The objective of the current retrospective cohort study was to identify vascular and/or neuropsychiatric risk factors predicting clinical progression in persons with subjective cognitive decline (SCD). Information on 1,525 persons with SCD (mean age = 73.8 [ SD = 8.1] years) was obtained from the National Alzheimer’s Coordinating Center. Clinical progression occurred from SCD to either amnestic mild cognitive impairment or Alzheimer’s dementia over an average of 4.7 ( SD = 2.9) years. Stepwise Cox regression was used. Compared to obesity (hazard ratio [HR] = 0.59) in the univariate unadjusted model, obesity (HR = 0.64), current smoking (HR = 2.02), and depressive symptoms (HR = 1.35) were significant after adjusting for covariates in the univariate model. In the multivariate adjusted model, obesity (HR = 0.64), current smoking (HR = 2.04), and depressive symptoms (HR = 1.36) remained significant predictors. Interventions should be designed to minimize transition by managing smoking and depressive symptoms. Further research is required for associations between obesity and clinical progression to test the hypothesis of obesity paradox.