Asymmetric dimethylarginine

a possible link between vascular disease and dementia

Muhammad Asif, Roy L. Soiza, Mark McEvoy, Arduino A. Mangoni

Research output: Contribution to journalReview article

17 Citations (Scopus)

Abstract

There is good epidemiological evidence that vascular disease predisposes to cognitive decline and dementia. The impact of vascular disease on dementia is likely to increase further because of the poor diagnosis and management of vascular risk factors, the increase in life expectancy, and the improved survival following major cardiovascular events, e.g. acute stroke. It is estimated that the adequate management of vascular risk factors, with pharmacological and/or nonpharmacological interventions, might result in a 50% reduction in the forecasted dementia prevalence. The exact mechanisms by which vascular risk factors and vascular disease adversely affect brain function remain unclear, but it is hypothesized that endothelial dysfunction plays an important role. Reduced synthesis and availability of endothelial nitric oxide (NO) may contribute to the development of dementia by at least two mechanisms: (1) favoring the onset and progression of atherosclerosis, vasoconstriction, and impaired cerebral blood flow regulation; and (2) reduced neuroprotection.Several studies have shown that asymmetric dimethylarginine (ADMA), an endogenous methylated form of the amino acid L-arginine, inhibits NO synthesis and favors oxidative stress and vascular damage. Unlike NO, ADMA concentrations are relatively stable and can be accurately measured in plasma. There is good evidence that higher plasma ADMA concentrations favor atherosclerosis and independently predict adverse cardiovascular and cerebrovascular outcomes in several patient groups. ADMA might represent a unifying pathophysiological pathway linking the presence of vascular risk factors with the onset and progression of cognitive decline and dementia. This review discusses the biological role of ADMA, its potential contribution to the onset and progression of dementia through vascular disease and atherosclerosis, the available evidence linking ADMA with cognitive impairment and dementia, and the strategies to characterize the predictive role of ADMA in cognitive impairment in epidemiological studies. Therapeutic implications and suggestions for future research directions are also discussed.

Original languageEnglish
Pages (from-to)347-356
Number of pages10
JournalCurrent Alzheimer Research
Volume10
Issue number4
DOIs
Publication statusPublished - 1 May 2013

Fingerprint

Vascular Dementia
Vascular Diseases
Dementia
Atherosclerosis
Nitric Oxide
Cerebrovascular Circulation
Life Expectancy
N,N-dimethylarginine
Vasoconstriction
Blood Vessels
Arginine
Epidemiologic Studies
Oxidative Stress
Stroke
Pharmacology
Amino Acids
Survival
Cognitive Dysfunction
vascular factor
Brain

Keywords

  • Alzheimer's disease
  • Asymmetric dimethylarginine
  • Dementia
  • Endothelium
  • Nitric oxide
  • Vascular disease

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Asymmetric dimethylarginine : a possible link between vascular disease and dementia. / Asif, Muhammad; Soiza, Roy L.; McEvoy, Mark; Mangoni, Arduino A.

In: Current Alzheimer Research, Vol. 10, No. 4, 01.05.2013, p. 347-356.

Research output: Contribution to journalReview article

Asif, Muhammad ; Soiza, Roy L. ; McEvoy, Mark ; Mangoni, Arduino A. / Asymmetric dimethylarginine : a possible link between vascular disease and dementia. In: Current Alzheimer Research. 2013 ; Vol. 10, No. 4. pp. 347-356.
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