Neuropsychiatric signs and symptoms clusters and regional amyloid on 18 F-FC119S PET in Alzheimer's disease

Abstract

Background

Neuropsychiatric signs and symptoms (NPS) are highly prevalent in Alzheimer's disease (AD), but whether co-occurring symptom constellations relate to regional amyloid deposition remains unclear.

Objective

To identify reproducible NPS clusters in AD and examine their associations with regional amyloid deposition using ¹⁸F-FC119S positron emission tomography (PET).

Methods

We included 143 patients with probable AD and positive amyloid PET. NPS were assessed with the Korean Neuropsychiatric Inventory, and hierarchical cluster analysis (Yule's Q, average linkage) identified symptom clusters. Regional amyloid burden in frontal, temporal, and parietal cortices was quantified by automated SUVRs. Clinical characteristics were compared using t tests, and associations between clusters and regional amyloid patterns were examined with Pearson's χ².

Results

Four clusters emerged: Group 1 (delusion, agitation–aggression, disinhibition, aberrant motor behavior); Group 2 (depression, anxiety, irritability); Group 3 (hallucination, euphoria, nighttime behavior, apathy); and Group 4 (eating abnormalities). Group 1 patients were older with worse global status (lower K-MMSE, higher CDR, lower Barthel); Group 2 showed higher GDS15 scores; Group 3 showed selectively lower K-MMSE; Group 4 showed no significant differences. On PET, Group 1 was associated with right frontal and right temporal positivity; Group 2 with left parietal negativity; Group 3 with right frontal positivity plus left parietal negativity; Group 4 showed no significant association.

Conclusions

In amyloid-confirmed, drug-naïve AD, distinct NPS clusters map onto specific regional amyloid patterns and global clinical profiles. These findings support a network-oriented view of NPS pathophysiology and may inform phenotyping and individualized management.