Cardiovascular and genetic determinants of cognitive deterioration in Alzheimer's Disease

Introduction: We aimed to evaluate the association between non-valvular atrial fibrillation(NVAF), vascular disease and cognitive impairment. We assessed if NVAF was associated to a larger atherosclerotic burden and a faster progression of dementia in patients with Alzheimer’s disease(AD). Materials and Methods: All subjects with mild-moderate AD followed by our clinic were enrolled. At baseline we collected data regarding clinical history and drug therapy. Framingham cardiovascular risk profile(FCRP) and mini-mental state examination(MMSE) were calculated. APOE genotype and carotid ultrasound were also assessed. Subjects were followed-up at 24 months with a neuropsychological evaluation and classified as stable or worsened to severe AD. Evolution to severe AD was considered as the main outcome. Statistic was calculated with GLM/multivariate models and binary logistic regression. Results: 310 consecutive patients affected by mild-moderate AD were finally included. NVAF was associated to a lower entry MMSE score, a higher mean IMT and a higher FCRP.APOE ε4 allele carriers with NVAF had the lowest MMSE (14.90±7.62), the highest mean IMT (1.16±0.17 mm) and the highest FCRP(26.24±3.96%). This group was also associated to the highest risk of clinical evolution to severe AD (OR: 1.749; 95%CI: 1.255- 2.437; p=0.001). Conclusion: Despite optimal anticoagulation, NVAF identified a subset of AD patients with a larger atherosclerotic burden and worse cognitive performance. The interaction between NVAF and ApoE ε4 genotype detected a subgroup with the highest vascular risk, the poorest cognitive function at the beginning of the study and the highest risk of evolution to severe AD in 24 months.