Sex-specific norms for verbal memory tests may improve diagnostic accuracy of amnestic MCI

Objective To examine whether the use of sex-specific norms and cut scores to identify memory impairment improves diagnostic accuracy of amnestic mild cognitive impairment (aMCI) compared to non-sex-specific (typical) norms/cut scores given the female advantage in verbal memory. Methods We calculated sex-specific and typical norms/cut scores (age and education specific) for impairment on the Rey Auditory Verbal Learning Test in the Mayo Clinic Study of Aging. Norms/cut scores were applied to 453 women and 532 men from the Alzheimer's Disease Neuroimaging Initiative. We compared sex differences in rates of aMCI (Jak/Bondi criteria) for sex-specific vs typical norms/cut scores. Using sex-specific cut scores as the true condition and typical cut scores as the predicted condition, we categorized participants as true positives (TPs), false positives (FPs), true negative (TNs), or false negative (FNs). In cross-sectional analyses within sex, we compared positivity rates of CSF hyperphosphorylated tau/β-amyloid (Aβ) and cortical Aβ deposition ([¹⁸F]AV45 PET) and APOE e4 frequency among diagnostic comparison groups. Results The frequency of aMCI was higher in men when using typical norms/cut scores. Using sex-adjusted norms/cut scores led to the identification of 10% FNs (missed aMCI cases) among women and 10% FPs among men. Biomarker analyses supported the hypothesis that sex-specific diagnostic criteria improves diagnostic accuracy. Biomarkers rates were higher in FNs vs TNs and similar in FNs and TPs. Biomarker rates were lower in FPs vs TPs and similar between FPs and TNs. Conclusion Results suggest that non-sex-specific aMCI diagnostic criteria led to a 20% diagnostic error rate. Accounting for sex differences in verbal memory performance may improve aMCI classification.