Abstract 13659: Cerebral Small Vessel Disease is a Potent Independent Risk Factor for Alzheimer’s Disease

Abstract

Alzheimer’s Disease (AD) is the leading cause of dementia worldwide. Current treatments may slow the progression of the disease but cannot reverse the pathology, thereby confirming the medical need for measures of prevention and early detection. Recent studies established a connection between cardiovascular disease (CVD) risk factors and AD. Small vessel disease, which shares similar risk factors and pathology as CVD, is receiving attention as a potential risk factor for AD as well. We sought to quantify the risk associated with confirmed diagnosis of cerebral small vessel disease (CSVD) for the development of AD as a first step to defining the condition as a treatment target for preventing AD. We hypothesized patients with image-based evidence of CSVD would have a greater risk of having AD.In this retrospective clinical study, we selected patients from the National Alzheimer’s Coordinating Center database with image-based evidence of CSVD including lacunar infarction, microhemorrhage, and white matter hyperintensity (n=3,895). We quantified the risk of each of these conditions for association with clinical AD, elevated β-amyloid, and tau protein accumulation. In addition, we compared the rates of AD development between men and women within these CSVD populations. Using a linear regression analysis, we controlled for shared comorbidities between CSVD and AD. We observed an increased risk as defined by odds ratio (OR) of AD in patients with microhemorrhage (OR=1.32, p=0.04). Patients with white matter hyperintensity also exhibited increased risk of developing AD, which increased with disease severity (Moderate: OR= 1.63, p<0.01; Extensive: OR=2.72, p<0.01). Lacunar infarction did not demonstrate independent risk for developing AD. CSVD did not confer any additional risk for increased tau protein or amyloid based on imaging. The risk of AD was not higher for women as compared to men with confirmed CSVD. Here we elucidate a clear association between CSVD and risk of AD and observe increased risk with the extent of the disease. With a more comprehensive understanding of these relationships, CSVD imaging could be used as an early biomarker for accelerated AD and provide an opportunity to test methods for controlling CSVD as a novel early intervention.