Circulating asymmetric dimethylarginine and cognitive decline: A 4‐year follow‐up study of the 1936 Aberdeen Birth Cohort

Deborah E. Malden; Arduino A. Mangoni; Richard J. Woodman; Frank Thies; Chris McNeil; Alison D. Murray; Roy L. Soiza

doi:10.1002/gps.5355

Circulating asymmetric dimethylarginine and cognitive decline: A 4‐year follow‐up study of the 1936 Aberdeen Birth Cohort

Deborah E. Malden^* (Corresponding Author), Arduino A. Mangoni, Richard J. Woodman, Frank Thies, Chris McNeil, Alison D. Murray, Roy L. Soiza

^*Corresponding author for this work

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Abstract

Background The underlying mechanisms leading to dementia and Alzheimer's disease (AD) are unclear. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, may be associated with cognitive decline, but population-based evidence is lacking.

Methods Change in cognitive performance was assessed in participants of the Aberdeen Birth Cohort of 1936 using longitudinal Raven's progressive matrices (RPM) between 2000 and 2004. Multiple linear regression was used to estimate the association between ADMA concentrations in 2000 and change in cognitive performance after adjustment for potential confounders.

Results A total of 93 participants had complete information on cognitive performance between 2000 and 2004. Mean plasma ADMA concentrations were approximately 0.4 mu mol/L lower in those participants with stable or improved RPM scores over follow-up compared with participants whose cognitive performance worsened. In confounder-adjusted analysis, one SD (0.06 mu mol/L) increase in ADMA at 63 years of age was associated with an average reduction in RPM of 1.26 points (95% CI 0.14-2.26) after 4 years.

Conclusion Raised plasma ADMA concentrations predicted worsening cognitive performance after approximately 4 years in this cohort of adults in late-middle age. These findings have implications for future research, including presymptomatic diagnosis or novel therapeutic targets for dementia and AD.

Original language	English
Pages (from-to)	1181-1188
Number of pages	8
Journal	International Journal of Geriatric Psychiatry
Volume	35
Issue number	10
Early online date	8 Jun 2020
DOIs	https://doi.org/10.1002/gps.5355
Publication status	Published - 31 Oct 2020

Bibliographical note

ACKNOWLEDGEMENTS
The authors gratefully acknowledge all participants of the ABC36 study. They acknowledge their colleagues, Prof Lawrence Whalley, Prof Ian Deary and the late Prof John Starr who developed the study. F.T. acknowledges support by the Rural and Environment Science and Analytical Services Division of the Scottish government (RESAS).
Funding Information
NHS Grampian R&D Endowments. Grant Number: 11/08 Scottish government
Rural and Environment Science and Analytical Services Division

Keywords

Dementia
Alzheimer’s disease
nitric oxide
asymmetric dimethylarginine
cognitive decline
risk prediction
DEMENTIA
biomarkers
ALZHEIMERS-DISEASE
diagnosis
RISK
CEREBROSPINAL-FLUID
DIABETES-MELLITUS
BLOOD BIOMARKERS
PLASMA
NITRIC-OXIDE
HYPERTENSION
Alzheimer's disease

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Circulating asymmetric dimethylarginine and cognitive decline: A 4‐year follow‐up study of the 1936 Aberdeen Birth Cohort. / Malden, Deborah E. (Corresponding Author); Mangoni, Arduino A.; Woodman, Richard J. et al.
In: International Journal of Geriatric Psychiatry, Vol. 35, No. 10, 31.10.2020, p. 1181-1188.

Research output: Contribution to journal › Article › peer-review

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abstract = "Background The underlying mechanisms leading to dementia and Alzheimer's disease (AD) are unclear. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, may be associated with cognitive decline, but population-based evidence is lacking.Methods Change in cognitive performance was assessed in participants of the Aberdeen Birth Cohort of 1936 using longitudinal Raven's progressive matrices (RPM) between 2000 and 2004. Multiple linear regression was used to estimate the association between ADMA concentrations in 2000 and change in cognitive performance after adjustment for potential confounders.Results A total of 93 participants had complete information on cognitive performance between 2000 and 2004. Mean plasma ADMA concentrations were approximately 0.4 mu mol/L lower in those participants with stable or improved RPM scores over follow-up compared with participants whose cognitive performance worsened. In confounder-adjusted analysis, one SD (0.06 mu mol/L) increase in ADMA at 63 years of age was associated with an average reduction in RPM of 1.26 points (95% CI 0.14-2.26) after 4 years.Conclusion Raised plasma ADMA concentrations predicted worsening cognitive performance after approximately 4 years in this cohort of adults in late-middle age. These findings have implications for future research, including presymptomatic diagnosis or novel therapeutic targets for dementia and AD.",

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AU - McNeil, Chris

AU - Murray, Alison D.

AU - Soiza, Roy L.

N1 - ACKNOWLEDGEMENTS The authors gratefully acknowledge all participants of the ABC36 study. They acknowledge their colleagues, Prof Lawrence Whalley, Prof Ian Deary and the late Prof John Starr who developed the study. F.T. acknowledges support by the Rural and Environment Science and Analytical Services Division of the Scottish government (RESAS). Funding Information NHS Grampian R&D Endowments. Grant Number: 11/08 Scottish government Rural and Environment Science and Analytical Services Division

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N2 - Background The underlying mechanisms leading to dementia and Alzheimer's disease (AD) are unclear. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, may be associated with cognitive decline, but population-based evidence is lacking.Methods Change in cognitive performance was assessed in participants of the Aberdeen Birth Cohort of 1936 using longitudinal Raven's progressive matrices (RPM) between 2000 and 2004. Multiple linear regression was used to estimate the association between ADMA concentrations in 2000 and change in cognitive performance after adjustment for potential confounders.Results A total of 93 participants had complete information on cognitive performance between 2000 and 2004. Mean plasma ADMA concentrations were approximately 0.4 mu mol/L lower in those participants with stable or improved RPM scores over follow-up compared with participants whose cognitive performance worsened. In confounder-adjusted analysis, one SD (0.06 mu mol/L) increase in ADMA at 63 years of age was associated with an average reduction in RPM of 1.26 points (95% CI 0.14-2.26) after 4 years.Conclusion Raised plasma ADMA concentrations predicted worsening cognitive performance after approximately 4 years in this cohort of adults in late-middle age. These findings have implications for future research, including presymptomatic diagnosis or novel therapeutic targets for dementia and AD.

AB - Background The underlying mechanisms leading to dementia and Alzheimer's disease (AD) are unclear. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, may be associated with cognitive decline, but population-based evidence is lacking.Methods Change in cognitive performance was assessed in participants of the Aberdeen Birth Cohort of 1936 using longitudinal Raven's progressive matrices (RPM) between 2000 and 2004. Multiple linear regression was used to estimate the association between ADMA concentrations in 2000 and change in cognitive performance after adjustment for potential confounders.Results A total of 93 participants had complete information on cognitive performance between 2000 and 2004. Mean plasma ADMA concentrations were approximately 0.4 mu mol/L lower in those participants with stable or improved RPM scores over follow-up compared with participants whose cognitive performance worsened. In confounder-adjusted analysis, one SD (0.06 mu mol/L) increase in ADMA at 63 years of age was associated with an average reduction in RPM of 1.26 points (95% CI 0.14-2.26) after 4 years.Conclusion Raised plasma ADMA concentrations predicted worsening cognitive performance after approximately 4 years in this cohort of adults in late-middle age. These findings have implications for future research, including presymptomatic diagnosis or novel therapeutic targets for dementia and AD.

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Circulating asymmetric dimethylarginine and cognitive decline: A 4‐year follow‐up study of the 1936 Aberdeen Birth Cohort

Abstract

Bibliographical note

Keywords

UN SDGs

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