Alzheimer’s Screening Tools May Misdiagnose Women: Key Sex Differences Revealed

Standard cognitive screening tools for Alzheimer’s disease may not detect the disease’s progression equally in women and men, according to new research from Georgia State University. The findings, published in the journal Brain Communications, suggest that current tests like the Mini-Mental State Examination (MMSE) could underestimate underlying brain changes in women, potentially delaying diagnosis and treatment.

Nearly two-thirds of Americans living with Alzheimer’s are women, according to the Alzheimer’s Association. The new study adds to growing evidence that the disease may manifest differently across sexes, with implications for clinical care and early intervention.

How Alzheimer’s Affects the Brain Differently

The research team, led by Mukesh Dhamala, a professor of physics and neuroscience at Georgia State, analyzed brain scans from 332 individuals at various stages of Alzheimer’s progression. Their findings revealed distinct patterns in how the disease affects men’s and women’s brains.

In men, brain shrinkage appeared earlier in the disease’s progression, particularly during the transition from normal cognitive health to mild cognitive impairment (MCI). In women, however, the brain showed steeper and more widespread decline during the shift from MCI to full-blown Alzheimer’s disease.

“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,” Dhamala said. “Screening tools may need sex-calibrated interpretation.”

The study suggests that women’s brains may compensate for early damage by recruiting additional regions to support cognitive performance. This compensation could explain why women’s cognitive scores and structural brain changes do not always align in the same way as men’s.

The Limits of One-Size-Fits-All Screening

Current Alzheimer’s screening tools, such as the MMSE, are administered the same way to both sexes, with no adjustments for biological differences. Dhamala described this as a design limitation that may obscure how far the disease has progressed in women.

The research highlights the need for sex-specific approaches in diagnosis and treatment. “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.”

While the findings are not yet a basis for personal medical advice, they underscore the importance of discussing family history, genetic risk, and overall brain health with a doctor. Dhamala emphasized that staying mentally and physically active, along with managing vascular health, remains among the best evidence-based strategies for reducing Alzheimer’s risk.

Looking Ahead: Earlier, More Precise Interventions

The study was conducted by Chandrama Mukherjee, a doctoral student in Georgia State’s physics and astronomy department, under Dhamala’s guidance. The team’s next steps include tracking patients over time and examining how hormones and genetics influence these sex-based differences.

Dhamala believes the research could eventually lead to earlier intervention windows for women, particularly during midlife and postmenopausal stages when hormonal changes may play a neuroprotective role. “In women, this may eventually help identify more targeted windows for intervention,” he said.

The long-term hope is that these findings will contribute to more personalized Alzheimer’s care, improving outcomes for both women and men. For now, the study serves as a reminder that cognitive screening tools, while valuable, may not tell the full story—especially for women.

The research appears in the journal Brain Communications and was originally reported by Georgia State University.