Abstract
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. 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. A total of 93 participants had complete information on cognitive performance between 2000 and 2004. Mean plasma ADMA concentrations were approximately 0.4 μmol/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 μmol/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. 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.
Highlights
Alzheimer’s disease (AD) is a neurodegenerative disorder characterised by a rapid decline in cognition in old age, which is distinct from the normal ageing process
This study aims to investigate the relationship between plasma Asymmetric dimethylarginine (ADMA) concentrations and the change in cognitive performance across four years in the 1936 Aberdeen Birth Cohort (ABC36) study
Prior to confounder adjustment, no significant differences in baseline age, years of education, childhood MHT score, smoking habits, or alcohol consumption were observed between participants who improved or maintained their cognitive performance scores
Summary
Alzheimer’s disease (AD) is a neurodegenerative disorder characterised by a rapid decline in cognition in old age, which is distinct from the normal ageing process. Diabetes is associated with a 2- to 3-fold increased risk of vascular events[6,7] and a 50% increased risk of dementia[8] and a 20% increase in the rate of cognitive decline.[9,10,11] large genomewide association studies have confirmed associations between ‘vascular risk’ genes and the development of AD,[12] with the strongest known genetic risk factor being a mutation in the apolipoprotein E4 gene, which encodes a cholesterol transporter protein.[13] Vascular endothelial dysfunction, an abnormality that is associated with the presence of virtually all known cardiovascular risk factors, is frequently seen in AD Despite this evidence, there is a lack of population-based research investigating the roles of vascular changes, oxidative stress, lipid metabolism and inflammation in AD pathogenesis.[14,15]. These findings have implications for future research, including presymptomatic diagnosis or novel therapeutic targets for dementia and AD
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
