BACKGROUND The association between brain white matter lesions and cognitive impairment in old age is well established. However, little is known about this association in midlife. As this information will inform policy for early preventative healthcare initiatives, we investigated non-periventricular frontal, temporal, parietal and occipital lobe white matter hyperintensities (WMH) in relation to cognitive function in 428 (232 women) community-dwelling adults aged 44 to 48 years. RESULTS Frontal white matter lesions were significantly associated with greater intraindividual RT variability in women, while temporal WMH were associated with face recognition deficits in men. Parietal and occipital lobe lesions were unrelated to cognitive performance. These findings did not differ when education and a range of health variables, including vascular risk factors, were taken into account. CONCLUSION Gender differences in WMH-cognition associations are discussed, and we conclude that small vessel disease is present in midlife and has functional consequences which are generally not recognized. Preventative strategies should, therefore, begin early in life.David Bunce's collaboration in this work was supported by the Leverhulme Trust and the British Academy. The study was funded by NHMRC of Australia Unit Grant No. 973302, Program Grant No. 179805, NHMRC project grant No. 157125, grants from the Australian Rotary Health Research Fund and the Australian Brewers Foundation. Nicolas Cherbuin is funded by NHMRC Research Fellowship No. 471501. Kaarin Anstey is funded by NHMRC Research Fellowship No. 366756. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript
