Authors: Sun, Yan | Hu, He-Ying | Hu, Hao | Huang, Liang-Yu | Tan, Lan | Yu, Jin-Tai
Article Type:
Research Article
Abstract:
Background: Cerebral small vessel disease (CSVD) has been suggested to contribute to the pathogenesis of Alzheimer’s disease (AD). Objective: This study aimed to comprehensively investigated the associations of CSVD burden with cognition and AD pathologies. Methods: A total of 546 non-demented participants (mean age, 72.1 years, range, 55–89; 47.4% female) were included. The longitudinal neuropathological and clinical correlates of CSVD burden were assessed using linear mixed-effects and Cox proportional-hazard models. Partial least squares structural equation model (PLS-SEM) was used to assess the direct and indirect effects of CSVD burden on cognition. Results: We found that higher CSVD burden was associated
…with worse cognition (MMSE, β= –0.239, p = 0.006; MoCA, β= –0.493, p = 0.013), lower cerebrospinal fluid (CSF) Aβ level (β= –0.276, p < 0.001) and increased amyloid burden (β= 0.048, p = 0.002). In longitudinal, CSVD burden contributed to accelerated rates of hippocampus atrophy, cognitive decline, and higher risk of AD dementia. Furthermore, as the results of PLS-SEM, we observed both significant direct and indirect impact of advanced age (direct, β= –0.206, p < 0.001; indirect, β= –0.002, p = 0.043) and CSVD burden (direct, β= –0.096, p = 0.018; indirect, β= –0.005, p = 0.040) on cognition by Aβ-p-tau-tau pathway. Conclusion: CSVD burden could be a prodromal predictor for clinical and pathological progression. Simultaneously, we found that the effects were mediated by the one-direction-only sequence of pathological biomarker changes starting with Aβ, through abnormal p-tau, and neurodegeneration.
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Keywords: Alzheimer’s disease, cerebral small vessel disease, cerebrospinal fluid biomarkers, cognition, partial least squares structural equation pathway model
DOI: 10.3233/JAD-221207
Citation: Journal of Alzheimer's Disease,
vol. 93, no. 1, pp. 283-294, 2023
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