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Association of Plasma YKL-40 With MRI, CSF, and Cognitive Markers of Brain Health and Dementia.
Pase, Matthew P; Himali, Jayandra J; Puerta, Raquel; Beiser, Alexa S; Gonzales, Mitzi M; Satizabal, Claudia L; Yang, Qiong; Aparicio, Hugo J; Kojis, Daniel J; Decarli, Charles S; Lopez, Oscar L; Longstreth, Will; Gudnason, Vilmundur; Mosley, Thomas H; Bis, Joshua C; Fohner, Alison; Psaty, Bruce M; Boada, Mercè; García-González, Pablo; Valero, Sergi; Marquié, Marta; Tracy, Russell; Launer, Lenore J; Ruiz, Agustín; Fornage, Myriam; Seshadri, Sudha.
Afiliación
  • Pase MP; From the Turner Institute for Brain and Mental Health (M.P.P.), Monash University, Australia; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (J.J.H., M.M.G.), University of Texas Health Sciences Center, San Antonio; ACE Alzheimer Center (R.P., M.B., P.G.-G., S.V., M.M., A.R.),
  • Himali JJ; From the Turner Institute for Brain and Mental Health (M.P.P.), Monash University, Australia; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (J.J.H., M.M.G.), University of Texas Health Sciences Center, San Antonio; ACE Alzheimer Center (R.P., M.B., P.G.-G., S.V., M.M., A.R.),
  • Puerta R; From the Turner Institute for Brain and Mental Health (M.P.P.), Monash University, Australia; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (J.J.H., M.M.G.), University of Texas Health Sciences Center, San Antonio; ACE Alzheimer Center (R.P., M.B., P.G.-G., S.V., M.M., A.R.),
  • Beiser AS; From the Turner Institute for Brain and Mental Health (M.P.P.), Monash University, Australia; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (J.J.H., M.M.G.), University of Texas Health Sciences Center, San Antonio; ACE Alzheimer Center (R.P., M.B., P.G.-G., S.V., M.M., A.R.),
  • Gonzales MM; From the Turner Institute for Brain and Mental Health (M.P.P.), Monash University, Australia; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (J.J.H., M.M.G.), University of Texas Health Sciences Center, San Antonio; ACE Alzheimer Center (R.P., M.B., P.G.-G., S.V., M.M., A.R.),
  • Satizabal CL; From the Turner Institute for Brain and Mental Health (M.P.P.), Monash University, Australia; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (J.J.H., M.M.G.), University of Texas Health Sciences Center, San Antonio; ACE Alzheimer Center (R.P., M.B., P.G.-G., S.V., M.M., A.R.),
  • Yang Q; From the Turner Institute for Brain and Mental Health (M.P.P.), Monash University, Australia; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (J.J.H., M.M.G.), University of Texas Health Sciences Center, San Antonio; ACE Alzheimer Center (R.P., M.B., P.G.-G., S.V., M.M., A.R.),
  • Aparicio HJ; From the Turner Institute for Brain and Mental Health (M.P.P.), Monash University, Australia; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (J.J.H., M.M.G.), University of Texas Health Sciences Center, San Antonio; ACE Alzheimer Center (R.P., M.B., P.G.-G., S.V., M.M., A.R.),
  • Kojis DJ; From the Turner Institute for Brain and Mental Health (M.P.P.), Monash University, Australia; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (J.J.H., M.M.G.), University of Texas Health Sciences Center, San Antonio; ACE Alzheimer Center (R.P., M.B., P.G.-G., S.V., M.M., A.R.),
  • Decarli CS; From the Turner Institute for Brain and Mental Health (M.P.P.), Monash University, Australia; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (J.J.H., M.M.G.), University of Texas Health Sciences Center, San Antonio; ACE Alzheimer Center (R.P., M.B., P.G.-G., S.V., M.M., A.R.),
  • Lopez OL; From the Turner Institute for Brain and Mental Health (M.P.P.), Monash University, Australia; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (J.J.H., M.M.G.), University of Texas Health Sciences Center, San Antonio; ACE Alzheimer Center (R.P., M.B., P.G.-G., S.V., M.M., A.R.),
  • Longstreth W; From the Turner Institute for Brain and Mental Health (M.P.P.), Monash University, Australia; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (J.J.H., M.M.G.), University of Texas Health Sciences Center, San Antonio; ACE Alzheimer Center (R.P., M.B., P.G.-G., S.V., M.M., A.R.),
  • Gudnason V; From the Turner Institute for Brain and Mental Health (M.P.P.), Monash University, Australia; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (J.J.H., M.M.G.), University of Texas Health Sciences Center, San Antonio; ACE Alzheimer Center (R.P., M.B., P.G.-G., S.V., M.M., A.R.),
  • Mosley TH; From the Turner Institute for Brain and Mental Health (M.P.P.), Monash University, Australia; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (J.J.H., M.M.G.), University of Texas Health Sciences Center, San Antonio; ACE Alzheimer Center (R.P., M.B., P.G.-G., S.V., M.M., A.R.),
  • Bis JC; From the Turner Institute for Brain and Mental Health (M.P.P.), Monash University, Australia; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (J.J.H., M.M.G.), University of Texas Health Sciences Center, San Antonio; ACE Alzheimer Center (R.P., M.B., P.G.-G., S.V., M.M., A.R.),
  • Fohner A; From the Turner Institute for Brain and Mental Health (M.P.P.), Monash University, Australia; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (J.J.H., M.M.G.), University of Texas Health Sciences Center, San Antonio; ACE Alzheimer Center (R.P., M.B., P.G.-G., S.V., M.M., A.R.),
  • Psaty BM; From the Turner Institute for Brain and Mental Health (M.P.P.), Monash University, Australia; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (J.J.H., M.M.G.), University of Texas Health Sciences Center, San Antonio; ACE Alzheimer Center (R.P., M.B., P.G.-G., S.V., M.M., A.R.),
  • Boada M; From the Turner Institute for Brain and Mental Health (M.P.P.), Monash University, Australia; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (J.J.H., M.M.G.), University of Texas Health Sciences Center, San Antonio; ACE Alzheimer Center (R.P., M.B., P.G.-G., S.V., M.M., A.R.),
  • García-González P; From the Turner Institute for Brain and Mental Health (M.P.P.), Monash University, Australia; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (J.J.H., M.M.G.), University of Texas Health Sciences Center, San Antonio; ACE Alzheimer Center (R.P., M.B., P.G.-G., S.V., M.M., A.R.),
  • Valero S; From the Turner Institute for Brain and Mental Health (M.P.P.), Monash University, Australia; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (J.J.H., M.M.G.), University of Texas Health Sciences Center, San Antonio; ACE Alzheimer Center (R.P., M.B., P.G.-G., S.V., M.M., A.R.),
  • Marquié M; From the Turner Institute for Brain and Mental Health (M.P.P.), Monash University, Australia; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (J.J.H., M.M.G.), University of Texas Health Sciences Center, San Antonio; ACE Alzheimer Center (R.P., M.B., P.G.-G., S.V., M.M., A.R.),
  • Tracy R; From the Turner Institute for Brain and Mental Health (M.P.P.), Monash University, Australia; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (J.J.H., M.M.G.), University of Texas Health Sciences Center, San Antonio; ACE Alzheimer Center (R.P., M.B., P.G.-G., S.V., M.M., A.R.),
  • Launer LJ; From the Turner Institute for Brain and Mental Health (M.P.P.), Monash University, Australia; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (J.J.H., M.M.G.), University of Texas Health Sciences Center, San Antonio; ACE Alzheimer Center (R.P., M.B., P.G.-G., S.V., M.M., A.R.),
  • Ruiz A; From the Turner Institute for Brain and Mental Health (M.P.P.), Monash University, Australia; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (J.J.H., M.M.G.), University of Texas Health Sciences Center, San Antonio; ACE Alzheimer Center (R.P., M.B., P.G.-G., S.V., M.M., A.R.),
  • Fornage M; From the Turner Institute for Brain and Mental Health (M.P.P.), Monash University, Australia; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (J.J.H., M.M.G.), University of Texas Health Sciences Center, San Antonio; ACE Alzheimer Center (R.P., M.B., P.G.-G., S.V., M.M., A.R.),
  • Seshadri S; From the Turner Institute for Brain and Mental Health (M.P.P.), Monash University, Australia; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (J.J.H., M.M.G.), University of Texas Health Sciences Center, San Antonio; ACE Alzheimer Center (R.P., M.B., P.G.-G., S.V., M.M., A.R.),
Neurology ; 102(4): e208075, 2024 Feb 27.
Article en En | MEDLINE | ID: mdl-38290090
ABSTRACT
BACKGROUND AND

OBJECTIVES:

Higher YKL-40 levels in the CSF are a known biomarker of brain inflammation. We explored the utility of plasma YKL-40 as a biomarker for accelerated brain aging and dementia risk.

METHODS:

We performed cross-sectional and prospective analyses of 4 community-based cohorts in the United States or Europe the Age, Gene/Environment Susceptibility-Reykjavik Study, Atherosclerosis Risk in the Communities study, Coronary Artery Risk Development in Young Adults study, and Framingham Heart Study (FHS). YKL-40 was measured from stored plasma by a single laboratory using Mesoscale Discovery with levels log transformed and standardized within each cohort. Outcomes included MRI total brain volume, hippocampal volume, and white matter hyperintensity volume (WMHV) as a percentage of intracranial volume, a general cognitive composite derived from neuropsychological testing (SD units [SDU]), and the risk of incident dementia. We sought to replicate associations with dementia in the clinic-based ACE csf cohort, which also had YKL-40 measured from the CSF.

RESULTS:

Meta-analyses of MRI outcomes included 6,558 dementia-free participants, and for analysis of cognition, 6,670. The blood draw preceded MRI/cognitive assessment by up to 10.6 years across cohorts. The mean ages ranged from 50 to 76 years, with 39%-48% male individuals. In random-effects meta-analysis of study estimates, each SDU increase in log-transformed YKL-40 levels was associated with smaller total brain volume (ß = -0.33; 95% CI -0.45 to -0.22; p < 0.0001) and poorer cognition (ß = -0.04; 95% CI -0.07 to -0.02; p < 0.01), following adjustments for demographic variables. YKL-40 levels did not associate with hippocampal volume or WMHV. In the FHS, each SDU increase in log YKL-40 levels was associated with a 64% increase in incident dementia risk over a median of 5.8 years of follow-up, following adjustments for demographic variables (hazard ratio 1.64; 95% CI 1.25-2.16; p < 0.001). In the ACE csf cohort, plasma and CSF YKL-40 were correlated (r = 0.31), and both were associated with conversion from mild cognitive impairment to dementia, independent of amyloid, tau, and neurodegeneration status.

DISCUSSION:

Higher plasma YKL-40 levels were associated with lower brain volume, poorer cognition, and incident dementia. Plasma YKL-40 may be useful for studying the association of inflammation and its treatment on dementia risk.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Demencia / Enfermedad de Alzheimer / Disfunción Cognitiva Tipo de estudio: Observational_studies / Prevalence_studies / Risk_factors_studies / Systematic_reviews Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Neurology Año: 2024 Tipo del documento: Article
Texto completo
Imprimir
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Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Demencia / Enfermedad de Alzheimer / Disfunción Cognitiva Tipo de estudio: Observational_studies / Prevalence_studies / Risk_factors_studies / Systematic_reviews Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Neurology Año: 2024 Tipo del documento: Article