Bit · Neuro
Dementia — Alzheimer vs Vascular vs FTD vs Lewy Body vs NPH
Five major causes of progressive cognitive decline. The pivot is the order in which the deficits appear and the supporting feature.
Mechanism
Dementia is a progressive decline in cognition severe enough to impair function. Five main causes account for most cases:
- Alzheimer disease (60–70%) — most common dementia. Insidious onset. Earliest: memory (especially short-term). Histology: amyloid plaques (β-amyloid) + neurofibrillary tangles (hyperphosphorylated tau). Atrophy starts in hippocampus and temporoparietal cortex. Genetics: APOE ε4 (risk allele); APP, PSEN1, PSEN2 mutations (early-onset autosomal dominant); chromosome 21 trisomy (Down syndrome → AD by 40s).
- Vascular dementia — stepwise decline (each step = a small stroke). Often history of HTN, CAD, smoking. MRI: multiple lacunes or white-matter ischemia.
- Frontotemporal dementia (Pick disease) — early personality / behavioural change (disinhibition, apathy) or early aphasia, with memory relatively preserved early. Younger onset (50s–60s). Histology: Pick bodies (tau aggregates) or TDP-43.
- Dementia with Lewy bodies (DLB) — fluctuating cognition + visual hallucinations + parkinsonism + REM sleep behaviour disorder. Histology: α-synuclein Lewy bodies in cortex. Sensitive to neuroleptics (severe reactions). Distinguish from Parkinson disease dementia by order: DLB has dementia first (or within 1 year of motor sx); PDD has motor first, dementia later.
- Normal pressure hydrocephalus (NPH) — triad: wet, wobbly, wacky (urinary incontinence, gait disturbance, dementia). Ventricles enlarged out of proportion to atrophy. CSF pressure normal. Reversible with VP shunt in selected patients.
Differentiator Table
| Type | Earliest deficit | Pathology | Distinguishing feature |
|---|---|---|---|
| Alzheimer | Short-term memory | Amyloid plaques + neurofibrillary tangles | Insidious gradual decline; hippocampal atrophy |
| Vascular | Often executive / focal | Multi-infarct or white-matter ischemia | STEPWISE decline; vascular risk factors |
| Frontotemporal (Pick) | Personality / behaviour OR aphasia | Pick bodies / TDP-43 | Younger onset; disinhibition; relative memory sparing early |
| DLB | Fluctuating cognition + visual hallucinations | α-synuclein (cortical Lewy bodies) | Parkinsonism + REM sleep behaviour disorder; neuroleptic sensitivity |
| NPH | Gait + urinary incontinence + cognition | Ventriculomegaly with normal pressure | WET, WOBBLY, WACKY; potentially reversible with shunt |
The Pivot
Three questions:
- What was the FIRST deficit? Memory → Alzheimer. Behavior/personality → FTD. Gait + incontinence → NPH. Visual hallucinations + parkinsonism → DLB.
- Stepwise or smooth? Stepwise → vascular.
- Imaging? Hippocampal atrophy → AD. Frontotemporal atrophy → FTD. Lacunes / white matter disease → vascular. Big ventricles out of proportion to atrophy → NPH.
NBME-Style Stem
A 72-year-old man presents with 8 months of fluctuating cognition, vivid visual hallucinations of small animals, and resting tremor of the left hand. His wife reports he acts out his dreams at night. Cognitive testing shows variable attention from day to day. Which of the following is the most likely diagnosis?
Concept Anchor
Five dementias, five different brain-disease mechanisms, five different opening symptoms — the deficit that arrives FIRST tells you which one.