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

Abstract

BackgroundThe 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 the baseline demographic and imaging biomarker comparisons of the LEADS cohort to late- onset AD (LOAD) subjects from the Alzheimer- s Disease Neuroimaging Initiative (ADNI3).Method123 amyloid- positive EOAD, 47 amyloid- negative EOnonAD, 60 cognitively normal young controls were compared to 130 amyloid- positive LOAD, 110 amyloid- negative LOnonAD and 286 amyloid- negative cognitively normal older controls. To account for the effect of cognitive aging between EO and LO populations, each cognitive measure was Z- transformed. Cortical and hippocampal atrophy were quantified using W- scores adjusted for age, sex and total intracranial volume. Z- scores and W- scores were compared using t- test or Wilcoxson rank test as appropriate. All p- values were corrected for multiple comparisons using the false discovery rate correction.ResultEOAD showed greater pathology burden and greater cortical atrophy (AD signature) relative to LOAD. EOAD also showed greater cognitive impairment across all cognitive tests. EOAD showed greater functional impairment, more depression but less neuropsychiatric behaviors overall compared to LOAD (Table 1 and Figure 1, all ps<0.05). Repeating the analyses stratified by cognitive stage (MCI/dementia) or CDR global rating (0.5/1) did not result in any major differences.EOnonAD differed from LOnonAD by also showing greater impairment on all cognitive and functional measures There were no significant differences in amyloid and tau burden, or atrophy W- scores between these groups. EOnonAD were more depressed and showed more functional impairment compared to LOnonAD (Table 2 and Figure 2, all ps<0.05). Repeating the analyses split by cognitive stage (MCI/dementia) or CDR global rating (0.5/1) did not result in any major differences.ConclusionConsistent with our preexisting hypotheses, EOAD and EOnonAD perform much worse relative to their LO counterparts. EOAD also show greater pathological burden as expected. The reported analyses were done in chronological rather than disease time (time since disease onset). Benchmarking individuals along the disease spectrum might prove to be a better strategy especially when conducting analyses on rate of disease progression.