Alzheimer's Disease
Most common cause of dementia (60-70%)
CSF Biomarkers
Aβ42 ↓or Aβ42/40 ratio ↓
p-tau 181/217 ↑most specific
t-tau ↑neurodegeneration
Blood (emerging)
p-tau 217NfL ↑
Imaging
MRI:Hippocampal & entorhinal atrophy
FDG-PET:Temporoparietal hypometabolism
Amyloid PET:+
Tau PET:+
Aβ plaques + NFT (Braak I-VI) → neuronal loss
Lewy Body Dementia
α-synuclein (Lewy bodies) — 2nd most common
Core Features (1 of 4)
Fluctuating cognitionVisual hallucinationsParkinsonismRBD
CSF / Blood
RT-QuIC:α-synuclein seed detection
NfL ↑may be higher vs AD
Imaging — KEY
MRI:Relatively preserved hippocampus
FDG-PET:Occipital hypometabolism
DAT-SPECT:− Loss of DAT
MIBG:− Reduced cardiac uptake
Parkinson's Disease Dementia
α-synuclein — same pathology as DLB
Key Distinction from DLB
Parkinsonismpreceded dementia by ≥1 year
Biomarkers
Same as DLBα-synuclein RT-QuIC +
Imaging
DAT-SPECT:− Loss of dopaminergic transporters
FDG-PET:Posterior cortical hypometabolism
MRI:Often normal early
Frontotemporal Dementia
bvFTD · svPPA · nfvPPA — Tau or TDP-43
Subtypes
bvFTDSemantic PPAnfvPPA
CSF / Blood
Tau FTD:p-tau ↑ (Pick's disease)
TDP-43 FTD:TDP-43 in CSF (50%)
NfL ↑all subtypes
GRN mutation:progranulin ↓
Imaging
MRI:"Knife-edge" frontal/temporal atrophy
FDG-PET:Frontal/temporal hypometabolism
Tau PET:− (vs AD)
Vascular Dementia
Cerebrovascular disease — 2nd most common
CSF / Blood
Aβ42:Normal
t-tau:Normal or mildly ↑
NfL ↑vascular injury
Imaging — KEY
MRI:Multi-infarct pattern, lacunes
WMH:White matter hyperintensities (Fazekas)
Microbleeds:Caused by amyloid or hypertension
DAT-SPECT:+ Normal
Stepwise decline+ focal neurological signs
Normal Pressure Hydrocephalus
🍷 Potentially REVERSIBLE — "Wet, Wacky, Wobbly"
Classic Triad
Urinary incontinenceDementiaGait apraxia
CSF / Blood
No specific biomarker
CSF pressure:Normal (hence "normal pressure")
Imaging — KEY
Evans index:>0.3 (frontal horn / skull)
Ventricular enlargementdisproportionate to atrophy
Callosal angle:<90° (upward deviation)
MRI:Transependymal CSF egress
💡VP shunt can reverse symptoms — always consider!
Creutzfeldt-Jakob Disease
⚡ Prion disease — FASTEST progression (weeks-months)
CSF / Blood — KEY
14-3-3 protein:Neuronal destruction (↑)
Tau:>1000 pg/mL (very high!)
RT-QuIC:Prion seed detection
NfL:Extremely high (rapid neurodegeneration)
Imaging — KEY
MRI DWI:Cortical ribboning + basal ganglia hyperintensity
FDG-PET:Diffuse cortical hypometabolism
EEG:Periodic sharp waves (1-2 Hz)
⚠️Rapid progression: death usually <1 year from onset
Wernicke-Korsakoff Syndrome
🍷 Thiamine (B1) deficiency — usually chronic alcohol
Wernicke's Triad
AtaxiaOphthalmoplegiaConfusion
Korsakoff's
Anterograde amnesia+ confabulation
Biomarkers
Blood thiamine ↓
CSF thiamine ↓
Imaging — KEY
MRI:Mammillary body atrophy, medial thalamic T2 hyperintensity, periaqueductal gray
CT:Ventricular enlargement possible
Wernicke: acute, reversible with B1. Korsakoff: often permanent.