Little is known about the adverse effects of substances, such as pesticides and metals, on the development of mild cognitive dysfunction (MCD). Cross-sectional and prospective data from the Maastricht Aging Study were used to find out the potential neurotoxicity of particular substances. Exposure to pesticides, for example by arable farmers and gardeners, was associated with increased risks of MCD. Exposure to metals and organic solvents was not associated with MCD. Our findings might reflect subtle changes in brain function among people exposed to pesticides.