So, is my almost Master's the best of both worlds?
Higher Education May Be a Double-Edged Sword in Alzheimer's
Key Takeaways
- Higher education was tied to slower tau accumulation at amyloid-negative stages but accelerated accumulation at amyloid-positive stages.
- Differences in tau accumulation between education levels varied across multiple brain regions.
- The findings do not contradict other data linking higher education with greater cognitive reserve, the researchers pointed out.
Higher education appeared to protect against tau accumulation during the amyloid-negative stages of Alzheimer's disease but was associated with accelerated tau accumulation in amyloid-positive stages, data from three cohorts suggested.
In amyloid PET-negative groups, people who achieved higher education had slower tau accumulation than those with lower education (right middle temporal gyrus, P=0.03).
In amyloid PET-positive groups, however, more education was tied to faster tau accumulation (left middle temporal gyrus, P=0.03), said Tengfei Guo, PhD, of the Shenzhen Bay Laboratory in China, and colleagues. This group also had greater connectivity-associated tau spread compared with people with less education (P=0.048).
Differences in tau accumulation in people with high versus low education varied significantly between amyloid-positive and amyloid-negative groups in the left anterior middle temporal gyrus (P=0.007), inferior temporal gyrus (P=0.03), right parieto-occipital sulcus (P=0.04), and superior peripheral visual area (P=0.04), the researchers reported in JAMA Neurology.
Amyloid-targeted treatment with solanezumab appeared to mitigate plasma phosphorylated-tau217 (p-tau217)-associated tau accumulation in people with higher education who had Alzheimer's, they noted.
"This multimodal, multicenter, and multiethnic cohort study highlighted the dual role of higher educational attainment in tau accumulation," Guo and co-authors wrote.
"The findings also underscore the potential of amyloid beta-targeting treatment at preclinical stages to slow tau progression in patients with Alzheimer's disease, particularly those with higher educational attainment," they added.
Education -- a proxy for cognitive reserve -- often correlates with better cognition, greater gray matter volume, improved network efficiency, and enhanced inter-network brain connectivity in older adults, Guo and colleagues observed.
"However, its association with Alzheimer's disease pathologies, particularly tau, remains underexplored," they said. "Although some studies found no significant association, others suggest that higher educational attainment may correlate with greater tau burden in temporoparietal regions in Alzheimer's disease.
The analysis included data from 887 people across three independent cohorts: the Alzheimer's Disease Neuroimaging Initiative (ADNI, 377 participants; mean age 73), the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) study of solanezumab in amyloid-positive people and its companion LEARN study of amyloid-negative people (395 participants; mean age 72), and the Greater Bay Area Healthy Aging Brain Study (GHABS, 115 participants; mean age 66).
ADNI and GHABS represented Northern American and Southern Chinese populations, respectively; A4 was a multicenter trial. Participants had amyloid and tau PET imaging; a subset also had plasma p-tau217 measures.
Participants were dichotomized into high or low education status based on their cohort-specific median years of education in either the amyloid-negative group (17, 16, and 14 years, respectively, for ADNI, LEARN, and GHABS) or the amyloid-positive group (16, 16, and 11 years for ADNI, A4, and GHABS).
The findings do not contradict epidemiological evidence that links higher education with greater cognitive reserve and less risk of developing dementia, Guo and co-authors pointed out.
"A recent study by our group showed that higher educational attainment was associated with greater brain reserve, potentially delaying the onset of significant brain atrophy by a median of 1.9 years," they wrote. "We hypothesize that the cognitive benefits of higher educational attainment stem from greater brain reserve developed early in life, which helps buffer against cognitive decline."
Other theories "similarly propose that higher educational attainment fosters brain reserve, providing individuals with more to lose as the disease progresses," Guo and co-authors noted.
"Notably, our significant findings were predominantly observed in individuals with cognitive impairment," they added.
The study had several limitations, the researchers acknowledged. Regional results from 200 brain regions of interest did not survive multiple comparison corrections. "Despite this, the highly consistent findings across cohorts suggest a modest association between higher educational attainment and tau accumulation, warranting cautious interpretation," they wrote.
The GHABS study lacked longitudinal tau-PET scans, limiting validation of the ADNI and A4 findings, they added.
Disclosures
This study was funded by grants from the National Natural Science Foundation of China, the Guangdong Basic and Applied Basic Science Foundation for Distinguished Young Scholars, and the Shenzhen Bay Laboratory.
Guo reported receiving travel funds to attend the 2023 Alzheimer's Association International Conference and serving on the editors' board of Alzheimer's & Dementia journal. Co-authors had no disclosures.
Primary Source
JAMA Neurology
Source Reference: Cai Y, et al "Higher educational attainment and accelerated tau accumulation in Alzheimer disease" JAMA Neurol 2025; DOI: 10.1001/jamaneurol.2025.1801.
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