Behavioral Neurology and Dementia: Syndrome Before Biomarker
Name the syndrome, then the protein
Every dementia question rewards the candidate who characterizes the cognitive profile and behavior before jumping to pathology. Start with the affected domain: memory-predominant, language-predominant, visuospatial, executive-behavioral, or fluctuating attention.
Alzheimer disease typically begins with episodic memory loss (impaired encoding), then spreads to language and visuospatial function. Supportive biomarkers include low CSF amyloid-beta 42 with elevated phosphorylated tau, positive amyloid PET, and temporoparietal or medial temporal atrophy. Logopenic primary progressive aphasia is usually Alzheimer pathology, a classic trap.
Dementia with Lewy bodies is suggested by fluctuating cognition, formed visual hallucinations, spontaneous parkinsonism, REM sleep behavior disorder, and severe neuroleptic sensitivity. Parkinson disease dementia follows motor onset by at least a year.
Frontotemporal lobar degeneration presents as behavioral variant (disinhibition, apathy, hyperorality, loss of empathy, executive deficits with relatively preserved memory) or as nonfluent/agrammatic or semantic variant aphasia. Semantic variant shows anterior temporal atrophy with loss of word meaning and object naming; nonfluent variant shows effortful, agrammatic speech.
Other patterns. Rapid decline with myoclonus, ataxia, and periodic sharp-wave complexes suggests Creutzfeldt-Jakob disease; confirmatory testing is CSF RT-QuIC. Gait apraxia, urinary incontinence, and ventriculomegaly out of proportion to atrophy suggest normal pressure hydrocephalus. Stepwise decline with vascular risk factors suggests vascular contributions.
Traps: depression can mimic dementia but improves with cueing; delirium is a fluctuating attention disorder, not a dementia subtype; anticholinergic and sedative medications commonly worsen cognition.
Rule of thumb: fluctuating cognition plus visual hallucinations plus parkinsonism equals Lewy body disease until proven otherwise.