Association of Cerebral Small Vessel Disease Burden with Neuropsychiatric Symptoms in Non-Demented Elderly: A Longitudinal Study

Article type: Research Article

Authors: Cao, Qiao-Ling^{a; 1} | Sun, Yan^{b; 1} | Hu, Hao^b | Wang, Zuo-teng^c | Tan, Lan^{a; *} | Yu, Jin-Tai^{d; *} | Alzheimer’s Disease Neuroimaging Initiative²

Affiliations: [a] Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, China | [b] Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China | [c] Department of Neurology, Qingdao Municipal Hospital, College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, China | [d] Department of Neurology and Institute of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, China

Correspondence: [*] Corresponding authors: Jin-Tai Yu, MD, PhD, Department of Neurology, Huashan Hospital, Fudan University, No. 12 Wulumuqi Road, Shanghai, China. E-mail: [email protected] and Lan Tan, MD, PhD, Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, No. 5 Donghai Middle Road, Qingdao, China. Tel.: +86 21 52888160; Fax: +86 21 62483421; E-mail: [email protected].

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

Note: [2] Data used in the preparation of this paper were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) data-base (https://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 the writing of this paper. A complete listing of ADNI investigators can be found at https://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.

Abstract: Background:The links between cerebral small vessel disease (CSVD) burden and neuropsychiatric symptoms (NPS) have not been fully studied. Objective:We aimed to explore the associations of the CSVD burden with Neuropsychiatric Inventory (NPI) total scores and its subsyndromes in the elderly without dementia. Methods:We investigated 630 non-demented participants from the Alzheimer’s Disease Neuroimaging Initiative. All of them had NPI assessments and 3 Tesla MRI scans at baseline and 616 had longitudinal NPI assessments during the follow-up. Linear mixed-effects models were used to investigate the cross-sectional and longitudinal associations of CSVD burden with NPI total scores and its subsyndromes. Results:Higher CSVD burden longitudinally predicted more serious neuropsychiatric symptoms, including NPS (p < 0.0001), hyperactivity (p = 0.0006), affective symptoms (p = 0.0091), and apathy (p < 0.0001) in the total participants. Lacunar infarcts (LIs), white matter hyperactivities (WMHs), and cerebral microbleeds (CMBs) might play important roles in the occurrence of NPS, since they were longitudinally associated with specific neuropsychiatric subsyndromes. LIs contributed to hyperactivity (p = 0.0092), psychosis (p = 0.0402), affective symptoms (p = 0.0156), and apathy (p < 0.0001). WMHs were associated with hyperactivity (p = 0.0377) and apathy (p = 0.0343). However, CMBs were only related to apathy (p = 0.0141). Conclusion: CSVD burden was associated with multiple neuropsychiatric symptoms, suggesting the importance of monitoring and controlling vascular risk factors. Different markers of CSVD were associated with specific subsyndromes of NPS, suggesting that different markers tended to occur in different encephalic regions.

Keywords: Alzheimer’s Disease Neuroimaging Initiative, cerebral small vessel disease burden, neuropsychiatric subsyndrome, non-demented elders

DOI: 10.3233/JAD-220128

Journal: Journal of Alzheimer's Disease, vol. 89, no. 2, pp. 583-592, 2022