Causal association of cardiovascular risk factors with Alzheimer’s disease

Abstract Background Alzheimer’s Disease (AD) frequently coexist with cerebrovascular disease (CVD) and makes it difficult for researchers to delineate the two pathologies with available diagnostic criteria. Neuroimaging techniques, especially FDG‐PET can help differentiate the two pathologies based on the characteristic temporo‐parietal metabolic deficitsin AD and regional patchy deficits in CVD. Co‐occurrence of the both patterns can be seen in mixed cases.Existing literature supports a possible role for cardiovascular risk factors in AD pathogenesis. This study aims to determine whether cardiovascular risk factors have a causative association with typical AD pathogenesis or it has an association with mixed AD. Method Baseline brain FDG‐PET images of participants with a diagnosis of AD from two large clinical trials of hydromethylthionine were classified into “typical AD” and “mixed” patterns through visual analysis. Causal association of independent variable age and dependent variables cardiovascular risk factors, White matter hyperintensities (WMH), AD subtypes and severity of cognitive impairment depicted with ADAS Cog scores were analysed using Structural equation modelling (SEM). Result Out of a total 794 participants, 533 (67.1%) were classified as typical AD and 261 (32.8%) were classified as mixed. Overall, the people with a mixed pattern were significantly younger than the people with a typical AD pattern. Age significantly influenced cardiovascular risk factors, WMH and typical AD subtype. The severity of cognitive impairment was significantly influenced by cardiovascular risk factors, WMH and typical AD subtype. Interestingly, cardiovascular risk factors had a statistically significant positive influence on typical AD subtype in comparison to mixed. Conclusion It is well known fact that the cardiovascular risk factors are commonly associated with cerebrovascular disease but contrary to our expectations cardiovascular risk factors have a causal association with typical AD.