Association of Pathologic and Volumetric Biomarker Changes With Cognitive Decline in Clinically Normal Adults
Bernard J Hanseeuw1, Heidi I L Jacobs1, Aaron P Schultz1
1From the Department of Radiology (B.J.H., H.I.L.J., N.J.G., J.A.B., J.S.S., J.S., H.-S.Y., M.N., J.C.P., G.E.F., K.A.J.), Massachusetts General Hospital, the Gordon Center for Medical Imaging, Boston; Department of Neurology (B.J.H.), Cliniques Universitaires Saint-Luc, Brussels, Belgium; Faculty of Health, Medicine and Life Sciences (H.I.L.J.), School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, the Netherlands; Department of Neurology (A.P.S., R.F.B., M.E.F., M.P., Y.T.Q., P.V., J.P.C., G.A.M., R.A., K.P., D.M.R., R.A.S., K.A.J.), Massachusetts General Hospital; Center for Alzheimer Research and Treatment (R.F.B., P.V., G.A.M., R.A., K.P., D.M.R., R.A.S., K.A.J.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston; Melbourne School of Psychological Sciences (R.F.B.), University of Melbourne, Australia; and Department of Psychiatry (J.G.), and Department of Biostatistics (B.C.H.), Massachusetts General Hospital, Harvard Medical School, Boston.
Hippocampal volume (HV) atrophy predicts cognitive decline independently of Alzheimer's biomarkers. Serial HV measures may reveal non-AD pathologies contributing to memory impairment in older adults.
Area of Science:
- Neuroimaging
- Cognitive Neuroscience
- Gerontology
Background:
- Hippocampal volume (HV) atrophy is a known memory impairment biomarker but lacks specificity for Alzheimer's disease (AD).
- This study explores HV atrophy's role in cognition, considering potential co-pathologies.
- Assessing HV atrophy's unique contribution to cognitive decline is crucial for understanding non-AD contributions.
Purpose of the Study:
- To assess associations between beta-amyloid (Aβ), tau, HV, and cognition over 10 years.
- To determine the independent contribution of HV atrophy to cognitive decline after adjusting for Aβ and tau.
- To investigate the role of HV measures in identifying non-AD pathologies.
Main Methods:
- Prospective cohort study of 128 cognitively normal older adults from the Harvard Aging Brain Study.
- Longitudinal MRI for HV, PET for Aβ and tau, and cognitive assessments (Preclinical Alzheimer Cognitive Composite) were collected.
- Sequential models were used to evaluate biomarker contributions to cognitive decline.
Main Results:
- Faster HV atrophy correlated with faster cognitive decline (R² = 0.28, p < 0.0001).
- HV atrophy independently predicted cognitive decline, accounting for 10% of the variance beyond Aβ and tau.
- Combined imaging biomarker changes explained 45% of cognitive decline variance.
Conclusions:
- Longitudinal hippocampal atrophy is linked to cognitive decline, irrespective of Aβ or tau levels.
- HV atrophy may indicate non-AD pathologies (e.g., TDP-43, vascular) impacting cognition.
- Serial HV measurements offer insights into non-AD pathologies not detectable by current AD biomarkers.
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