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Neuroscience 2 > Clinical Features of Alzheimer's Disease > Flashcards

Clinical Features of Alzheimer's Disease Flashcards

Describe the typical clinical presentation of AD, contrasting it with other common causes of cognitive impairment and dementia Be aware of atypical presentations and how they relate to different patterns of brain atrophy Discuss the different factors thought to influence the development of clinical AD, including genetics and predisposing factors, as well as evaluating other influences such as trauma, diet, and educational attainment Discuss the main current treatments for AD and their limitation

1
Q

Name three examinations for Alzheimer’s disease

A

Mini mental state examination (MMSE), Montreal cognitive assessment (MoCA), Addenbrooke’s cognitive assessment (ACE)

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2
Q

Define episodic memory

A

Memory for specific events, or episodes, in life

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3
Q

Define semantic memory

A

Memory that processes ideas and concepts that are not drawn from personal experience - in other words, knowledge of the world, e.g. capital cities

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4
Q

Define procedural memory

A

Memory for knowing how perform motor tasks, such as riding a bike or making a cup of tea

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5
Q

Define working memory

A

Short-term memory concerned with immediate conscious perceptual and linguistic processing - such as remembering a telephone number or sentence

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6
Q

Which memory deficits typically develop first in Alzheimer’s disease

A

Episodic memory deficits, especially for recent events, with relative sparing of remote events

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7
Q

What structures are disrupted to cause the initial memory deficits in AD?

A

Medial temporal lobe structures - especially the entorhinal cortex and hippocampus

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8
Q

Atrophy of which regions correlates with increasing disability and dependence in Alzheimer’s disease?

A

Parietal and frontal regions

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9
Q

Which functions are typically impaired as the disease progresses?

A

Executive function, attention, language, visuospatial function, personality, behaviour, and motor control

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10
Q

Name the gross pathological features of Alzheimer’s disease

A

General brain atrophy, paticularly pronounced at the hippocampus and entorhinal cortex, with enlargement of the ventricles

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11
Q

Which subset of patients often present atypically?

A

Younger patients

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12
Q

Give three atypical presenting symptoms of AD

A

1) Speech disturbances/ progressive aphasia
2) Behavioural symptoms
3) Progressive visuospatial symptoms (secondary to posterior cortical atrophy)

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13
Q

State the core features of posterior cortical atrophy

A

Insidious onset with gradual progression of visual complaints such as simultagnosia, optic ataxia, dressing apraxia, or environmental disorientation (but normal ocular examination due to intact primary visual functions) with relatively preserved anterograde memory and insight

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14
Q

Define progressive aphasia

A

Loss of the ability to read, with fluctuating difficulty in speaking and mispronunciation or loss of words (despite remembering what an object is, the individual cannot name it).

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15
Q

Which variant of aphasia is Alzheimer’s disease associated with?

A

Logopaenic primary progressive aphasia

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16
Q

State the symptoms and signs of logopaenic primary progressive aphasia

A

Impaired word finding, associated with asymmetric left-sided temporal atrophy, but relative linguistic fluency

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17
Q

Summarise the main 6 domains affected by Alzheimer’s disease

A

Memory, language, attention, calculation, executive function, and praxis

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18
Q

Define dementia

A

The loss of 2 or more cognitive domains, including memory, to a level sufficient to cause impairment of daily function

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19
Q

Name the four main causes of dementia

A

Alzheimer’s disease, dementia with Lewy bodies, vascular dementia, and frontotemporal lobar degeneration

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20
Q

Define semantic dementia

A

Loss of understanding of basic knowledge about the world

21
Q

Define behavioural-variant frontotemporal dementia

A

Complete loss of inhibition

22
Q

What is mixed dementia?

A

The combination of Alzheimer’s disease and vascular dementia

23
Q

What percentage of dementia cases are early-onset (below 65)?

A

5%

24
Q

Where are beta-amyloid plaques found in the brain?

A

Extracellularly

25
Q

Where are neurofibrillary tangles found and what are they made of?

A

Intracellularly, consisting of hyperphosphorylated tau

26
Q

Do cognitive deficits correlate better with tau deposition or amyloid-beta deposition?

A

Tau deposition

27
Q

Name 6 structures targeted by amyloid-beta

A

Entorhinal cortex, hippocampus, limbic system, posterior cingulate cortex, precuneus, lateral parietal cortex (latter 3 all involved in default mode network)

28
Q

How does Alzheimer’s disease affect the level of amyloid-beta in the CSF?

A

It decreases

29
Q

Describe the effect of pre-clinical Alzheimer’s pathology on fMRI

A

Disruption of functional networks both during cognitive tasks and at rest, with increased atrophy compared to a normal control

30
Q

State 5 risk factors for Alzheimer’s disease

A

Increasing age, vascular pathology (e.g. hypertension, dyslipidaemia), trauma, female gender, APOE4 allele, poor diet, lack of exercise

31
Q

Describe the link between TBI and Alzheimer’s disease

A

TBI leads to chronic inflammation and an increase in amyloid levels

32
Q

What is APOE?

A

A cholesterol transporter protein involved in amyloid-beta clearance, and the greatest genetic susceptibility factor to Alzheimer’s disease

33
Q

Name three genes that can host mutations leading to autosomal dominant familial Alzheimer’s disease

A

Amyloid precursor protein (APP), presenilin 1, presenilin 2

34
Q

How many individuals with trisomy 21 develop dementia by age 60?

A

40%

35
Q

Define mild cognitive impairment

A

A pre-Alzheimer’s disease stage where patients have more memory or cognitive problems than expected for their age, but no functional impairment

36
Q

Define subjective cognitive impairment

A

A pre-Alzheiner’s disease stage where disease pathogenesis has begun but there have been no cognitive changes on testing

37
Q

Which structures are affected to produce symptoms of amnestic dementia?

A

Medial temporal lobe and limbic system

38
Q

Which structures are affected to produce symptoms of primary progressive aphasia?

A

Left perisylvian region

39
Q

Which structures are affected to produce symptoms of progressive visuospatial dysfunction?

A

Bilateral parieto-temporal-occipital lobes

40
Q

Which structures are affected to produce symptoms of progressive comportment or executive dysfunction?

A

Bilateral frontal and anterior temporal lobes

41
Q

Give 3 advantages and 3 disadvantages of using neuropsychology to diagnose probable AD?

A

+) Low cost, portable, establishes a baseline, useful for assessing competencies and guiding recommendations
-) Time intensive, variance in population, affected by culture and education, lacks specificity and sensitivity (can be confounded, e.g. by depression), single snapshot of longitudinal process

42
Q

Give 2 advantages and 2 disadvantages of using CSF analysis to diagnose probable AD?

A

+) Pathology specific for tau and amyloid-beta, sensitive

-) Invasive, dependent on processing and assay stability

43
Q

Which areas are selectively cholinergically denervated in AD?

A

Cerebral cortex - most severe in the temporal lobes and adjacent limbic and paralimbic areas - with cholinergic loss correlating with dementia severity

44
Q

Name 3 acetylcholinesterase inhibitors approved to treat mild-moderate AD

A

Donepezil, galantamine, rivastigmine

45
Q

Give 3 disadvantages of acetylcholinesterase inhibitors for treating AD

A

No effect on survival, GI side effects which may be intolerable, decrease heart rate so can increase the risk of falls and collapse

46
Q

What is memantine?

A

A low to moderate affinity NMDA glutamate receptor open-channel blocker

47
Q

When is memantine used in AD?

A

In severe disease, to improve cognition and function

48
Q

Why should antipsychotics be avoided in AD?

A

They are associated with worsening of cognition, parkinsonian symptoms, falls, and death

Neuroscience 2 (30 decks)

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