Author:
Gontrum Eva Q.,Paolillo Emily W.,Lee Shannon,Diaz Valentina,Ehrenberg Alexander,Saloner Rowan,Mundada Nidhi S.,La Joie Renaud,Rabinovici Gil,Kramer Joel H.,Casaletto Kaitlin B.
Abstract
<b><i>Introduction:</i></b> We comprehensively evaluated how self- and informant-reported neuropsychiatric symptoms (NPS) were differentially associated with cerebral amyloid-beta (Aβ) PET levels in older adults without dementia. <b><i>Methods:</i></b> Two hundred and twenty-one participants (48% female, age = 73.4 years ± 8.4, Clinical Dementia Rating = 0 [<i>n</i> = 184] or 0.5 [<i>n</i> = 37]) underwent an Aβ-PET scan (florbetapir or PIB), comprehensive neuropsychological testing, and self-reported (Geriatric Depression Scale – 30 item [GDS-30]) and informant-reported interview (Neuropsychiatric Inventory Questionnaire [NPI-Q]) of NPS. Cerebral Aβ burden was quantified using centiloids (CL). NPI-Q and GDS-30 queried the presence of NPS within 4 subdomains and 6 subscales, respectively. Regression models examined the relationship between NPS and Aβ-PET CL. <b><i>Results:</i></b> 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 were associated with higher Aβ-PET. When simultaneously entered, only self-reported cognitive concern was associated with Aβ-PET in the GDS-30 model, while both informant-reported anxiety and depression were 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. <b><i>Conclusions:</i></b> 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.