Cognitive disorders of old age

Question 1

Discuss variability of cognitive decline between individuals

Answer 1

VERY high degree of normal variability

For example, while delayed recall performance is within quite a narrow range of scores for people in their 40s, that range increases markedly for people in their 80s.

Question 2

What is cognitive decline without functional impaired considered?

Answer 2

Prodrome (warning sign of disease) - known as mild cognitive impairment MCI

Question 3

What is MCI?

Answer 3

MCI is a subclinical disease -e.g. minor vascular episodes that were not noticed-, and is difficult to distinguish from normal aging

Question 4

Describe how normal cognitive decline also varies?

Answer 4

Varies across domains of cognition: performance declines with increasing age for processing speed, working memory, LTM, and reasoning, but NOT for world knowledge (=semantic memory)

Crystallized intelligence (the ability to use the knowledge that was previously acquired through education and experience) and skill learning (e.g. mirror drawing) are also preserved, although the latter may take longer.

However, it is also important to differentiate between the effects on these and the effects on sensory processing - vision, hearing etc. - e.g. slower processing speed may result from slower input acquisition! and effects between cognitive impairments themselves - e.g. slower reasoning may result from impaired working memory

Question 5

Why is studying cognitive decline also difficult?

Answer 5

because cross-sectional studies are flawed (e.g. better performance in computerized tasks for younger people not because of age, but because of the generation they belong to) and longitudinal studies are difficult to plan and obtain funding for

Question 6

Describe the Oxford Cognitive Screen?

Answer 6

Assesses the major cognitive domains of:

• memory
• language
• perception
• attention
• number
• praxis

Question 7

What is cognitive decline with old age accompanied by?

Answer 7

Brain atrophy, especially affecting the lateral PFC, the hippocampus, and the caudate (Raz et al, 2005). Hippocampal degeneration is in line with memory impairment

Question 8

Describe patient HM

Answer 8

Had hippocampus removed
CANT:
- form new episodic memories

CAN:

• remember events before surgery
• perform digit span (working memory)
• learn new tasks (implicit memory)
• remember over short time span (short term memory)
• spared language, intelligence, etc

Question 9

What did HM teach us?

Answer 9

Hippocampus needed for EXPLICIT memory formation (episodic and semantic)
not implicit (muscle memory and conditioned responses)

Question 10

Describe how brain activity changes with age. How can these phenomena be interpreted respectively?

Answer 10

• Overactivity in older relative to younger subjects is reported: may be compensation for decreased number of neurons? (Smith et al, 2001);
- compensation, i.e. recruitment of additional neurons to maintain performance

• Hemisphere asymmetry reduction in older adults - HAROLD (Cabeza et al, 2002);
- de-differentiation, i.e. loss of regional specificity - ‘age-related difficulty in recruiting specialised neural mechanisms’

• Posterior-anterior shifting with aging: PASA (Davis et al, 2008)
- scaffolding, i.e. dynamic ongoing process of plasticity

Question 11

In Cabeza et al, is the loss of regionalisation observed more in high-functioning old or low-functioning old? Why?

Answer 11

High-functioning old

Low-performing older adults recruited a similar network as young adults but used it inefficiently, whereas high-performing older adults counteracted age-related neural decline through a plastic reorganisation of neurocognitive networks

Question 12

What is dementia?

Answer 12

set of symptoms including memory loss, mood changes and problems with communicating and reasoning

Question 13

What does dementia diagnosis require?

Answer 13

• multiple cognitive deficits (including amnesia);
• functional impairment;
• clear consciousness (i.e. not in coma);
• change from previous level;
• long duration (> 6 months).

Question 14

What are the subtypes of dementia? What are their causes? Discuss their primary sites/features

Answer 14

AD (60-80%) - amyloid plaques and tau tangles - MTL, parietal lobes -> frontal

Fronto-temporal dementia (5-20%)- several sub-types; tau, TDP-43, FUS - frontal variant (behave), temporal variant (semantic/aphasia)

vascular (5-15%) - vascular pathology - step-wise progression

Lewy-body (2-8%) - Lewy bodies - motor symptoms, sleep disturbance

Question 15

What are the primary disturbances in each type of dementia?

Answer 15

• Episodic memory => AD;
• Semantic and/or frontal deficits => FTD;
• Step-wise progression => VD;
• Visual hallucinations, fluctuating deficits =>DwLB.

Question 16

What are the standard neuropsychological tests for dementia?

Answer 16

• MMSE – Mini-mental state examination. Max score 30. MCI < 27; AD < 25
o Example questions:
1.What is the year, month, day, date time
2.Repeat 3 items (apple, table, penny) immediately and after 2 minute delay
3.Spell ‘world’ backwards
4.What is this? (pen, watch)
5.Obey written instruction: “Close your eyes”

• ACE-R – Addenbrooke’s Cognitive Examination (revised): Includes MMSE, but more detail. Maximum score = 100, AD < 88
• MOCA – Montreal Cognitive Assessment: Max score 30. MCI = 19-25; MD = 11-21

Question 17

Describe the role that neuropsychology has in differential diagnosis

Answer 17

• Alzheimer’s Disease (AD)
o Primary episodic memory deficit

• Fronto-temporal dementia (FTD)
o Several variants, but semantic and/or frontal deficits are primary

• Vascular dementia (VaD)
o Step-wise progression

• Dementia with Lewy Bodies (DLB)
o Visual hallucinations, fluctuating deficits

Question 18

Describe Scheltens et al 2002

Then Schuff et al 2009

Answer 18

• AD shows progressive hippocampal atrophy and and hippocampal memory deficits; although the hippocampus is majorly affected, it must be noted that atrophy is present all the brain
• Rate of hippocampal atrophy is high in AD>MCI>control

Question 19

Describe Rascovsky 2002

Answer 19

patients with FTD performed significantly worse than patients with AD on letter and category fluency tests but significantly better on the MDRS memory subscale, block design test, and clock drawing test

Question 20

Describe Simons, Graham and Hodges 2002

Answer 20

PYRAMIDS AND PALM TREES

• allows tester to establish whether a subject’s difficulty in naming or pointing to a named picture is due to a difficulty un retrieving semantic information from pictures or a difficulty in retrieving semantic information from words
• patients with semantic dementia = = worse semantic and better episodic
• patients with AD = better semantic, worse episodic

Question 21

differential diagnosis of AD vs VaD

Answer 21

differential diagnosis of AD vs VaD is difficult, ad VaD pathology can be anywhere, and memory deficits are primary in each case, although often worse in AD (Mathias & Burke, 2009); there is evidence suggesting that perception (emotion recognition) is differentially impaired in VaD (Shimokawa et al, 2000, 2003)

Question 22

• differential diagnosis of AD vs DLB

Answer 22

• differential diagnosis of AD vs DLB can be achieved by cognitive specificity of deficits, e.g. visual perceptual, attentional executive, verbal/non-verbal, and verbal memory (Collerton et al, 2003)

Question 23

What do meta-analyses reveal about diiferential diagnoses?

Answer 23

• despite differential diagnosis, meta-analyses reveal that standard neuropsychological tests have a lot of overlap for AD vs FTD, AD vs VaD, and AD vs DLB; therefore, diagnostic boundaries are not clear

Question 24

What are differential diagnoses complicated?

Answer 24

• differential diagnosis is complicated by the fact that cognition is affected in other disorders of aging, e.g. Parkinson’s disease (once thought of as purely motor, but now it is recognized that a large proportion of PD patients will develop Parkinson’s disease dementia (PDD)), stroke (huge variability in impact, cause aphasia and neglect, incidence of stroke-associated dementia increases with age) and depression (associated with many diseases and disorders, can cause cognitive impairments that mimic dementia); underlying disease or co-morbidities must be taken into account when considering specific tests for cognitive impairments, e.g. it is easy to check with anti-depressants if the cognitive impairments are due to depression or other causes

Question 25

Facts about dementia

Answer 25

• Around 850,000 people in the UK have dementia – predicted to reach 1 million by ~2022
• Incidence increases dramatically with age
• Dementia costs the UK around £26 billion per year (and rising)
Mild cognitive impairment = cognitive impairment without functional impairment, ~ 50% will convert to dementia

Question 26

Current focus of treatment

Answer 26

The current focus of research is on early detection (of mild cognitive impairment + biomarkers?) and prevention through both neuroprotective treatment and lifestyle/non-pharmacological interventions: exercise/cognitive training!

Question 27

Describe examples of biomarkers

Answer 27

• the development of imaging biomarker suggests apoE as a biomarker for AD, as, even at age 20, the hippocampus of patients that will develop AD behaves differently; basal ganglia networks connectivity is being used to try to predict PD, and intervene therapeutically in useful time (disease is irreversible when symptoms are manifested);