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

Joni V Lindbohm; Nina Mars; Keenan A Walker; Archana Singh-Manoux; Gill Livingston; Eric J Brunner; Pyry N Sipilä; Kalle Saksela; Jane E Ferrie; Ruth C Lovering; Stephen A Williams; Aroon D Hingorani; Rebecca F Gottesman; Henrik Zetterberg; Mika Kivimäki

doi:10.1002/alz.12419

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

Alzheimers Dement. 2022 Apr;18(4):612-624. doi: 10.1002/alz.12419. Epub 2021 Aug 2.

Authors

Joni V Lindbohm^{1

2}, Nina Mars³, Keenan A Walker⁴, Archana Singh-Manoux^{1

5}, Gill Livingston^{6

7}, Eric J Brunner¹, Pyry N Sipilä², Kalle Saksela⁸, Jane E Ferrie^{1

9}, Ruth C Lovering¹⁰, Stephen A Williams¹¹, Aroon D Hingorani^{12

13

14}, Rebecca F Gottesman¹⁵, Henrik Zetterberg^{16

17

18}, Mika Kivimäki^{1

2}

Affiliations

¹ Department of Epidemiology and Public Health, University College London, London, UK.
² Department of Public Health Clinicum, University of Helsinki, Helsinki, Finland.
³ Institute for Molecular Medicine Finland (FIMM) HiLIFE, University of Helsinki, Helsinki, Finland.
⁴ Laboratory of Behavioral Neuroscience, Intramural Research Program, National Institute on Aging, Baltimore, Maryland, USA.
⁵ Epidemiology of Ageing and Neurodegenerative diseases, Université de Paris, Paris, France.
⁶ Division of Psychiatry, University College London, London, UK.
⁷ Camden and Islington Foundation Trust, London, UK.
⁸ Department of Virology, University of Helsinki and HUSLAB, Helsinki University Hospital, Helsinki, Finland.
⁹ Bristol Medical School (PHS), University of Bristol, Bristol, UK.
¹⁰ Functional Gene Annotation, Institute of Cardiovascular Science, University College London, London, UK.
¹¹ SomaLogic, Inc., Boulder, Colorado, USA.
¹² Institute of Cardiovascular Science, University College London, London, UK.
¹³ British Heart Foundation Research Accelerator, University College London, London, UK.
¹⁴ Health Data Research, London, UK.
¹⁵ Department of Neurology, The Johns Hopkins University, Baltimore, Maryland, USA.
¹⁶ Department of Neurodegenerative Disease and UK Dementia Research Institute, University College London, London, UK.
¹⁷ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
¹⁸ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.

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.

Keywords: cognitive decline; cohort study; dementia; longitudinal study; proteomics.

Publication types

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

MeSH terms

Alzheimer Disease*
Atherosclerosis* / epidemiology
Blood Proteins
Cognitive Dysfunction* / epidemiology
Dementia* / epidemiology
Humans
Prospective Studies
tau Proteins

Substances

Blood Proteins
tau Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding