The interaction of global small vessel disease burden and Alzheimer's disease pathologies do not change the independent association of amyloid‐beta with hippocampal volume: A longitudinal study on mild cognitive impairment subjects

Abstract The purpose of this study was to investigate whether the co‐existence of global small vessel disease (SVD) burdens and Alzheimer's disease (AD) pathologies change hippocampal volume (HV) and cognitive function of mild cognitive impairment (MCI) subjects. We obtained MRI images, cerebrospinal fluid biomarkers (Aβ 1‐42 and p‐tau), and neuropsychological tests of 310 MCI subjects from ADNI. The global SVD score was assessed. We used linear regression and linear mixing effect to analyze the effects of global SVD burdens, AD pathologies, and their interactions (SVD*AD) on baseline and longitudinal HV and cognition respectively. We used simple mediation effect to analyze the influencing pathways. After adjusting for global SVD and SVD*AD, Aβ remained independently correlated with baseline and longitudinal HV (std β = 0.294, p = .007; std β = 0.292, p < .001), indicating that global SVD did not affect the correlation between Aβ and HV. Global SVD score was correlated with longitudinal but not baseline HV (std β = 0.470, p = .050), suggesting that global SVD may be more representative of long‐term permanent impairment. Global SVD, AD pathologies, and SVD*AD were independently correlated with baseline and longitudinal cognitions, in which the association of Aβ (B = 0.005, 95% CI: 0.005; 0.024) and p‐tau (B = −0.002, 95% CI: −0.004; −0.000) with cognition were mediated by HV, suggesting that HV is more likely to explain the progression caused by AD pathology than SVD. The co‐existence of global SVD and AD pathologies did not affect the individual association of Aβ on HV; HV played a more important role in the influence of AD pathology on cognition than in SVD.