memory and dementia

Question 1

what is dementia

Answer 1

• Dementia - describes a collection of symptoms associated with impaired cognitive abilities and the ability to carry out day-to-day activities:
  
  • Memory loss
  • Difficulty sustaining attention
  • Language
  • Disorientation is space and time
  • Mood, social, and behavioural changes
    · Dementia is NOT a diagnosis in it’s own right but can be caused by a number of biological diseases.
• Although dementia is more common in older adulthood, it is NOT a normal part of ageing.

Question 2

how prevelant is dementia

Answer 2

· In the UK - 850,000 people estimated to be living with dementia, this is roughly 1 in 14 people over the age of 65 years.
· This figure is increasing -> 2 million people in the UK will have dementia by 2050.
· Alzheimer’s disease is the most common causes of dementia -> 60-70% cases.
- Other common pathologies include cerebrovascular disease and neocortical Lewy body disease.

Question 3

alzheimers disease

Answer 3

· Neurodegenerative disease - progressive, irreversible deterioration in cognitive abilities and daily function.
· In most people, symptoms of Alzheimer’s Disease appear after age 60.
· First discovered it by Alois Alzheimer, in the 1950s.
- This was due to a woman coming in Auguste D, she was diagnosed at 51.

Question 4

individual differences in symptom progression

Answer 4

· The way that a person experiences Alzheimer’s disease will depend on many factors, e.g., genes, physical health, personality and emotional resilience, the medication they take and the support they can rely on.
· Cognitive status over time for 9 participants followed over 5 years.
- Rusted and Sheppard, 2002

Question 5

atrophy

Answer 5

· Neuronal loss, reduction in grey and white matter volume.
· Topographical progression: i) medial temporal lobe, ii) wider temporal regions, parietal and frontal areas, iii) widespread atrophy with visual and motor areas spared until late disease stages.
- Commonly looked at using structural magnetic resonance imaging.

Question 6

hippocampal atrophy and memory

Answer 6

Brain slices showing gradual loss of hippocampal volume in people with Mild Cognitive impairment over 36 months.

Question 7

neurotransmitter production and function is impaired

Answer 7

· Synaptic dysfunction - altered communication between neurons.
· Loss of cell bodies in Nucleus Basalis of Meynert very early marker of Alzheimer’s.
· These cell bodies are involved in the production of acetylcholine (cholinergic neurotransmitter system).
- Medications to reduce dementia symptoms boost brain’s supply of acetylcholine.

Question 8

measuring in vivo

Answer 8

· Quantification and localisation of amyloid and tau:
- Cerebrospinal fluid
- Bloods
- Positron emission tomography (PET) scans

Question 9

localisation of amyloid

Answer 9

· B-amyloid deposition first occurs in structures of the default mode network - the posterior cingulate cortex, precuneus, and medial prefrontal cortex.
- Associated with cognitive deficits and altered brain activity.

Question 10

localisation of tau

Answer 10

· Tau deposition follows Braak staging; localised to MTL in earliest stages of disease.
- Density of tau correlates better wit memory loss than amount of B-amyloid.

Question 11

biomarker profile

Answer 11

· B-amyloid deposition can occur without clinical dementia.
- 25-30% of healthy older adults have diagnostically significant levels
- Co-occurrence of B-amyloid and abnormal tau deposits drive neurodegeneration and progression of Alzheimer’s Disease.

Question 12

lifespan approach

Answer 12

· Characterising risk - who is most at risk and why?
· Prevention - what actions can we take to manage risk of future neurodegeneration?
· Early detection- how do we spot individuals in the very earliest stages of Alzheimer’s Disease?
- Monitoring and lifestyle management - how does Alzheimer’s affect the lives of those living with dementia and what can we do to help?

Question 13

what types of memory are affected

Answer 13

· Episodic memory - short and long term
· Semantic memory
· Working memory - flexibility of representations
· Spatial memory
- Lexicon

Question 14

how do we assess memory impairment

Answer 14

· Benefits of in-clinical memory assessment: quick, easy-to administer, widespread adoption.
- Novel methods e.g., VR tests of spatial memory, smartphone-based measures.

Question 15

targeting the cognitive functions most vulnerable to early change

Answer 15

· Mnemonic discrimination is the ability to encode and retrieve distinct memories from among events which share many common features.
- Memory tasks utilize perceptually and conceptually similar to test mnemonic discrimination or lure discrimination.

Question 16

mnemonic discrimination

Answer 16

• Mnemonic discrimination errors:
  · Are increase in individuals with a diagnosis of Mild Cognitive Impairment.
  · Correlate with covert Alzheimer’s pathology in older adults without a diagnosis.
  · Are caused by altered brain function (proxied via fMRI BOLD response) in the memory regions of the medial temporal lobe.
  · As such, mnemonic discrimination tasks are a valuable tool for characterising mid-life risk.
• Performance on this task is used as a tool for testing out new interventions.

Question 17

everyday life - tea making

Answer 17

· Multiple cognitive processes involved in even simple day to day tasks….
- Semantic memory - what makes tea?
- Spatial memory - where is the sugar?
- Autobiographic memory - dad likes two sugars?
- Working memory - what have I just done?
- Observation studies: a really important tool for a) learning how Alzheimer’s affects daily function, and b) thinking about how to promote independence for longer.

Question 18

everyday life - tea making 2

Answer 18

· Tea-making errors made by Stroke and Closed Head Injury patients:
- Omissions - failing to use milk
- Sequence - adding mil to kettle
- Substitution - stirring cup with a fork
- Additions - blending two routines
- Spatial - holding wrong end of spoon
- Other - quantity errors/task fail
· Rusted and Sheppard (2002) longitudinally monitored individuals living with dementia’s tea-making abilities over 5 years.
· Different approaches to measuring tea-making ability:
- Verbal description from memory
- Observation in own kitchen
- Observation in novel environment
- Instructing someone else how to make tea

Question 19

mean proportion of items recalled from own protocol

Answer 19

· Memories not lost, jumbled or fragmented; instead, difficult to access.
- Signpost for interventions: engage procedural memory, increase cues at transition points in routine.

Question 20

risk factors

Answer 20

· Challenge - how do we detect who will develop Alzheimer’s and when?
- Huge individual differences in the impact of normal ageing and neurodegenerative disease.

Question 21

our genes play a big role

Answer 21

· Deterministic genes are more closely tied to familial or early-onset Alzheimer’s. These account for <1% of cases.
- Chromosome 21, chromosome 14.
· Risk genes are associated with a higher incidence of Alzheimer’s but are not sufficient to cause it. Linked to ‘sporadic’ Alzheimer’s disease.
- Chromosome 19
- Polygenic risk

Question 22

APOE e4

Answer 22

· Associated with substantially greater risk of future Alzheimer’s disease and poorer cognitive ageing in healthy older adulthood.
- Cognitive, structural and functional brain differences from youth.

Question 23

summary

Answer 23

· Alzheimer’s is a biological disease, not just part of healthy ageing. The hallmark pathologies of Alzheimer’s (amyloid, tau and neurodegeneration) are observable prior to clinically relevant impairment.
· Memory deficits are a key component of dementia, but not at all. Developing novel assessment techniques, including observation of real-world behaviours, can allow us to diagnose the disease early, monitor symptoms, and improve the lives of people living with dementia.
- Age and genetic risk factors play a huge role in our likelihood of developing dementia. However, there are things we can do to reduce risk. Lifestyle and environmental changes can reduce risk for dementia by as much as 40%.