Features of Cerebral Small Vessel Disease Contributes to the Differential Diagnosis of Alzheimer’s Disease

Background: Cerebral small vessel disease (CSVD), which comprises the typical features of white matter hyperintensity (WMH) and Vichor-Robin spaces (VRSs) in the brain, is one of the leading causes of aging-related cognitive decline and, ultimately, contributes to the occurrence of dementia, including Alzheimer’s disease (AD). Objective: To investigate whether CSVD imaging markers modify the pathological processes of AD and whether these markers improve AD diagnosis. Methods: 208 participants were enrolled in the China Aging and Neurodegenerative Initiative (CANDI). Fluid AD biomarkers were detected using a single-molecule array, and cerebral small vessel dysfunction was determined using magnetic resonance imaging. Results: WMH contributed to AD pathology only within the NC and MCI groups (CDR ≤0.5), whereas VRSs had no effect on AD pathology. The associations between AD biomarkers and cognitive mental status were consistent with the presence of CSVD pathology. That is, within individuals without CSVD pathology, the MMSE scores were correlated with AD fluid biomarkers, except for plasma Aβ42 and Aβ40. Increased plasma p-Tau levels were associated with worse cognitive performance in individuals with WMH (β= –0.465, p = 0.0016) or VRSs (β= –0.352, p = 0.0257) pathology. Plasma AD biomarkers combined with CSVD markers showed high accuracy in diagnosing dementia. Conclusion: Findings from this cross-sectional cohort study support the notion that CSVD is a risk factor for dementia and highlights that vascular pathology can promote AD biomarker levels, especially in the early course of the disease. Moreover, our results suggest that adding a vascular category to the ATN framework improves the diagnostic accuracy of AD.