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Investigating the Factor Structure of the Preclinical Alzheimer Cognitive Composite and Cognitive Function Index across Racial/Ethnic, Sex, and Aβ Status Groups in the A4 Study

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Abstract

Background

Disparities in Alzheimer’s disease (AD) are well-documented among different racial/ethnic groups and between sex/genders. Neuropsychological assessment provides important information about cognitive changes and can offer valuable insights into disparities. However, neuropsychological measures must be comparable across racial/ethnic and sex/gender groups to accurately interpret disparities.

Objectives

To evaluate measurement invariance (equivalence) of the Preclinical Alzheimer Cognitive Composite (PACC) and the Cognitive Function Index across racial/ethnic, sex/gender, and β-amyloid (Aβ) status groups.

Design, Setting, Participants

Cross-sectional analysis of screening data from the Anti-Amyloid in Asymptomatic AD (A4) Study. The study enrolled participants aged 65–85 from sites across the United States, Canada, Australia, and Japan.

Measurements

Participants completed the PACC and the Cognitive Function Index. Participants classified as cognitively normal also underwent a Positron Emission Tomography (PET) scan to determine Aβ status.

Results

Participants self-identified as non-Hispanic White (n=5241), non-Hispanic Black (n=267), Asian (n=228), or Hispanic White (n=225) as well as male (n=2885) or female (n=3076). Among those who underwent a PET scan, 3115 were classified as Aβ− and 1309 were classified as Aβ+. We found support for a one-factor model for both the PACC and Cognitive Function Index across the full sample and in samples stratified by race/ethnicity, sex/gender, and Aβ status. The one-factor model of the PACC and Cognitive Function Index demonstrated scalar measurement invariance across racial/ethnic, sex/gender, and Aβ status groups.

Conclusions

Our findings suggest that performance on the PACC and Cognitive Function Index can be compared across the racial/ethnic, sex/gender, and Aβ status groups examined in this study.

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Acknowledgements

We would like to acknowledge the dedication of all the participants, the site personnel, and all the partnership team members who continue to make the A4 and LEARN Studies possible. The complete A4 Study Team list is available on: a4study.org/a4-study-team

Funding

The A4 Study is a secondary prevention trial in preclinical Alzheimer’s disease, aiming to slow cognitive decline associated with brain amyloid accumulation in clinically normal older individuals. The A4 Study is funded by a public-private-philanthropic partnership, including funding from the National Institutes of Health-National Institute on Aging (U19AG010483; R01AG063689), Eli Lilly and Company, Alzheimer’s Association, Accelerating Medicines Partnership, GHR Foundation, an anonymous foundation and additional private donors, with in-kind support from Avid, Cogstate, Albert Einstein College of Medicine, US Against Alzheimer’s disease, and Foundation for Neurologic Diseases. The companion observational Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) Study is funded by the Alzheimer’s Association and GLTR Foundation. The A4 and LEARN Studies are led by Dr. Reisa Sperling at Brigham and Women’s Hospital, Harvard Medical School and Dr. Paul Aisen at the Alzheimer’s Therapeutic Research Institute (ATRI), University of Southern California. The A4 and LEARN Studies are coordinated by ATRI at the University of Southern California, and the data are made available through the Laboratory for Neuro Imaging at the University of Southern California. The participants screening for the A4 Study provided permission to share their de-identified data in order to advance the quest to find a successful treatment for Alzheimer’s disease. MR receives post-doctoral support from Canadian Institutes of Health Research (430246).RAS receives support from the Alzheimer’s Association, NIH R01 AG010483, GHR Foundation, Eli Lilly Company, NIH U24 AG057437). JSR receives support from the Harquail Centre for Neuromodulation, the Dr. Sandra Black Centre for Brain Resilience & Recovery, Canadian Institutes of Health Research (173253–438475), and the Alzheimer’s Society of Canada.

Author information

Authors and Affiliations

  1. LC Campbell Cognitive Neurology Research Unit, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada

    M. Ruthirakuhan, M. Wood Alexander, W. Swardfager, S. E. Black & J. S. Rabin

  2. Rehabilitation Sciences Institute, University of Toronto, Toronto, Canada

    M. Wood Alexander, S. E. Black & J. S. Rabin

  3. Department of Education, ICT and Learning, Ostfold University College, Halden, Norway

    H. Cogo-Moreira

  4. Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA

    T. Robinson, R. Amariglio, R. F. Buckley & R. A. Sperling

  5. Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

    R. Amariglio, R. F. Buckley & R. A. Sperling

  6. Melbourne School of Psychological Sciences, University of Melbourne, Parkville, Victoria, Australia

    R. F. Buckley

  7. Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    R. A. Sperling

  8. Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada

    S. E. Black & J. S. Rabin

  9. Harquail Centre for Neuromodulation, Sunnybrook Research Institute, Toronto, Ontario, Canada

    J. S. Rabin

  10. Sunnybrook Health Sciences Centre, Room M6-178, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada

    J. S. Rabin

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  1. M. Ruthirakuhan
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  7. R. A. Sperling
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  9. S. E. Black
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  10. J. S. Rabin
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Corresponding author

Correspondence to J. S. Rabin.

Ethics declarations

Conflict of interest: MR, MWA, HCM, TR, RA, RFB, WS, JSR have nothing to disclose. RAS has served as a paid consultant for AC Immune, Acumen, Alynlam, Cytox, Genentech, Janssen, JOMDD, Nervgen, Neuraly, Neurocentria, Oligomerix, Prothena, Renew, Shionogi, Vigil Neuroscience, Ionis, Vaxxinity. SB has served as a paid consultant for Roche, Biogen, NovoNordisk. She serves on the advisory board for Conference Board of Canada, World Dementia Council, National Institute of Neurological Disorders and Stroke, University of Rochester Contribution to the Mission and Scientific Leadership of the Small Vessel VCID Biomarker Validation Consortium.

Ethical standards: The study protocol was approved by the local institutional review board (IRB) of each site. Study procedures were completed only after participants signed an IRB approved informed consent form.

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Ruthirakuhan, M., Wood Alexander, M., Cogo-Moreira, H. et al. Investigating the Factor Structure of the Preclinical Alzheimer Cognitive Composite and Cognitive Function Index across Racial/Ethnic, Sex, and Aβ Status Groups in the A4 Study. J Prev Alzheimers Dis 11, 48–55 (2024). https://doi.org/10.14283/jpad.2023.98

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  • DOI: https://doi.org/10.14283/jpad.2023.98

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