Little is known about whether persons with mentally demanding jobs are protected against cognitive impairment and whether this association is independent of intellectual abilities and other confounders. Longitudinal data from the Maastricht Aging Study (MAAS) were used to examine this association. After the 1993-1995 baseline examination, there was a first 3-year follow-up examination (1996-1998) among 630 men and women, aged 50 to 80, who exhibited no cognitive impairment at baseline. Persons with mentally demanding jobs had lower risks of developing cognitive impairment during follow-up (36 cases), compared with persons without such jobs (odds ratio = 0.79; 95% confidence interval: 0.65-0.96). About 1.5% of the persons with high mental work demands developed impairment compared to 4% of the persons with few work demands. The protective effect was independent of intellectual abilities and other confounders. Our findings provide evidence that continued and potentially modifiable mental stimulation during adult life may protect men and women against cognitive impairment.