New findings indicate that cognitive health in old age depends in part on cognitive development in early life.
Shahram Oveisgharan, MD
Data from the Rush Memory and Aging Project (MAP), a clinical-pathological community-based cohort study, suggest that early-life cognitive enrichment (ELCE) was associated with better late-life cognitive health, in part through an association with fewer Alzheimer disease (AD) pathological changes.
The study, conducted by Shahram Oveisgharan, MD, assistant professor, Rush Alzheimer’s Disease Center, Rush University Medical Center, and colleagues showed that a higher level of ELCE was associated with less cognitive decline (mean, —0.13 [standard deviation (SD), 0.19] units per year; range, ­–1.74 to 0.85).
After using a linear regression mode that controlled age at death, sex, and educational level, a higher level of ELCE was associated with a lower global AD pathology score (estimate, —0.057; standard error [SE], 0.022; P = .01). However, ELCE was not associated with any dementia-related pathological changes. Notably, lower levels of tau (estimate, —0.188; SE, 0.076; P = .01) and d β-amyloid (estimate, −0.136; SE, 0.066; P = .04) were associated with higher level of ELCE as well.
At baseline, a self-report demonstrated that ELCE was derived from early-life socioeconomic status, availability of cognitive resources at 12 years of age, frequency of participation in cognitively stimulating activities, and early-life foreign language instruction. In the analysis, the 813 participants had a mean age of 90.1 (SD, 6.3) years at the time of death, and 562 (69%) of them were women.
Researchers also assessed the association of ELCE in the presence of terms for vascular risk factors and diseases, participants’ self-perceived socioeconomic status, and late-life cognitive activity level. They found that the association of a higher level of ELCE with a lower level of AD pathology score persisted (estimate in the model including vascular risk factors, −0.052 [SE, 0.022; P = .02]; estimate in the model including vascular diseases, −0.052 [SE, 0.022; P = .02]; estimate in the model including socioeconomic status, −0.089 [SE, 0.035; P = .01]; estimate in the model including cognitive activity, −0.060 [SE, 0.022; P = .007]).
Multiple cases of data from this project and others have confirmed hypotheses about the benefits from early-life cognitive enrichment and healthy lifestyle habits. Recently, research pooled from MAP and the Chicago Health and Aging Project (CHAP) revealed that a combination of at least 4 of the 5 specified health behaviors—physical activity, not smoking, light-to-moderate alcohol consumption, high-quality diet, and cognitive activities–led to a lower risk of AD.
Further data showed that the risk of AD was 60% lower (pooled hazard ratio [HR] 0.40; 95% CI, 0.28—0.56) in those with 4 to 5 health risk factors compared to participants with 0 to 1 healthy lifestyle factors. Additionally, those with 2 to 3 healthy lifestyle factors had a 37% lower risk (pooled HR 0.63; 95% CI, 0.47—0.84) than those with 0 to 1 healthy lifestyle risk factors.2
Additional data from MAP was published in January, demonstrating that higher dietary intake of flavonols may be associated with a lower risk of developing AD dementia. With that, the dietary intake of several types these phytochemicals were inversely associated with incident Alzheimer dementia.
The hazard ratios (HR) for the fifth vs. first quintiles of intake of flavonols were: total flavonol, 0.52 (95% CI, 0.33—0.84); for kaempferol, 0.49 (95% CI, 0.31–0.77); for myricetin, 0.62 (95% CI, 0.4–0.97); and for isorhamnetin, 0.62 (95% CI, 0.39–0.98). The only type without the association was quercetin (HR, 0.69; 95% CI, 0.43–1.09). The tests for linear trends were also significant for all assessments aside from quercetin (P = .06).3
A breakthrough study conducted by Richard Isaacson, MD, director of the Alzheimer’s Prevention Clinic, Weill Cornell Memory Disorders Program at Weill Cornell Medical College/New York-Presbyterian Hospital, and colleagues, published in October 2019, also suggested that adherence to individually tailored interventions, including behavioral, dietary, pharmacologic, educational, and other recommendations can have a positive impact on cognition and reduce risk in patients across the clinical spectrum who have a family history of Alzheimer disease.
Results of the study placed extra emphasis on the importance of early intervention and good adherence, with data demonstrating that higher compliance in patients across the spectrum, from cognitively normal to those with mild cognitive impairment (MCI) due to AD, resulted in significantly better improvement in cognition than seen in natural history cohorts.4
1. Oveisgharan S, Wilson RS, Lei Y, Schneider JA, Bennett DA. Association of early-life cognition enrichment with Alzheimer disease pathological changes and cognitive decline. JAMA Neurol. Published online June 29, 2020. doi: 10.1001/jamaneurol.2020.1941.
2. Combination of healthy lifestyle traits may substantially reduce Alzheimer’s [news release]. NIH. Published June 17, 2020. Accessed July 1, 2020. nih.gov/news-events/news-releases/combination-healthy-lifestyle-traits-may-substantially-reduce-alzheimers
3. Holland TM, Agarwal P, Wang Y, et al. Dietary flavonols and risk of Alzheimer dementia. Neurology. 2020;94:1-8. doi:10.1212/WNL.
4. Isaacson RS, Hristov H, Saif N, et al. Individualized clinical management of patients at risk for Alzheimer's dementia. Alzheimer’s Dement. Published online October 30, 2019. doi: 10.1016/j.jalz.2019.08.198.