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Association of Pathologic and Volumetric Biomarker Changes With Cognitive Decline in Clinically Normal Adults.
Hanseeuw, Bernard J; Jacobs, Heidi I L; Schultz, Aaron P; Buckley, Rachel F; Farrell, Michelle E; Guehl, Nicolas J; Becker, John A; Properzi, Michael; Sanchez, Justin S; Quiroz, Yakeel T; Vannini, Patrizia; Sepulcre, Jorge; Yang, Hyun-Sik; Chhatwal, Jasmeer P; Gatchel, Jennifer; Marshall, Gad A; Amariglio, Rebecca; Papp, Kathryn; Rentz, Dorene M; Normandin, Marc; Price, Julie C; Healy, Brian C; El Fakhri, Georges; Sperling, Reisa A; Johnson, Keith A.
Afiliação
  • Hanseeuw BJ; From 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
  • Jacobs HIL; From 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
  • Schultz AP; From 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
  • Buckley RF; From 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
  • Farrell ME; From 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
  • Guehl NJ; From 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
  • Becker JA; From 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
  • Properzi M; From 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
  • Sanchez JS; From 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
  • Quiroz YT; From 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
  • Vannini P; From 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
  • Sepulcre J; From 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
  • Yang HS; From 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
  • Chhatwal JP; From 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
  • Gatchel J; From 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
  • Marshall GA; From 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
  • Amariglio R; From 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
  • Papp K; From 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
  • Rentz DM; From 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
  • Normandin M; From 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
  • Price JC; From 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
  • Healy BC; From 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
  • El Fakhri G; From 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
  • Sperling RA; From 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
  • Johnson KA; From 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
Neurology ; 101(24): e2533-e2544, 2023 Dec 12.
Article em En | MEDLINE | ID: mdl-37968130
ABSTRACT
BACKGROUND AND

OBJECTIVES:

Hippocampal volume (HV) atrophy is a well-known biomarker of memory impairment. However, compared with ß-amyloid (Aß) and tau imaging, it is less specific for Alzheimer disease (AD) pathology. This lack of specificity could provide indirect information about potential copathologies that cannot be observed in vivo. In this prospective cohort study, we aimed to assess the associations among Aß, tau, HV, and cognition, measured over a 10-year follow-up period with a special focus on the contributions of HV atrophy to cognition after adjusting for Aß and tau.

METHODS:

We enrolled 283 older adults without dementia or overt cognitive impairment in the Harvard Aging Brain Study. In this report, we only analyzed data from individuals with available longitudinal imaging and cognition data. Serial MRI (follow-up duration 1.3-7.0 years), neocortical Aß imaging on Pittsburgh Compound B PET scans (1.9-8.5 years), entorhinal and inferior temporal tau on flortaucipir PET scans (0.8-6.0 years), and the Preclinical Alzheimer Cognitive Composite (3.0-9.8 years) were prospectively collected. We evaluated the longitudinal associations between Aß, tau, volume, and cognition data and investigated sequential models to test the contribution of each biomarker to cognitive decline.

RESULTS:

We analyzed data from 128 clinically normal older adults, including 72 (56%) women and 56 (44%) men; median age at inclusion was 73 years (range 63-87). Thirty-four participants (27%) exhibited an initial high-Aß burden on PET imaging. Faster HV atrophy was correlated with faster cognitive decline (R2 = 0.28, p < 0.0001). When comparing all biomarkers, HV slope was associated with cognitive decline independently of Aß and tau measures, uniquely accounting for 10% of the variance. Altogether, 45% of the variance in cognitive decline was explained by combining the change measures in the different imaging biomarkers.

DISCUSSION:

In older adults, longitudinal hippocampal atrophy is associated with cognitive decline, independently of Aß or tau, suggesting that non-AD pathologies (e.g., TDP-43, vascular) may contribute to hippocampal-mediated cognitive decline. Serial HV measures, in addition to AD-specific biomarkers, may help evaluate the contribution of non-AD pathologies that cannot be measured otherwise in vivo.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Contexto em Saúde: 1_ASSA2030 Problema de saúde: 1_doencas_nao_transmissiveis Assunto principal: Doença de Alzheimer / Disfunção Cognitiva Limite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Neurology Ano de publicação: 2023 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Contexto em Saúde: 1_ASSA2030 Problema de saúde: 1_doencas_nao_transmissiveis Assunto principal: Doença de Alzheimer / Disfunção Cognitiva Limite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Neurology Ano de publicação: 2023 Tipo de documento: Article