Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Feb;20(2):1112-1122.
doi: 10.1002/alz.13500. Epub 2023 Oct 26.

Maximizing utility of neuropsychological measures in sex-specific predictive models of incident Alzheimer's disease in the Framingham Heart Study

Maria Teresa Ferretti  1   2 , Huitong Ding  3   4 , Rhoda Au  3   4   5   6   7 , Chunyu Liu  4   8 , Sherral Devine  3   4 , Sanford Auerbach  7 , Jesse Mez  7 , Ashita Gurnani  7 , Yulin Liu  3   4 , Antonella Santuccione  2 , Ting Fang Alvin Ang  3   4   6
Affiliations

Maximizing utility of neuropsychological measures in sex-specific predictive models of incident Alzheimer's disease in the Framingham Heart Study

Maria Teresa Ferretti et al. Alzheimers Dement. 2024 Feb.

Abstract

Introduction: Sex differences in neuropsychological (NP) test performance might have important implications for the diagnosis of Alzheimer's disease (AD). This study investigates sex differences in neuropsychological performance among individuals without dementia at baseline.

Methods: Neuropsychological assessment data, both standard test scores and process coded responses, from Framingham Heart Study participants were analyzed for sex differences using regression model and Cox proportional hazards model. Optimal NP profiles were identified by machine learning methods for men and women.

Results: Sex differences were observed in both summary scores and composite process scores of NP tests in terms of adjusted means and their associations with AD incidence. The optimal NP profiles for men and women have 10 and 8 measures, respectively, and achieve 0.76 mean area under the curve for AD prediction.

Discussion: These results suggest that NP tests can be leveraged for developing more sensitive, sex-specific indices for the diagnosis of AD.

Keywords: Alzheimer's disease; machine learning; neuropsychological measures; process making; sex differences.

PubMed Disclaimer

Conflict of interest statement

M.T.F. is the co‐founder of the Women's Brain Project. In the past 2 years she has received consulting and speaking fees from Roche, Eli Lilly, and Lundbeck unrelated to this project. A.S.C. is an official employee of Altoida and works as Chief Medical Officer. She is also co‐founder and pro bono CEO of the Women's Brain Project. R.A. is a scientific advisor to Signant Health and a scientific consultant to Biogen and the Davos Alzheimer's Collaborative (DAC). She also serves as Director of the Global Cohort Program for DAC. The other authors declare no conflicts of interest. Author disclosures are available in the supporting information.

Figures

FIGURE 1
FIGURE 1
Sample selection process. *BPA started in year 2005 and 1775 were excluded due to the absence of NP error measures. AD, Alzheimer's disease; BPA, Boston Process Approach; NP, neuropsychological
FIGURE 2
FIGURE 2
ROC of optimal NP profiles for incident AD prediction in men (A) and women (B). The mean ROC of 10‐folder cross‐validation is shown by the blue line. AD, Alzheimer's disease; AUC, area under the curve; NP, neuropsychological; ROC, receiver operating characteristic
See this image and copyright information in PMC

References

    1. Payami H, Zareparsi S, Montee KR, et al. Gender difference in apolipoprotein E‐associated risk for familial Alzheimer disease: a possible clue to the higher incidence of Alzheimer disease in women. Am J Hum Genet. 1996;58(4):803. - PMC - PubMed
    1. Ferretti MT, Iulita MF, Cavedo E, et al. Sex differences in Alzheimer disease—the gateway to precision medicine. Nat Rev Neurol. 2018;14(8):457‐469. - PubMed
    1. Liu C, Li Y, Nwosu A, et al. Sex‐specific biomarkers in Alzheimer's disease progression: framingham Heart Study. Alzheimer's Dement:Diagn Assess Dis Monit. 2022;14(1):e12369. - PMC - PubMed
    1. Banks SJ, Shifflett B, Berg JL, et al. Sex‐specific composite scales for longitudinal studies of incipient Alzheimer's disease. Alzheimer's Dement: Transl Res Clin Interv. 2019;5:508‐514. - PMC - PubMed
    1. Buckley RF, Mormino EC, Amariglio RE, et al. Sex, amyloid, and APOE ε4 and risk of cognitive decline in preclinical Alzheimer's disease: findings from three well‐characterized cohorts. Alzheimer's Dement. 2018;14(9):1193‐1203. - PMC - PubMed

Publication types