A small study of patients at a Seoul memory clinic found that the relationship between blood-based Alzheimer’s markers and brain structure differed by education level among women.
Among women with 7 to 16 years of schooling, higher blood p-tau/amyloid ratios were associated with thinner cortexes across five measured brain regions. The association was not statistically significant among women with 0 to 6 years of education.
What the study found
The cross-sectional study included 80 patients with mild cognitive impairment or dementia. The group included 58 women and 22 men, with an average age of 77.9 years and an average of about 7.4 years of schooling.
Researchers collected blood samples, brain MRI scans and standard cognitive screening results. The main analysis included 53 women with complete MRI and blood-marker data.
In women with 7 to 16 years of education, a higher ratio of phosphorylated tau to amyloid-beta 42 in the blood was associated with thinner cortical tissue in the frontal, parietal, temporal, occipital and insular regions.
For women with 0 to 6 years of schooling, cortical thickness was not significantly associated with the blood markers in any of the measured regions. The estimates pointed slightly toward greater thickness, but the findings were not statistically significant.
The education-by-biomarker interaction appeared in every region tested. It was strongest in the occipital and temporal cortexes and weakest, though still statistically significant, in the parietal cortex. The pattern remained when researchers used different education cutoffs and when they analyzed schooling as a continuous number of years.
Why education matters to the interpretation
The researchers used years of schooling as a stand-in for cognitive reserve, a concept describing factors that may help the brain cope with disease-related changes. They divided education into two groups: 0 to 6 years and 7 to 16 years.
The findings do not show that education caused differences in cortical thickness or changed the effect of Alzheimer’s-related pathology. They show an association in this particular group of patients.
The researchers proposed that inflammation, swelling or blood-vessel damage might help explain why some less-educated women appeared to have preserved cortical thickness despite blood-marker findings. Those possible mechanisms were not tested in the study.
Sex differences in the full sample
Across all 80 patients, women had a higher log-transformed p-tau/amyloid ratio than men: −0.37 compared with −0.53. Women also had a thicker frontal cortex on average, at 4.2 millimeters versus 3.2 millimeters.
Similar differences in the other four brain regions were not statistically significant. Raw Mini-Mental State Examination scores were lower in women than men, but the difference disappeared after adjustment for age and education.
Cortical thickness was not associated with Mini-Mental State Examination scores in the women-only models.
What remains unknown
The study cannot determine whether a preserved-looking cortex in less-educated women later becomes thinner, or whether the pattern predicts future cognitive changes. It also cannot establish whether the findings apply to men, because there were only 22 men and most had at least seven years of education.
The researchers said the results raise the possibility that a normal-looking structural MRI could underestimate Alzheimer’s-related damage in women with little formal education. They also emphasized that larger, better-balanced studies with long-term follow-up are needed.
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