case study of the three social care case studies, which were all undertaken in care home settings.

The case studies aimed to understand the features and contextual factors associated with good practice regarding the design, delivery and implementation of dementia education and training and its impact on care practices.

The research questions addressed were:

What models of dementia education and training were sites adopting?

How did staff perceive the training?

How did the training impact on staff knowledge, attitudes and practices?

How did people with dementia and their family members experience care in homes/units where staff had received training?

What were the specific barriers and facilitators to effective training implementation?

We employed an embedded [ 23 ], collective [ 19 ] case study design.

Case selection

A ‘case’ was defined as a care home provider organisation, which could include a single care home or multiple sites, as long as staff at all sites accessed the same training programmes. Eighteen social care providers in England and Scotland, including fourteen care home providers and four domiciliary care organisations who had responded to the audit were considered for inclusion. They were shortlisted using a positive deviance approach [ 24 ] by researchers blinded to site identity, and then ranked against a set of good practice criteria. These criteria were developed from the outcomes of the literature review [ 17 ]. They included how comprehensively training covered subjects and associated learning outcomes within the national Dementia Training Standards Framework for England [ 25 ] alongside training length and delivery methods (see Additional file  1 for full criteria and shortlisting process).

We had aimed to include at least one domiciliary care site in the three case studies. However, neither of the two sites which achieved high ratings against the good practice criteria were able to participate due to staffing issues affecting key individuals who would have needed to support the research. The three top ranking care home sites that were approached all consented to participate.

Data collection

Consistent with a multiple case study approach [ 18 ], a range of data types were collected at each site (see Table  1 ) including semi-structured interviews with the dementia training lead, training facilitators and home managers and semi-structured individual or focus group interviews with staff who had attended training. Interviews were facilitated using a topic guide but conducted flexibly by the researcher to gain a thorough understanding of individuals’ experiences and views. Topic guides were unique for each participant type e.g. managers, training leads, training facilitators, staff, but contained questions based around the Richards and DeVries and Kirkpatrick Frameworks including organisational culture and processes (e.g. Could you tell me a bit about your organisation’s training strategy and the place of dementia training within this?), training design and delivery (e.g. What aspects have gone well in organisation and delivery and what has proved more tricky?), reactions (e.g. You’ve all taken part in [insert description] dementia training recently. Could I ask your opinions on the training you received?), learning and behaviour (e.g. Thinking about those team members who received [insert name of training here], can you identify any changes in their knowledge, or their competency in relation to dementia?) and outcomes (e.g. Do you think the training programme is having the impact you hoped for on care? Can you give us some examples?). They were audio recorded and transcribed verbatim, with interviews lasting for 30–60 min and focus group discussions around 60-min. The focus group discussions used the same topic guide but also included vignettes that presented a short story of the experiences of a person living with dementia in a care home in written and pictorial format. Focus group participants were asked to identify examples of good and poor practice contained within the vignettes, which helped to explore their knowledge and attitudes towards dementia care. The vignettes were developed by members of the project’s expert by experience group, which was comprised of people living with dementia and their family members.

Each site provided copies of the training materials, which were audited using a good practice in training tool developed by the research team [ 26 ], based on the findings of the systematic review [ 17 ]. This includes items such as content and how well it mapped to the Dementia Training Standards Framework, whether it used interactive delivery methods, accuracy and readability of materials, tailoring to audience and training length. Researchers observed training sessions being delivered to staff, recording data using a qualitative observational template developed by the study team, based on the underpinning theoretical models. Short satisfaction cards, including three fixed (How satisfied are you with this service? How well did the staff understand your feelings and needs? How well were staff able to answer your questions about dementia?) and one open-response question (Any other comments about your care either positive or negative?), were given to care home residents with dementia and/or relatives. Respondents were also invited to take part in a telephone or face-to-face interview to discuss their care experiences. Only one resident in one of the sites completed an interview.

Care was observed in at least one unit of each participating site using Dementia Care Mapping (DCM) [ 27 ]. DCM collects data on residents’ experiences of care including behaviour (from 23 possible codes; Behaviour Category Code – BCC), level of mood and engagement (from a six-point scale (− 5, − 3, − 1, + 1, + 3, + 5: Mood and Engagement Value – ME)) and the quality of staff interactions with residents (Personal Enhancers and Personal Detractors). Up to eight hours of observation over both morning and afternoon periods were conducted by study researchers trained in DCM in public areas of the care home. As dementia training had been provided in all case study sites for a number of years prior to the study and was ongoing during data collection, no data was able to be collected before dementia training commenced. Therefore, analysis focussed on whether the outcomes the training aimed to achieve e.g. person-centred care, skilled communication, resident well-being, were present in the care homes.

Consent and ethical issues

Ethical approval for the study was given by the Yorkshire and the Humber – Bradford Leeds NHS Research Ethics Committee [REC Ref 15/YH/0488]. The research team made the initial approach to participate to the individual who completed the audit earlier in the project, and arranged to visit the care home to meet with key staff such as the owner, training lead, facilitators and unit managers. Once formal written organisational consent from senior management was gained, the researcher visited each site again and gained written informed consent from all study participants. Where a resident lacked capacity to give informed consent, advice on their participation was gained from a relative or staff consultee in accordance with Mental Capacity Act [ 28 ] guidance. Adopting consent processes utilised in previous studies that have included general observations of care practices with people with dementia [ 29 ], verbal approval to record anonymised data was gained from residents and staff prior to DCM observation. In keeping with the principles of process consent [ 30 ] researchers assessed ongoing consent throughout. To ensure all individuals within the care home were aware of ongoing observations posters were displayed in prominent positions on the units before and during observation period, containing a photograph of the researcher and giving details about the study and how and with whom to ask questions or raise a concern.

Data analysis

The study team undertook analysis of the full set of data for each case study site individually followed by cross-case analysis. Interview, focus group and training observation data were analysed using the thematic analysis method, template analysis [ 31 , 32 ] using NVivo 11 [ 33 ]. Starting with a priori themes drawn from the underpinning theoretical frameworks [ 20 , 22 ] a coding template was developed that underpinned data analysis across the whole study. This was achieved through CAS, JO, CS, MD, SB and NB undertaking collaborative coding of three initial transcripts (one social care, one acute care and one mental health Trust) and discussion of the identified themes. A further six transcripts (representing the range of service settings) were then coded by CS, MD and NB to refine the template. This final template was then used to code the remaining data.

DCM data were analysed using standard DCM guidelines, including preparing summaries of data at an individual resident and group level. Copies of training materials were reviewed and their content mapped against the learning outcomes contained within the Dementia Core Skills Education and Training Framework [ 25 ]. The audit tool [ 26 ] of good practice in dementia training was used to audit each training programme. The responses to patient and carer satisfaction cards were summarised using descriptive statistics and manual thematic analysis.

Once analysis of each data source for a site was complete, a within case analysis [ 19 ] was conducted. This involved summarising each data source, triangulating across sources, and synthesising into a written ‘story of the case’ [ 34 ]. This was followed by cross-case analysis [ 19 ] across the three sites using convergence coding [ 35 ]. Convergence coding involved creation of a data grid highlighting themes and findings, supporting comparison of areas of agreement, partial agreement and dissonance [ 36 ].

The organisations recruited varied in terms of size and number of units participating in the study (Table  2 ), although all were within provider organisations who owned a small number of care homes (≤7) and were located across England and Scotland. All had an internal training lead/trainer who was responsible for delivery of dementia training across all homes within the organisation. The key themes and issues identified in the analysis are presented by site in Table  3 .

Design and delivery

All sites offered a range of training provision (Table 2 ) that was mostly bespoke and developed by the training lead. The majority of training was delivered face-to-face in small groups, with some sites including other delivery methods. In one site, a standardised workbook that covered required dementia training content for Scotland was used. However, the training lead had tailored the delivery method by including additional monthly face-to-face discussion groups where staff could reflect on application of learning, recognising the importance of co-learning.

We thought in order to change practice that it has to be facilitated within the team … all the reflective exercises are about people that they actually care for. Thought it was more real … and group facilitation rather than just giving people the folder with the information. (Training Lead SC040)

In another site, a self-directed workbook was also used but the approach was under review due to both the local Council and the training lead identifying this method was not appropriate, as the training was not being completed.

They are given a booklet but basically left with it . (Dementia Lead SC042)

The training facilitator in one site highlighted how she had removed as much written material as possible from the training, upon recognising that staff did not find it helpful to their learning.

Giving lots of hand-outs was not effective because it was just people getting stressed out because they couldn’t find a hand-out or they had too much information to read to process and they weren’t really focussing on the training (SC076 Training Facilitator)

Dementia training was offered to all staff working in the care homes irrespective of role.

You’re not going to have laundry staff that are experts in dementia because they don’t have to be. It’s not their role. But you still want your workforce to be fit for purpose and have an awareness with the client group they’re working with. (Training Lead SC040)

During training observations it was noted that the training leads in each site delivered content flexibly to meet the needs of the group, for example by tailoring examples they provided to the group participants and their role and asking for and responding to learner’s own practice examples to inform discussion. The trainers recognised the importance of tailoring provision to the needs of the organisation and range of staff attending.

Reaction to training

Staff responses to the training were generally positive across the three sites. During focus groups, interviews and immediately following training staff made comments such as interesting (SC040 Staff Member 026), informative (SC040 Staff Member 025) and t he best training I’ve ever been on (SC042 training observation field note). Key themes related to training reaction included the value of small group, face-to-face learning, a dislike for e-learning and the benefits of using case scenarios.

Overwhelmingly staff identified the importance of face-to-face learning and the ongoing support provided by the sites for staff during and after training.

I find personally I understand things better when it’s in a training setting, er, there is a group of you, when you know, er, giving ideas and all talking together about it rather than a question on a page. (SC042 Staff Member 034)

In one of the two sites (SC040) that utilised self-directed study via a work book, the training lead had added monthly reflective face-to-face sessions. However, one staff member commented that they would prefer it to be delivered as a full face-to-face session rather than

… having people go home and work on it on their own and then come back into the course just to talk about it. (Staff Member SC040 013)

In the other site the delivery approach had not yet been revised and staff commented on how unhelpful they found the method.

because it is how you respond to a person verbally. You can’t do that out of a book can you? (SC042 Focus Group P1)

On-line modules formed a component of induction in one site and had previously been part of training in another, however this was not viewed favourably by those in leadership positions, who saw it as little more than a tick-box exercise.

You know a monkey could sit and do it. (Unit Manager SC040 020). … ‘cause they can copy and they can say just tick tick, tick, that’s fine (SC076 Training Lead).

Staff also noted they found interactive learning activities and the use of video or other forms of case study scenarios particularly helpful in helping them to apply learning to practice.

Mostly the scenarios … . This scenario thing and it was exactly like, exact same as one of the residents in here. (SC040 Staff Member 013).

Videos have worked well … If you could find a decent video that supports a point that you’re trying to make and you can see it in practice it’s really good because issues that we have … role play is wonderful but it doesn’t really…it’s not an accurate simulation of someone with dementia. (SC076 Training Facilitator)

There was evidence from the interviews, focus groups (including vignette-based discussions) and observations of care practice that a range of learning had taken place. Key themes were gaining empathy and knowledge about the lived experience of dementia, and understanding individual needs. These themes were a consistent outcome of training across all three sites.

I feel I’ve gained a lot of understanding about dementia and how it progresses and you’ve sort of put yourself in their shoes and you think well that could be me some day, so I would hope that whoever’s looking after me would give me the care that I would expect and understand. (SC040 Focus Group P4)

… you just feel as though you need to help them more, whereas before I’d have dismissed them. I won’t say I was awful but I would have, I would have thought: Oh silly old fool or … . Whereas now I think I’ve got much more empathy with them and feeling more towards them. (SC042 Focus Group P1)

The importance of understanding and providing care that was person-centred and met individual residents’ needs was identified as a learning point by staff at two sites.

Staff can step back and say ‘that’s why that person does that. Now we know what to do’. (Staff Member SC040 014)

So you’ve got to individualise when you’re caring. (SC076 Focus Group 3 P2)

One staff member reported finding some content during the session overwhelming and that s/he only took in the information upon,

… reflect[ing] on it when you’re on the floor. (SC040 Staff member 026).

The learning that took place ‘on the job’ was also identified as important by a staff member at another site.

I think for training is good in some ways but to be here is more life, true, real-life, the way it is. For me it can be both but to be here you learn more. (SC042 Focus Group, P2).

Spreading training over 2-h sessions over a number of weeks, with some reflective activities to complete outside of the training room was also identified as helpful in supporting learning.

[It gives me a chance to] go home and it’s good just to sit, relaxing, writing your scenarios. You know what you’ve to do and what you’ve to say and you get time to think about it. (Staff Member SC040 026)

In another site opportunity to continue reflecting in a supported way outside of formal training was also offered through ‘drop-in’ sessions or provision of additional support materials.

They’ve got you in the back of their minds on you, on their radar to help you with other stuff as well as the Booklet. (SC042 Staff Member 033).

While most staff commented positively about the value of training, some of the more experienced staff in two of the sites indicated that for them there had been little new information covered in training they had attended.

With the Induction Training, there was nothing, nothing added to what I already knew. (SC042 Staff Member 034).

Whilst for other less experienced staff coverage of dementia in the initial induction was not in-depth enough to help them feel confident when commencing work in the home, or training content did not provide enough support to help them in the range of often challenging situations they might find themselves.

… how to get out of situations if somebody has got hold of my hair, how do I get out of that? (SC042 Staff Member 033).

Behaviour change

Themes related to behaviour change included adopting a more empathic and understanding approach, improved communication, provision of meaningful activity, a shift from task to person-focussed care.

Staff in two of the care homes (SC040, SC042) identified how training had helped them to deliver care that was more empathic and was understanding of resident behaviours and what they communicated about individual needs.

SC042 Staff Member P2: We’ve got one lady who goes back to when she was in the War and she was deported and she gets terribly upset and she thinks we’re keeping her in. So we just take her outside on the decking for a little bit, then she is okay. She’s not a prisoner of war anymore. ‘Cause she thinks we’re keeping her a prisoner. But I wouldn’t have known to treat her like that unless I’d known that that’s how dementia can affect you.

I: What might you have done before?

P2: Well, probably said, ‘Look you’re okay, sit down, have a cup of tea’ and basically get on with it, which I probably would have.

As a result of improved staff understanding one manager noted there was a demonstrable reduction in drugs used to manage behaviour in people with dementia, due to staff being able to support needs through psychosocial approaches.

There has been a real marked reduction in the number of drugs and that I can prove. That’s documented and it’s easy to do. (Unit Manager Sc040 020)

In two sites (SC040, SC076) improved staff communication was a behavioural outcome of training. Staff gave examples of approaches the training had taught them, such as wording questions so residents can give a yes/no answer. Keeping language simple and using picture prompts. There was also increased confidence in staff to communicate with residents.

I’m having a joke with them you know, talk about their families and they like talking about- you know talking about their families.. (Staff Member SC040 026).

Talk softer, come down to their level. It’s easier just to say ‘here’s your dinner’ you know and put it in front of them. I don’t do that anymore (SC076 Focus Group 1 P1)

The DCM data showed that in four of the five units observed there were more personal enhancers than detractors observed on average, per participant than detractors (see Fig.  1 ) and overall detraction levels were low. In one unit (B) at site SC040, however, more detractors were observed than enhancers during the mapping period. This indicates that in that unit on the days observations took place not all staff were communicating in person-centred ways.

Average number of personal detractors and enhancers observed per participant per hour by site and unit

All three sites indicated that implementing new activities in the home had resulted from staff attending training. In one home (SC040) this included one-to-one engagement, hand massages and cookery classes. They had also arranged visits from external professionals who gave Indian Head Massages, ran dance classes or delivered group music sessions. The latter two were particularly highlighted as being enjoyed by the residents.

You would not believe how good it is [the music session], it’s just amazing, such a good feeling. (Unit Manager SC040 020)

They just get on with it, some of them make themselves a drink and stuff. And I think just not saying: ‘Oh you can’t do that’ is wrong. It’s about observing them doing it, making sure they’re safe. I think that’s a good thing we’ve learnt from training, let them be independent. (SC042 Staff Member 802).

In site SC076 staff used a new SMART TV to look for old films, singers or YouTube clips that residents might enjoy. In site SC040 the maintenance worker had started promoting vegetable-growing amongst the residents after attending training. He understood what the residents needed in order to support them to take part in the project. The residents were able to sow the seeds, care for the potatoes, harvest them and then peel them ready to be eaten.

Making a shift from a task focussed to person-centred care was another behaviour change reported. In site SC040 staff commented that they felt they had ‘permission’ to focus on person-centred care such as activities and spending time with residents, rather than feeling they should be completing tasks. This change in behaviour was noted by the training lead.

[They are no longer focussed on] they have to do this for this time and this for this time and the individual gets lost so I think we’re breaking that down. (Training Lead SC040)

In site SC076 the manager identified that person-centred approaches had also been extended to the support of family members.

I think people exhibit more patience, more individualised care, more person-centred care. I think that goes for relatives as well. We support relatives in an individualised person-centred way, because some of the relatives need that care (Home Manager SC076)

Staff in one care home noted how training was one part of the bigger picture that had supported a shift in culture.

It validated that for us we were on the right track. Obviously things always need to be tweaked, I know that, but I think it was giving a bit of confidence that we’re on the right track. (SC040 Focus Group P3).

Outcomes and impact

Themes related to outcomes and impact included improved resident well-being and decreased distress; disparities and variability of experience; and high resident and relative satisfaction.

Staff across all three sites consistently stated they felt that, as a result of the changes staff had made to practice, residents were experiencing greater well-being and were less frequently distressed.

I do think the training has impacted on their wellbeing in a positive way [. . . ] The carers take a more, a better interest in, you know, what the person like(s) and needs are and how they can make it a better day for them. (SC040 Staff Member 014)

It made them less agitated, they had something to concentrate on, something to do which improved their mood massively. When you work out what activity is right for the right person you then get a better mood all day. (Home Manager SC042)

Our observations of care showed that while resident well-being was generally moderately good and levels of ill-being were low, this did differ between units within the same organisation and across different residents living in the same unit. Figure  2 presents the average Mood and Engagement Value per resident over the period they were observed, known in DCM as their Individual Well and Ill-being Score.

Individual Well and Ill-being Scores by setting

We found similar results when looking at engagement in activities (see Fig.  3 ). In some units, residents spent more of the observation period in disengaged and distressed behaviours (e.g. passive observation, disengagement, sleep, distress and repetitive behaviours) and less time engaged in active behaviours (e.g. interacting with others, singing, reminiscing, physical exercise, sensory stimulation, work-like activity etc).

Percentage of time spend in different behaviours during DCM observations

The residents’ and relatives’ satisfaction cards showed high overall satisfaction with care received and respondents felt staff understood their/the residents’ feelings and needs and were knowledgeable about dementia. The qualitative comments included positive aspects and some suggestions for ways care could be improved.

We’re only allowed one shower a week. They have a nice way with them. (Respondent 3 SC040)

My mum used to live in another home but since she came here she is much happier. The dementia care staff know their stuff and nothing is too much trouble. (Respondent 1 SC042)

My Auntie is very well cared for and all her needs are met. All the carers are very patient with her. There is always someone who can answer any questions I may have (Respondent 1 SC076)

In one site, a resident chose to take part in an interview. They said that they felt they were given choices at mealtimes through being given a menu with two different meal options to choose between and believed that staff members respected these choices.

Training barriers

Despite the sites being chosen for the positive aspects of their training, all still experienced a range of barriers to delivery and implementation. Common barriers across the sites included staff time, staffing levels and turnover, lack of dedicated training facilities and difficulties in gaining feedback from staff.

Staff time, staffing levels and turnover

In all three sites a lack of time, staffing levels and turnover were a challenge to training delivery and implementation. This included difficulties being able to free up staff to attend training due to difficulties covering shifts, the need to constantly train new staff in the more basic levels of training due to turnover and a lack of time for staff to implement learning in practice.

Eight people is an awful lot of people off the floor, you can’t, it is just impossible to do (SC040 Manager 019)

Turnover at the moment is really quite difficult to manage (SC042 Dementia Lead)

Two sites had previously required staff to undertake learning in their own time either via face-to-face or self-directed means. This had not been successful in terms of staff reaction to training or completion rates. As one manager stated:

You can’t just expect them to pitch up and not be paid (SC040 Manager 020)

P1 It’s not completed by any means. It was meant to be completed ages ago, P2 I’ve lost mine. (SC042 Focus Group)

Lack of dedicated training facilities

In two of the sites there were no dedicated training facilities available, meaning training was delivered in a lounge or other room in the care home that was often cramped and unsuitable.

Venues are normally an issue because you normally get put into a lounge. A lounge doesn’t have a lot of space really. Sometimes the rooms are quite small and that limits the number of people you can have in the room and limits, you might wanna do – can’t really facilitate or there may not be sufficient wi-fi… (Training Facilitator SC076)

Difficulties in getting feedback on training

In two sites the training lead/facilitators mentioned difficulties they experienced in getting honest and practical feedback from staff about how useful the training had been as well as impact on care practice.

It’s difficult to get out because they all say “We enjoy the training”. “Great, ok, what did you like?” You can ask it verbally or you……if you ask it verbally you get a better answer. If you ask them to write it down it doesn’t really come through…all of it. “Which bit was particularly useful for you?” “Yeah, well everything.” Ok. There’s not really real constructive to feed back in. (SC076 Training Facilitator)

I can’t say I’ve had fabulous feedback in terms of change (SC040 Training Facilitator)

Facilitating factors

Common facilitators of training delivery and implementation across the good practice sites included commitment of the organisation and management, skilled training facilitation and strong peer and team support.

Commitment of the organisation and management

The importance of organisational and managerial commitment to dementia training was a strong feature of all of the sites. This included an organisational culture and ethos that valued training, home or unit managers who supported training attendance and implementation in practice, and strong leadership for dementia training via a dementia and/or training lead.

As a company [name] are really, really keen and up there to make sure the staff are fit for purpose, well trained and can deliver good care and they feel quite passionate about it I think (SC040 Training Facilitator)

So, it has to come from the top. You can have the best carers in the world, but it makes no difference if the people at the top don’t want to actually give people time to learn, (SC042 Dementia Lead)

Skilled training facilitation

Skilled and flexible training facilitation was mentioned as a facilitator in all sites. The trainers made learning memorable and managers commented that staff often talked about dementia training when back on the units afterwards.

[The Training Lead] is quite flexible, she will come into the homes if the homes are struggling or short staff and she’s got people that need to do training. She’ll come round here rather than go out there. (SC042 Manager)

Strong peer and team support

Having a staff team who were motivated to learn, supportive of one another and who felt empowered to make suggestions for practice change was a facilitator at all three sites.

[Name of colleague] is really good at raising stuff. Because she’s an admin worker, her perspective is different. And she will quite often say: ‘But, why can’t you? Why?’ and sometimes in an organisation, that is what you need- people that will challenge, because otherwise you end up with, you all do it that way, because you all do it, and that way can lead to stagnation, bad practice. (SC076 Unit Manager)

The case studies identified a range of elements of good practice in relation to training design, delivery and implementation that are applicable not only to dementia training, but to broader training delivery within care home settings. As was reported by Beeber et al. [ 5 ] the design and delivery methods utilised were important and in the case studies particularly impacted on staff reactions to training and subsequent uptake. Findings across the three sites strongly support the use of face-to-face delivery, interactive and engaging teaching methods and the tailoring of training to the setting and staff roles of those attending. The preference for and benefits of face-to-face, interactive training in care home settings are reported in the international research literature see for example [ 37 , 38 ]. This were also a common feature of training delivery preferences of staff in other settings (e.g. acute hospitals [ 39 ]) within the broader What Works study. However, implementation of such methods is pragmatically challenging in light of the staffing and resource barriers that were identified at all sites, as well as the broad range of subjects and learning outcomes that staff training must address in order to meet national standards [ 40 , 41 ] (see for example [ 42 , 43 ]). Staffing issues and having the resources to support staff to attend and implement training have been reported as challenging within social care workforce development and intervention research [ 44 , 45 , 46 , 47 ]. This suggests that care provider organisations and researchers should consider resource and staffing issues and how they will be addressed or accommodated, before embarking on new programmes of staff training in care home settings.

In the case study sites, an organisational ethos and culture of commitment to dementia training, which was evidenced throughout the management team, helped to overcome some of the resource issues. This, coupled with the presence of dedicated training staff to develop, facilitate and champion training, provided a positive context in which training could be carried out and implemented despite the challenges. The importance of both top-down and bottom-up approaches to changing care practice through educational programmes in care home settings has been reported in other research. This includes active executive and management involvement and the presence of individual(s) to ‘champion’ implementation [ 13 , 38 , 47 ]. Where managers are seen as ‘far removed’ this can be a barrier to training implementation [ 46 ]. The organisational culture was also reflected in the peer support, and staff engagement in training attendance and in subsequent implementation. Resistance to change among staff teams [ 48 ] and the impact that individuals who are ‘rigid’, ‘closed-minded’ or ‘indifferent’ can have on colleagues’ motivation is another potential barrier [ 46 ]. This indicates that in the design of training programmes, trainers and organisations should not only consider the content and delivery but also how to prepare and engage the organisation and individual staff members. Without a team and organisational culture that is largely supportive of training and its implementation, the many barriers that exist are likely to prevent optimal impact [ 49 , 50 ].

It was disappointing that we were not able to recruit any domiciliary/home care organisations into the study. It is likely that some of the issues, barriers and facilitators may be similar to those experienced in care home settings due to the similarities there are in demographics and prior educational experience of both workforces. However, we would also anticipate domiciliary care providers and staff to experience a range of additional challenges associated with lone working, use of zero hours contracts [ 51 ] and a geographically spread workforce.

Limitations

There are a number of limitations in this study. While the case studies were in-depth, we were only able to include the three top-performing audit respondents in ‘best practice’ case studies. Therefore, the sample is not representative of the typical or average care home. Given staff had already accessed a range of dementia training, it was not possible to understand the direct impact on outcomes of individual training packages included in the case study. The respondents to the satisfaction survey for residents with dementia and their family members may reflect participation bias. Residents and family members who are more satisfied may be more likely to respond than others. Relatives who are dissatisfied may be concerned about raising issues if given their loved one is still being cared for in the care home. It is difficult to draw any firm conclusions about the impact of training on staff practice and resident outcomes from the observational data.

Conclusions and recommendations

Despite care homes being one of the most researched settings in terms of dementia training and its impact, relatively little is still known about how the emergent design and delivery features of effective training (e.g. face-to-face, tailored, flexible, interactive) can be implemented practically. Likewise, while an understanding of the ideal setting conditions for training and other psychosocial interventions is evolving, how these can be facilitated and sustained is still poorly understood or implemented. More research is still needed on the practical aspects of sustainable and impactful dementia training delivery and implementation in care home settings.

This study has added to our understanding of effective dementia education and training for care home staff. It suggests that training that is most likely to lead to positive outcomes across staff reactions, learning, behaviour change and outcomes for people with dementia has the following qualities. It:

Is delivered face-to-face to a small group using interactive methods such as discussion, case studies and practical exercises and activities;

Is tailored to the setting and role of staff attending and was inclusive of all staff working in direct care and non-care roles;

Provides ongoing support outside of the training room for staff to reflect on learning and implement training;

Includes methods that support staff to engage with the lived experience of people with dementia;

Is delivered by an experienced training facilitator who is able to engage and work flexibly with staff;

Is one component of achieving an organisational commitment to and culture of person-centred care;

Is supported by the home owners and management team in terms of resource and development of an organisational culture that values learning.

Availability of data and materials

The datasets generated and/or analysed during the current study are not publicly available but are available from the corresponding author on reasonable request.

Abbreviations

Behavioural Category Code

Dementia Care Mapping

Mood and Engagement Value

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Acknowledgements

We would like to thank all of the participating sites and individuals who gave their time freely to take part in this research. We would like to thank other members of the research team Dr. Sarah Smith, Dr. Sahdia Parveen, Dr. Andrea Capstick and Dr. David Meads, who contributed to study design and implementation. We would like to thank the members of the lay advisory group who provided insight and advice on study design, materials, analysis and dissemination. We would also like to thank Dr. Andrew Hart for his involvement in data analysis.

This study was funded by the National Institute for Health Research Policy Research Programme (NIHR PRP) under Grant PR-R10–0514-12006. The views expressed in the publication are those of the author(s) and not necessarily those of the NHS, the NIHR, the Department of Health and Social Care, ‘arms’ length bodies or other government departments.

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Contributions

CAS was Chief Investigator of the study and contributed to study design, data analysis and interpretation and drafting this manuscript. CS contributed to data acquisition, data analysis and interpretation and revising the manuscript. MD contributed to data acquisition, data analysis and interpretation and revising the manuscript. NB contributed to data acquisition, data analysis and interpretation and revising the manuscript. AD contributed to study design, data interpretation and revising the manuscript. SB contributed to data analysis, interpretation and revising the manuscript. JO was Lead for the Case study work package and contributed to study design, data analysis and interpretation and revising the manuscript. All authors have read and approved the final manuscript.

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Correspondence to Claire A. Surr .

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Ethical approval for the study was given by the Yorkshire and the Humber – Bradford Leeds NHS Research Ethics Committee [REC Ref 15/YH/0488]. All participants gave informed, written consent to participate.

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Additional file 1:.

Inclusion criteria and steps for selection of the case study sites. (DOCX 62 kb)

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Surr, C.A., Sass, C., Drury, M. et al. A collective case study of the features of impactful dementia training for care home staff. BMC Geriatr 19 , 175 (2019). https://doi.org/10.1186/s12877-019-1186-z

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This slide deck has been developed by Line Damsgaard, MD, Danish Dementia Research Centre, Rigshospitalet, University of Copenhagen, Denmark; and Professor Serge Gauthier, McGill University, Montréal, Québec, Canada, in collaboration with Cambridge (a division of Prime, Cambridge, UK).

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References: 1. Knopman DS, Amieva H, Petersen RC, et al. Alzheimer disease. Nat Rev Dis Primers 2021; 7 (1): 33.

2. Therriault J, Zimmer ER, Benedet AL, et al. Staging of Alzheimer’s disease: past, present, and future perspectives. Trends Mol Med 2022; 28 (9): 726–741.

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References: 1. Atri A. The Alzheimer’s disease clinical spectrum: diagnosis and management. Med Clin North Am 2019; 103 (2): 263–293.

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Case Report of a 63-Year-Old Patient With Alzheimer Disease and a Novel Presenilin 2 Mutation

Jennie l. wells.

* Department of Medicine, Division of Geriatric Medicine, Schulich School of Medicine and Dentistry, Western University

† St. Joseph’s Health Care London—Parkwood Institute

Stephen H. Pasternak

‡ Molecular Medicine Research Group, Robarts Research Institute

§ Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada

Early onset Alzheimer disease (EOAD) is a neurodegenerative dementing disorder that is relatively rare (<1% of all Alzheimer cases). Various genetic mutations of the presenilin 1 ( PSEN1 ) and presenilin 2 ( PSEN2 ) as well as the amyloid precursor protein (APP) gene have been implicated. Mutations of PSEN1 and PSEN2 alter γ-secretase enzyme that cleaves APP resulting in increase in the relative amount of the more amyloidogenic Aβ42 that is produced. 1

PSEN2 has been less studied than PSEN1 and fewer mutations are known. Here, we report a case of a 63-year-old woman (at the time of death) with the clinical history consistent with Alzheimer D, an autopsy with brain histopathology supporting Alzheimer disease (AD), congophylic angiopathy, and Lewy Body pathology, and whose medical genetic testing reveals a novel PSEN2 mutation of adenosine replacing cytosine at codon 222, nucleotide position 665 (lysine replacing threonine) that has never been previously reported. This suggests that genetic testing may be useful in older patients with mixed pathology.

CASE REPORT

The patient was referred to our specialty memory clinic at the age of 58 with a 2-year history of repetitiveness, memory loss, and executive function loss. Magnetic resonance imaging scan at age 58 revealed mild generalized cortical atrophy. She is white with 2 years of postsecondary education. Retirement at age 48 from employment as a manager in telecommunications company was because family finances allowed and not because of cognitive challenges with work. Progressive cognitive decline was evident by the report of deficits in instrumental activities of daily living performance over the past 9 months before her initial consultation in the memory clinic. Word finding and literacy skills were noted to have deteriorated in the preceding 6 months according to her spouse. Examples of functional losses were being slower in processing and carrying out instructions, not knowing how to turn off the stove, and becoming unable to assist in boat docking which was the couple’s pastime. She stopped driving a motor vehicle about 6 months before her memory clinic consultation. Her past medical history was relevant for hypercholesterolemia and vitamin D deficiency. She had no surgical history. She had no history of smoking, alcohol, or other drug misuse. Laboratory screening was normal. There was no first-degree family history of presenile dementia. Neurocognitive assessment at the first clinic visit revealed a Mini Mental State Examination (MMSE) score of 14/30; poor verbal fluency (patient was able to produce only 5 animal names and 1 F-word in 1 min) as well as poor visuospatial and executive skills (Fig. ​ (Fig.1). 1 ). She had fluent speech without semantic deficits. Her neurological examination was pertinent for normal muscle tone and power, mild ideomotor apraxia on performing commands for motor tasks with no suggestion of cerebellar dysfunction, normal gait, no frontal release signs. Her speech was fluent with obvious word finding difficulties but with no phonemic or semantic paraphrasic errors. Her general physical examination was unremarkable without evidence of presenile cataracts. She had normal hearing. There was no evidence of depression or psychotic symptoms.

Visuospatial and executive function testing at age 58.

At the time of the initial assessment, her mother was deceased at age 79 after a hip fracture with a history long-term smoking and idiopathic pulmonary fibrosis. Her family believes that there is possible German and Danish descent on her father’s side. Her father was alive and well at age 80 at the time of her presentation with a history coronary artery disease. He is still alive and well with no functional or cognitive concerns at age 87 at the time of writing this report. Her paternal grandfather died at approximately age 33 of appendicitis with her paternal grandmother living with mild memory loss but without known dementia or motor symptoms until age 76, dying after complications of abdominal surgery. Her paternal uncle was diagnosed with Parkinson disease in his 40s and died at age 58. Her maternal grandmother was reported to be functionally intact, but mildly forgetful at the time of her death at age 89. The maternal grandfather had multiple myocardial infarctions and died of congestive heart failure at age 75. She was the eldest of 4 siblings (ages 44 to 56 at the time of presentation); none had cognitive problems. She had no children.

Because of her young age and clinical presentation with no personality changes, language or motor change, nor fluctuations, EOAD was the most likely clinical diagnosis. As visuospatial challenges were marked at her first visit and poor depth perception developing over time, posterior cortical variant of AD was also on the differential as was atypical presentation of frontotemporal dementias. Without fluctuations, Parkinsonism, falls, hallucinations, or altered attention, Lewy Body dementia was deemed unlikely. After treatment with a cholinesterase inhibitor, her MMSE improved to 18/30, tested 15 months later with stability in function. Verbal fluency improved marginally with 7 animals and 3 F-words. After an additional 18 months, function and cognition declined (MMSE=13/30) so memantine was added. The stabilizing response to the cholinesterase inhibitor added some degree of confidence to the EOAD diagnosis. In the subsequent 4 years, she continued to decline in cognition and function such that admission to a care facility was required with associated total dependence for basic activities of daily living. Noted by family before transfer to the long-term care facility were episodic possible hallucinations. It was challenging to know if what was described was misinterpretation of objects in view or a true hallucination. During this time, she developed muscle rigidity, motor apraxias, worsening perceptual, and language skills and became dependent for all activities of daily livings. At the fourth year of treatment, occasional myoclonus was noted. She was a 1 person assist for walking because of increased risk of falls. After 1 year in the care home, she was admitted to the acute care hospital in respiratory distress. CT brain imaging during that admission revealed marked generalized global cortical atrophy and marked hippocampal atrophy (Fig. ​ (Fig.2). 2 ). She died at age 63 of pneumonia. An autopsy was performed confirming the cause of death and her diagnosis of AD, showing numerous plaques and tangles with congophilic amyloid angiopathy. In addition, there was prominent Lewy Body pathology noted in the amygdala.

Coronal view, computed tomographic image, patient age 63, showing significant generalized atrophy and dramatic hippocampal atrophy.

Three years before her death informed consent was obtained from the patient and family to perform medical genetic testing for EOAD. The standard panel offered by the laboratory was selected and included PSEN1 , PSEN2 , APP, and apoE analysis. Tests related to genes related to frontotemporal dementia were not requested based on clinical presentation and clinical judgement. This was carried out with blood samples and not cerebrospinal fluid because of patient, family, and health provider preference. The results revealed a novel PSEN2 mutation with an adenosine replacing cytosine at nucleotide position 665, codon 222 [amino acid substation of lysine for threonine at position 221 (L221T)]. This PSEN2 variant was noted to be novel to the laboratory’s database, noting that models predicted that this variant is likely pathogenic. The other notable potentially significant genetic finding is the apoliprotein E genotype was Є 3/4 .

β-amyloid (Aβ) is a 38 to 43 amino acid peptide that aggregates in AD forming toxic soluble oligomers and insoluble amyloid fibrils which form plaques. Aβ is produced by the cleavage of the APP first by an α-secretase, which produces a 99 amino acid C-terminal fragment of APP, and then at a variable “gamma” position by the γ-secretase which releases the Aβ peptide itself. It is this second γ-cleavage which determines the length and therefore the pathogenicity of the Aβ peptides, with 42 amino acid form of Aβ having a high propensity to aggregate and being more toxic.

The γ-secretase is composed of at least 4 proteins, mAph1, PEN2, nicastrin, and presenilin . Of these proteins, presenilin has 2 distinct isoforms ( PSEN1 and PSEN2 ), which contain the catalytic site responsible for the γ-cleavage. PSEN mutants are the most common genetic cause of AD with 247 mutations described in PSEN1 and 48 mutations described in PSEN2 (Alzgene database; www.alzforum.org/mutations ). PSEN2 mutations are reported to be associated with AD of both early onset and variable age onset as well as with other neurodegenerative disorders such as Lewy Body dementia, frontotemporal dementia, Parkinson dementia, and posterior cortical atrophy. 2 – 4 In addition, PSEN2 has associations with breast cancer and dilated cardiomyopathy. 3

PSEN2 mutants are believed to alter the γ-secretase cleavage of APP increasing the relative amount of the more toxic Aβ42. The mean age of onset in PSEN2 mutations, is 55.3 years but the range of onset is surprisingly wide, spanning 39 to 83 years. Over 52% of cases are over 60 years. All cases have extensive amyloid plaque and neurofibrillary tangles, and many have extensive alpha-synuclein pathology as well. 5

In considering the novelty of this reported PSEN2 mutation, a literature search of Medline, the Alzgene genetic database of PSEN2 and the Alzheimer Disease and Frontotemporal Dementia Mutation Databases (AD&FTMD) were completed ( www.molgen.vib-ua.be/ADMutations ). The mutation presented here (L221T) has never been described before.

Although this mutation has not been described, we believe that it is highly likely to be pathogenic. This mutation is not conservative, as it replaces a lysine residue which is positively charged with threonine which is an uncharged polar, hydrophilic amino acid. The mutation itself occurs in a small cytoplasmic loop between transmembrane domain 4 and 5, which is conserved in the PSEN1 gene, and in PSEN2 is highly conserved across vertebrates, including birds and zebrafish all the way to Caenorhabditis elegans , but differs in Drosophila melanogaster (fruit fly) (Fig. ​ (Fig.3). 3 ). We examined this mutation using several computer algorithms which examine the likelihood that a mutation will not be tolerated. Both SIFT ( http://sift.bii.a-star.edu.sg ) and PolyPhen-2.2.2 (HumVar) ( www.bork.embl-heidelberg.de/PolyPhen ) predicts that this variant is pathogenic. Interestingly, it is noted that PSEN1 mutations after amino acid 200 develop amyloid angiopathy. 5 , 7

PSEN2 sequence showing that lysine at position 221 is evolutionarily conserved. A 30 amino acid span of PSEN2 ( Homo sapiens ) is shown covering K221, which is shown in red. Amino acids which differ for are highlighted. Sequences shown are PSEN1 and PSEN2 (from H. sapiens ), Pan troglodytes (chimpanzee), Macaca mullatta (Rhesus Macaque monkey), Mus musculus (mouse), Gallus gallus (chicken), Caenorhabditis elegans , Danio rerio (zebrafish), Drosophila melanogaster (Drosophila; fruit fly). *Amino acids are identical across all samples; “:” conservative mutations with input sequence. Alignment performed using the tool MUSCLE. 6 PSEN indicates presenilin .

This patient also had an additional risk factor for AD, being a heterozygote for the apoЄ4 allele. Among other mechanisms, its presence reduces clearance of Aβ42 from the brain and increases glial activation. 8 Although the apoЄ4 allele is known to lower the age of onset of dementia in late onset AD, it has not been clearly shown to influence age of onset of EOAD in a limited case series. 9 It should be noted that heterozygote state may have contributed to an acceleration of her course given the known metabolism of apoЄ4 and its association with accelerated cerebral amyloid and known reduction in age of onset. 10

Given that there is no definite family history of autosomal dominant early onset dementia, it is likely that her PSEN2 mutation was a new random event. With the unusually wide age of onset it is conceivable that one of her parents could still harbor this PSEN2 mutation. The patient’s father, however, is currently 87 and living independently at the time of writing this manuscript, making him highly unlikely to be an EOAD carrier. Nonpaternity is an alternate explanation for the lack of known first-degree relative with EOAD; however, this is deemed unlikely by the family member who provided the supplemental history. Her mother died at age 79, so she could conceivably carry our mutation but we do not have access to this genetic material. Without extensive testing of many family members it would be impossible to speculate about autosomal recessive form of gene expression. In addition, the genetic testing requested was limited to presenilins , APP, and apoE mutations. Danish heritage may add Familial Danish dementia as a remote consideration; however, Familial Danish dementia has a much different clinical presentation with long tract signs, cerebellar dysfunction, onset in the fourth decade as well as hearing loss and cataracts at a young age. 11 This disease has high autosomal dominant penetration which also makes it less likely in the patient’s context. This specific gene (chromosome 13) was not tested. The autopsy findings do not support this possibility. There are reports of Familial AD pedigrees in Germany, including a Volga pedigree with PSEN141I mutation in exon 5, but this is clearly separate from our mutation which is in exon 7. Our mutation was also not observed in a recent cohort of 23 German individuals with EOAD which underwent whole genome sequencing, but did find 2 carriers of the Volga pedigree. It is also possible that both the PSEN2 mutation and the ApoE genotype contributed to her disease and early onset presentation. This case illustrates the multiple pathology types which occur in individuals bearing PSEN2 mutations, and highlights the later ages in which patients can present with PSEN2 mutations. 12

ACKNOWLEDGMENT

The authors acknowledge Gwyneth Duhn, RN, BNSc, MSc, for her support of this paper.

The authors declare no conflicts of interest.

Watch CBS News

Air pollution may be to blame for thousands of dementia cases each year, researchers say

By Alexander Tin

Edited By Paula Cohen

August 14, 2023 / 6:26 PM EDT / CBS News

Nearly 188,000 dementia cases in the U.S. each year may have been caused by air pollution, researchers estimate, with bad air quality from wildfires and agriculture showing the strongest links to a person's risk of Alzheimer's disease and other kinds of dementia later in life. 

Published Monday in the journal JAMA Network Open, the  new estimates are the latest to underscore the range of health risks scientists have long warned are being driven by air pollution. 

While studies have already linked overall bad air quality to a number of health problems , including the risk of developing dementia, the new study offers a finer-grained look at how specific causes of air pollution seem to be more strongly linked to dementia than others. 

Their findings were based on an analysis of data collected from a decades-long survey backed by the National Institutes of Health , following up with thousands of older adults around the country every two years about their health.

Researchers then combined those data with detailed air quality modeling, estimating what different people may have been exposed to in the specific areas where they lived. 

They focused on what scientists call PM 2.5 air pollution, a benchmark for very small particles — less than 2.5 micrometers wide, a fraction of the diameter of a human hair — that can be inhaled from the air. These types of particles can come from a variety of sources, including vehicle exhaust and wildfire smoke , and are linked to health effects ranging from coughing and shortness of breath to worsening asthma to an increased risk of death from heart disease.

"The environmental community has been working very hard for the past 10 to 15 years to be able to predict exposures," said Sara Adar, associate chair of epidemiology at the University of Michigan's School of Public Health.

Those drew on a range of data, including measurements from the Environmental Protection Agency and details about nearby factors that could affect their air quality. 

"They model all sources at once. Coal-fired power plants, agriculture, wildfires, traffic, all these different emission sources, and then they turn off the source in the model one at a time. And then they can see the difference in what levels are there with the emissions sources, and what are there without them," said Adar.

Their modeling had found the higher risk even after adjusting for a range of potential factors that could have led to muddled results, like sex, race and ethnicity, educational status and wealth. 

They also were able to adjust for whether people previously lived in urban or rural areas. 

While they also had information for where people moved during the survey, Adar acknowledged they did not have enough data to model every exposure or check for every difference throughout the course of their life — like where people were born — which might have impacted their results.

"Dementia takes a long time to develop. It's not something that might be, 'oh you've got a bad exposure last week, and now you have dementia.' It's more likely to build up over a lifetime," said Adar. 

Beyond the direct emissions from wildfires and agriculture, Adar noted their analysis was able to take into account other kinds of air pollution that can also be traced back to these sources.

In addition to the smoke emitted from wildfires, other toxic molecules can be carried with the smoke as they burn through communities. Farming can also worsen air pollution, resulting from the ammonia that are released by sources like manure and fertilizer.

"Farms will release a lot of ammonia gas, and then in the air with the sunlight and other pollutants out there, they'll react to make particles, and those particles are what we see are likely toxins for the brain," said Adar.

Adar and Boya Zhang, also a researcher at the school, say they hope their new findings could drive more targeted interventions to address this dementia risk. 

"Unlike many other common risk factors for dementia (eg, hypertension, stroke, and diabetes), exposures to air pollution can be modified at the population level, making it a prime target for large-scale prevention efforts," the study's authors wrote.

• Air Pollution
• Alzheimer's Disease

Alexander Tin is a digital reporter for CBS News based in the Washington, D.C. bureau. He covers the Biden administration's public health agencies, including the federal response to infectious disease outbreaks like COVID-19.

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Harris Chooses Walz

A guide to the career, politics and sudden stardom of gov. tim walz of minnesota, now vice president kamala harris’s running mate..

This transcript was created using speech recognition software. While it has been reviewed by human transcribers, it may contain errors. Please review the episode audio before quoting from this transcript and email [email protected] with any questions.

Hey, it’s Michael. Before we get started, I want to tell you about another show made by “The New York Times” that pairs perfectly with “The Daily.” It’s called “The Headlines.” It’s a show hosted by my colleague, Tracy Mumford, that quickly catches you up on the day’s top stories and features insights from “The Times” reporters who are covering them, all in about 10 minutes or less.

So if you like “The Daily”— and if you’re listening, I have to assume you do — I hope that means you’re going to “The Headlines” as well. You can now find “The Headlines” wherever you get your podcasts. So find it, subscribe to it, and thank you. And now, here’s today’s “Daily.”

From “The New York Times,” I’m Michael Barbaro. This is “The Daily.”

[MUSIC PLAYING]

Today, the story of how a little known Midwestern governor became Kamala Harris’s choice for a running mate. My colleague Ernesto Londoño walks us through the career, politics, and sudden stardom of Governor Tim Walz of Minnesota.

It’s Wednesday, August 7.

Ernesto, over the past few days, we watched Vice President Harris bring the final three contenders for her running mate to her house in Washington, DC, for a set of in-person interviews. And then we watched as she seemed to narrow her pool of choices down to a final two — the governor of Pennsylvania, Josh Shapiro, and the governor of Minnesota, Tim Walz. And now, of course, we know that she has made her choice. What has she told us about her campaign strategy, the way she views this race, in ultimately choosing Tim Walz?

Michael, I think what the choice tells us is that Kamala Harris was drawn to two qualities that Governor Walz brings to the table. And what’s interesting is they may seem to be in tension. For starters, here’s the ultimate everyday man, somebody who grew up in a small town in Middle America, served in the National Guard, was a high school teacher, a football coach, very plain-spoken, goes to campaign events wearing T-shirts and baseball caps, is a gun owner and very proud about it. He sort of embodies the Midwest.

And she clearly thinks that that is going to bring the kind of moderate, white, working class voters that the campaign needs in swing states to come to them, to make this feel like a balanced ticket and something that will give her enough of the crucial votes to defeat Donald Trump in the fall.

On the other hand, as governor, he passed a slew of pretty progressive legislation in the past couple of years, everything from abortion rights to gun control. So these things are likely to appeal to bread and butter Democrats.

But the question is, when voters have examined these two facets of Tim Walz, may it bring them enough enthusiasm from the base and enough undecided voters that the campaign desperately needs, or at some point, do these two aspects of him start canceling each other out?

Right. In short, you’re saying Harris is betting on a dual appeal from Walz to two essential constituencies, but the risk is that the appeal to one of them is just much, much greater than to the other.

Right. You could definitely see a scenario where voters, once they’ve examined Tim Walz’s story and legacy, may conclude that both of these candidates are quite liberal.

OK, so tell us the story of Tim Walz, a story that I think a lot of us don’t know because we really don’t know Walz all that well, and how he has come to embody these two qualities and that tension that you just described.

Michael, the origin story of Tim Walz’s political career is quite fascinating.

He and his wife were teachers in a small city south of Minneapolis. And in 2004, when George W. Bush was running for re-election, Walz took a group of his students to a political rally in his hometown. They wanted to just see the president make his case. And a strange scuffle happened when they were trying to get in.

Well, one of the kids had a John Kerry sticker on his wallet. And this is where the individual says, well, you’re not going to be allowed to enter. You’ve been deemed a threat.

Apparently, one of the students had a sticker for Bush’s rival, John Kerry, on his wallet. And security officials at the rally didn’t want to let them in.

And I said, oh, it’s OK. They’re with me. And who are you? And I said, I’m Tim Walz. I’m their teacher here, and showed them my ID. And they said, well, you two have been deemed a threat to the president. And I said, well, that’s not true. And it kind of escalated.

And this really ticked off Tim Walz. He was really upset. There was a fight and a confrontation at the rally.

At this point in time, I’m kind of nervous. I’m getting arrested. So I’m like saying, well, I’m Teacher of the Year in Mankato. And they didn’t care about that. And it was kind of a sad epiphany moment, how it felt for people to be looked right through by people. These people didn’t see me. And this is happening.

And ultimately, he sort of walks away from this moment feeling really sick of the Bush administration, the politics of the day. And he turns around and volunteers for the Kerry campaign.

And then the more interested he becomes in politics in this era, he starts looking around his congressional district, and there’s a Republican who’s held the seat for many, many years. This was a largely rural district in southern Minnesota. And there’s no reason to believe that a newcomer to politics, somebody without a donor base, could make a run for this seat and win.

But Walz signs up for this weekend boot camp, where expert campaigners train newcomers who want to run for office. And he gets really enthused by the idea that he can pull it off. So he starts raising money with the support of an army of students who become so thrilled and energized by the prospect that their nerdy and kind geography teacher is making this uphill bid for a congressional race.

So his campaign staff is basically his former students.

That’s right. And he proves to be a formidable candidate. He draws a lot of attention to his experience in the classroom and as a coach.

When I coached football, these stands held about 3,000 people. That’s a lot. It’s also the number of American soldiers who have died fighting in Iraq.

He’s a very strong advocate for pulling out of the war in Iraq.

Serving right now are kids that I taught, coached, and trained to be soldiers. They deserve a plan for Iraq to govern itself, so they can come home.

And one thing that happens in the campaign that is really surprising to people is he comes out as being in favor of same-sex marriage. Now, it’s useful to remember that this is 2006, when the vast majority of Democrats, Democrats running for most elected office, were not ready to come out in favor of same-sex marriage.

And here’s a guy who’s new to politics, who’s trying to unseat a Republican who’s held on to his seat for more than 12 years, taking what appeared to be a reckless position on something. And when he was asked about it at the time, Tim Walz told a supporter, this just happens to be what I believe in. And I’d rather lose a race that I’ve ran being true and consistent to my values than try to run as somebody I’m not.

And of course, he wins.

Yes. To everybody’s surprise, he pulled it off.

So from the get-go, he shows a kind of maverick, “politics be damned” quality, taking stands that he knows may be unpopular among the voters he’s trying to win over. But he’s got some innate political gifts that are all making it work.

Yeah, I think that first campaign showed us that Tim Walz had real political chops. He was a very effective campaigner. And people really liked him. When he was knocking on doors, when he was introducing himself to voters, they saw him as somebody who was very genuine and who was admirable.

So once he gets elected in this conservative leaning district in Minnesota, what does he actually do in Congress?

In Congress, he develops a reputation for being somebody who can work across the aisle. And this is a period where Democrats and Republicans were deeply polarized over the Iraq War. He spends a lot of his time lobbying to expand benefits for veterans, so it’s easier for them to go to college after their service, and also becomes a leading voice in the quest to repeal Don’t Ask, Don’t Tell, the policy that prohibited openly gay servicemen from serving in uniform.

And he remained really popular. He easily won re-election five times. The last time he runs for his seat happens to be 2016, when President Trump wins his district by about 15 points.

And still, voters kept Tim Walz in office.

I think it’s important to note what you just said. Walz is distinguishing himself as a Democrat who can take some pretty progressive positions, as he did in that first campaign on gay rights, as he did with Don’t Ask, Don’t Tell, and keep winning in very Trump-friendly districts of his state.

That’s right. And as he’s serving his sixth term in office, he sets his sights on the governor’s mansion and decides to run for office in 2018. He wins that race easily. And early on, during his time as governor, the eyes of the world are on Minnesota after a police officer kills George Floyd. And what we see is massive looting and protests in Minneapolis.

Right, and remind us how Governor Walz handles that violence, those protests.

Yeah, I think that’s a crucial chapter in Tim Walz’s political career and one that will come under scrutiny in the days ahead.

After George Floyd was killed on a Monday —

People are upset, and they’re tired. And being Black in Minnesota already has a stigma and a mark on your back.

— protests took root in Minneapolis.

Y’all want to sit out here and shoot off your rubber bullets and tear gas.

And they got progressively larger and more violent.

There comes a point where the mayor and the police chief in Minneapolis plead for help. They ask the governor to send in the National Guard. And crucially, that request was not immediately heeded.

This is the third precinct here. There are fires burning to the left of it at the —

And at the height of the crisis, a police precinct building was abandoned.

There’s someone climbing up the wall right now, kicking the window in, trying to climb up the wall.

Because city officials grew concerned that protesters were about to overrun it and may attack the cops inside their own turf.

[EXPLOSIONS]

And the building is set on fire.

Right, a very memorable image. I can recall it happening in real-time.

Yeah, and in the days that followed, I think there were a lot of questions of why the governor didn’t send in troops earlier and whether a more muscular, decisive response could have averted some of the destruction that spread through the city.

And how does Walz end up explaining his decision not to send in the National Guard more quickly?

The governor and his administration have said that they were really, really dealing with an unprecedented challenge. And I think there was a concern that sending in troops into this really, really tense situation could have done more to escalate rather than pacify things on the street.

But in the weeks and months that followed, there were a lot of questions about Governor Walz’s leadership. And there were critics who said, during what may have been the most challenging week of his life, we saw a governor who was indecisive and who waited too long to send in resources that ultimately allowed the city to get to a semblance of order.

Right, and it feels like this is a moment that will almost assuredly be used against him by Donald Trump and JD Vance, the Republican ticket, which has made law and order so central to their message in this campaign.

Yeah, absolutely. And here in Minnesota, that was certainly a liability for him when he ran for re-election in 2022. But voters kept him in office, and he won that race handily. And not only did he win, but Democrats managed to flip the Senate and have full control of the legislature on his watch.

And that sets in motion one of the most productive legislative sessions in Minnesota history, where Tim Walz and his allies in the House and the Senate managed to pass a trove of really progressive legislation, oftentimes on a party vote.

Tell us about some of that legislation.

Well, Minnesota becomes the first state in the wake of the Supreme Court ending the constitutional right to abortion to actually codify this right under state statute. And they did a lot more stuff. They had a huge budget surplus, and they used that, for instance, to fund meals for all school children.

They managed to pass a couple of gun control laws that were very contentious. They gave the right to undocumented immigrants to get driver’s licenses. They legalized recreational marijuana. And finally, the governor takes a pretty bold stance on this issue of gender affirming care for transgender kids and teenagers, and says that Minnesota will be a safe haven for people who want that health care.

So, Ernesto, so how should we think about that blitz of legislation and the largely progressive tone of it, given the way that Walz had campaigned and succeeded up to that moment as somebody with such broad appeal across the political spectrum?

When the governor was asked whether this had been too much too quickly in terms of progressive legislation, his answer was that these were broadly popular policies, that these are issues Democrats had campaigned on. And here, Democrats had a window of opportunity where they were in control of the governor’s mansion and control of the House, the Senate, and that when you have political capital, you spend it.

But when you start listening to Republicans in Minnesota, they say, here’s a guy who campaigned on this mantra of “One Minnesota.” That was his campaign slogan. And he sort of came into office with this promise that he would govern in a bipartisan way, reach across the aisle.

But when they had all the votes they needed to pass their policies, Republicans felt that Walz was not bothering to bring them into the fold and to pass legislation that was going to be palatable to conservatives in the state. So I think people who once regarded him as a moderate now start seeing him as somebody who, when he had the power, acted in ways that were really progressive and liberal.

So at the height of his power, Governor Walz emerges as somebody who, when given a shot at getting done what he really wants to get done with a Democratic legislature, is a pretty progressive leader, even at the risk of being somewhat at odds with his earlier image as more moderate, because in his mind, enough people in the state are behind these policies.

Yeah, and I think he assumed that he had banked enough goodwill and that people across the state liked him enough to tolerate policies they may have disagreed with. And I think it’s safe to say, among the people who cover him here regularly, there was never any real hint that Tim Walz was eyeing a run for higher office. He’s not somebody who has written the kind of political memoir that oftentimes serves as a case of what you would bring to a national ticket or to the White House. And he seems pretty happy with a state job.

So it was a huge surprise when Tim Walz starts going viral through a string of cable news appearances right after President Biden drops out of the race, and the Democrats are scrambling to put Harris at the top of the ticket. And what becomes clear is that Walz is very forcefully auditioning for the role of vice president, and Vice President. Harris starts taking him very seriously.

We’ll be right back.

So, Ernesto, tell us about this cable news audition that Governor Walz undertakes over the past few weeks and how, ultimately, it seemed to help him land this job of being Harris’s running mate.

I think Walz does something really interesting, and that is that he says that Democrats shouldn’t be talking about Trump and Vance as existential threats. He kind of makes the case that Democrats have been in this state of fear and paralysis for too long, and that it’s not serving them well. So the word he latches onto is “weird.”

Well, it’s true. These guys are just weird.

It is. It is.

And they’re running for he-man women hater’s club or something. That’s what they go at. That’s not what people are interested in.

And I think one other thing we see in Walz is somebody who’s putting himself out there as a foil to JD Vance.

That angst that JD Vance talks about in “Hillbilly Elegy,” none of my hillbilly cousins went to Yale, and none of them went on to be venture capitalists or whatever. It’s not —

I think the case he’s making is that Tim Walz is a more authentic embodiment of small town values.

What I know is, is that people like JD Vance know nothing about small town America. My town had 400 people in it, 24 kids in my graduating class. 12 were cousins. And he gets it all wrong. It’s not about hate.

And behind the scenes, people from Tim Walz’s days on Capitol Hill start calling everybody they know in the Harris campaign and the Harris orbit and saying, here’s a guy who has executive experience as governor, but also somebody who has a really impressive record from his time on Capitol Hill and somebody who could be an asset in helping a Harris administration pass tough legislation. So you should take a hard look at this guy.

Which is, of course, exactly what Harris ends up doing. And I want to talk for a moment about how Harris announces Walz as her running mate on Tuesday morning. She did it in an Instagram message. And it felt like the way she did it very much embraced this idea that you raised earlier, Ernesto, that Walz contains these two appeals, one to the Democratic base, one to the white working class.

Harris specifically cites the work that Walz did with Republicans on infrastructure and then cites his work on gun control. She mentions that he was a football coach and the founder of the high school Gay Straight Alliance. She’s straddling these two versions of Walz.

But I want to linger on the idea for a moment of Walz’s vulnerabilities, because once he becomes Harris’s running mate, Harris and Walz are going to lose a fair amount of control over how they present him to the country, because he’s going to become the subject of very fierce attacks from the Republicans in this race. So talk about that for just a moment.

Yeah, I mean, it’s important to keep in mind that Governor Walz has never endured the scrutiny of a presidential race. So the questions he’s going to be asked and the way his record is going to be looked at is going to be different and sharper. I think the Harris campaign is billing him as, first and foremost, a fighter for the middle class. And I think that certainly will have some appeal.

But I think in coming days, there’s going to be a lot of attention drawn to parts of his record that may be unpopular with many voters. For instance, giving undocumented immigrants driver’s licenses, which Governor Walz championed. It’s likely to provide fodder for an attack ad.

The very dramatic footage of Minneapolis burning in 2020 is also something that I think people will be drawn to. And there’s going to be interest in reexamining what the governor did and what he could have done differently to avert the chaos.

And on Tuesday, we saw that the Trump campaign wasted no time in trying to define Tim Walz as soft on crime, permissive on immigration policy. And they also made clear they wanted to relitigate the era of George Floyd’s killing. And specifically, they want to try to tie him to the effort at the time to defund the police, which is a movement that Walz personally never endorsed.

So the Republican attack here will be pretty simple. Walz is liberal. Harris is liberal. So, in their efforts to speak to especially white working class and rural voters in swing states, the Trump campaign is going to say this is not the ticket for that group of voters. This is the ticket of burning police precincts and gun control. And of course, that may not be fair, but that’s very likely going to be the message over the next couple of months.

Right. I think there’s going to be effort to portray him as a radical liberal who has used his small town roots to put on this sort of veneer of being a moderate and a really sort of understanding and being part of the segments of the electorate that I think are critical in this election.

I want to speak for just a moment about the person Harris did not pick when she chose Walz because many Democrats had felt that Walz was a potentially too liberal seeming running mate for a candidate, Kamala Harris, who herself comes from a blue state and is caricatured by the Republicans as liberal herself.

And the person she didn’t choose was Governor Josh Shapiro of Pennsylvania, who was seen as having a huge appeal in that particular key swing state, but also presented risks of his own of alienating parts of the Democratic base with his well-documented support for Israel and his criticism of campus protesters. How should we think about the fact that, ultimately, Harris chose Walz over Shapiro?

Yeah, I think in the final stretch of this campaign to be the vice presidential pick, we started seeing a lot of acrimony in pockets of the Democratic base, drawing attention to the fact that Governor Shapiro could be divisive on Gaza, which has really sort of split the party in recent months.

So I think at the end of the day, they made a calculation that Tim Walz would be more of a unifying figure and would be somebody who would inspire and energize enough pockets of the electorate that they need, particularly in the Midwest, to make him the stronger and more exciting pick and somebody who wouldn’t force them to go back to defending and relitigating the Biden administration’s record on Israel and on the war in Gaza.

Right, and then, on Tuesday night, we got our first glimpse of Harris and Walz together on stage for the first time at a campaign rally. I’m curious, what struck you about their debut together.

Good evening, Philadelphia.

I think everybody was watching the opening scene of this rally to see what the chemistry between these two people was going to be like. And they both seemed giddy. They were literally, at times, bouncing with enthusiasm.

Since the day that I announced my candidacy, I set out to find a partner who can help build this brighter future.

So Pennsylvania, I’m here today because I found such a leader.

Governor Tim Walz of the great state of Minnesota.

They soon got down to business. And that business was how to define Tim Waltz for voters who don’t know him well.

To those who know him best, Tim is more than a governor.

And right off the bat, we saw that Kamala Harris really highlighted a lot of pieces of his pre-political career.

To his former high school football players, he was Coach.

She repeatedly called him Coach Walz, Mr. Walz, evoking his time in the classroom, and even used his military title from his days in the Army.

To his fellow veterans, he is Sergeant Major Walz.

And then when it came time for Tim Walz to introduce himself on this massive stage —

Welcome the next vice president of the United States, Tim Walz.

— he drew a lot of attention to his small town roots.

I was born in West Point, Nebraska. I lived in Butte, a small town of 400.

He said something that he said repeatedly recently in campaign appearances, which is —

In Minnesota, we respect our neighbors and their personal choices that they make. Even if we wouldn’t make the same choice for ourselves, there’s a golden rule — mind your own damn business.

The golden rule of small towns is you mind your own damn business, which is something he said in the context of his argument that Republicans have been limiting, rather than expanding, people’s rights. But he also drew attention to the fact that he’s a gun owner.

By the way, as you heard, I was one of the best shots in Congress. But in Minnesota, we believe in the Second Amendment, but we also believe in common sense gun violence laws.

And then when it came time to draw a sharp contrast with their opponents, Tim Walz said, these guys are phonies.

Donald Trump is not fighting for you or your family. He never sat at that kitchen table like the one I grew up at, wondering how we were going to pay the bills. He sat at his country club in Mar-a-Lago, wondering how he can cut taxes for his rich friends.

He said it’s actually people like me and Kamala Harris who come from humble origins and showed what is possible in America when you hail from a working class background, and you seize opportunities that were available to you.

Thank you, Philadelphia. Thank you, Vice President. God bless America.

So when it comes to this question of Walz’s dual identities and dual appeals, what did we learn on day one of this new Democratic ticket, do you think?

I think the campaign is trying to convey that these two facets of Tim Walz’s life are not mutually exclusive, that they don’t need to be in tension. They don’t cancel each other out. They’re both part of Tim Walz’s story. And I think that’s how they’re going to present him from now until Election Day.

Ernesto, thank you very much. We appreciate it.

It’s my pleasure, Michael.

Here’s what else you need to know today. On Tuesday, Hamas said that Yahya Sinwar, one of the masterminds behind the deadly October 7 attacks on Israel, had consolidated his power over the entire organization. Until now, Sinwar had held the title of Hamas’s leader in Gaza. But with the assassination of Hamas’s top political leader by Israel last week, Hamas said that Sinwar would take on that title as well. Sinwar remains a major target of Israel and is believed to have been hiding in tunnels underneath Gaza since October 7.

And the US Department of Justice has charged a Pakistani man with ties to Iran with trying to hire a hitman to assassinate political figures in the United States. The man recently traveled to the US and was arrested in New York last month. American authorities believe that his potential targets likely included former President Trump.

Today’s episode was produced by Alex Stern, Eric Krupke, and Olivia Natt. It was edited by Lisa Chow and Patricia Willens, contains original music by Pat McCusker and Marion Lozano, and was engineered by Alyssa Moxley. Our theme music is by Jim Brunberg and Ben Landsverk of Wonderly. Special thanks to Nick Pittman and Minnesota Public Radio.

That’s it for “The Daily.” I’m Michael Barbaro. See you tomorrow.

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Earlier this summer, few Democrats could have identified Gov. Tim Walz of Minnesota.

But, in a matter of weeks, Mr. Walz has garnered an enthusiastic following in his party, particularly among the liberals who cheer on his progressive policies. On Tuesday, Vice President Kamala Harris named him as her running mate. Ernesto Londoño, who reports for The Times from Minnesota, walks us through Mr. Walz’s career, politics and sudden stardom.

On today’s episode

Ernesto Londoño , a reporter for The Times based in Minnesota, covering news in the Midwest.

Background reading

Who is Tim Walz , Kamala Harris’s running mate?

Mr. Walz has faced criticism for his response to the George Floyd protests.

There are a lot of ways to listen to The Daily. Here’s how.

We aim to make transcripts available the next workday after an episode’s publication. You can find them at the top of the page.

The Daily is made by Rachel Quester, Lynsea Garrison, Clare Toeniskoetter, Paige Cowett, Michael Simon Johnson, Brad Fisher, Chris Wood, Jessica Cheung, Stella Tan, Alexandra Leigh Young, Lisa Chow, Eric Krupke, Marc Georges, Luke Vander Ploeg, M.J. Davis Lin, Dan Powell, Sydney Harper, Michael Benoist, Liz O. Baylen, Asthaa Chaturvedi, Rachelle Bonja, Diana Nguyen, Marion Lozano, Corey Schreppel, Rob Szypko, Elisheba Ittoop, Mooj Zadie, Patricia Willens, Rowan Niemisto, Jody Becker, Rikki Novetsky, Nina Feldman, Will Reid, Carlos Prieto, Ben Calhoun, Susan Lee, Lexie Diao, Mary Wilson, Alex Stern, Sophia Lanman, Shannon Lin, Diane Wong, Devon Taylor, Alyssa Moxley, Olivia Natt, Daniel Ramirez and Brendan Klinkenberg.

Our theme music is by Jim Brunberg and Ben Landsverk of Wonderly. Special thanks to Sam Dolnick, Paula Szuchman, Lisa Tobin, Larissa Anderson, Julia Simon, Sofia Milan, Mahima Chablani, Elizabeth Davis-Moorer, Jeffrey Miranda, Maddy Masiello, Isabella Anderson, Nina Lassam and Nick Pitman.

An earlier version of this episode misstated the subject that Walz’s wife taught. She taught English, not Social Studies.

How we handle corrections

Ernesto Londoño is a Times reporter based in Minnesota, covering news in the Midwest and drug use and counternarcotics policy. More about Ernesto Londoño

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