P1‐028: OCCUPATIONAL COGNITIVE REQUIREMENTS ARE AN IMPORTANT PROXY MEASURE OF COGNITIVE RESERVE: EVIDENCE FROM THE AGECODE AND DELCODE STUDIES
2018-07-01

Identification of modifiable protective factors is a crucial aim of Alzheimer's disease (AD) prevention research. In this regard, higher occupational cognitive requirements (OCR) in mid-life may promote increased cognitive reserve. However, previous study results were inconsistent and used imprecise measurements of OCR. We therefore adapted a recently developed, detailed OCR measure derived from the US Department of Labor's Occupational Information Network (O*NET) database, and tested whether it moderates effects of genetic risk and biomarkers of AD pathology on cognitive function in two independent studies of ageing and AD. We applied growth curve modelling to longitudinal data from a population based cohort (AgeCoDe, n=2369) of non-demented individuals above age 75 at baseline to test whether higher OCR would attenuate APOE4 associated cognitive decline. In addition, we used data of n=317 participants of the DELCODE study (123 healthy controls, 96 with Subjective Cognitive Decline, 52 MCI, 25 AD dementia, 21 cognitively normal relatives of AD dementia patients; mean age =70.2 (SD=5.9)). We tested with regression analyses whether higher OCR moderate the cross-sectional association between hippocampal volume and CSF AD biomarkers with performance in 5 cognitive domain scores derived from confirmatory factor analysis of an extensive neuropsychological test-battery. To operationalize OCR, we linked individual's detailed lifetime occupation information to O*NET data according to the method of Poole et al. (2016). This method summarizes ratings of cognitive demands in 10 work-related tasks (e.g. processing information, thinking creatively). In AgeCoDe, detrimental effects of ApoE4 on cognitive decline in the MMSE were significantly attenuated for those with high OCR scores (Figure 1). Similarly, in DELCODE the expected cross-sectional associations of lower hippocampal volume and more pathological CSF Abeta42/Tau ratio with a decrease in cognitive performance were significantly less pronounced in those with higher OCR scores (Figure 2). Results remained similar after adjustment for educational level. Ooccupational cognitive requirements score as a moderator of APOE4 related cognitive decline in the AgeCoDe study. Note: The graph shows longitudinal cognitive trajectories of global cognition (MMSE scores) in individuals with/without positive APOE4 status and either low (1 standard deviation below the sample mean) or high (1 standard deviation above the sample mean) values in the occupational cognitive requirements (OCR) score. Detrimental effects of positive APOE4 status on cognitive decline were significantly attenuated for those with high OCR scores (interaction effect OCR*APOE status, p=0.040). Ooccupational cognitive requirements score as a moderator of the cross-sectional association of verbal memory perfomance with hippocampal volume and CSF Abeta42/Tau ratio, respectively. Note: The graphs show cross-sectional associations of left hippocampal volume and CSF Abeta42/Tau ratio with a verbal memory factor score in the DELCODE study sample. Significant (p≤0.05) moderating effects of occupational cognitive requirements (OCR) score in line with the cognitive reserve hypothesis were observed for these associations: Detrimental effects of lower hippocampal volume and more pathological Abeta42/Tau levels were less strong in individuals with higher OCR scores (green line) as compared to those with lower OCR scores (blue line). We observed moderating effects of OCR on the association of genetic risk and AD biomarkers with cognition. These results provide important, novel evidence that OCR contribute to cognitive reserve in late-life. In addition, they validate the recently developed, O*NET based operationalization of this protective factor with data from two independent cohorts.