Cognitive enrichment, including intellectual and physical activities, has been shown to delay cognitive impairment; however, its role in the pathophysiology of Alzheimer's disease has yielded contradictory results. A team of researchers from the Mayo Clinic in Rochester, MN, conducted a study on the impact of education on the pathophysiology of Alzheimer's disease (Vemuri P, et al. Neurology. 2016;86:1128-1135).
Discrepancies in Alzheimer's disease biomarker studies regarding lifestyle enrichment can be partly explained by differences between cohorts, sample sizes, and paradigms of enrichment. More important, however, variations in patient education levels may contribute to the conflicting results; education occurs during sensitive periods of brain development, and, therefore, may have a significant impact on Alzheimer's disease biomarker trajectories.
Prashanthi Vemuri, PhD, Assistant Professor of Radiology, Mayo Clinic, and colleagues, followed 393 individuals (aged 70-89 years) with APOE genotype and without dementia who had participated in the Mayo Clinic Study of Aging. They used 3 biomarkers to assess the pathophysiology of Alzheimer's disease, including (1) Pittsburgh compound B as an indicator of cerebral amyloidosis, (2) fluorodeoxyglucose (FDG) as an indicator of brain metabolism, and (3) hippocampal volume as an indicator of neurodegeneration.
All the participants completed questionnaires related to education level, primary occupation throughout life, midlife weekly cognitive activity, and physical activity. The results were analyzed in relation to the 3 biomarkers noted above.
Older age and APOE4 status were significantly associated with higher levels of amyloid deposition. In addition, high midlife cognitive activity was associated with lower amyloid deposition in APOE4 carriers with high education, suggesting a link between high cognitive enrichment and low amyloid deposition, especially in highly educated individuals. These results may be attributed to the link between education, APOE4 status, and amyloid deposition, the researchers suggest.
“Higher levels of education and higher levels of midlife cognitive activities somehow forestall amyloid deposition, which is evident in APOE4 carriers because APOE4 carriers are accumulating amyloid at an earlier age and at a faster rate than APOE4 noncarriers,” wrote Dr Vemuri and colleagues.
Older age and APOE4 gene status were also linked to lower glucose metabolism, a finding consistent with previous studies. Furthermore, this study showed that APOE4 was not associated with lower FDG uptake in highly educated participants, suggesting that “high education in APOE4 carriers may be protective via nonimpaired glucose metabolism,” the authors wrote.
Older age was further linked to lower hippocampal volume, but APOE4 status did not impact hippocampal atrophy trajectories. Overall, enrichment activities did not affect biomarkers of neurodegeneration. Although this finding is contradictory to some previous data, the effect of lifestyle enrichment on neurodegeneration varies, depending on the biomarker used and the disease stage.
Taken together, these results suggest that lifestyle enrichment variables, including education, occupation, midlife cognitive activity, and midlife physical activity, have some, albeit minimal, impact on Alzheimer's disease, especially on the rate of worsening. Overall, highly educated individuals with the APOE4 genotype and high midlife cognitive activity have lower amyloid deposition than APOE4 carriers with low midlife cognitive activity. Furthermore, age is associated with amyloid and neurodegeneration biomarker trajectories, and APOE4 status affected amyloid and FDG trajectories. Finally, APOE4 status was linked to lower FDG uptake in the entire cohort and in the lower education cohort.