Early life blood pressure, cognitive function and brain aging in mid-to-late life: A synthetic longitudinal cohort analysis

PURPOSEOver 6.9 million Americans above the age of 65 are living with Alzheimers Disease (AD) or related dementias (ADRDs), which are diseases characterized by cognitive decline and structural brain changes associated with accelerated brain aging. Cardiovascular risk factors, in particular hypertension, are well-studied risk factors for AD/ARD. Evidence suggests that the effects of hypertension on cognitive aging may vary by life stage, yet prior studies have focused on the effects of mid- or late-life hypertension or blood pressure, leaving other life stages, including early life, unstudied. However, owing to the logistical complexity of follow-up throughout the life course, cognitive aging cohorts lack early-life blood pressure exposure data and cognitive and brain aging outcome data in mid/late life. When such data are unavailable from any single data source, data fusion methods may be employed to pool two compatible data sources to impute an early-life blood pressure exposure history and produce a synthetic longitudinal cohort in which the associations between early-life blood pressure and mid/late-life cognition and brain aging can be estimated. The purpose of this work is to estimate the association between early-life blood pressure and mid- and late-life cognition and brain aging in a synthetic longitudinal cohort. METHODSWe pooled the Bogalusa Heart Study (BHS) to provide early-life blood pressure data (ages 4-16) and the CARDIA study to provide mid/late-life cognition & brain aging outcome data (ages 58-70) to generate a synthetic longitudinal cohort. Cognition was defined as cognitive domain scores (including executive function, memory, processing speed, and language) calculated by Z-transforming cognitive test scores within each cohort. Global cognition was calculated as the average of these Z-scores. Brain aging was defined using the Spatial Patterns of Atrophy for Recognition of Brain Aging, a measure of age-related brain atrophy using T1-weighted MRI scans. The cohorts overlapped in ages 17-57 for potential matching variables including blood pressure, sociodemographics, and vascular risk factors. Cognition overlapped between ages 41-58. We pooled data by distance-matching many-to-one (BHS to CARDIA) on mediators & confounders of each exposure-disease relationship that overlapped in age of measurement between the two cohorts. These variables included intermediate values of the exposure (blood pressure, ages 17-57), cognition (ages 41-58), in addition to sociodemographic and vascular risk factors. Linear regression models estimated the association between early life blood pressure & cognitive & brain aging outcomes. RESULTSBHS uniquely provided early life blood pressure data (ages 4-16), while CARDIA provided cognitive & brain aging data at ages 58-70. Matching is feasible between the ages of 17-57 on blood pressure, sociodemographics, and vascular risk factors, but 41-57 for cognition. CONCLUSIONSWe our results demonstrate the feasibility & suitability of two US-based cardiovascular cohorts for generating a synthetic lifecourse cohort to estimate early-life blood pressure and its association with mid/late-life cognitive & brain aging outcomes. Future studies should aim to use measures that more closely overlap between both cohorts. Additionally, future studies should interrogate greater spans, such as early life through late life.