Sex Differences Alter Alzheimer’s Screening Accuracy

A Georgia State University study reports that common cognitive screening tools used to monitor Alzheimer’s disease may not reflect underlying brain changes in the same way for women and men. The work, published in Brain Communications, adds to evidence that Alzheimer’s may progress differently by sex and that those differences may matter for clinical care.

The study focused on the 30-point Mini-Mental State Examination, or MMSE, a widely used screening test. The researchers note that mild cognitive impairment, or MCI, sits between normal aging and Alzheimer’s disease, and that a strong MMSE score during MCI may not fully capture what is happening in the brain for women. Mukesh Dhamala, the study’s senior author, said that a woman who scores well on the MMSE in the MCI stage may still show underlying brain changes that the score does not fully capture. He added that screening tools may need sex-calibrated interpretation.

To examine the issue, the team analyzed brain scans from 332 people across different disease stages. They found different patterns of brain change in men and women. In men, the brain showed more shrinkage earlier in the disease course, from normal cognitive health to MCI. In women, the decline was steeper and more widespread from MCI to Alzheimer’s disease.

The findings suggest that women may compensate in ways that help preserve cognitive performance earlier in the disease. Their cognitive scores were linked to a broader range of brain regions than men’s, which may indicate that additional areas are being recruited to support performance. This could help explain why structural brain changes and cognitive scores do not line up in the same way for women and men.

“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.”