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We sought to determine whether geriatric patients with late-life-onset major depression have more subcortical hyperintensities on MRI and greater cognitive impairment than age-matched geriatric patients with early-life-onset major depression, suggesting that subcortical disease may be etiologic in late-life depression. Most negative studies of the clinical significance of subcortical hyperintensities on MRI in geriatric patients have sampled from a restricted range of subjects, have employed limited batteries of neuropsychological tests, or have not quantified MRI changes; the present study attempted to address these limitations. Thirty subjects from a geriatric psychiatry inpatient service who were over 60 years of age and presented with major depression were divided into groups with onset of first depression after age 60 (mean = 72.4 years, 15 women, 0 men), and onset of first depression before age 60 (mean = 35.8 years, 12 women, 3 men). Quantitative analysis of MRI yielded the volume of: periventricular hyperintensities (PVH) and deep white-matter hyperintensities (DWMH). Subjects were administered a neuropsychological battery and measures of depression by raters blind to age of onset. The late-onset group had significantly more PVH and DWMH. They were also more impaired on executive and verbal and nonverbal memory tasks. Discriminant analysis using the severity or subcortical signal hyperintensities on MRI, cognitive index, and depression scores correctly predicted late versus early onset of depression in 87% of the early-onset group and 80% of the late-onset group. These findings suggest that late-life-onset depression may be associated with an increased severity of subcortical vascular disease and greater impairment of cognitive performance.