Abstract P506: Timing of Cognitive Test Score Decline Before Incident Dementia in Middle Age Adults: The Atherosclerosis Risk in Communities (ARIC) Study

Background: The most frequent dementias are a mix of Alzheimer’s, vascular and other pathologies which evolve over many years. Our objective is to determine how many years in advance of dementia cognitive scores are affected. Methods: 13,749 dementia-free ARIC participants had a cognitive exam at Visit 2 (1990-1992, mean age 57), 10,813 at Visit 4 (1996-1998), 5,605 at Visit 5 (2011-2013) and 3,516 at Visit 6 (2016-2017). Within 5-year intervals after each visit, we compared the combined mean of three cognitive tests (Delayed Word Recall, Digit Symbol Substitution, and Word Fluency) z-scores at baseline in two groups - participants who were diagnosed with dementia within each interval vs. those who survived to the interval without dementia. Baseline visit z-scores were adjusted for age, gender, race-center and education level in separate linear regression models for each visit. We plotted the adjusted z-score mean [95% confidence interval] by time interval following each visit. Results: Dementia incidence during follow-up yielded 2,981 , 2,397, 961 and 160 cases after Visits 2, 4, 5, and 6 respectively. The three-test combined scores were already significantly lower at 10-15 years before dementia compared to those who did not experience dementia by that period (Figure). As expected at intervals closer to dementia onset the differences between dementia and non-dementia groups increased, up to their widest point of approximately 1 SD at only 0-5 years prior to onset. Delayed Word and Digit Symbol Substitution tests has similar findings while Word Fluency began to decrease only within 5 years prior to dementia onset. Conclusion: We found that the differences in combined cognitive function z-score appeared to be associated with dementia diagnosis as early as 15 years prior to diagnosis. As we got closer to the diagnosis date, the difference in scores of people with and without dementia widened substantially. Periodic testing might allow us to intervene earlier in persons likely to develop dementia.