1. Early-life cognitive enrichment was associated with decreased Alzheimer’s disease pathology and cognitive decline in late-life.
Evidence Rating Level: 2 (Good)
Factors such as educational performance and childhood socioeconomic status impact cognitive decline and Alzheimer’s disease- (AD) related pathology later in life. While these are components of early-life cognitive enrichment (ECLE), ECLE has not been examined as a specific outcome in AD research. The Rush Memory and Aging Project (MAP), an ongoing community-based cohort study, aimed to assess ELCE and AD pathology through a mean summary score of neuritic and diffuse plaques and neurofibrillary tangles visualized by a modified Bielschowsky silver stain. Between January 1997 and June 2019, 1,018 MAP participants had passed away. A total of 813 of these participants had undergone brain autopsy, neuropathological examination, and complete ELCE data (M [SD] age = 90.1 [6.3] years, 69% female). Higher levels of ELCE were associated with lower global AD pathology scores (estimate -0.057, standard error [SE] 0.022, p = 0.01), amyloid-β (estimate -0.136, SE 0.066, p = 0.04), and tau (estimate -0.188, SE, 0.076, p = 0.01). Comparisons of ELCE and age at death estimates were utilized to contextualize effect size (estimate 0.007, SE 0.002, p = 0.003). Specifically, a one-unit increase in ELCE equated to an effect size associated with being eight years younger. The association between ELCE and AD pathology scores persisted when models included vascular risk factors (estimate 0.052, SE 0.022, p =0.02), vascular diseases (estimate -0.052, SE 0.022, p = 0.02), socioeconomic status (estimate -0.089, SE 0.035, p = 0.01), and cognitive activity (estimate -0.060, SE 0.022, p = 0.007). Less cognitive decline was associated with high levels of ELCE (mean [SD] = -0.13 [0.19] units per year, range -1.74 to 0.85). AD pathological changes indirectly accounted for 20% of the association between ELCE and rate of cognitive decline in later life, with 80% being a direct association. Overall, this study highlights the importance of early development and enriched environments in preventing late-life cognitive decline and AD pathology. Therefore, programs and policies that optimize early educational stimulation may reduce future healthcare burden mediated by neurodegenerative processes.
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