The authors examined the relationship between personality and cognitive impairment in 4,039 members of the Swedish Twin Registry. Neuroticism and extraversion scores were collected in 1973 at midlife, and cognitive impairment was assessed in the same group 25 years later. Data were analyzed with case-control and co-twin control designs. Greater neuroticism was associated with higher risk of cognitive impairment in the results from case-control, but not from co-twin, analyses. Compared with both extraversion and introversion, moderate extraversion was associated with lower risk of cognitive impairment in both case-control and co-twin designs, as was the combination of high neuroticism and low extraversion. Findings are discussed in the context of theories related to personality, psychological distress, arousal, and cognitive function.