RESUMO
Introduction: This study aimed to test the efficacy of a nutritional blend (NB) in improving nutritional biomarkers and preventing cognitive decline among older adults. Methods: A 1-year randomized, double-blind, multicenter, placebo-controlled trial with 362 adults (58.6% female, mean 78.3 years, SD = 4.8) receiving an NB or placebo. Erythrocyte ω-3 index and homocysteine concentrations were primary outcomes. Other outcomes included Patient-Reported Outcomes Measurement Information System (PROMIS) Applied Cognition-Abilities, composite cognitive score (CCS), Cognitive Function Instrument (CFI) self-assessment and study partner, hippocampal volume (HV), and Alzheimer's disease signature cortical thickness (CT). Results: A total of 305 subjects completed the follow-up. Supplementation increased ω-3 index and decreased homocysteine, but did not affect CCS, CFI self-assessment, HV, and CT. Placebo improved and treatment did not change PROMIS at 1 month. Intervention showed a positive effect on CFI study partner. Discussion: Although improving nutritional biomarkers, this 1-year trial with a multi-nutrient novel approach was not able to show effects on cognitive outcomes among older adults.
RESUMO
The incidence of neurodegenerative disease like Parkinson's disease and Alzheimer's disease (AD) increases dramatically with age; only a small percentage is directly related to familial forms. The etiology of the most abundant, sporadic forms is complex and multifactorial, involving both genetic and environmental factors. Several environmental pollutants have been associated with neurodegenerative disorders. The present article focuses on results obtained in experimental neurotoxicology studies that indicate a potential pathogenic role of lead and mercury in the development of neurodegenerative diseases. Both heavy metals have been shown to interfere with a multitude of intracellular targets, thereby contributing to several pathogenic processes typical of neurodegenerative disorders, including mitochondrial dysfunction, oxidative stress, deregulation of protein turnover, and brain inflammation. Exposure to heavy metals early in development can precondition the brain for developing a neurodegenerative disease later in life. Alternatively, heavy metals can exert their adverse effects through acute neurotoxicity or through slow accumulation during prolonged periods of life. The pro-oxidant effects of heavy metals can exacerbate the age-related increase in oxidative stress that is related to the decline of the antioxidant defense systems. Brain inflammatory reactions also generate oxidative stress. Chronic inflammation can contribute to the formation of the senile plaques that are typical for AD. In accord with this view, nonsteroidal anti-inflammatory drugs and antioxidants suppress early pathogenic processes leading to Alzheimer's disease, thus decreasing the risk of developing the disease. The effects of lead and mercury were also tested in aggregating brain-cell cultures of fetal rat telencephalon, a three-dimensional brain-cell culture system. The continuous application for 10 to 50 days of non-cytotoxic concentrations of heavy metals resulted in their accumulation in brain cells and the occurrence of delayed toxic effects. When applied at non-toxic concentrations, methylmercury, the most common environmental form of mercury, becomes neurotoxic under pro-oxidant conditions. Furthermore, lead and mercury induce glial cell reactivity, a hallmark of brain inflammation. Both mercury and lead increase the expression of the amyloid precursor protein; mercury also stimulates the formation of insoluble beta-amyloid, which plays a crucial role in the pathogenesis of AD and causes oxidative stress and neurotoxicity in vitro. Taken together, a considerable body of evidence suggests that the heavy metals lead and mercury contribute to the etiology of neurodegenerative diseases and emphasizes the importance of taking preventive measures in this regard.
