Alzheimer's Cognitive Tests May Mislead Women Due to Brain Changes, Study Finds

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 a new study from Georgia State University.

The research, published in the journal Brain Communications, adds to evidence suggesting Alzheimer’s progresses differently in men and women—and that these differences could impact clinical care. It also implies that doctors may need to interpret common tests differently based on sex.

Why Standard Tests May Fail Women with Alzheimer’s

The issue may stem from tools like the 30-point Mini-Mental State Examination (MMSE), a widely used screening test for cognitive impairment. The study found that women with mild cognitive impairment (MCI)—an intermediate stage between normal aging and Alzheimer’s—could score well on the MMSE despite underlying brain changes not captured by the test alone.

“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.” — Mukesh Dhamala, senior study author and professor of physics and neuroscience at Georgia State University

Dhamala notes that men and women undergo the same test without adjustments for sex, a limitation that may obscure differences in disease progression. To investigate further, the research team analyzed brain scans from 332 individuals at various stages of Alzheimer’s.

Key Findings: How Alzheimer’s Affects Men and Women Differently

The study revealed distinct patterns in brain changes between sexes:

• In men: Brain shrinkage occurred earlier, progressing from normal cognitive health to mild cognitive impairment.
• In women: A steeper and more widespread decline was observed from MCI to Alzheimer’s disease.

These differences suggest that women’s brains may compensate in ways that temporarily preserve cognitive performance. Their cognitive scores were linked to a broader range of brain regions than men’s, indicating the brain recruits additional areas to support function. This could explain why structural brain changes and cognitive scores do not align consistently for women and men.

What’s Next for Alzheimer’s Research and Treatment

The study, led by Chandrama Mukherjee, a doctoral student in Georgia State’s physics and astronomy department, under Dhamala’s guidance, sets the stage for future research. The next phase will track patients over time and explore how hormones and genetics influence these sex-based 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. 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.” — Mukesh Dhamala

Dhamala emphasizes that these findings are not yet a personal prescription. He advises maintaining mental and physical activity, managing vascular health, and discussing family history or genetic risk with a doctor as evidence-based steps to reduce Alzheimer’s risk.

However, he believes the research underscores the need for more personalized approaches in Alzheimer’s diagnosis and treatment.