Improved multimodal prediction of progression from MCI to Alzheimer's disease combining genetics with quantitative brain MRI and cognitive measures.

Humans Alzheimer Disease / diagnostic imaging Biomarkers Cognitive Dysfunction / diagnostic imaging Magnetic Resonance Imaging / methods Neuroimaging / methods Brain / diagnostic imaging Cognition Atrophy / pathology Disease Progression
Alzheimer's disease amyloid genetics magnetic resonance imaging memory mild cognitive impairment multimodal prediction tau

Journal

Alzheimer's & dementia : the journal of the Alzheimer's Association
ISSN: 1552-5279
Titre abrégé: Alzheimers Dement
Pays: United States
ID NLM: 101231978

Informations de publication

Date de publication:
11 2023
Historique:
revised: 21 03 2023
received: 12 01 2023
accepted: 04 04 2023
pmc-release: 02 11 2024
medline: 16 11 2023
pubmed: 3 5 2023
entrez: 3 5 2023
Statut: ppublish

Résumé

There is a pressing need for non-invasive, cost-effective tools for early detection of Alzheimer's disease (AD). Using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), Cox proportional models were conducted to develop a multimodal hazard score (MHS) combining age, a polygenic hazard score (PHS), brain atrophy, and memory to predict conversion from mild cognitive impairment (MCI) to dementia. Power calculations estimated required clinical trial sample sizes after hypothetical enrichment using the MHS. Cox regression determined predicted age of onset for AD pathology from the PHS. The MHS predicted conversion from MCI to dementia (hazard ratio for 80th versus 20th percentile: 27.03). Models suggest that application of the MHS could reduce clinical trial sample sizes by 67%. The PHS alone predicted age of onset of amyloid and tau. The MHS may improve early detection of AD for use in memory clinics or for clinical trial enrichment. A multimodal hazard score (MHS) combined age, genetics, brain atrophy, and memory. The MHS predicted time to conversion from mild cognitive impairment to dementia. MHS reduced hypothetical Alzheimer's disease (AD) clinical trial sample sizes by 67%. A polygenic hazard score predicted age of onset of AD neuropathology.

Identifiants

DOI: 10.1002/alz.13112 PMID: 37132098 PMC: PMC10620101
pubmed: 37132098
doi: 10.1002/alz.13112
pmc: PMC10620101
mid: NIHMS1898719
doi:

Substances chimiques

Biomarkers 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

5151-5158

Subventions

Organisme : NIA NIH HHS
ID : R00 AG057797
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG077202
Pays : United States
Organisme : NIH HHS
ID : U01 AG024904
Pays : United States
Organisme : NIA NIH HHS
ID : R00 AG057797
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG077202
Pays : United States
Organisme : NIH HHS
ID : U01 AG024904
Pays : United States

Informations de copyright

© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

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Auteurs

Emilie T Reas (ET)

Department of Neurosciences, University of California, San Diego, La Jolla, California, USA.
ORCID: 0000-0002-4110-5154

Alexey Shadrin (A)

NORMENT Centre, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.

Oleksandr Frei (O)

NORMENT Centre, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Center for Bioinformatics, Department of Informatics, University of Oslo, Blindern, Oslo, Norway.

Ehsan Motazedi (E)

NORMENT Centre, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.

Linda McEvoy (L)

Department of Radiology, University of California, San Diego, La Jolla, California, USA.

Shahram Bahrami (S)

NORMENT Centre, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.

Dennis van der Meer (D)

NORMENT Centre, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.

Carolina Makowski (C)

Department of Radiology, University of California, San Diego, La Jolla, California, USA.

Robert Loughnan (R)

University of California, San Diego, La Jolla, California, USA.

Xin Wang (X)

Department of Neurosciences, University of California, San Diego, La Jolla, California, USA.

Iris Broce (I)

Department of Neurosciences, University of California, San Diego, La Jolla, California, USA.

Sarah J Banks (SJ)

Department of Neurosciences, University of California, San Diego, La Jolla, California, USA.

Vera Fominykh (V)

NORMENT Centre, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.

Weiqiu Cheng (W)

NORMENT Centre, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.

Dominic Holland (D)

Department of Neurosciences, University of California, San Diego, La Jolla, California, USA.

Olav B Smeland (OB)

NORMENT Centre, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.

Tyler Seibert (T)

Department of Radiology, University of California, San Diego, La Jolla, California, USA.

Geir Selbaek (G)

University of Oslo, Universitetet i Oslo, Oslo, Norway.

James B Brewer (JB)

Department of Neurosciences, University of California, San Diego, La Jolla, California, USA.

Chun C Fan (CC)

Department of Radiology, University of California, San Diego, La Jolla, California, USA.
Population Neuroscience and Genetics Lab, University of California, San Diego, La Jolla, California, USA.
Center for Human Development, University of California, San Diego, La Jolla, California, USA.

Ole A Andreassen (OA)

NORMENT Centre, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.

Anders M Dale (AM)

Department of Neurosciences, University of California, San Diego, La Jolla, California, USA.
Department of Radiology, University of California, San Diego, La Jolla, California, USA.
Population Neuroscience and Genetics Lab, University of California, San Diego, La Jolla, California, USA.
Department of Psychiatry, University of California, San Diego, La Jolla, California, USA.

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