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Cortical signatures of cognition and their relationship to Alzheimer’s disease

  • ADNI: Friday Harbor 2011 Workshop SPECIAL ISSUE
  • Published:
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Abstract

Recent changes in diagnostic criteria for Alzheimer’s disease (AD) state that biomarkers can enhance certainty in a diagnosis of AD. In the present study, we combined cognitive function and brain morphology, a potential imaging biomarker, to predict conversion from mild cognitive impairment to AD. We identified four biomarkers, or cortical signatures of cognition (CSC), from regressions of cortical thickness on neuropsychological factors representing memory, executive function/processing speed, language, and visuospatial function among participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Neuropsychological factor scores were created from a previously validated multidimensional factor structure of the neuropsychological battery in ADNI. Mean thickness of each CSC at the baseline study visit was used to evaluate risk of conversion to clinical AD among participants with mild cognitive impairment (MCI) and rate of decline on the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) score. Of 307 MCI participants, 119 converted to AD. For all domain-specific CSC, a one standard deviation thinner cortical thickness was associated with an approximately 50 % higher hazard of conversion and an increase of approximately 0.30 points annually on the CDR-SB. In combined models with a domain-specific CSC and neuropsychological factor score, both CSC and factor scores predicted conversion to AD and increasing clinical severity. The present study indicated that factor scores and CSCs for memory and language both significantly predicted risk of conversion to AD and accelerated deterioration in dementia severity. We conclude that predictive models are best when they utilize both neuropsychological measures and imaging biomarkers.

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Acknowledgements

We gratefully acknowledge a conference grant from the National Institute on Aging (R13AG030995, PI: Mungas) that facilitated data analysis for this project. Dr. Gross was supported by an NIH Translational Research in Aging fellowship (T32AG023480-07, PI: Lipsitz) and the NIA (P01AG031720, PI: Inouye). Dr. McLaren was supported by NIA grant RO1 AG036694 (PI: Sperling) and K23 AG027171 (PI: Atri). Dr. Bruce Rosen (MGH-Harvard-MIT Martinos Center for Biomedical Imaging) provided guidance, space, and resources for this research. Dr. Johnson was supported by the NIA (R01 AG022538, PI: Johnson). Dr. Melrose was supported by a VA Career Development Award & UCLA Semel Scholar Award. Dr. Pa was supported by the NIA Career Development Award (K01 AG034175, PI: Pa). Dr. Park was supported by a grant from the National Institute of Aging (R01 AG031252 PI: Farias). Dr. Inouye holds the Milton and Shirley F. Levy Family Chair in Alzheimer’s Disease.

Data collection and sharing for this project was funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott; Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Amorfix Life Sciences Ltd.; AstraZeneca; Bayer HealthCare; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30 AG010129, K01 AG030514, and the Dana Foundation.

The contents do not represent the views of the Dept. of Veterans Affairs, the United States Government, or any other funding entities.

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Authors and Affiliations

  1. Institute for Aging Research, Harvard Medical School, Hebrew SeniorLife, 1200 Centre Street, Rm. 634, Boston, MA, USA

    Alden L. Gross & Sharon K. Inouye

  2. Division of Gerontology, Beth Israel Deaconess Medical Center, Boston, MA, USA

    Alden L. Gross & Sharon K. Inouye

  3. Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Department of Neurology, Columbia University Medical Center, New York, NY, USA

    Jennifer J. Manly

  4. Department of Neurology, University of California, San Francisco, CA, USA

    Judy Pa & Julene K. Johnson

  5. Institute for Health and Aging; Department of Social and Behavioral Sciences, University of California, San Francisco, CA, USA

    Julene K. Johnson

  6. Department of Neurology, University of California, Davis, CA, USA

    Lovingly Quitania Park

  7. Geriatric Research Education and Clinical Center, Edith Nourse Rogers Memorial Veterans Hospital, Bedford, MA, USA

    Meghan B. Mitchell & Donald G. McLaren

  8. Department of Neurology, Massachusetts General Hospital, Boston, MA, USA

    Meghan B. Mitchell & Donald G. McLaren

  9. VA Greater Los Angeles Healthcare System; and Dept. of Psychiatry & Biobehavioral Sciences, UCLA, Los Angeles, CA, USA

    Rebecca J. Melrose

  10. Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA

    Donald G. McLaren

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  1. Alden L. Gross
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Correspondence to Alden L. Gross.

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Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.ucla.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.ucla.edu/wpcontent/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf

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Gross, A.L., Manly, J.J., Pa, J. et al. Cortical signatures of cognition and their relationship to Alzheimer’s disease. Brain Imaging and Behavior 6, 584–598 (2012). https://doi.org/10.1007/s11682-012-9180-5

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