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To examine the association between presence of clinically relevant depressive symptoms (Center for Epidemiologic Studies Depression Scale [CES-D] score ≥ 16) and subsequent cognitive function (Mini-Mental State Examination [MMSE]) over a 7-year period in older Mexican Americans, a prospective cohort study was performed. Five southwestern states contributed data to the Hispanic Established Populations for Epidemiologic Studies of the Elderly. Participants included 2812 noninstitutionalized Mexican Americans aged 65 and older followed from 1993-1994 until 2000-2001. Cognitive change was assessed using the MMSE at baseline and at 2, 5, and 7 years of follow-up. Independent variables were sociodemographics, CES-D ≥ 16, medical conditions (hypertension, diabetes, coronary artery disease, and stroke), and activities of daily living (ADL) status. A general linear mixed model was used to estimate cognitive change.There was a cross-sectional association between CES-D ≥ 16 and lower MMSE score (estimate = -0.48; standard error [SE] -0.15; P < .01), independent of age, gender, education, marital status, time of interview, ADL limitations, vision impairment, and medical conditions. In the fully adjusted longitudinal model, subjects with clinically relevant depressive symptoms had a greater decline in MMSE score over 7 years than those without clinically relevant depressive symptoms (estimate = -0.17; SE = 0.05; P < .001), adjusting for sociodemographics, ADL and medical conditions. Each point increase in the CES-D score was associated with a decline of 0.010 point in MMSE score per year (SE = 0.002; P < 0.0001), adjusting for relevant confounders. Presence of clinically relevant depressive symptoms was associated with subsequent decline in cognitive function over 7 years in older Mexican Americans, independent of demographic and health factors. (J Geriatr Psychiatry Neurol 2007;20:145-152) Keywords: depression; cognition; elderly; Mexican Americans, Decline in cognitive ability contributes to loss of independent living and premature deaths in older adults.(1-3) An important step toward delaying or stopping cognitive decline is early recognition (and treatment) [...]