Pulse lineResearch With Heart Logo

Plasma proteins, cognitive decline, and 20-year risk of dementia in the Whitehall II and Atherosclerosis Risk in Communities studies.

TitlePlasma proteins, cognitive decline, and 20-year risk of dementia in the Whitehall II and Atherosclerosis Risk in Communities studies.
Publication TypeJournal Article
Year of Publication2021
AuthorsLindbohm JV, Mars N, Walker KA, Singh-Manoux A, Livingston G, Brunner EJ, Sipilä PN, Saksela K, Ferrie JE, Lovering RC, Williams SA, Hingorani AD, Gottesman RF, Zetterberg H, Kivimaki M
JournalAlzheimers Dement
Date Published2021 Aug 02
ISSN1552-5279
Abstract

INTRODUCTION: Plasma proteins affect biological processes and are common drug targets but their role in the development of Alzheimer's disease and related dementias remains unclear. We examined associations between 4953 plasma proteins and cognitive decline and risk of dementia in two cohort studies with 20-year follow-ups.

METHODS: In the Whitehall II prospective cohort study proteins were measured using SOMAscan technology. Cognitive performance was tested five times over 20 years. Linkage to electronic health records identified incident dementia. The results were replicated in the Atherosclerosis Risk in Communities (ARIC) study.

RESULTS: Fifteen non-amyloid/non-tau-related proteins were associated with cognitive decline and dementia, were consistently identified in both cohorts, and were not explained by known dementia risk factors. Levels of six of the proteins are modifiable by currently approved medications for other conditions.

DISCUSSION: This study identified several plasma proteins in dementia-free people that are associated with long-term risk of cognitive decline and dementia.

DOI10.1002/alz.12419
Alternate JournalAlzheimers Dement
PubMed ID34338426
Grant ListS011676 / / UK Medical Research Council /
K013351 / / UK Medical Research Council /
R024227 / / UK Medical Research Council /
221854/Z/20/Z / / The Wellcome Trust /
/ AG / NIA NIH HHS / United States
R01AG056477 / NH / NIH HHS / United States
R01AG062553 / NH / NIH HHS / United States
RG/16/11/32334 / BHF_ / British Heart Foundation / United Kingdom
311492 / / Academy of Finland /
75021 / / NordForsk /
HHSN268201700001I / HL / NHLBI NIH HHS / United States
HHSN268201700002I / HL / NHLBI NIH HHS / United States
HHSN268201700003I / HL / NHLBI NIH HHS / United States
HHSN268201700004I / HL / NHLBI NIH HHS / United States
HHSN268201700005I / HL / NHLBI NIH HHS / United States
R01HL087641 / / National Heart, Lung, and Blood Institute; National Institutes of Health; Department of Health and Human Services /
R01HL086694 / / National Heart, Lung, and Blood Institute; National Institutes of Health; Department of Health and Human Services /
U01HG004402 / HG / NHGRI NIH HHS / United States