P1‐525: amyloid aggregation is associated with decline on digit span backward in cognitively normal elderly monozygotic twins

In cognitively normal subjects, amyloid pathology may be associated with future cognitive decline. Aim of this study is to examine the role of genetic and environmental influences on the association between amyloid aggregation and cognitive decline using a monozygotic twin approach. Monozygotic twin-pairs share 100% of their genetic material and part of their early life exposures. Similarities within these twin-pairs are therefore related to genetic and/or shared environmental influences, whereas differences can only be explained by environmental exposures that are not shared within twin-pairs. We included 68 monozygotic twin-pairs and 2 singletons (n=138) from the EMIF-AD PreclinAD study (58% female, age=69.3±7.7, years of education=11.3±2.5, mean follow-up=23±2.8 months). We tested the relation between the baseline cerebrospinal fluid amyloid beta 1-42/1-40 (Aβ42/40) ratio (lower score indicates more abnormality, ADx Neurosciences/Euroimmun assay) with change in cognitive performance for tests of memory, attention, executive function and language. Data were analyzed using generalized estimating equations corrected for twin status, follow-up duration, age, sex and education. Cross-twin cross-trait and monozygotic twin difference analyses were performed to examine the role of genetic and environmental influences on the association between Aβ42/40 ratio and cognitive decline. At baseline a lower Aβ42/40 ratio was associated with lower visual memory and letter fluency scores (table 1). A lower Aβ42/40 ratio at baseline was associated with decline on the Digit Span Backwards (p<0.001, figure 1) and tended to be associated with decline in verbal memory (p=0.09). Cross-twin cross-trait analysis showed that the baseline Aβ42/40 ratio measured in one twin could predict decline on Digit Span Backwards in its co-twin (r=0.25, p=0.017). Differences within pairs in baseline Aβ42/40 ratio did not correlate with differences in change on Digit Span Backwards within pairs (p=0.80). Association baseline CSF Aβ42/40 ratio and Digit Span Backwards. Amyloid aggregation was associated with longitudinal decline on the Digit Span Backwards. The monozygotic twin analyses suggest that this association resulted from a shared underlying etiology, due to shared genetic and/or shared environmental factors. Our study provides further support for the relation between amyloid aggregation and impaired cognitive performance in cognitively normal individuals.