ABSTRACTObjectives:Disability in older adults is associated with a need for support in work, education, and community activities, reduced independence, and poorer quality of life. This study examines potential determinants of disability in a clinical sample of older adults across the continuum of cognitive decline, including sociodemographic, medical, psychiatric, and cognitive factors.Design:This is a cross-sectional study.Setting:Participants were recruited from a specialty clinic for adults “at risk” of or with early dementia (including subjective cognitive complaints, mild cognitive impairment, and early dementia).Participants:Four hundred forty-two older adults (mean age = 67.11, SD = 9.33) underwent comprehensive medical, neuropsychological, and mood assessments.Measurements:Disability was assessed via the self-report World Health Organization Disability Assessment Schedule 2.0. A stepwise (forward) linear regression model was computed to determine factors that contribute to disability within this group.Results:Depressive symptoms were the largest predictor, uniquely explaining 31.8% of the variance. Other contributing factors in the model included younger age, medical burden, and sleep quality, with all factors together accounting for a total of 50.4% of the variance in disability. Cognitive variables did not contribute to the model.Conclusions:Depressive symptoms account for a significant portion of the variance in disability, but other factors such as age, medical burden and sleep quality are also important contributors in older adults across the continuum of cognitive decline. The relative association of these variables with disability appears to differ for older (≥65 years) relative to younger (<65 years) participants. Given the relationship between disability and these risk factors, an integrative and multidisciplinary approach to risk reduction will likely be most effective, with potential carry over effects for physical and mental health.