Association Between β-Amyloid Accumulation and Incident Dementia in Individuals 80 Years or Older Without Dementia.

Journal

Neurology
ISSN: 1526-632X
Titre abrégé: Neurology
Pays: United States
ID NLM: 0401060

Informations de publication

Date de publication:
23 Jan 2024
Historique:
medline: 2 1 2024
pubmed: 2 1 2024
entrez: 2 1 2024
Statut: ppublish

Résumé

While the highest prevalence of dementia occurs in individuals older than 80 years, most imaging studies focused on younger populations. The rates of β-amyloid (Aβ) accumulation and the effect of Alzheimer disease (AD) pathology on progression to dementia in this age group remain unexplored. In this study, we examined the relationship between changes in Aβ deposition over time and incident dementia in nondemented individuals followed during a period of 11 years. We examined 94 participants (age 85.9 + 2.8 years) who had up to 5 measurements of Pittsburgh compound-B (PiB)-PET and clinical evaluations from 2009 to 2020. All 94 participants had 2 PiB-PET scans, 76 participants had 3 PiB-PET scans, 18 participants had 4 PiB-PET scans, and 10 participants had 5 PiB-PET scans. The rates of Aβ deposition were compared with 120 nondemented individuals younger than 80 years (69.3 ± 5.4 years) from the Australian Imaging, Biomarker, and Lifestyle (AIBL) study who had 3 or more annual PiB-PET assessments. By 2020, 49% of the participants developed dementia and 63% were deceased. There was a gradual increase in Aβ deposition in all participants whether they were considered Aβ positive or negative at baseline. In a Cox model controlled for age, sex, education level, APOE-4 allele, baseline Mini-Mental State Examination, and mortality, short-term change in Aβ deposition was not significantly associated with incident dementia (HR 2.19 (0.41-11.73). However, baseline Aβ burden, cortical thickness, and white matter lesions volume were the predictors of incident dementia. Aβ accumulation was faster ( There was an accelerated Aβ accumulation in cognitively normal individuals older than 80 years. Baseline Aβ deposition was a determinant of incident dementia and short-term change in Aβ deposition suggesting that an active Aβ pathologic process was present when these participants were cognitively normal. Consequently, age may not be a limiting factor for the use of the emergent anti-Aβ therapies.

Sections du résumé

BACKGROUND AND OBJECTIVES OBJECTIVE
While the highest prevalence of dementia occurs in individuals older than 80 years, most imaging studies focused on younger populations. The rates of β-amyloid (Aβ) accumulation and the effect of Alzheimer disease (AD) pathology on progression to dementia in this age group remain unexplored. In this study, we examined the relationship between changes in Aβ deposition over time and incident dementia in nondemented individuals followed during a period of 11 years.
METHODS METHODS
We examined 94 participants (age 85.9 + 2.8 years) who had up to 5 measurements of Pittsburgh compound-B (PiB)-PET and clinical evaluations from 2009 to 2020. All 94 participants had 2 PiB-PET scans, 76 participants had 3 PiB-PET scans, 18 participants had 4 PiB-PET scans, and 10 participants had 5 PiB-PET scans. The rates of Aβ deposition were compared with 120 nondemented individuals younger than 80 years (69.3 ± 5.4 years) from the Australian Imaging, Biomarker, and Lifestyle (AIBL) study who had 3 or more annual PiB-PET assessments.
RESULTS RESULTS
By 2020, 49% of the participants developed dementia and 63% were deceased. There was a gradual increase in Aβ deposition in all participants whether they were considered Aβ positive or negative at baseline. In a Cox model controlled for age, sex, education level, APOE-4 allele, baseline Mini-Mental State Examination, and mortality, short-term change in Aβ deposition was not significantly associated with incident dementia (HR 2.19 (0.41-11.73). However, baseline Aβ burden, cortical thickness, and white matter lesions volume were the predictors of incident dementia. Aβ accumulation was faster (
DISCUSSION CONCLUSIONS
There was an accelerated Aβ accumulation in cognitively normal individuals older than 80 years. Baseline Aβ deposition was a determinant of incident dementia and short-term change in Aβ deposition suggesting that an active Aβ pathologic process was present when these participants were cognitively normal. Consequently, age may not be a limiting factor for the use of the emergent anti-Aβ therapies.

Identifiants

DOI: 10.1212/WNL.0000000000207920 PMID: 38165336
pubmed: 38165336
doi: 10.1212/WNL.0000000000207920
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e207920

Auteurs

Oscar L Lopez (OL)

From the Departments of Neurology (O.L.L., W.E.K., M.D.I., B.E.S.), Psychiatry (O.L.L., V.L.V., A.D.C., W.E.K., T.P., H.J.A.), Neurosurgery (Y.-F.C.), Radiology (A.D.C., C.A.M., B.J.L.), Epidemiology (L.H.K.), and Human Genetics, Graduate School of Public Health (M.I.K.), University of Pittsburgh, PA; Department of Molecular Imaging and Therapy (C.R.), Austin Health, Melbourne; The Florey Institute of Neuroscience and Mental Health (C.R., V.D.), University of Melbourne; and CSIRO Health and Biosecurity (V.D.), Melbourne, Australia.
ORCID: 0000-0002-8546-8256

Victor L Villemagne (VL)

From the Departments of Neurology (O.L.L., W.E.K., M.D.I., B.E.S.), Psychiatry (O.L.L., V.L.V., A.D.C., W.E.K., T.P., H.J.A.), Neurosurgery (Y.-F.C.), Radiology (A.D.C., C.A.M., B.J.L.), Epidemiology (L.H.K.), and Human Genetics, Graduate School of Public Health (M.I.K.), University of Pittsburgh, PA; Department of Molecular Imaging and Therapy (C.R.), Austin Health, Melbourne; The Florey Institute of Neuroscience and Mental Health (C.R., V.D.), University of Melbourne; and CSIRO Health and Biosecurity (V.D.), Melbourne, Australia.

Yue-Fang Chang (YF)

From the Departments of Neurology (O.L.L., W.E.K., M.D.I., B.E.S.), Psychiatry (O.L.L., V.L.V., A.D.C., W.E.K., T.P., H.J.A.), Neurosurgery (Y.-F.C.), Radiology (A.D.C., C.A.M., B.J.L.), Epidemiology (L.H.K.), and Human Genetics, Graduate School of Public Health (M.I.K.), University of Pittsburgh, PA; Department of Molecular Imaging and Therapy (C.R.), Austin Health, Melbourne; The Florey Institute of Neuroscience and Mental Health (C.R., V.D.), University of Melbourne; and CSIRO Health and Biosecurity (V.D.), Melbourne, Australia.
ORCID: 0000-0003-0080-4597

Ann D Cohen (AD)

From the Departments of Neurology (O.L.L., W.E.K., M.D.I., B.E.S.), Psychiatry (O.L.L., V.L.V., A.D.C., W.E.K., T.P., H.J.A.), Neurosurgery (Y.-F.C.), Radiology (A.D.C., C.A.M., B.J.L.), Epidemiology (L.H.K.), and Human Genetics, Graduate School of Public Health (M.I.K.), University of Pittsburgh, PA; Department of Molecular Imaging and Therapy (C.R.), Austin Health, Melbourne; The Florey Institute of Neuroscience and Mental Health (C.R., V.D.), University of Melbourne; and CSIRO Health and Biosecurity (V.D.), Melbourne, Australia.
ORCID: 0000-0001-7395-9624

William E Klunk (WE)

From the Departments of Neurology (O.L.L., W.E.K., M.D.I., B.E.S.), Psychiatry (O.L.L., V.L.V., A.D.C., W.E.K., T.P., H.J.A.), Neurosurgery (Y.-F.C.), Radiology (A.D.C., C.A.M., B.J.L.), Epidemiology (L.H.K.), and Human Genetics, Graduate School of Public Health (M.I.K.), University of Pittsburgh, PA; Department of Molecular Imaging and Therapy (C.R.), Austin Health, Melbourne; The Florey Institute of Neuroscience and Mental Health (C.R., V.D.), University of Melbourne; and CSIRO Health and Biosecurity (V.D.), Melbourne, Australia.
ORCID: 0000-0001-5512-0251

Chester A Mathis (CA)

From the Departments of Neurology (O.L.L., W.E.K., M.D.I., B.E.S.), Psychiatry (O.L.L., V.L.V., A.D.C., W.E.K., T.P., H.J.A.), Neurosurgery (Y.-F.C.), Radiology (A.D.C., C.A.M., B.J.L.), Epidemiology (L.H.K.), and Human Genetics, Graduate School of Public Health (M.I.K.), University of Pittsburgh, PA; Department of Molecular Imaging and Therapy (C.R.), Austin Health, Melbourne; The Florey Institute of Neuroscience and Mental Health (C.R., V.D.), University of Melbourne; and CSIRO Health and Biosecurity (V.D.), Melbourne, Australia.
ORCID: 0000-0001-9811-0950

Tharick Pascoal (T)

From the Departments of Neurology (O.L.L., W.E.K., M.D.I., B.E.S.), Psychiatry (O.L.L., V.L.V., A.D.C., W.E.K., T.P., H.J.A.), Neurosurgery (Y.-F.C.), Radiology (A.D.C., C.A.M., B.J.L.), Epidemiology (L.H.K.), and Human Genetics, Graduate School of Public Health (M.I.K.), University of Pittsburgh, PA; Department of Molecular Imaging and Therapy (C.R.), Austin Health, Melbourne; The Florey Institute of Neuroscience and Mental Health (C.R., V.D.), University of Melbourne; and CSIRO Health and Biosecurity (V.D.), Melbourne, Australia.
ORCID: 0000-0001-9057-8014

Milos D Ikonomovic (MD)

From the Departments of Neurology (O.L.L., W.E.K., M.D.I., B.E.S.), Psychiatry (O.L.L., V.L.V., A.D.C., W.E.K., T.P., H.J.A.), Neurosurgery (Y.-F.C.), Radiology (A.D.C., C.A.M., B.J.L.), Epidemiology (L.H.K.), and Human Genetics, Graduate School of Public Health (M.I.K.), University of Pittsburgh, PA; Department of Molecular Imaging and Therapy (C.R.), Austin Health, Melbourne; The Florey Institute of Neuroscience and Mental Health (C.R., V.D.), University of Melbourne; and CSIRO Health and Biosecurity (V.D.), Melbourne, Australia.
ORCID: 0000-0002-8745-3293

Christopher Rowe (C)

From the Departments of Neurology (O.L.L., W.E.K., M.D.I., B.E.S.), Psychiatry (O.L.L., V.L.V., A.D.C., W.E.K., T.P., H.J.A.), Neurosurgery (Y.-F.C.), Radiology (A.D.C., C.A.M., B.J.L.), Epidemiology (L.H.K.), and Human Genetics, Graduate School of Public Health (M.I.K.), University of Pittsburgh, PA; Department of Molecular Imaging and Therapy (C.R.), Austin Health, Melbourne; The Florey Institute of Neuroscience and Mental Health (C.R., V.D.), University of Melbourne; and CSIRO Health and Biosecurity (V.D.), Melbourne, Australia.
ORCID: 0000-0003-3910-2453

Vincent Dore (V)

From the Departments of Neurology (O.L.L., W.E.K., M.D.I., B.E.S.), Psychiatry (O.L.L., V.L.V., A.D.C., W.E.K., T.P., H.J.A.), Neurosurgery (Y.-F.C.), Radiology (A.D.C., C.A.M., B.J.L.), Epidemiology (L.H.K.), and Human Genetics, Graduate School of Public Health (M.I.K.), University of Pittsburgh, PA; Department of Molecular Imaging and Therapy (C.R.), Austin Health, Melbourne; The Florey Institute of Neuroscience and Mental Health (C.R., V.D.), University of Melbourne; and CSIRO Health and Biosecurity (V.D.), Melbourne, Australia.
ORCID: 0000-0002-8051-0558

Beth E Snitz (BE)

From the Departments of Neurology (O.L.L., W.E.K., M.D.I., B.E.S.), Psychiatry (O.L.L., V.L.V., A.D.C., W.E.K., T.P., H.J.A.), Neurosurgery (Y.-F.C.), Radiology (A.D.C., C.A.M., B.J.L.), Epidemiology (L.H.K.), and Human Genetics, Graduate School of Public Health (M.I.K.), University of Pittsburgh, PA; Department of Molecular Imaging and Therapy (C.R.), Austin Health, Melbourne; The Florey Institute of Neuroscience and Mental Health (C.R., V.D.), University of Melbourne; and CSIRO Health and Biosecurity (V.D.), Melbourne, Australia.
ORCID: 0000-0002-9978-1374

Brian J Lopresti (BJ)

From the Departments of Neurology (O.L.L., W.E.K., M.D.I., B.E.S.), Psychiatry (O.L.L., V.L.V., A.D.C., W.E.K., T.P., H.J.A.), Neurosurgery (Y.-F.C.), Radiology (A.D.C., C.A.M., B.J.L.), Epidemiology (L.H.K.), and Human Genetics, Graduate School of Public Health (M.I.K.), University of Pittsburgh, PA; Department of Molecular Imaging and Therapy (C.R.), Austin Health, Melbourne; The Florey Institute of Neuroscience and Mental Health (C.R., V.D.), University of Melbourne; and CSIRO Health and Biosecurity (V.D.), Melbourne, Australia.
ORCID: 0000-0002-0595-0203

M Ilyas Kamboh (MI)

From the Departments of Neurology (O.L.L., W.E.K., M.D.I., B.E.S.), Psychiatry (O.L.L., V.L.V., A.D.C., W.E.K., T.P., H.J.A.), Neurosurgery (Y.-F.C.), Radiology (A.D.C., C.A.M., B.J.L.), Epidemiology (L.H.K.), and Human Genetics, Graduate School of Public Health (M.I.K.), University of Pittsburgh, PA; Department of Molecular Imaging and Therapy (C.R.), Austin Health, Melbourne; The Florey Institute of Neuroscience and Mental Health (C.R., V.D.), University of Melbourne; and CSIRO Health and Biosecurity (V.D.), Melbourne, Australia.
ORCID: 0000-0002-3453-1438

Howard J Aizenstein (HJ)

From the Departments of Neurology (O.L.L., W.E.K., M.D.I., B.E.S.), Psychiatry (O.L.L., V.L.V., A.D.C., W.E.K., T.P., H.J.A.), Neurosurgery (Y.-F.C.), Radiology (A.D.C., C.A.M., B.J.L.), Epidemiology (L.H.K.), and Human Genetics, Graduate School of Public Health (M.I.K.), University of Pittsburgh, PA; Department of Molecular Imaging and Therapy (C.R.), Austin Health, Melbourne; The Florey Institute of Neuroscience and Mental Health (C.R., V.D.), University of Melbourne; and CSIRO Health and Biosecurity (V.D.), Melbourne, Australia.
ORCID: 0000-0003-4897-6582

Lewis H Kuller (LH)

From the Departments of Neurology (O.L.L., W.E.K., M.D.I., B.E.S.), Psychiatry (O.L.L., V.L.V., A.D.C., W.E.K., T.P., H.J.A.), Neurosurgery (Y.-F.C.), Radiology (A.D.C., C.A.M., B.J.L.), Epidemiology (L.H.K.), and Human Genetics, Graduate School of Public Health (M.I.K.), University of Pittsburgh, PA; Department of Molecular Imaging and Therapy (C.R.), Austin Health, Melbourne; The Florey Institute of Neuroscience and Mental Health (C.R., V.D.), University of Melbourne; and CSIRO Health and Biosecurity (V.D.), Melbourne, Australia.
ORCID: 0000-0002-7148-8416

Classifications MeSH