Constructing and analyzing a synthetic life course cohort based on pooling two data sources: A case study of early adulthood depression symptomatology and late-life cognition

Abstract Background Synthetic cohorts created by combining two cohorts can be useful when no single data set includes both the exposure and outcome data of interest. We estimate the effects of depression in early adulthood on later-life memory outcome using two nationally representative cohorts separately and in a synthetic sample. Methods We used the National Longitudinal Study of Youth 1979 (NLSY; N=5, 747) and the Health and Retirement Study (HRS; N=6, 846) and a synthetic cohort combining exposure data from N=5, 680 NLSY participants (born 1957-1965) aged 55-63 in 2020 who completed midlife cognitive assessment between 2006-2020 with outcome data from N=9, 726 HRS participants born 1957-1964 who completed cognitive assessments when 47-63 years old and every 2-years thereafter. A 6-item version of the Centers for Epidemiologic Studies-Depression (CES-D) score (range 0-6) was measured from late adolescence through midlife in NLSY and in midlife in HRS. Memory was measured as the sum of immediate and delayed word recall scores up to twice in NLSY at age 48+ and up to 10 times in HRS at age 50+. We generated a synthetic life course cohort, matching HRS participants to NLSY participants based on 10 variables measured in midlife in both cohorts and posited to either confound or mediate the association between early life depressive symptoms and late-life memory. Matching variables included midlife depression and memory. We used confounder-adjusted linear mixed models to estimate the association between earliest reported depressive symptoms in NLSY and HRS with memory in the respective data sets and evaluated associations of early life depression symptoms with the repeated later life memory measures in the synthetic cohort. Results In NLSY, each increment in CES-D at age 23-31 was associated with lower average memory scores (β NLSYₗevel =-0. 050 95%CI (−0. 097, -0. 003) ) in midlife but no detectable difference in rate of memory decline (β NLSYₛlope =-0. 070 95%CI (−0. 382, 0. 242). In HRS, CES-D at average age 53 was associated with lower average memory (β HRSₗevel =-0. 163 (−0. 199, −0. 128) ) but not rate of decline (β HRSₛlope =-0. 021 (−0. 062, 0. 020) ). In the synthetic cohort, CES-D at age 23-27 was associated with lower memory score at age 50+ (β synthₗevel =-0. 044 95%CI (−0. 085, -0. 003) ) but not associated with rate of cognitive decline (β synthₛlope =0. 005 95%CI (−0. 052, 0. 062) ). Conclusions Depressive symptoms ages 23-31 predicted mid- to late-life memory function but had no clear association with memory decline. Combining data across cohorts spanning separate, but overlapping, parts of the life course is a promising approach to overcome data limitations in life course research, but it requires careful implementation to ensure that assumptions are met and estimates are appropriately interpreted.