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Neuropsychiatric Profiles and Cerebral Amyloid Burden in Adults without Dementia

Eva Gontrum,E. Paolillo,Shannon Y. Lee,V. Diaz,Alexander Ehrenberg,R. Saloner,Nidhi Mundada,R. La Joie,G. Rabinovici,J. Kramer,K. Casaletto

Published 2024 in Dementia and Geriatric Cognitive Disorders

ABSTRACT

Abstract Introduction: 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. Methods: Two hundred and twenty-one participants (48% female, age = 73.4 years ± 8.4, Clinical Dementia Rating = 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 [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. 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 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. 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. Plain Language Summary This study examines how patients’ and their caregivers’ report of neuropsychiatric symptoms are associated with amyloid burden, of the primary markers of risk for amyloid burden, in older adults without dementia. Amyloid burden was measured using a PET-CT scan, and neuropsychological symptoms were measured with a self-reported and an informant-reported questionnaire. We found that neuropsychiatric symptoms were associated with amyloid burden in older adults without dementia, and these relationships were stronger in older adults with greater cognitive and functional impairment. In particular, caregivers’ report of anxiety, depression, and irritability and patients’ report of cognitive concerns were associated with greater amyloid burden. Neuropsychiatric symptoms, observed by both the patient and the informant, may be promising first identifiers of the neuropathology associated with Alzheimer’s disease and related dementias. Although neuropsychiatric symptoms have been characterized in persons with dementia, we do not yet have a clear understanding of how neuropsychiatric symptoms appear in non-dementia stages or which instruments may be the most sensitive screening tools for neuropsychiatric symptoms in older adults without dementia. These older adults without dementia may exist in a window of opportunity for behavioral and pharmacologic interventions that may prevent or slow clinical progression.

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