1. Based on a retrospective cohort study of Alzheimer’s disease patients, history of cardiovascular risk factors was not associated with increased risk of late-onset Alzheimer’s disease, but history of stroke was strongly associated with this diagnosis.
2. History of hypertension was inversely associated with risk of late-onset Alzheimer’s disease.
Evidence Rating Level: 2 (Good)
Study Rundown: While cardiovascular disease (CVD) and cerebrovascular disease contribute to certain types of dementia, the impact of CVD risk factors on late-onset Alzheimer’s disease (LOAD) is uncertain. This retrospective study of two longitudinal familial cohorts examined the impact of known CVD risk factors and stroke on the risk of LOAD.
The results of the study showed that a history of cardiovascular risk factors (hypertension, type 2 diabetes, coronary artery disease) was not associated with increased risk of late-onset Alzheimer’s disease, but history of stroke was strongly associated with this diagnosis. This is one of the first studies to investigate the association between LOAD and CVD risk factors in an observational study, as previous studies were cross-sectional in nature. However further study in a prospective or randomized fashion would help to elucidate any causal relationships. Other limitations include lack of inclusion of relevant confounders: BMI, smoking status, physical activity.
In-Depth [retrospective cohort]: This study was conducted using two longitudinal cohorts. The first was the National Institute on Aging Late-Onset Alzheimer Disease/National Cell Repository for Alzheimer Disease family study (NIA-LOAD Study) data from 23 Alzheimer disease US centers. The second, replication cohort, was from the Washington Heights-Inwood Columbia Aging Project (WHICAP), a prospective, population-based study of aging and dementia in Medicare recipients 65 years and older in northern Manhattan, NY. Inclusion criteria for the combined study were: 60 years or older at enrollment, diagnosis of probable or possible LOAD according to known clinical criteria, assessment of all CVD risk factors, and pedigree information available. The association of CVD risk factors (hypertension, type-2 diabetes, heart disease as defined by history of MI, CHF or other heart disease) and LOAD were assessed using generalized mixed logistic regression models. A secondary variable of history of stroke was also assessed. Models were adjusted for genetic causes of LOAD (apolipoprotein E e4 allele). Data analysis was performed from 2003 to 2015.
A total of 6553 NIA-LOAD and 5972 WHICAP participants were used to analyze this association between LOAD and CVD risk factors. In the NIA-LOAD study, hypertension was associated with decreased risk of LOAD (OR 0.63; 95%CI 0.55-0.72). Type 2 diabetes and heart disease were not associated with LOAD. History of stroke was associated with increased risk of LOAD (OR 2.23; 95%CI 1.75-2.83). Adjustment for APOE ε4 did not alter the association results. The association between stroke and increased risk of LOAD was robust in the WHICAP replication sample.
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