A childhood rich with intellectual stimulation may help the brain resist the onslaught of Alzheimer’s disease decades later, according to a study published June 29 in JAMA Neurology. Researchers led by David Bennett at Rush University Medical Center in Chicago found fewer Aβ plaques and tau tangles in the brains of people who had spent their youths steeped in a cognitively rich environment. Such early life enrichment also came with slower cognitive decline in the final years of life, an effect that was partially mediated by protection against AD pathology. The findings suggest that an early life investment in cerebral pursuits pays off decades down the road.
- Early life cognitive enrichment associated with reduced AD pathology later.
- This correlated with less cognitive decline.
- This pathology finding accounts for one-fifth of the observed cognitive protection.
“This is the largest study on the association between early life cognitive enrichment and AD pathology to date. Its findings highlight the importance of the first two decades of life for healthy aging occurring decades later,” commented Michael Ewers of the University of Munich.
Multiple studies have linked early life markers of intelligence or educational attainment to reduced risk for dementia in late life (Snowdon et al., 1996; Russ et al., 2017; Oct 2018 news). Even so, the question remains whether these intellectual investments make the brain more resistant to developing neuropathology in the first place, and/or more resilient in the presence of a given amount of neuropathology (Jun 2014 news).
First author Shahram Oveisgharan and colleagues investigated associations between childhood cognitive enrichment, AD pathology, and cognitive decline among 813 participants in the Rush Memory and Aging Project. The participants were tracked for cognitive changes for an average of seven years before they died. At enrollment, they filled out extensive questionnaires about their lives, and the researchers used this information to develop a composite measure of their early life cognitive enrichment. ELCE scores comprised four main components: early life socioeconomic status, based on education levels of the parents and the number of children in the family; availability of cognitive resources, such as a newspaper subscription, encyclopedias, or a globe, at 12 years of age; frequency of participation in cognitively stimulating activities such as reading; and years of foreign-language instruction by 18 years of age. Each of these four indicators were weighted differently and standardized, and a participant’s total ELCE score ranged from -2.0 to 1.7, with a median of 0. Higher scores denoted more enrichment. The researchers acknowledge a recall bias in their study, as participants, most of whom were in their 70s by the time they enrolled, were asked to remember events that took place in their first years of life.
Even so, strong associations emerged. The researchers found that higher ELCE scores associated with lower burdens of Aβ plaques, fewer tau tangles, and lower global AD pathology scores, which take both pathologies into account. For context, a 1-unit increase in ELCE had a similar impact on AD pathology as did being eight years younger. Neither ApoE genotype, age at death, sex, nor vascular risk factors muddled the relationship between ELCE and AD pathology. Strikingly, the association also remained when the researchers controlled for the participants’ self-reported socioeconomic status at enrollment, or their participation in cognitive activities in late life, suggesting that the effect was not driven by late-life advantages reaped from cognitive seeds sown in childhood.
The researchers found no association between ELCE and any of eight other non-AD brain pathologies measured in the study. Together, the findings suggested that early life cognitive enrichment somehow imbued the brain with resistance to AD pathology.
Furthermore, higher ELCE scores correlated with a more gradual cognitive slide late in life, such that a 1-unit increase in ELCE came with a 25 percent slower rate of decline. Ultimately, the researchers calculated that reduced AD pathology accounted for 20 percent of ELCE’s association with cognitive decline, leaving 80 percent of the association independent of amyloid and tau pathology.
“Although only 20 percent of the variability in the rate of cognitive changes explained by ELCE could be attributed to ELCE’s association with lower AD pathology, the effect of ELCE on Aβ and pathologic tau is remarkable,” Ewers wrote, adding that studies assessing lifestyle and cognitive enrichment in mid- and late life have not found links to AD pathology.
Oveisgharan was struck by the connection between ELCE and AD pathology. While the mechanisms involved are unclear, he hypothesized that cognitive stimulation in early life may be particularly suited to protect the brain against the AD neuropathological cascade, which starts decades prior to symptom onset.
ELCE may also boost cognitive resilience in the face of any brain pathology that does develop, including AD pathology or cerebrovascular disease, Oveisgharan noted.
Though the observational study cannot prove causation, Oveisgharan said the findings support the idea that intellectual stimulation in early childhood not only opens to the door to educational and job opportunities, but also improves cognitive health decades down the road. This makes enrichment programs that serve youth in disadvantaged or marginalized communities all the more important, he said.
In their accompanying editorial, Timothy Hohman of Vanderbilt University Medical Center in Nashville and Catherine Kaczorowski of the Jackson Laboratory in Bar Harbor, Maine, agreed. “Such policy reform has critical implications for reducing the burden of age-related cognitive impairment and would counteract systemic injustices that perpetuate health inequities and contribute to the well-documented disparities in AD,” they wrote.
“If the findings stand up to further scrutiny, the public health implications are obvious,” wrote Perminder Sachdev of the University of New South Wales in Sydney. He noted that to make early life enrichment universal, attention should go to improving the educational experience itself. “One must of course remember that data from this study refers to experiences in the early 20th century, as the participants in this study were a mean 90.1 years at the time of their death,” Sachdev added. “Whether the same would be true of childhood experiences a century later is difficult to know.”
Rachel Buckley of Massachusetts General Hospital in Boston added that the cohort is more female, white, and highly educated than the general U.S. population, so understanding the benefits of early life cognitive enrichment on downstream pathology in a more diverse sample is important. To Buckley’s mind, the study raised questions such as: “What is the exact nature of this early life enrichment? Does it remain important to downstream events even if someone ‘lapses’ in their enrichment when they are older? Or is it more about setting up ‘good practices’ while someone is young? What part of the enrichment process lends most to these positive downstream effects, or are all things ‘equally good’?”—Jessica Shugart
- Intelligence Matters More for Brain Reserve, but Education Helps
- A Life of Cognitive Enrichment May Fend Off Dementia. But How?
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- Oveisgharan S, Wilson RS, Yu L, Schneider JA, Bennett DA. Association of Early-Life Cognitive Enrichment With Alzheimer Disease Pathological Changes and Cognitive Decline. JAMA Neurol. 2020 Jun 29; PubMed.