Dementia and Neurodegeneration — Imaging Patterns

Neurodegenerative disease leaves predictable imaging fingerprints — atrophy patterns on T1 MPRAGE (which lobe, which nucleus), signal abnormalities on T2 / SWI / DWI for specific diagnoses, and molecular biomarkers on PET (amyloid, tau, FDG, DaTscan). This page maps the patterns to the syndromes — AD, FTD, DLB, MSA, PSP, CBD, CJD, NPH — and the signs you should never miss.

Alzheimer Disease (AD)

Structural MRI

• Medial temporal lobe atrophy: hippocampus + entorhinal cortex (Scheltens MTA score 0–4).
• Parietal atrophy: precuneus + posterior cingulate (Koedam visual score).
• Bilateral, symmetric, progressive.
• Spares sensorimotor cortex.
• Whole-brain atrophy + ventricular enlargement (Evans index rises).

Functional / Molecular Imaging

• FDG-PET: bilateral parietotemporal + posterior cingulate / precuneus hypometabolism. Spares sensorimotor + occipital.
• Amyloid PET: positive (loss of gray-white contrast).
• Tau PET: positive starting MTL (Braak I-II) → temporoparietal (III-IV) → diffuse cortical (V-VI).

AD Variants

• Logopenic PPA: left temporoparietal atrophy + amyloid-positive in most.
• Posterior cortical atrophy (PCA): bilateral parieto-occipital atrophy; often AD pathology.
• Frontal variant AD: mimics FTD; amyloid PET positive distinguishes.

Frontotemporal Dementia (FTD) Spectrum

Behavioral Variant FTD (bvFTD)

• Frontal + anterior temporal atrophy — bilateral but often asymmetric.
• Sparing of posterior cortex (early).
• FDG-PET: bilateral frontal hypometabolism.
• Amyloid PET: typically negative.

Semantic Variant PPA (svPPA / Semantic Dementia)

• Anterior temporal lobe atrophy — typically asymmetric (often left).
• “Knife-edge” temporal pole.
• FDG: anterior temporal hypometabolism.

Non-Fluent Variant PPA (nfvPPA)

• Left inferior frontal + insular atrophy.
• FDG: left inferior frontal hypometabolism.

FTD-MND (Motor Neuron Disease)

• FTD + ALS-like motor signs.
• C9orf72 hexanucleotide expansion in many cases.

Dementia with Lewy Bodies (DLB)

Structural MRI

• Relatively preserved hippocampi compared to AD.
• Generalized atrophy possible.
• No specific structural sign.

Molecular / Functional Imaging

• DAT-SPECT (DaTscan): abnormal — asymmetric putaminal uptake loss.
• I-123 MIBG cardiac scintigraphy: reduced cardiac uptake (sympathetic denervation).
• FDG-PET: occipital hypometabolism + “cingulate island sign” (preserved posterior cingulate relative to surrounding parietal hypometabolism) — distinguishes from AD.
• Polysomnography: RBD (REM sleep behavior disorder) is a core feature.

Progressive Supranuclear Palsy (PSP)

Structural MRI Signs

• Hummingbird sign: midbrain atrophy with preserved pons → midbrain looks like a hummingbird beak on sagittal T1.
• Morning glory sign: concave (atrophic) midbrain tegmentum on axial.
• Mickey Mouse sign: atrophic midbrain with prominent cerebral peduncles.
• MR Parkinsonism Index (MRPI): (P/M × MCP/SCP) — high values support PSP.
• Midbrain : pons ratio <0.52 supports PSP.
• Cerebral peduncle and superior cerebellar peduncle atrophy.

Functional Imaging

• FDG-PET: bilateral midbrain + frontal hypometabolism.
• DAT-SPECT: abnormal (but doesn’t distinguish from PD).

Multiple System Atrophy (MSA)

MSA-C (Cerebellar Predominant)

• Cerebellar atrophy.
• Middle cerebellar peduncle atrophy.
• Pontine atrophy + “hot cross bun” sign: cruciform T2 hyperintensity in pons (degenerated pontocerebellar fibers).

MSA-P (Parkinsonian Predominant)

• Putaminal atrophy + low T2 signal (iron).
• Slit-like dorsolateral putaminal T2 hyperintensity.
• “Putaminal rim sign” (T2 hyperintense rim on 1.5T; less specific on 3T due to normal rim).

Common to Both

• Autonomic dysfunction.
• DAT-SPECT abnormal.
• MIBG: variable.

Corticobasal Degeneration (CBD)

Imaging

• Asymmetric frontoparietal atrophy contralateral to the clinically affected side.
• FDG-PET: asymmetric frontoparietal + basal ganglia hypometabolism.
• DAT-SPECT: abnormal (often asymmetric).

Huntington Disease (HD)

Imaging

• Caudate + putaminal atrophy: caudate “flattening” of normally convex curve into lateral ventricle → “boxcar” ventricles.
• Frontal atrophy.
• FDG-PET: caudate + putaminal hypometabolism (early, before structural atrophy).

Creutzfeldt-Jakob Disease (CJD)

Sporadic CJD (sCJD)

• Cortical ribbon DWI restriction: highly suggestive of sCJD in the appropriate rapidly progressive dementia context — but NOT pathognomonic. Mimics include status epilepticus / postictal change, severe hypoglycemia, hypoxic-ischemic injury, HSV encephalitis, hyperammonemia, and MELAS stroke-like episodes. Always correlate with EEG, CSF (14-3-3, RT-QuIC), and clinical trajectory.
• Basal ganglia (caudate + putamen) DWI restriction.
• FLAIR hyperintensity in same regions.
• Asymmetric findings common.
• Spares thalamus typically.

Variant CJD (vCJD)

• Pulvinar sign: bilateral posterior thalamus (pulvinar) FLAIR/T2 hyperintensity — highly characteristic.
• “Hockey stick sign”: pulvinar + dorsomedial thalamus.
• Cortical involvement less prominent than sporadic.

Genetic CJD

• Variable imaging features.
• PRNP sequencing confirms (see Genetics).

Normal Pressure Hydrocephalus (NPH)

Imaging Criteria

• Ventriculomegaly out of proportion to atrophy: Evans index >0.3 (frontal horn width / max biparietal diameter).
• DESH pattern (Disproportionately Enlarged Subarachnoid space Hydrocephalus): tight high convexity sulci + enlarged Sylvian fissures + enlarged ventricles.
• Callosal angle <90° on coronal at the level of posterior commissure.
• Transependymal CSF flow: smooth periventricular T2/FLAIR halo.
• Aqueduct CSF flow void: prominent on T2 (high-velocity flow).

Imaging Mimics

• Age-related ventriculomegaly (proportional to atrophy) — NOT NPH.
• Other communicating hydrocephalus (post-SAH, post-meningitis).

Cerebral Amyloid Angiopathy (CAA)

Imaging

• Lobar microbleeds (SWI): cortical/subcortical, multiple, elderly, sparing deep gray.
• Cortical superficial siderosis: linear hemosiderin deposition along cortex (SWI).
• Lobar ICH: posterior > anterior; classic location for CAA.
• White matter changes: leukoaraiosis (especially posterior).
• Boston 2.0 criteria for CAA diagnosis (multidimensional imaging-based).
• Distinguishes from hypertensive vasculopathy (deep microbleeds).

Small Vessel Disease (SVD) / Subcortical Vascular Dementia

Imaging Features

• White matter hyperintensities (WMH): confluent periventricular T2/FLAIR.
• Lacunes: small (<15 mm) deep infarcts in lenticulostriate / pontine / thalamoperforator territory.
• Microbleeds: deep (basal ganglia, thalamus, pons) on SWI.
• Perivascular spaces dilated: especially in basal ganglia (état criblé).
• Fazekas score for WMH severity (0–3 periventricular + 0–3 deep).

CADASIL

• Anterior temporal pole T2 hyperintensity: characteristic.
• External capsule + corpus callosum (genu) T2 hyperintensities.
• Deep gray microbleeds + lacunes.
• NOTCH3 mutation (see Genetics).

Adult Leukodystrophies (Briefly)

• ALSP (CSF1R): frontal-predominant white matter + thin corpus callosum + adult onset.
• X-ALD (adrenomyeloneuropathy): adult-onset spastic paraparesis + neuropathy + adrenal insufficiency; MRI may be normal in AMN; cerebral form shows posterior white matter T2 hyperintensity + enhancement.
• CTX: cerebellar + cerebral white matter + dentate signal change.
• See Leukodystrophy / Genetics pages for full coverage.

Pitfalls and Pearls

• Hippocampal atrophy is not specific to AD: also FTD, vascular dementia, CJD, normal aging.
• Cingulate island sign on FDG-PET: highly specific for DLB.
• Hummingbird sign + axial morning glory: PSP.
• Hot cross bun pons: MSA-C.
• Slit-like dorsolateral putaminal T2 hyperintensity: MSA-P (more reliable than putaminal rim on 3T).
• Cortical ribbon DWI restriction: highly suggestive of sCJD in a rapidly progressive dementia context — not pathognomonic. Mimics: status / postictal, hypoglycemia, HIE, HSV encephalitis, hyperammonemia, MELAS. Correlate with EEG + 14-3-3 + RT-QuIC.
• Bilateral pulvinar T2 hyperintensity: variant CJD; also Fabry, mitochondrial.
• Hockey stick sign: variant CJD pulvinar + dorsomedial thalamus.
• NPH vs atrophy: DESH pattern + callosal angle <90° supports NPH; proportional sulcal + ventricular enlargement = atrophy.
• Amyloid PET positivity rises with age: ~30% of cognitively normal 70-year-olds positive; clinical context essential.
• Tau PET correlates with cognitive decline better than amyloid does — tau is the “executor.”
• Boston 2.0 criteria for CAA: incorporate lobar microbleeds + cortical superficial siderosis + lobar ICH + age.
• CAA-related inflammation (CAA-ri): subacute encephalopathy + leukoencephalopathy + microbleeds + responds to steroids — don’t miss it.
• “Knife-edge” temporal pole: semantic dementia.
• Boxcar ventricles + caudate flattening: HD.
• Anti-IgLON5 disease: hypothalamic + brainstem MRI changes + REM sleep behavior disorder + dysphagia — emerging autoimmune/tauopathy syndrome.

References

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3. Wenning GK, Stankovic I, Vignatelli L, et al. The Movement Disorder Society criteria for the diagnosis of multiple system atrophy. Mov Disord. 2022;37(6):1131-1148.
4. Zerr I, Kallenberg K, Summers DM, et al. Updated clinical diagnostic criteria for sporadic Creutzfeldt-Jakob disease. Brain. 2009;132(10):2659-2668.
5. Charidimou A, Boulouis G, Frosch MP, et al. The Boston criteria version 2.0 for cerebral amyloid angiopathy: a multicentre, retrospective, MRI-neuropathology diagnostic accuracy study. Lancet Neurol. 2022;21(8):714-725.
6. Relkin N, Marmarou A, Klinge P, et al. Diagnosing idiopathic normal-pressure hydrocephalus. Neurosurgery. 2005;57(3 Suppl):S4-S16.
7. Jack CR Jr, Bennett DA, Blennow K, et al. NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease. Alzheimers Dement. 2018;14(4):535-562.