Introduction: We comprehensively evaluated how self- and informant-reported neuropsychiatric symptoms (NPS) differentially associated with cerebral amyloid-beta (Aβ) PET levels in older adults without dementia.
Methods: 221 participants (48% female, age=73.4y±8.4, CDR=0 [n=184] or 0.5 [n=37]) underwent an Aβ-PET scan (Florbetapir or PIB), comprehensive neuropsychological testing, and self-reported (Geriatric Depression Scale- 30 item), and informant-reported interview (Neuropsychiatric Inventory Questionnaire) of NPS. Cerebral Aβ burden was quantified using Centiloids (CL). NPI-Q and GDS-30 queried presence of NPS within 4 subdomains and 6 subscales, respectively. Regression models examined the relationship between NPS and Aβ-PET CL.
Results: Both higher self- and informant-reported NPS were associated with higher Aβ burden. Among specific NPI-Q subdomains, informant-reported changes in depression, anxiety, and irritability were all associated with higher Aβ-PET. Similarly, self-reported (GDS-30) subscales of depression, apathy, anxiety, and cognitive concern associated with higher Aβ-PET. When simultaneously entered, only self-reported cognitive concern associated with Aβ-PET in the GDS-30 model, while both informant-reported anxiety and depression associated with Aβ-PET in the NPI-Q model. Clinical status moderated the association between self-reported NPS and Aβ-PET, such that the positive relationship between self-perceived NPS and Aβ burden strengthened with increasing functional difficulties.
Conclusions: In a cohort of older adults without dementia, both self- and informant-reported measures of global NPS, particularly patient-reported cognitive concerns and informant-reported anxiety and depression, corresponded with cerebral Aβ burden. NPS may appear early in the prodromal disease state and relate to initial AD proteinopathy burden, a relationship further exaggerated in those with greater clinical severity.