Last Minute Review
Dementia — Last Minute Review
A last-minute review of high-yield facts — dense tables and one-liners for RITE/Board prep. Not a substitute for the full notes.
Major Dementias — Head-to-Head Comparison
| Feature | AD | DLB | FTD (bvFTD) | VaD |
|---|---|---|---|---|
| Age Onset | >65 (sporadic); 30–60 (familial) | >50 | 45–65 | >60 |
| Presenting Symptom | Episodic memory loss (encoding deficit) | Visual hallucinations, fluctuating cognition, RBD | Personality change, disinhibition, apathy | Stepwise cognitive decline, executive dysfunction |
| Memory | Early, prominent (encoding failure — poor recognition) | Less impaired early; retrieval deficit (recognition better) | Relatively preserved early | Retrieval deficit; recognition > recall |
| Behavior | Apathy, depression; late agitation/sundowning | Depression, apathy, anxiety, Capgras delusion | Disinhibition, compulsions, hyperorality, loss of empathy | Apathy, depression, pseudobulbar affect |
| Hallucinations | Late, if present | Recurrent, well-formed visual (core feature per McKeith 2017 criteria; core features = fluctuating cognition, visual hallucinations, RBD, parkinsonism) | Rare | Rare |
| Motor Features | Normal until late | Spontaneous parkinsonism (symmetric); RBD; falls | Parkinsonism late; may overlap CBS/PSP/MND | Focal signs, gait disorder, pseudobulbar palsy |
| EEG | Generalized slowing (nonspecific) | Fluctuating generalized slowing; posterior slow waves | Usually normal early | Focal slowing (if infarct) |
| MRI | Hippocampal/medial temporal atrophy; posterior parietal | Relative hippocampal preservation vs AD; generalized atrophy | Frontal + anterior temporal atrophy (often asymmetric) | White matter lesions, lacunes, strategic infarcts |
| PET/SPECT | FDG: temporoparietal hypometabolism; amyloid PET +; tau PET + | FDG: occipital hypometabolism; DAT scan ↓ uptake | FDG: frontal/anterior temporal hypometabolism | Patchy hypometabolism matching vascular territory |
| CSF | Aβ42 ↓, p-tau ↑, t-tau ↑ | May have low Aβ42 (co-AD pathology); α-synuclein SAA emerging | Neurofilament light ↑; no specific marker | No specific fluid biomarker |
| Pathology | Aβ42 plaques + hyperphosphorylated tau NFTs (3R+4R) | α-synuclein Lewy bodies (neocortical + limbic distribution drives DLB cognition; brainstem-predominant = PD) | Tau (3R or 4R) or TDP-43 | Vascular injury ± mixed AD pathology |
| Genetics | PSEN1 (14), APP (21), PSEN2 (1); APOE ε4 risk | GBA, SNCA (rare); APOE ε4 risk factor | C9orf72, MAPT, GRN | NOTCH3 (CADASIL); HTRA1 (CARASIL) |
| Treatment | Lecanemab and donanemab (anti-amyloid mAbs); AChE inhibitors; memantine | Rivastigmine; avoid typical antipsychotics; melatonin for RBD | SSRIs (trazodone); no disease-modifying therapy | Vascular risk factor management; AChE inhibitors (modest) |
💎 Board Pearl
The encoding deficit in AD (poor recognition AND recall) distinguishes it from the retrieval deficit in DLB/VaD/subcortical dementias (recognition preserved, recall impaired). This is a classic board differentiator.FTD Variants
| Variant | Core Features | Language | Behavior | Atrophy Pattern | Pathology | Genetics |
|---|---|---|---|---|---|---|
| bvFTD | Early personality change, disinhibition, apathy, loss of empathy, hyperorality, executive dysfunction | Echolalia, perseveration (late) | Prominent from onset: disinhibition, compulsions, social inappropriateness | Frontal + anterior temporal (often asymmetric) | Tau (3R or 4R) or TDP-43 | C9orf72 (TDP-43); MAPT (tau); GRN (TDP-43) |
| nfvPPA (nonfluent/agrammatic) | Effortful, halting, agrammatic speech; apraxia of speech | Nonfluent; grammar errors; comprehension preserved for single words | Intact early | Left posterior frontal / insular (perisylvian) | Tau (4R — CBD/PSP-type) | Usually sporadic; occasional MAPT |
| svPPA (semantic) | Loss of word meaning; surface dyslexia; prosopagnosia (right-sided) | Fluent but empty speech; anomia; lost single-word comprehension | Behavioral changes late (overlap bvFTD) | Left anterior temporal “knife-edge” atrophy | TDP-43 (Type C) | Rarely familial |
| lvPPA (logopenic) | Word-finding pauses; phonemic paraphasias; impaired sentence repetition | Slow, hesitant; intact grammar; intact single-word comprehension | Intact early | Left posterior temporal / inferior parietal | AD pathology (Aβ + tau) in most cases | AD genetics (APOE ε4 risk) |
| FTD-ALS/MND | bvFTD + upper and lower motor neuron signs; poor prognosis (2–3 yr) | Variable | bvFTD-type behavioral changes | Frontal atrophy + motor cortex involvement | TDP-43 | C9orf72 (most common genetic link FTD–ALS) |
| Abbreviations: bvFTD = behavioral variant frontotemporal dementia; nfvPPA = nonfluent/agrammatic variant primary progressive aphasia; svPPA = semantic variant PPA; lvPPA = logopenic variant PPA; FTD-ALS/MND = FTD with amyotrophic lateral sclerosis/motor neuron disease; CBS = corticobasal syndrome; PSP = progressive supranuclear palsy | ||||||
💎 Board Pearl
lvPPA is the “language phenotype of AD” — most cases have underlying amyloid + tau pathology, unlike nfvPPA (tau) and svPPA (TDP-43). Memory aid: svPPA = TDP, nfvPPA = tau, lvPPA = AD. Criteria: bvFTD per Rascovsky 2011 criteria (≥3 of 6 behavioral features for possible bvFTD); PPA classified per Gorno-Tempini 2011 classification. Tau isoforms: Pick disease = 3R; CBD / PSP = 4R; AD = mixed 3R + 4R.Alzheimer Disease — Genetics & Biomarkers
AD Genetics
| Gene | Chromosome | Inheritance | Mechanism |
|---|---|---|---|
| APP | 21 | Autosomal dominant | Amyloid precursor protein; Down syndrome (trisomy 21) → extra APP copy → universal AD neuropathology by age 40; clinical dementia typically emerges in the 50s (mean onset ~55 yr) |
| PSEN1 | 14 | Autosomal dominant | Most common cause of familial early-onset AD; γ-secretase subunit; onset 30–50 yr; most aggressive |
| PSEN2 | 1 | Autosomal dominant | Rarest familial form; γ-secretase subunit; variable onset 40–70 yr |
| APOE ε4 | 19 | Risk factor (NOT deterministic) | Strongest genetic risk factor for sporadic AD; ε4 heterozygote ~3× risk; ε4/ε4 homozygote ~12–15× risk; ε2 is protective |
| TREM2 | 6 | Risk factor | Microglial receptor; variants impair amyloid clearance; ~2–4× risk (similar to single ε4 allele) |
AD Biomarkers
| Biomarker | AD Pattern | Interpretation |
|---|---|---|
| CSF Aβ42 | Decreased | Trapped in plaques; Aβ42/40 ratio more accurate than Aβ42 alone |
| CSF p-tau (181, 217) | Increased | Specific for AD tau pathology; p-tau 217 emerging as most accurate single fluid biomarker |
| CSF t-tau | Increased | Nonspecific marker of neuronal injury (also ↑ in CJD, stroke) |
| Amyloid PET (florbetapir, florbetaben, flutemetamol) | Positive (cortical uptake) | Highly sensitive; a negative amyloid PET makes biologically defined AD very unlikely |
| Tau PET (flortaucipir) | Positive (temporal → parietal spread) | Correlates with clinical severity; follows Braak staging pattern |
| FDG-PET | Temporoparietal hypometabolism | Posterior cingulate involved early; occipital cortex spared (unlike DLB) |
| MRI | Hippocampal / medial temporal atrophy | Posterior parietal atrophy in posterior cortical atrophy variant |
| Plasma p-tau 217 | Increased | Blood-based biomarker; high accuracy for AD diagnosis; clinical adoption growing |
💎 Board Pearl
The AT(N) framework defines AD biologically: A+ (amyloid positive) is required to be on the Alzheimer continuum. A+T+N+ = full AD pathological change. A− = not AD, regardless of T or N status.Continue reading — sign in
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