Search the Database

Dementia

• Microbiome–gut–brain dysfunction in prodromal and symptomatic Lewy body diseases
  Lewy body diseases, such as Parkinson’s disease and dementia with Lewy bodies, vary in their clinical phenotype but exhibit the same defining pathological feature, α-synuclein aggregation. Microbiome–gut–brain dysfunction may play a role in the initiation or progression of disease processes, though there are multiple potential mechanisms. We discuss the need to evaluate gastrointestinal mechanisms of pathogenesis across Lewy body diseases, as disease mechanisms likely span across diagnostic categories and a ‘body first’ clinical syndrome may better account for the heterogeneity of clinical presentations across the disorders. We discuss two primary hypotheses that suggest that either α-synuclein aggregation occurs in the gut and spreads in a prion-like fashion to the brain or systemic inflammatory processes driven by gastrointestinal dysfunction contribute to the pathophysiology of Lewy body diseases. Both of these hypotheses posit that dysbiosis and intestinal permeability are key mechanisms and potential treatment targets. Ultimately, this work can identify early interventions targeting initial disease pathogenic processes before the development of overt motor and cognitive symptoms.
  [Ryman, S., Vakhtin, A. A., Richardson, S. P., & Lin, H. C. (2023). Microbiome–gut–brain dysfunction in prodromal and symptomatic Lewy body diseases. Journal of neurology, 270(2), 746-758. https://link.springer.com/article/10.1007/s00415-022-11461-9 ]
• Pesticides, cognitive functions and dementia: A review
  Pesticides are widely-used chemicals commonly applied in agriculture for the protection of crops from pests. Depending on the class of pesticides, the specific substances may have a specific set of adverse effects on humans, especially in cases of acute poisoning. In past years, evidence regarding sequelae of chronic, low-level exposure has been accumulating. Cognitive impairment and dementia heavily affect a person’s quality of life and scientific data has been hinting towards an association between them and antecedent chronic pesticide exposure. Here, we reviewed animal and human studies exploring the association between pesticide exposure, cognition and dementia. Additionally, we present potential mechanisms through which pesticides may act neurotoxically and lead to neurodegeneration. Study designs rarely presented homogeneity and the estimation of the exposure to pesticides has been most frequently performed without measuring the synergic effects and the possible interactions between the toxicants within mixtures, and also overlooking low exposures to environmental toxicants. It is possible that a Real-Life Risk Simulation approach would represent a robust alternative for future studies, so that the safe exposure limits and the net risk that pesticides confer to impaired cognitive function can be examined. Previous studies that evaluated the effect of low dose chronic exposure to mixtures of pesticides and other chemicals intending to simulate real life exposure scenarios showed that hormetic neurobehavioral effects can appear after mixture exposure at doses considered safe for individual compounds and these effects can be exacerbated by a coexistence with specific conditions such as vitamin deficiency. However, there is an overall indication, derived from both epidemiologic and laboratory evidence, supporting an association between exposure to neurotoxic pesticides and cognitive dysfunction, dementia and Alzheimer’s disease.
  [Aloizou, A.M., Siokas, V., Vogiatzi, C., Peristeri, E., Docea, A., Petrakis, D., Provatas, A., Folia, V., Chalkia, C., Vinceti, M. and Wilks, M., 2020. Pesticides, cognitive functions and dementia: A review. Toxicology Letters.]
• Association between background exposure to organochlorine pesticides and the risk of cognitive impairment: A prospective study that accounts for weight change
  Background exposure to organochlorine (OC) pesticides was recently linked to cognitive impairment and dementia in cross-sectional and case–control studies. This prospective study was performed to evaluate if OC pesticides at baseline are associated with the future risk of cognitive impairment in elderly, with particular focus on weight change. Plasma concentrations of 3 OC pesticides (p,p′-DDE, trans-nonachlor, and hexachlorobenzene) were measured among 989 men and women aged 70 years in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS). Cognitive impairment was validated by reviewing medical records. During the ten year follow-up, cognitive impairment was developed in 75 subjects. When weight change from age 70 to 75 was considered in analyses, elderly with incident cases before age 75 were excluded to keep the prospective perspective, leaving 795 study subjects and 44 incident cases. The summary measure of 3 OC pesticides predicted the development of cognitive impairment after adjusting for covariates, including weight change. Compared to subjects with OC pesticides < 25th percentile, adjusted hazard ratios (HRs) in those with 25th–
  [Lee, D.H., Lind, P.M., Jacobs Jr, D.R., Salihovic, S., van Bavel, B. and Lind, L., 2016. Association between background exposure to organochlorine pesticides and the risk of cognitive impairment: a prospective study that accounts for weight change. Environment international, 89, pp.179-184.]
• Neurobehavioral effects of long-term exposure to pesticides: results from the 4-year follow-up of the PHYTONER Study
  The aim of the PHYTONER study is to investigate the role of pesticides on neurobehavioral performances in French vineyard workers. 929 workers affiliated to the health insurance system for farmers in the Bordeaux area of south-western France were enrolled in the study in 1997–1998. They were contacted for a first follow-up in 2001–2003. Participants completed a questionnaire and nine neurobehavioral tests. They were classified according to their life-long pesticide exposure, as directly exposed, indirectly exposed or non-exposed. Educational level, age, sex, alcohol consumption, smoking, psychotropic drug use and depressive symptoms were taken into account in the analysis. 614 subjects were available for investigation at follow-up. Follow-up analysis confirmed that the risk of obtaining a low performance on the tests was higher in exposed subjects, with ORs ranging from 1.35 to 5.60. Evolution of performances over the follow-up period demonstrated that exposed subjects had the worst decreases in performance. The risk of having a two-point lower score on the Mini-Mental State Examination was 2.15 (95% CI 1.18 to 3.94) in exposed subjects. These results suggest long-term cognitive effects of chronic exposure to pesticides and raise the issue of the risk of evolution towards dementia. The PHYTONER study is the first to provide prospective data on the natural history of neurological disorders associated with pesticide exposure.
  [Baldi, I., Gruber, A., Rondeau, V., Lebailly, P., Brochard, P. and Fabrigoule, C., 2011. Neurobehavioral effects of long-term exposure to pesticides: results from the 4-year follow-up of the PHYTONER study. Occupational and environmental medicine, 68(2), pp.108-115.]
• Alzheimer disease: Risk of dementia and Alzheimer disease increases with occupational pesticide exposure
  Occupational exposure to pesticides increases the risk of developing dementia and Alzheimer disease (AD) in later life, according to this longitudinal population-based cohort study. The results of this study provide further evidence that certain environmental factors are risk factors for these debilitating conditions.
  [Jones N.2010. Nat Rev Neurol. 6(7):353]