Table 3

Some important ‘chameleons’ of dementia diagnosis

DiseaseChameleonsSome useful features to identify the chameleon
Alzheimer’s diseaseMimics*
Transient epileptic amnesia†Clinical seizures (not invariable), prominent fluctuation, ‘vacational' amnesia‡; abnormal (extended) EEG, may have other features of limbic encephalitis, auto-antibodies / cancer
Obstructive sleep apnoea†Daytime somnolence, non-refreshing sleep, heavy snoring (from partner); abnormal sleep study
Normal-pressure hydrocephalus†May have gait apraxia, urinary dysfunction; MRI hydrocephalus and associated features
VascularMRI: strategic (eg, thalamic) infarct, other vascular patterns (including deep micro-haemorrhages)
Traumatic brain injury/chronic traumatic encephalopathyHistory of significant (especially recurrent) head trauma
Dementia with Lewy bodies frontotemporal dementia and other neurodegenerative disordersVary according to underlying pathology; may have genetic mutation (frontotemporal dementia, familial prion), some entities (eg, argyrophilic grain disease, limbic-predominant age-related TDP-43 encephalopathy) currently only diagnosed post mortem
Posterior cortical atrophy
Logopenic aphasia
Behavioural variant frontotemporal-like
Corticobasal syndrome
Young onset (sporadic)
Positive Alzheimer markers in CSF (raised total / phospho-tau, reduced beta-amyloid42 and beta-amyloid42/40 ratio), cortical micro-haemorrhages associated with amyloid angiopathy
Rapid (may have beta-amyloid angiitis)Positive Alzheimer CSF and MRI markers, cortical microhaemorrhages/siderosis on MRI
FamilialYoung, autosomal dominant family history (may be censored); may have spastic paraparesis/other neurological signs (especially PS1 mutations), prominent neuropsychiatric features, white matter change on MRI; PS1, PS2 or APP mutation (in addition to Alzheimer CSF markers)
Dementia with Lewy bodiesMimics
Progressive supranuclear palsy and corticobasal syndromeSupranuclear gaze palsy, prominent asymmetric apraxia/axial rigidity; poor levodopa response
Alzheimer-likeFlorid delirium, prominent fluctuations, early visual hallucinations, REM sleep behaviour disorder, emerging parkinsonism
Behavioural variant frontotemporal-like
Vascular cognitive impairmentMimics
Infectious/inflammatory/autoimmune†Suggestive history, autoantibodies, blood/CSF serology (eg, human immunodeficiency virus and syphilis)
Genetic arteriopathiesYoung, lack of vascular risk factors, suggestive family history; migraine, psychiatric features, MRI involvement of anterior temporal lobe, NOTCH3 mutations with CADASIL
Primary leukodystrophiesYoung, lack of vascular risk factors, suggestive MRI (confluent, symmetric white matter change), positive diagnostic tests
Behavioural variant frontotemporal-likeMRI: significant vascular change, lack of suggestive atrophy profile
Prominent amnestic/focal ‘cortical’ deficitsMRI: strategic infarct (especially thalamus, parietal)
Frontotemporal dementia§Mimics
‘Frontotemporal dementia phenocopy’ (especially older men)Normal brain MRI/ fluorodeoxyglucose-PET; some frontotemporal dementia cases (especially C9orf72 mutations) may be very slowly progressive—phenocopy cases often show better preserved insight than is usual with frontotemporal dementia
Frontal variant of Alzheimer’s diseaseProminent associated episodic memory deficit, relatively prominent posterior atrophy on MRI, Alzheimer biomarkers (CSF, amyloid PET)
VascularMRI: vascular features
Dementia with Lewy bodiesVisual hallucinations, REM sleep behaviour disorder
Amnestic/Alzheimer-likeNegative Alzheimer biomarkers
Corticobasal syndromeMay have GRN mutation
Motor neurone diseaseMay have C9orf72 mutations
Very young onset/rapidMRI: disproportionate caudate atrophy (FUS-opathy)
  • Here, chameleons are either ‘mimics’—a different disease that presents similarly to the typical syndrome, listed in the left-most column—or ‘variants’—an alternative, atypical presentation of the same disease process that causes the typical syndrome.

  • *Negative Alzheimer markers may be helpful but Alzheimer pathology frequently coexists with other entities (seizures, obstructive sleep apnoea more common in Alzheimer’s disease).

  • †Potentially reversible process.

  • ‡No recollection at all of salient events such as vacations (typically in Alzheimer’s disease, there is some recollection of the episode, although degraded).

  • §Presentation with behavioural variant here taken to be typical (clinical mimics of primary progressive aphasia syndromes are very uncommon).

  • APP, amyloid precursor protein; CADASIL, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; C9orf72, mutation of chromosome 9 open reading frame 72; CSF, cerebrospinal fluid; EEG, electroencephalogram; FUS, fused-in-sarcoma protein; GRN, progranulin gene; NOTCH3, neurogenic locus notch homolog protein 3 mutations; PET, positron emission tomography; PS1, presenilin 1 gene mutation; PS2, presenilin 2 gene mutation.