Amyloid Pathology Modulates the Associations of Neuropsychiatric Symptoms with Cognitive Impairments and Neurodegeneration in Non-Demented Elderly

Article type: Research Article

Authors: Guo, Yun^{a; 1} | Sun, Yan^{b; 1} | Li, Meng^b | Qi, Wan-Yi^c | Tan, Lan^{d; *} | Tan, Meng-Shan^{a; d; *} | for the Alzheimer’s Disease Neuroimaging Initiative²

Affiliations: [a] School of Clinical Medicine, Weifang Medical University, Weifang, China | [b] Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China | [c] Department of Neurology, Qingdao Municipal Hospital, Dalian Medical University, Dalian, Qingdao, China | [d] Department of Neurology, Qingdao Hospital, University of Health and Rehabilitation Sciences, Qingdao, China

Correspondence: [*] Correspondence to: Prof. Meng-Shan Tan, MD, PhD, and Prof. Lan Tan, MD, PhD, Department of Neurology, Qingdao Hospital, University of Health and Rehabilitation Sciences, Qingdao, China (Qingdao Municipal Hospital). Tel.: +86 532 8890 5659; Fax: +86 532 8890 5659; E-mails: tanmengshan@163.com (M.S.T.); dr.tanlan@163.com (L.T.).

Note: [1] These authors contributed equally to this work.

Note: [2] The longitudinal data used in preparation for 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 the 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:The associations between neuropsychiatric symptoms (NPSs) and Alzheimer’s disease (AD) have been well-studied, yet gaps remain. Objective:We aimed to examine the associations of four subsyndromes (hyperactivity, psychosis, affective symptoms, and apathy) of NPSs with cognition, neurodegeneration, and AD pathologies. Methods:Totally 1,040 non-demented elderly (48.07% males) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) were included. We assessed the relationships between NPSs and AD neuropathologies, cognition, neurodegeneration, and clinical correlates in cross-sectional and longitudinal via multiple linear regression, linear mixed effects, and Cox proportional hazard models. Causal mediation analyses were conducted to explore the mediation effects of AD pathologies on cognition and neurodegeneration. Results:We found that individuals with hyperactivity, psychosis, affective symptoms, or apathy displayed a poorer cognitive status, a lower CSF amyloid-β (Aβ) level and a higher risk of clinical conversion (p < 0.05). Hyperactivity and affective symptoms were associated with increasing cerebral Aβ deposition (p < 0.05). Except psychosis, the other three subsyndromes accompanied with faster atrophy of hippocampal volume (p < 0.05). Specific NPSs were predominantly associated with different cognitive domains decline through an 8-year follow-up (p < 0.05). Moreover, the relationships between NPSs and cognitive decline, neurodegeneration might be associated with Aβ, the mediation percentage varied from 6.05% to 17.51% (p < 0.05). Conclusions:NPSs could be strongly associated with AD. The influences of NPSs on cognitive impairments, neurodegeneration might be partially associated with Aβ.

Keywords: Alzheimer’s disease, amyloid, cerebrospinal fluid, cognition, neurodegeneration, neuropsychiatric symptoms

DOI: 10.3233/JAD-230918

Journal: Journal of Alzheimer's Disease, vol. 97, no. 1, pp. 471-484, 2024