Risk Factors for Progression to Alzheimer’s Disease in African Americans in a Large National Cohort

ABSTRACT Objectives To investigate risk factors for progression to Alzheimer’s disease and related dementias (ADRD) in African Americans and non-Hispanic Caucasians in a large US cohort. Design A matched case-control design using electronic health records (EHRs) from 2000 – 2017. Setting Cerner EHRs database covering more than 600 Cerner client hospitals. Participants 79,120 patients aged 65 and older (#ADRD=39,560, #non ADRD older adults=39,560) from an initial cohort of 49,826,000 patients. Measurements We converted ICD9 or ICD10 diagnosis codes into PheWas codes to increase clinical relevance. Then we detected ADRD as having both ADRD diagnosis codes and medications. We considered PheWas codes for Alzheimer’s disease, dementia with cerebral degenerations, senile dementia, and vascular dementia. We considered ADRD medications including acetylcholine and memantine. Results Using two-step propensity score matching, we built an African American cohort of 4,429 and a 4,570-person matched Caucasian cohort that was similar in terms of onset age, observation length, sex, and known ADRD risks (diabetes, vascular disease, heart disease, head injury, and obesity). Older African Americans had a statistically significant progression from cerebrovascular risk (transient ischemic attack) to ADRD incidence (treatment effect coefficient = 0.0978, p -value <0.000) whereas the matched Caucasians did not (treatment effect coefficient = 0.403, p -value = 0.196). Conclusion Our extensive causal analysis using a nationwide EHR discovered disease progression pathways to ADRD. The carefully matched cohorts from different racial groups showed different progression, which partly explains the racial disparities in ADRD incidence. IMPACT STATEMENT We certify that this work is confirmatory of recent novel clinical research. We confirmed that cerebrovascular disease increases the risk of ADRD incidence more in older African Americans than in non-Hispanic Caucasians when diabetes is controlled. 1,2 This research adds large-scale and nationwide epidemiological evidence on racial disparities due to cerebrovascular risk.