Atrial fibrillation, vascular phenotype, APOE genotype and Alzheimer's Disease: a perspective cohort study

Background: An associa6on between non-valvular atrial fibrilla6on (NVAF) and cogni6ve impairment has been hypothesized. We sought to evaluate whether and how permanent NVAF (pNVAF) is associated to progression of cogni6ve impairment in pa6ents with probable Alzheimer’s disease (pr-AD) in the presence of vascular or gene6c risk factors. Methods: 310 consecu6ve pa6ents affected by mild-moderate pr-AD were included and followed for a 24–month period. At the end of the follow-up, based on the results of the neuropsychological evalua6on, pa6ents were classified as stable or deteriorated to severe pr-AD. Clinical history, therapy, 6me in therapeu6c range for an6coagula6on, Framingham cardiovascular risk profile (FCRP), CHA2DS2-VASc score, mini-mental state examina6on (MMSE), APOE genotype, brain CT-scan, caro6d ultrasound and ECG were collected. Mul6variate logis6c and general linear models were adopted to assess predictors of the outcome. Results: Despite an6coagulant therapy, pNVAF was associated to lower entry MMSE, higher mean in6mamedia thickness (mIMT) and higher FCRP, as shown in Fig.1. The lowest MMSE (14.90±7.62), the highest mIMT (1.16±0.17 mm) and FCRP (26.24±3.96) values were detected in APOE ε4 allele carriers affected by pNVAF. This group of pa6ents showed the highest risk of cogni6ve deteriora6on (OR:5.894;95%CI: 1.112-31.234;p=0.037), as shown in Fig.2. pNVAF was associated to an increased risk of cogni6ve deteriora6on in subjects with high FCRP, CHA2DS2-VASc or mIMT. Conclusions: pNVAF seems to identify pr-AD pa6ents with a significant atherosclero6c burden and reduced cogni6ve performances. The interac6on between pNVAF and APOE ε4 genotype, especially in the presence of aggregated risk factors and vascular damage is associated to a significant increase of the risk of faster cogni6ve deteriora6on. Fig.