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
Name three examinations for Alzheimer’s disease
Mini mental state examination (MMSE), Montreal cognitive assessment (MoCA), Addenbrooke’s cognitive assessment (ACE)
Define episodic memory
Memory for specific events, or episodes, in life
Define semantic memory
Memory that processes ideas and concepts that are not drawn from personal experience - in other words, knowledge of the world, e.g. capital cities
Define procedural memory
Memory for knowing how perform motor tasks, such as riding a bike or making a cup of tea
Define working memory
Short-term memory concerned with immediate conscious perceptual and linguistic processing - such as remembering a telephone number or sentence
Which memory deficits typically develop first in Alzheimer’s disease
Episodic memory deficits, especially for recent events, with relative sparing of remote events
What structures are disrupted to cause the initial memory deficits in AD?
Medial temporal lobe structures - especially the entorhinal cortex and hippocampus
Atrophy of which regions correlates with increasing disability and dependence in Alzheimer’s disease?
Parietal and frontal regions
Which functions are typically impaired as the disease progresses?
Executive function, attention, language, visuospatial function, personality, behaviour, and motor control
Name the gross pathological features of Alzheimer’s disease
General brain atrophy, paticularly pronounced at the hippocampus and entorhinal cortex, with enlargement of the ventricles
Which subset of patients often present atypically?
Younger patients
Give three atypical presenting symptoms of AD
1) Speech disturbances/ progressive aphasia
2) Behavioural symptoms
3) Progressive visuospatial symptoms (secondary to posterior cortical atrophy)
State the core features of posterior cortical atrophy
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
Define progressive aphasia
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).
Which variant of aphasia is Alzheimer’s disease associated with?
Logopaenic primary progressive aphasia
State the symptoms and signs of logopaenic primary progressive aphasia
Impaired word finding, associated with asymmetric left-sided temporal atrophy, but relative linguistic fluency
Summarise the main 6 domains affected by Alzheimer’s disease
Memory, language, attention, calculation, executive function, and praxis
Define dementia
The loss of 2 or more cognitive domains, including memory, to a level sufficient to cause impairment of daily function
Name the four main causes of dementia
Alzheimer’s disease, dementia with Lewy bodies, vascular dementia, and frontotemporal lobar degeneration
Define semantic dementia
Loss of understanding of basic knowledge about the world
Define behavioural-variant frontotemporal dementia
Complete loss of inhibition
What is mixed dementia?
The combination of Alzheimer’s disease and vascular dementia
What percentage of dementia cases are early-onset (below 65)?
5%
Where are beta-amyloid plaques found in the brain?
Extracellularly
Where are neurofibrillary tangles found and what are they made of?
Intracellularly, consisting of hyperphosphorylated tau
Do cognitive deficits correlate better with tau deposition or amyloid-beta deposition?
Tau deposition
Name 6 structures targeted by amyloid-beta
Entorhinal cortex, hippocampus, limbic system, posterior cingulate cortex, precuneus, lateral parietal cortex (latter 3 all involved in default mode network)
How does Alzheimer’s disease affect the level of amyloid-beta in the CSF?
It decreases
Describe the effect of pre-clinical Alzheimer’s pathology on fMRI
Disruption of functional networks both during cognitive tasks and at rest, with increased atrophy compared to a normal control
State 5 risk factors for Alzheimer’s disease
Increasing age, vascular pathology (e.g. hypertension, dyslipidaemia), trauma, female gender, APOE4 allele, poor diet, lack of exercise
Describe the link between TBI and Alzheimer’s disease
TBI leads to chronic inflammation and an increase in amyloid levels
What is APOE?
A cholesterol transporter protein involved in amyloid-beta clearance, and the greatest genetic susceptibility factor to Alzheimer’s disease
Name three genes that can host mutations leading to autosomal dominant familial Alzheimer’s disease
Amyloid precursor protein (APP), presenilin 1, presenilin 2
How many individuals with trisomy 21 develop dementia by age 60?
40%
Define mild cognitive impairment
A pre-Alzheimer’s disease stage where patients have more memory or cognitive problems than expected for their age, but no functional impairment
Define subjective cognitive impairment
A pre-Alzheiner’s disease stage where disease pathogenesis has begun but there have been no cognitive changes on testing
Which structures are affected to produce symptoms of amnestic dementia?
Medial temporal lobe and limbic system
Which structures are affected to produce symptoms of primary progressive aphasia?
Left perisylvian region
Which structures are affected to produce symptoms of progressive visuospatial dysfunction?
Bilateral parieto-temporal-occipital lobes
Which structures are affected to produce symptoms of progressive comportment or executive dysfunction?
Bilateral frontal and anterior temporal lobes
Give 3 advantages and 3 disadvantages of using neuropsychology to diagnose probable AD?
+) 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
Give 2 advantages and 2 disadvantages of using CSF analysis to diagnose probable AD?
+) Pathology specific for tau and amyloid-beta, sensitive
-) Invasive, dependent on processing and assay stability
Which areas are selectively cholinergically denervated in AD?
Cerebral cortex - most severe in the temporal lobes and adjacent limbic and paralimbic areas - with cholinergic loss correlating with dementia severity
Name 3 acetylcholinesterase inhibitors approved to treat mild-moderate AD
Donepezil, galantamine, rivastigmine
Give 3 disadvantages of acetylcholinesterase inhibitors for treating AD
No effect on survival, GI side effects which may be intolerable, decrease heart rate so can increase the risk of falls and collapse
What is memantine?
A low to moderate affinity NMDA glutamate receptor open-channel blocker
When is memantine used in AD?
In severe disease, to improve cognition and function
Why should antipsychotics be avoided in AD?
They are associated with worsening of cognition, parkinsonian symptoms, falls, and death
