Vascular Pathology Is Associated with Rate of Cognitive Decline Independent of AD Pathology (Einstein Aging Study) (P6.222)

Objective: To examine the separate and joint influence of vascular pathology and Alzheimer’s disease (AD) pathology on the rate of cognitive decline in older adults. Background: Presence of vascular pathology exacerbates the clinical presentation of AD and increases risk of clinically evident cognitive impairment. Methods: The Einstein Aging Study (EAS) autopsy series comprises 223 well characterized individuals, including 62 eligible for this study. Eligible participants were free of dementia at study baseline, and had a clinical evaluation within 5 years of death. The Blessed-information memory-concentration test (BIMC) was used to assess global cognitive status. AD pathology was quantified based on Braak stage (<3 vs. ≥ 3). The Vascular Lesion Score (VLS) quantified vascular pathology. The association of vascular pathology with antemortem rates of cognitive decline adjusted for level of AD pathology was assessed using linear mixed effects models with years prior to death as the time scale. Results: The mean age at enrollment was 81.8 and the mean age at death was 89.0 years. Compared to persons free of vascular lesions, those with moderate/severe vascular pathology showed faster cognitive decline (difference in annual rate of change in BIMC=0.74; p=0.03). Braak stage was also associated with greater cognitive decline (p=0.03). The association of VLS with cognitive decline persisted after adjustment for AD pathology (Difference in rate of change in BIMC=0.68, p=0.04). There was an interaction between vascular and AD pathology; vascular pathology had a greater effect on cognitive decline in persons who had higher Braak stages. (p for interaction = 0.03). Conclusions: Vascular brain pathology is associated with the rate of cognitive decline after adjusting for level of AD pathology. The effect of vascular pathology on cognitive decline is greater among individuals with higher burden of AD pathology. Disclosure: Dr. Ezzati has nothing to disclose. Dr. Wang has nothing to disclose. Dr. Lipton has received personal compensation for activities with Allergan, American Headache Society, Autonomic Technologies, Boston Scientific, Bristol Myers Squibb, Cognimed, Colucid, Eli-Lilly, eNeura Therapeutics, Merck, Novartis, Pfizer, Teva, and V Dr. Altschul has nothing to disclose. Dr. Katz has received research support from Bristol Myers Squibb. Dr. Dickson has nothing to disclose. Dr. Derby has nothing to disclose.