Comparison of subjective cognitive decline and polygenic risk score in the prediction of all-cause dementia, Alzheimer's disease and vascular dementia.


Journal

Alzheimer's research & therapy
ISSN: 1758-9193
Titre abrégé: Alzheimers Res Ther
Pays: England
ID NLM: 101511643

Informations de publication

Date de publication:
19 Aug 2024
Historique:
received: 19 02 2024
accepted: 12 08 2024
medline: 20 8 2024
pubmed: 20 8 2024
entrez: 19 8 2024
Statut: epublish

Résumé

Polygenic risk scores (PRS) and subjective cognitive decline (SCD) are associated with the risk of developing dementia. It remains to examine whether they can improve the established cardiovascular risk factors aging and dementia (CAIDE) model and how their predictive abilities compare. The CAIDE model was applied to a sub-sample of a large, population-based cohort study (n = 5,360; aged 50-75) and evaluated for the outcomes of all-cause dementia, Alzheimer's disease (AD) and vascular dementia (VD) by calculating Akaike's information criterion (AIC) and the area under the curve (AUC). The improvement of the CAIDE model by PRS and SCD was further examined using the net reclassification improvement (NRI) method and integrated discrimination improvement (IDI). During 17 years of follow-up, 410 participants were diagnosed with dementia, including 139 AD and 152 VD diagnoses. Overall, the CAIDE model showed high discriminative ability for all outcomes, reaching AUCs of 0.785, 0.793, and 0.789 for all-cause dementia, AD, and VD, respectively. Adding information on SCD significantly increased NRI for all-cause dementia (4.4%, p = 0.04) and VD (7.7%, p = 0.01). In contrast, prediction models for AD further improved when PRS was added to the model (NRI, 8.4%, p = 0.03). When APOE ε4 carrier status was included (CAIDE Model 2), AUCs increased, but PRS and SCD did not further improve the prediction. Unlike PRS, information on SCD can be assessed more efficiently, and thus, the model including SCD can be more easily transferred to the clinical setting. Nevertheless, the two variables seem negligible if APOE ε4 carrier status is available.

Sections du résumé

BACKGROUND BACKGROUND
Polygenic risk scores (PRS) and subjective cognitive decline (SCD) are associated with the risk of developing dementia. It remains to examine whether they can improve the established cardiovascular risk factors aging and dementia (CAIDE) model and how their predictive abilities compare.
METHODS METHODS
The CAIDE model was applied to a sub-sample of a large, population-based cohort study (n = 5,360; aged 50-75) and evaluated for the outcomes of all-cause dementia, Alzheimer's disease (AD) and vascular dementia (VD) by calculating Akaike's information criterion (AIC) and the area under the curve (AUC). The improvement of the CAIDE model by PRS and SCD was further examined using the net reclassification improvement (NRI) method and integrated discrimination improvement (IDI).
RESULTS RESULTS
During 17 years of follow-up, 410 participants were diagnosed with dementia, including 139 AD and 152 VD diagnoses. Overall, the CAIDE model showed high discriminative ability for all outcomes, reaching AUCs of 0.785, 0.793, and 0.789 for all-cause dementia, AD, and VD, respectively. Adding information on SCD significantly increased NRI for all-cause dementia (4.4%, p = 0.04) and VD (7.7%, p = 0.01). In contrast, prediction models for AD further improved when PRS was added to the model (NRI, 8.4%, p = 0.03). When APOE ε4 carrier status was included (CAIDE Model 2), AUCs increased, but PRS and SCD did not further improve the prediction.
CONCLUSIONS CONCLUSIONS
Unlike PRS, information on SCD can be assessed more efficiently, and thus, the model including SCD can be more easily transferred to the clinical setting. Nevertheless, the two variables seem negligible if APOE ε4 carrier status is available.

Identifiants

pubmed: 39160600
doi: 10.1186/s13195-024-01559-9
pii: 10.1186/s13195-024-01559-9
doi:

Types de publication

Journal Article Comparative Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

188

Informations de copyright

© 2024. The Author(s).

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Auteurs

Kira Trares (K)

Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Im Neuenheimer Feld 581, 69120, Heidelberg, Germany. k.trares@dkfz-heidelberg.de.

Hannah Stocker (H)

Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Im Neuenheimer Feld 581, 69120, Heidelberg, Germany.

Joshua Stevenson-Hoare (J)

Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Im Neuenheimer Feld 581, 69120, Heidelberg, Germany.

Laura Perna (L)

Department Genes and Environment, Max Planck Institute of Psychiatry, Kraepelinstraße 2-10, 80804, Munich, Germany.

Bernd Holleczek (B)

Saarland Cancer Registry, Neugeländstraße 9, 66117, Saarbrücken, Germany.

Konrad Beyreuther (K)

Network Aging Research, Heidelberg University, Bergheimer Straße 20, 69115, Heidelberg, Germany.

Ben Schöttker (B)

Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Im Neuenheimer Feld 581, 69120, Heidelberg, Germany.
Network Aging Research, Heidelberg University, Bergheimer Straße 20, 69115, Heidelberg, Germany.

Hermann Brenner (H)

Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Im Neuenheimer Feld 581, 69120, Heidelberg, Germany.
Network Aging Research, Heidelberg University, Bergheimer Straße 20, 69115, Heidelberg, Germany.

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