Background: There is a not a clear understanding of the potential time-period windows for lifestyle interventions. This study examined how smoking and harmful drinking across early midlife affect cognitive performance in later life. Methods: Data is from Medical Research Council National Survey of Health and Development (NSHD). Cognitive abilities were measured at age 60-64. Information about alcohol consumption was collected via food diaries at multiple time points across life (ages 36, 43, 53 and 60-64). Information about smoking was collected via interviews and questionnaires at ages 20, 25, 31, 36, 43, 53 and 60- 64. Multivariable logistic regression was used, adjusting for gender, childhood cognition at age 8, education and socioeconomic status. Findings: Drinking in moderation across midlife appears to be protective against poor memory in later life (OR=0.86, 95% CI (0.63-1.16)). In contrast, harmful drinking at 43 and 53 years was associated with higher odds of poor memory (OR=1.36, 95% CI (0.79-2.33)), (OR=1.26, 95% CI (0.65-2.43)). Drinking heavily, particularly at age 43, was also associated with higher odds of slow search speed at the same age (OR=1.66, 95% CI (1.01-2.76)). An increase in the number of smoking pack-years was associated with low memory (OR=2.17, 95% CI (1.33-3.54)) and slow search speed (OR=1.65, 95% CI (1.03-2.64)). Interpretation: These results may be suggesting that intervention may be more beneficial in the decades preceding clinical the manifestation of neuropathological burden
