L42-48 Flashcards
Describe the typical cognitive decline associated with healthy aging including the effect of aging on mental speed, episodic memory, semantic memory and procedural memory.
Typical cognitive declines:
Processing speed, attention (complex tasks, not simple tasks), memory (mixed), visuospatial (complex tasks, not simple) and executive functions (mixed)
- mental speed: declines with age (peaks around 30 yo)
- episodic memory: declines (stable untill 50-60 yo)
- semantic memory: no large impact
- procedural memory: no large impact (some inconsistent findings, however)
- free recall: declines (cued and recognition remains stable)
Describe the role of cognitive reserve in aging and neurodegeneration.
An AD patient with higher cognitive reserve will have a later onset of neuropathology
Describe the typical memory impairments found in early neurodegenerative diseases as Alzheimer’s disease.
Most prominent symptoms of AD:
- impaired episodic memory, especially encoding of verbal info
Other deficits of mild/very mild degree
- executive functions
- attention and psychomotor speed
- language test
- visuospatial functions
Explain the term “dementia”.
- symptom, not a disease
- evidence of significant cognitive decline
- the cognitive deficits interferewith independence in everyday activities
- do not occur exclusively in the contex of delirium
- are not better explained by other mental disorders
Name some common neurodegenerative dementia disorders.
AD, Lewy body- and frontotemporal dementia
Describe the most important risk factors for Alzheimer’s disease.
Age
Describe the pathophysiology of Alzheimer’s disease with special emphasis on protein accumulation and its localization.
Plaques:
- amyloid beta plaques
- high expression of amyloid precursor protein (related to synaptic plasticity) in active brain areas
- in sporadic AD: clearance and not production is causing accumulation
- evidence suggests that intermediate stages of fibrillation are most toxic
Tangles:
- Tau neurofibrillary tangles
- Tau stabilizes microtubules, (phoshorylate and dephosphorylate to allow change)
- when hyperphosphorylated microtubules destabilize
- when a neuron degenerate, tau is released
Describe typical symptoms of Alzheimer’s disease when the temporal lobe is affected.
- episodic memory deficits: forgetting appointments, what you just talked about, recent events
- semantic memory causing aphasia: difficulties in the ability to match words or images to their meanings
- language: usually problems with nouns, uses other words, difficulty in understanding
Explain the association between pathophysiology and symptom development in Alzheimer’s disease.
Pathology often precedes clinical symptoms by decades:
- amyloid accumulation precedes neurogeneration, which precedes symptoms
Describe the use of different biomarkers diagnose Alzheimer’s disease.
Positive biomarkers (normal biomarkers in elderly with normal cognition): they will get AD if they live long enough? Risk factor, not disease marker?
Describe treatments for Alzheimer’s disease: symptomatic.
- reduces symptoms with stability over a 1 year, then continued progression
- cholinesterase inhibitors and NMDA antagonists - targeted at improving synaptic transmission
Explain the term “dementia disorders”.
Disorders with dementia as a core symptom. Neuropathology are localized differently in different dementia disorders. Mixed pathology are very common.
Describe the primary symptomatology of frontotemporal dementia: behavior.
- disinhibition with inappropriate or socially unacceptable behavior
- emotionally blunted
- lack of empathy
Describe the primary symptomatology of Lewy body dementia.
- progressive dementia
- deficits in attention and executive functions
- fluctating cognition
- recurrent complex visual hallucinations
- spontaneous features of parkinsonism
- REM sleep disorder
Explain the difference in amyloid-beta pathology in familial vs sporadic AD.
Familial: increased production
Sporadic: decreased clearance
Describe the typical course of disease of Alzheimer’s disease.
Mean survival: 7 y
Describe typical symptoms of Alzheimer’s disease when the parietal lobe is affected.
- problems with finding the way, find or locate items in space, problems with reading, calculation
Describe typical symptoms of Alzheimer’s disease when the frontal lobe is affected.
- problems with performing or solving complex tasks, keeping overview of tasks, change in behavior and personality
Describe the primary symptomatology of frontotemporal dementia: cognition.
- lack of planning/organizing skills
- reduced abstract thinking
- reduced judgement
Describe the primary symptomatology of frontotemporal dementia: language
- progressive nonfluent aphasi: breakdown in speech, effortfull, hesitant (similar to stroke)
- due to semantic memory deficits: increasing difficulty naming and word comprehension, loss of knowledge of words, objects and concepts
Describe treatments for Alzheimer’s disease: potential disease-modifying new treatments.
- reduces pathology (and symptoms) with a slower progression of the disease
- monoclonal antibodies against A-beta
- promising, but only 1 % of MABs cross the BBB
- aducanumab approved by FDA to remove A-beta in 2021
- new therapy: tau aggregation inhibitor
