Neuropsychiatric Correlates of Small Vessel Disease Progression in Incident Cognitive Decline: Independent and Interactive Effects

Article type: Research Article

Authors: Kan, Cheuk Ni^{a; b; 1} | Gyanwali, Bibek^{a; b; 1} | Hilal, Saima^{a; b; c; d} | Ng, Kok Pin^e | Venketasubramanian, Narayanaswamy^f | Chen, Christopher Li-Hsian^{a; b} | Xu, Xin^{b; g; *}

Affiliations: [a] Memory Aging and Cognition Centre, National University Health System, Singapore, Singapore | [b] Department of Pharmacology, National University of Singapore, Singapore, Singapore | [c] Departments of Epidemiology and Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands | [d] Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore | [e] Department of Neurology, National Neuroscience Institute, Singapore, Singapore | [f] Raffles Neuroscience Centre, Raffles Hospital, Singapore, Singapore | [g] Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

Correspondence: [*] Correspondence to: Dr. Xu Xin, Zhejiang University School of Medicine, Hangzhou, 310058, China. E-mail: xuxinsummer@zju.edu.cn.

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

Abstract: Background:Cerebral small vessel disease (SVD) and neuropsychiatric symptoms (NPS) independently increase the risk of cognitive decline. While their co-existence has been reported in the preclinical stage of dementia, longitudinal data establishing the prognosis of their associations, especially in an Asian context remains limited. Objective:This study investigated the role of SVD and NPS progressions on cognitive outcomes over 2 years in a dementia-free elderly cohort. Methods:170 dementia-free elderly with baseline and 2-year neuropsychological assessments and MRI scans were included in this study. White matter hyperintensities (WMH), lacunes, and microbleeds (CMBs) were graded as markers of SVD. The Neuropsychiatric Inventory (NPI) was used to measure NPS. Generalized estimating equations modelling evaluated the relationship between NPI change and SVD progression. Logistic regression evaluated the risk of incident cognitive decline with both SVD and NPS. All models were adjusted for demographics, baseline cerebrovascular diease, and medial temporal lobe atrophy. Results:Higher NPI scores were associated with higher SVD burden at baseline. Subjects with WMH progression had greater increase in total NPI (β[SE] = 0.46[0.19], p = 0.016), driven by hyperactivity subsyndrome (β[SE] = 0.88[0.34], p = 0.007). Subjects with incident CMBs had greater increase in psychosis subsyndrome (β[SE] = 0.89[0.30], p < 0.001). Subjects with progressions in both SVD and NPS were more likely to develop cognitive decline over 2 years (OR[95% CI] = 4.17[1.06–16.40], p < 0.05). Conclusion:Our findings support worsening of NPS as a clinical indicator of SVD progression and are associated with cognitive decline over 2 years. Early detection of NPS and targeted interventions on SVD burden may improve NPS outcomes.

Keywords: Cerebral small vessel disease, cognitive impairment, dementia, lacune, microbleeds, neurobehavioral symptoms, Neuropsychiatric Inventory, white matter hyperintensities

DOI: 10.3233/JAD-190999

Journal: Journal of Alzheimer's Disease, vol. 73, no. 3, pp. 1053-1062, 2020