Studies link brain health, vitamin D and lifelong learning to lower Alzheimer’s vulnerability

New research found that maintaining good overall brain health may help reduce the impact of Alzheimer’s-related changes on cognitive function, while higher serum levels of 25-hydroxyvitamin D in midlife were tied to lower levels of subsequent tau pathology and a lifetime enriched with intellectually stimulating activities was associated with lower risks of Alzheimer’s disease dementia and mild cognitive impairment in late life. The findings came from studies of independently living older adults in the United States, Framingham Heart Study Generation 3 participants, and adults in the Rush Memory and Aging Project.

In one study, researchers analysed data from more than 600 older adults in the United States aged 65 to 80, who were living independently and had no signs of dementia or memory impairment. They used blood tests and MRI scans to assess early Alzheimer’s-related changes and overall brain health, examined life and social factors such as years of education, income, savings and financial security, and conducted cognitive tests measuring memory, attention, processing speed, working memory and executive function. The main finding was that maintaining good overall brain health may help reduce the impact of Alzheimer’s-related changes on cognitive function. The study also observed early evidence that people with a higher socioeconomic status may be less affected by Alzheimer’s-related changes when it comes to memory, although more research is needed to confirm this relationship.

In a prospective cohort study, higher serum levels of 25-hydroxyvitamin D in midlife were tied to lower levels of subsequent tau pathology, an Alzheimer’s disease biomarker. Over 16 years, higher vitamin D levels in midlife were associated with lower global tau PET (β = -0.022, 95% CI -0.040 to -0.004, P=0.010) and composite tau PET deposition (β = -0.023, 95% CI -0.043 to -0.003, P=0.016). There was no association between vitamin D levels and subsequent amyloid PET burden.

That analysis studied dementia-free participants who had serum vitamin D measured from 2002 to 2005 and had amyloid or tau PET scans between 2016 and 2019. Overall, 793 participants had serum vitamin D measured; 424 had amyloid PET, 369 had tau PET, and 360 had both amyloid and tau PET imaging. The analysis included 435 participants. Mean age was 39.2 years and 53.8% were women, and the average time between blood sampling and PET was 16.2 years. A high level of vitamin D was defined as greater than 30 ng/mL; a low level was less than that. The mean serum vitamin D level was 38 ng/mL, 34% of participants had baseline levels below 30 ng/mL, and 5.1% were taking vitamin D supplements.

Longitudinal research also showed that a lifetime enriched with intellectually stimulating activities — including reading, writing, or frequently visiting museums — was associated with lower risks of Alzheimer’s disease dementia and mild cognitive impairment in late life. Over nearly 8 years of follow-up, each 1-point increase in lifetime cognitive enrichment correlated with a 38% lower risk of Alzheimer’s dementia (HR 0.62, 95% CI 0.52-0.73) and a 33% lower risk of developing mild cognitive impairment (HR 0.67, 95% CI 0.58-0.78). Compared with people in the lowest 10% of lifetime enrichment, those in the top 10% developed mild cognitive impairment an average of 7 years later and had dementia onset 5.4 years later.

That study included 1,939 adults who were dementia-free at baseline. Baseline age was 79.6 years, 75% of the sample was female, and mean education level was 15 years. Participants completed surveys reflecting cognitive enrichment at three life stages and had annual clinical evaluations. The researchers followed participants for an average of 7.6 years; in that period, 551 people developed Alzheimer’s disease dementia.

A subset of 948 participants who died during the study had neuropathology data. Each 1-point higher of lifetime enrichment was associated with higher global cognition (P<0.001) and slower rate of decline (P=0.02) proximate to death, independent of neuropathology. The relationship between lifelong intellectual stimulation and higher cognitive function persisted after adjusting for Alzheimer’s pathologies at autopsy, suggesting higher resilience.

The studies noted limitations. In the vitamin D study, the cohort was mostly Caucasian, serum vitamin D was measured once and may have changed over time, and only 22 participants used vitamin D supplements at baseline. In the lifelong learning study, participants reported details about their early and midlife experiences late in life, which carries risks of potential recall bias and reliability, and the sample included mainly white individuals of European descent who were highly educated. The brain health study said more research is needed to confirm the relationship between socioeconomic status and memory performance in people with Alzheimer’s-related changes.