Mild cognitive impairment (MCI) is a subclinical cognitive decline in the elderly that increases the risk of conversion to Dementia. Delaying the onset of conversion from normal cognition to MCI has public health relevance by potentially reducing the magnitude of cognitive dysfunction related disability. It has been suggested that cognitive reserve, comprised of IQ and behaviors associated with memory facilitation and problem solving, may delay onset of MCI. Time to onset of MCI may also be associated with the risk factor of the APOE-4 allele. MCI classification criteria is inconsistent across studies, suggesting additional public health need to standardize an accurate method of screening. This study examined the association between cognitive reserve, APOE-4, and time to onset of MCI. Data from the 8 year Gingko Evaluation of Memory Study (GEM) clinical trial were used to examine these aims in a sample of n=2,284 cognitively normal individuals. The GEM MCI classification algorithm was extended over 8 years to examine normal cognition survival. Indicators of cognitive reserve were IQ, average monthly frequency of cognitive reserve behaviors, and number of different cognitive reserve behaviors engaged in each month. APOE-4 presence was defined as having at least one copy of the APOE-4 allele. N=1,226 (53.68%) individuals remained cognitively normal over the eight year followup compared to n=1,058 (46.32%) who developed incident MCI over eight year followup. Incident MCI individuals had significantly higher age (p<0.0001) and education (p=0.0320) at entry and were more likely to be male (p=0.0497), Asian/Pacific Islander, Black, or “Other” identified race (p=0.0078). Incident MCI individuals had significantly lower frequency of reading newspapers (p=0.0228) and solving crosswords (p=0.0301), as well as IQ (p=0.0002). Neither the average monthly frequency of cognitive reserve behaviors (p=0.6662) nor the number of different cognitive reserve behaviors engaged in each month were significantly associated with MCI onset (p=0.7809). Age (p<0.0001), education (p<0.0001), IQ (p<0.0001), and APOE-4 presence (p<0.0001) were significantly associated with time to MCI onset in a Cox proportional hazard model adjusted for age, education, IQ, APOE-4 presence, cognitive reserve behavior frequency, and number of different cognitive reserve behaviors engaged in each month
