Cognitive, neuropsychiatric and imaging comparisons between early‐onset and late‐onset Alzheimer’s disease participants from LEADS and ADNI3

Abstract Background The overarching goal of the Longitudinal Early‐onset Alzheimer Disease study (LEADS) is to optimally characterize early‐onset AD (EOAD) and establish an EOAD clinical trials network. Here we report baseline demographic imaging biomarker comparisons LEADS cohort late‐onset (LOAD) subjects from Alzheimer’s Neuroimaging Initiative (ADNI3). Method 123 amyloid‐positive EOAD, 47 amyloid‐negative EOnonAD, 60 cognitively normal young controls were compared 130 LOAD, 110 LOnonAD 286 older controls. To account for effect cognitive aging between EO LO populations, each measure was Z‐transformed. Cortical hippocampal atrophy quantified using W‐scores adjusted age, sex total intracranial volume. Z‐scores t‐test or Wilcoxson rank test as appropriate. All p‐values corrected multiple false discovery rate correction. Result showed greater pathology burden cortical (AD signature) relative LOAD. also impairment across all tests. functional impairment, more depression but less neuropsychiatric behaviors overall LOAD ( Table 1 Figure 1, ps<0.05). Repeating analyses stratified by stage (MCI/dementia) CDR global rating (0.5/1) did not result in any major differences. EOnonAD differed showing on measures There no significant differences amyloid tau burden, these groups. depressed 2 , split Conclusion Consistent with our preexisting hypotheses, perform much worse their counterparts. show pathological expected. reported done chronological rather than disease time (time since onset). Benchmarking individuals along spectrum might prove be a better strategy especially when conducting progression.