Improving Detection of Amnestic Mild Cognitive Impairment with Sex-Specific Cognitive Norms

Background: Despite a female advantage in verbal memory, normative data for verbal memory tests used to diagnose Alzheimer's disease (AD) dementia and amnestic mild cognitive impairment (aMCI) often are not sex-adjusted. Objective: To determine whether sex-adjusted norms improve aMCI diagnostic accuracy when accuracy was evaluated by progression to AD dementia over time. Methods: Non-sex-specific and sex-specific verbal memory test norms were incorporated into Jak/Bondi aMCI criteria and applied to older (age 65-90) non-demented women (N=1,036) and men (N=355) from the Rush Memory and Aging Project. Using sex-specific aMCI diagnosis as the true condition versus non-sex-specific aMCI diagnosis as the predicted condition, we identified True Positives, False Positives, True Negatives, and False Negatives and compared AD dementia risk over 10 years among groups. Results: Rates of aMCI were higher in men versus women (chi(2) = 15.39,p < 0.001) when determined based on typical diagnostic criteria, but this difference reversed when using sex-specific diagnostic criteria (chi(2) = 8.38, p = 0.004). We identified 8% of women as False Negatives and 12% of men as False Positives. Risk of incident AD dementia in False Positive men was significantly lower than in True Positive men (HR = 0.26, 95% CI = 0.12-0.58, p = 0.001). Risk of incident AD dementia in False Negative women was substantially higher than in True Negative women (HR = 3.11, 95% CI = 2.09-4.63, p < 0.001). Conclusion: Results suggest that previous reports of higher aMCI rates in men versus women may be an artifact of non-sex-adjusted norms/cut-scores. Incorporation of sex-specific norms/cut-scores for verbal memory impairment into aMCI diagnostic criteria may improve diagnostic accuracy and avoid diagnostic errors in approximately 20%.

Automated summary

This study found that sex-adjusted norms improve diagnostic accuracy for aMCI, avoiding diagnostic errors. The risk of false negative in women and false positive in men is significantly higher than expected.