Both cognitive reserve and subjective cognitive decline are closely related to the risk of dementia. We investigated whether cognitive reserve can modify the risk of dementia developing from subjective cognitive decline.Longitudinal population-based study.The prospective study analyzed data from 2099 participants aged 65 or over from the Cognitive Function and Ageing Study-Wales (CFAS-Wales).Dementia was ascertained through the comprehensive judgment symptoms of geriatric mental state automated geriatric examination for computer assisted taxonomy (GMS-AGECAT). Subjective cognitive decline was evaluated by 2 questions in the baseline interview. Cognitive reserve indicators were derived from 3 previously identified factors: early life education, mid-life occupational complexity, and late-life cognitive activities. We used logistic regression models to estimate dementia risk in relation to subjective cognitive decline and indicators of cognitive reserve. The interaction between subjective cognitive decline and cognitive reserve were evaluated by additive and multiplicative scales.Baseline subjective cognitive decline and low cognitive reserve significantly increased the risk of dementia, after 2 years of follow-up. There was an additive interaction between subjective cognitive decline and cognitive reserve [the relative excess risk due to interaction = -0.63, 95% confidence interval (CI) = -0.89 to -0.36, P for additive interaction <0.001]. There was no multiplicative interaction between subjective cognitive decline and cognitive reserve indicator (P = .138). Statistically significant association between subjective cognitive decline and dementia was found only in the low-level and medium-level cognitive reserve group (OR = 3.78, 95% CI = 1.50-9.55 and OR = 3.64, 95% CI = 1.09-12.2, respectively), but not in the high-level groups.Cognitive reserve attenuated subjective cognitive decline associated risk of developing dementia. This finding suggests the need for greater emphasis on detecting prodromal dementia when older patients having lower cognitive reserve present with subjective cognitive decline.