ATLANTA — A Georgia State University study shows standard cognitive screening tools used to monitor Alzheimer’s disease may not reflect underlying brain changes in the same way for women and men.
According to the Alzheimer’s Association , nearly two-thirds of Americans living with Alzheimer’s are women. New Georgia State research , published in the journal Brain Communications, adds to growing evidence that Alzheimer’s may progress differently in men and women — and that those differences could matter in clinical care. It also suggests doctors may need to interpret common tests differently for each sex.
The issue may involve standard screening tools like the 30-point Mini-Mental State Examination, or MMSE. Mild cognitive impairment (MCI) is an intermediate stage between normal aging and Alzheimer’s disease — and this research suggests that, for women, a good MMSE score during that stage may not fully reflect underlying brain changes.
“A woman who scores well on the MMSE in the MCI stage may still be showing underlying brain changes that are not fully captured by that score alone,” said Mukesh Dhamala , the study’s senior author and a professor of physics and neuroscience at Georgia State University. “Screening tools may need sex-calibrated interpretation.”
Dhamala noted that men and women are given the same test, with no adjustments for sex — a design limitation his research suggests may mask differences in how far the disease has progressed in the brain.
To understand why, the research team analyzed brain scans from 332 people at different stages of the disease. They found that Alzheimer’s affects men’s and women’s brains differently.
In men, the brain showed more shrinkage earlier in the disease’s progression, from normal cognitive health to MCI. In women, the brain showed steeper and more widespread decline from MCI to Alzheimer’s disease.
The findings suggest the brain may be compensating in women in ways that help maintain cognitive performance earlier in the disease. Their cognitive scores were tied to a broader range of brain regions than men’s, suggesting the brain may be recruiting additional areas to support performance.
That may help explain why structural brain changes and cognitive scores may not align in the same way for women and men.
The study was led by Chandrama Mukherjee, a doctoral student in Georgia State’s Department of Physics and Astronomy , under Dhamala’s guidance. The work lays a foundation for the next phase of research, including tracking patients over time and examining how hormones and genetics influence these differences.
“If this line of research succeeds, the larger impact would be a move away from a one-size-fits-all framework for Alzheimer’s disease,” Dhamala said. “Diagnosis could become more sex-informed, biomarkers could be interpreted differently in men and women, and treatment trials could be designed with the understanding that disease timing and brain vulnerability may not be the same across sexes.”
Dhamala is clear that the findings are not yet a personal prescription.
Staying mentally and physically active, managing vascular health and discussing family history or genetic risk with a doctor remain among the best evidence-based steps. But he believes the research should help shape an important conversation many women are having with their doctors right now.
“The long-term hope is that findings like ours will lead to sex-specific screening windows and earlier, more precise interventions,” he said.
For women, Dhamala believes that window may eventually open earlier than is currently recognized.
“In women, this may eventually help identify more targeted windows for intervention, including midlife and postmenopausal stages when neuroprotective hormonal changes may be especially relevant,” he said.
- Story by André Walker
Brain Communications
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