Dementia Flashcards
% breakdown of dementia types?
60-70% Alzheimer’s disease (AD).
10-15% Vascular dementia.
10% Mixed (e.g., AD + vascular).
Key pathological features of Alzheimer’s Disease (AD)?
Amyloid plaques (extracellular Aβ aggregates).
Neurofibrillary tangles (intracellular hyperphosphorylated Tau).
Synaptic loss, neuronal death (especially cholinergic cells).
Genetic causes of early-onset Alzheimer’s disease (EOAD)?
Mutations in:
APP (Chr 21): ↑ Aβ (especially Aβ42) → amyloid plaques
PSEN1 (Chr 14): γ-secretase subunit → ↑ Aβ42
PSEN2 (Chr 1): γ-secretase subunit → ↑ Aβ42 (less common)
🧠 PSEN = Presenilin genes
🧬 Inherited in autosomal dominant pattern
Major genetic risk factor for late-onset AD?
ApoE4 allele (↓ Aβ clearance)
Amyloidogenic vs. non-amyloidogenic APP processing?
Amyloidogenic: β-secretase + γ-secretase → Aβ42 (toxic, fibrillogenic).
Non-amyloidogenic: α-secretase + γ-secretase → non-toxic fragments.
How does hyperphosphorylated Tau cause damage?
Disrupts microtubules → neuritic dystrophy → neurofibrillary tangles (NFTs) → neuronal dysfunction
Why are AChE inhibitors used in AD? Side effects of AChE inhibitors?
AD involves loss of cholinergic neurons (nucleus basalis of Meynert in basal forebrain). AChE inhibitors (e.g., donepezil, rivastigmine, galantamine) ↑ ACh → improve memory/mood (symptomatic relief only).
AChE inhibitor SEs:
Nausea, vomiting, dizziness, diarrhea
Role of memantine?
MDA receptor antagonist (blocks glutamate excitotoxicity); used in moderate-severe AD or AChE inhibitor intolerance.
Modifiable vs. non-modifiable AD risks?
Non-modifiable: Age, genetics (ApoE4, Down syndrome), family history.
Modifiable: Vascular (hypertension, diabetes), depression, head injury, low education
How does AD differ from frontotemporal dementia (FTD)?
AD: Memory loss first, Aβ/Tau pathology.
FTD: Behavior/personality changes early, Tau/TDP-43 pathology (no Aβ)
What is BPSD?
Behavioral/Psychological Symptoms of Dementia (agitation, aggression, depression, psychosis)
Key pathological proteins in Frontotemporal dementia (FTD)?
Tau (MAPT gene mutations) → Tauopathies (e.g., Pick’s disease).
TDP-43 (common in FTD-ALS overlap).
No amyloid plaques (unlike AD).
How does FTD differ from AD genetically?
FTD is linked to MAPT mutations (Tau pathology), while AD is linked to APP/PSEN1/PSEN2 (Aβ) or ApoE4 (late-onset)
Treatment options for FTD?
No disease-modifying therapies; manage symptoms (SSRIs for behavior, speech therapy for aphasia). AChE inhibitors are not effective
Key clinical features of vascular dementia vs. AD?
Stepwise decline (not gradual like AD).
Focal neurological signs (e.g., gait problems, weakness).
Executive dysfunction early (e.g., poor planning).
How to differentiate FTD, AD, and vascular dementia?
FTD: Early behavior/language changes, Tau/TDP-43, no memory loss early.
AD: Early memory loss, Aβ plaques/Tau tangles.
Vascular: Stepwise decline, vascular risk factors, focal neurological signs.
What are the core clinical features of Lewy Body Dementia (LBD)
- Fluctuating cognition (e.g., attention/alertness varies daily).
- Visual hallucinations (often vivid, early in disease).
- Parkinsonism (bradykinesia, rigidity, gait instability).
Suggestive symptoms:
- REM sleep behavior disorder (acting out dreams).
- sensitivity to antipsychotics
How does LBD differ from Alzheimer’s disease (AD)?
Early hallucinations/parkinsonism (AD: late psychosis, rare motor signs).
Memory loss is less prominent early (AD: memory decline is primary).
Neuroleptic sensitivity (LBD patients worsen with antipsychotics)
What is the pathological hallmark of LBD?
Alpha-synuclein Lewy bodies (intracellular aggregates) in cortex + substantia nigra.
How is LBD treated?
Cognitive symptoms: AChE inhibitors (e.g., rivastigmine, donepezil).
Parkinsonism: Low-dose levodopa (but may worsen hallucinations).
Psychosis: Quetiapine or clozapine (avoid typical antipsychotics).
Sleep disturbances: Melatonin or clonazepam (for REM sleep disorder).
Why must antipsychotics be used cautiously in LBD?
High risk of neuroleptic sensitivity reactions (e.g., severe rigidity, confusion, or death)
How to distinguish Lewy body dementia (LBD) from Parkinson’s Disease Dementia (PDD)?
LBD: Dementia precedes or occurs within 1 year of parkinsonism. (Pre-motor dementia)
PDD: Dementia develops after 1+ years of motor symptoms. (After-motor dementia)
Which gene mutations are protective against Alzheimer’s disease?
- ApoE2 allele (variant of Apolipoprotein E); enhances clearance of Aβ and reduces amyloid plaque formation
- APP A673T mutation (in the Amyloid Precursor Protein gene); Reduces production of amyloid-beta (Aβ), the toxic protein that forms plaques in AD.
Lewy bodies, abnormal protein clumps, are found in both Dementia with Lewy Bodies (DLB) and Parkinson’s Disease (PD), but their distribution and timing can differ. How?
Lewy bodies are spherical, intracellular deposits formed of alpha-synuclein + ubiquitin
DLB: Lewy bodies are predominantly in the limbic system and neocortex, with brainstem involvement.
PD: Lewy bodies are primarily in the brainstem (notably the substantia nigra), with possible spread to the limbic system and neocortex in later stages.
