Background: Hopelessness has been associated with increased cardiovas- cular disease mortality and morbidity, subclinical atherosclerosis and meta- bolic syndrome. This study investigates the relation between midlife hopelessness and white matter lesions (WMLs) 20 years later in a Finnish population of men and women. Methods: Participants of the Cardiovascular Risk Factors, Aging and Incidence of Dementia (CAIDE) study in Finland were derived from random, population-based samples previously surveyed in 1972,1977, 1982 or 1987. In 1998, 1449 (73%) individuals aged 65-79 years participated in the re-examination. A subgroup (n1⁄4112, including 39 dementia cases, 31 mild cognitive impairment (MCI) cases and 42 con- trols) underwent 1.5T MRI scanning at re-examination, and WMLs were as- sessed from FLAIR-images using a semi-quantitative visual rating scale. Hopelessness was measured by 2 questionnaire items (expectations about future and reaching goals). Results: Subjects with increased hopelessness had a significantly higher risk of developing more severe WMLs two de- cades later. OR (95% CI) was 4.35 (1.36-13.46) in ordinal regression anal- yses adjusted for age, sex education, follow-up time, presence of the APOEe4 allele, systolic blood pressure, BMI, history of stroke, heart infarct, smoking and level of midlife leisure physical activity. Conclusions: Higher levels of hopelessness at midlife seem to be related to more severe WMLs later in life. Since WMLs may contribute to late-life cognitive impairment, lifestyle management of midlife vascular risk factors (which also increase the risk of dementia and cognitive impairment) may have better effects if people’s expectations are more thoroughly discussed.