Are delta-aminolevulinate dehydratase inhibition and metal concentrations additional factors for the age-related cognitive decline?

Int J Environ Res Public Health. 2014 Oct 17;11(10):10851-67. doi: 10.3390/ijerph111010851.


Aging is often accompanied by cognitive impairments and influenced by oxidative status and chemical imbalances. Thus, this study was conducted to examine whether age-related cognitive deficit is associated with oxidative damage, especially with inhibition of the enzyme delta-aminolevulinate dehydratase (ALA-D), as well as to verify the influence of some metals in the enzyme activity and cognitive performance. Blood ALA-D activity, essential (Fe, Zn, Cu, Se) and non-essential metals (Pb, Cd, Hg, As, Cr, Ni, V) were measured in 50 elderly and 20 healthy young subjects. Cognitive function was assessed by tests from Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery and other. The elderly group presented decreased ALA-D activity compared to the young group. The index of ALA-D reactivation was similar to both study groups, but negatively associated with metals. The mean levels of essential metals were within the reference values, while the most toxic metals were above them in both groups. Cognitive function impairments were observed in elderly group and were associated with decreased ALA-D activity, with lower levels of Se and higher levels of toxic metals (Hg and V). Results suggest that the reduced ALA-D activity in elderly can be an additional factor involved in cognitive decline, since its inhibition throughout life could lead to accumulation of the neurotoxic compound ALA. Toxic metals were found to contribute to cognitive decline and also to influence ALA-D reactivation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Brazil / epidemiology
  • Cognition Disorders / blood
  • Cognition Disorders / enzymology
  • Cognition Disorders / epidemiology*
  • Cognition*
  • Enzyme Inhibitors / blood
  • Enzyme Inhibitors / toxicity*
  • Female
  • Humans
  • Male
  • Metals, Heavy / blood*
  • Metals, Heavy / toxicity
  • Middle Aged
  • Oxidative Stress*
  • Porphobilinogen Synthase / antagonists & inhibitors
  • Porphobilinogen Synthase / blood*
  • Selenium / deficiency


  • Enzyme Inhibitors
  • Metals, Heavy
  • Porphobilinogen Synthase
  • Selenium