This retrospective study examined baseline motor and nonmotor symptom profiles associated with amyloid-β (Aβ) copathology in 152 drug-naive, newly diagnosed Parkinson's disease (PD) patients who underwent Aβ imaging, olfactory testing, autonomic function tests, neuropsychological assessment, and NPI-Q.
Aβ-positive PD patients (n=59) had worse olfactory function (CC-SIT OR=0.821), greater dysautonomia (CASS OR=1.380), more mood disturbance (NPI-Q-mood OR=1.057), higher motor disability (UPDRS-III OR=1.080), and higher APOE ε4 carrier odds (OR=3.643) — all independent predictors of Aβ positivity — despite comparable striatal dopamine transporter uptake vs. Aβ-negative patients (n=93).
- Retrospective, single-center design limits generalizability. - Aβ positivity was defined by imaging only; neuropathological confirmation was not available. - Causal direction cannot be established; symptoms may reflect shared neurodegeneration rather than Aβ-specific effects.
In newly diagnosed, drug-naive PD patients, a clinical cluster of prominent olfactory loss, autonomic dysfunction, mood disturbance, and motor deficits out of proportion to dopaminergic imaging findings — especially with APOE ε4 — should raise suspicion for concurrent AD (amyloid) pathology. Consider earlier Aβ evaluation in this phenotype to inform prognosis and trial eligibility.
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