Affective Neuropsychiatric Symptoms as Early Signs of Dementia Risk in Older Adults

Article type: Research Article

Authors: Jang, Jung Yun^a | Ho, Jean K.^b | Blanken, Anna E.^b | Dutt, Shubir^b | Nation, Daniel A.¹ | the Alzheimer’s Disease Neuroimaging Initiative¹

Affiliations: [a] Veterans Affairs Boston Healthcare System, Boston, MA, USA | [b] Department of Psychology, University of Southern California, Los Angeles, CA, USA | [c] Department of Psychological Science, University of California, Irvine, Irvine, CA, USA | [d] Institute of Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, USA

Correspondence: [*] Daniel A. Nation, PhD, University of California, Irvine, 4564 Social and Behavioral Sciences Gateway, Irvine, CA 92697-7085, USA. Tel.: +1 949 824 9339; [email protected].

Note: [1] Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf

Abstract: Background:Affective neuropsychiatric symptoms (aNPS: depression, anxiety, apathy, irritability) have been linked to increased dementia risk. However, less is known whether this association is independent of Alzheimer’s disease (AD) pathophysiology. Objective:To investigate the contribution of early aNPS to dementia risk in cognitively normal (CN) older adults and mild cognitive impairment (MCI) patients, with and without AD biomarker abnormality. Methods:Participants included 763 community-dwelling, stroke-free older adults identified as CN and 617 with MCI at baseline, drawn from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. Baseline assessments included a neuropsychological battery, the Neuropsychiatric Inventory (NPI), and apolipoprotein E ɛ4 (ApoE4) genotyping. A participant subset completed cerebrospinal fluid (CSF) AD biomarker assessment. Time to progression to dementia was measured based on months at follow-up when an individual was diagnosed with dementia, over the follow-up period of 48 months. Results:Latent class analysis identified 3 subgroups of older adults in CN and MCI, indicated by the baseline profiles of neuropsychiatric symptoms (NPS). Subgroups with higher aNPS were at increased risk of progression to dementia in both CN (HR = 3.65, 95% CI [1.80, 7.40]) and MCI (HR = 1.52, 95% CI [1.16, 2.00]; HR = 1.86 [1.05, 3.30]) groups, adjusting for age, sex, global cognition, and ApoE4, compared with their counterparts with minimal NPS. There was no difference between higher aNPS and minimal NPS subgroups in their CSF AD biomarker profiles. Conclusion:Findings suggest that aNPS may represent a neurobiological vulnerability that uniquely contribute to the dementia risk, independent of AD biomarker profiles.

Keywords: Alzheimer’s disease, CSF biomarkers, dementia, neuropsychiatric symptoms

DOI: 10.3233/JAD-200190

Journal: Journal of Alzheimer's Disease, vol. 77, no. 3, pp. 1195-1207, 2020