H - 06 Associations between Non-verbal Reasoning Abilities and Brain Pathology in a Colombian Cohort with Autosomal Dominant Alzheimer’s Disease

Declines in non-verbal reasoning abilities have been linked to Alzheimer's disease (ad) progression. Individuals with autosomal dominant ad (ADAD) are genetically determined to develop early-onset dementia. We examined the relation between non-verbal reasoning abilities and brain pathology in a Colombian cohort with ADAD due to the Presenilin-1 (PSEN1) E280A mutation.A total of 25 carriers of the PSEN1 E280A mutation (16 cognitively-unimpaired carriers [x- age = 35.25 +/- 4.04]; 9 with mildly impaired (age = 45.56 +/- 2.60), and 27 non-carriers (age = 36.11 +/- 5.59) were included. A summary non-verbal reasoning score was calculated from performance on the Judgment of Line Orientation and the Spanish WAIS-IV Matrix Reasoning and Visual Puzzles subtests. Participants also completed the Mini-mental State Examination (MMSE) and underwent amyloid and tau PET imaging. Mann-Whitney U test and education-adjusted Spearman partial correlations were used to examine group differences and associations between pathology levels and non-verbal reasoning.Compared to carriers, non-carriers had higher MMSE and non-verbal reasoning scores (p = 0.006). In carriers only, lower non-verbal reasoning was associated with greater mean cortical amyloid (r = -0.427, p = 0.037) and greater precuneus tau (r = -0.516, p = 0.010). No significant associations were observed after excluding the impaired carriers from the analyses.Our findings suggest that changes in non-verbal reasoning abilities are evident in early symptomatic ADAD stages and are related to ad brain pathology. Future longitudinal work is needed to characterize the progression of non-verbal reasoning deficits in ADAD. Future research should also examine performance between older adults and people at risk for sporadic ad.