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

Article type: Research Article

Authors: Sundermann, Erin E.^{a; *} | Barnes, Lisa L.^{b; c} | Bondi, Mark W.^{a; d} | Bennett, David A.^{b; c} | Salmon, David P.^e | Maki, Pauline M.^f

Affiliations: [a] Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA | [b] Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, IL, USA | [c] Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA | [d] Veterans Affairs San Diego Healthcare System, La Jolla, CA, USA | [e] Department of Neuroscience, University of California, San Diego, La Jolla, CA, USA | [f] Department of Psychiatry, Psychology and OBGYN, University of Illinois at Chicago, Chicago, IL, USA

Correspondence: [*] Correspondence to: Erin E Sundermann, PhD, UCSD ACTRI building, office 2W517, 9452 Medical Center Drive (MC 0875), La Jolla, CA 92037, USA. Tel.: +1 858 246 5507; E-mail: esundermann@health.ucsd.edu.

Abstract: BackgroundDespite 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. ObjectiveTo determine whether sex-adjusted norms improve aMCI diagnostic accuracy when accuracy was evaluated by progression to AD dementia over time. MethodsNon-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. ResultsRates of aMCI were higher in men versus women (χ2 = 15.39, p < 0.001) when determined based on typical diagnostic criteria, but this difference reversed when using sex-specific diagnostic criteria (χ2 = 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). ConclusionResults 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%.

Keywords: Amnestic mild cognitive impairment, diagnosis, incident Alzheimer’s disease, sex differences, verbal memory

DOI: 10.3233/JAD-215260

Journal: Journal of Alzheimer's Disease, vol. 84, no. 4, pp. 1763-1770, 2021