Non‐amnestic initial cognitive symptoms have faster trajectories of clinical progression than amnestic symptoms in Alzheimer’s, Lewy body and mixed dementia neuropathologies

Abstract

AbstractBackgroundDiagnostic guidelines currently exist for typical and atypical Alzheimer’s disease (AD). Significant heterogeneity exists among initial predominant clinical symptoms among Lewy body‐related pathology (LRP) in addition to primary AD pathology (ADP) and. However, the clinical relevance of initial amnestic or non‐amnestic cognitive symptoms among them are unclear. Our objective was to determine if initial cognitive symptoms had similar rates of functional decline across ADP, LRP and mixed ADP‐LRP neuropathologies.MethodA retrospective longitudinal cohort study was conducted among 2422 participants with autopsy confirmed ADP, LRP, or mixed ADP‐LRP in the National Alzheimer Coordinating Center database from June 20, 2005, to September 4, 2019. All participants had a Clinical Dementia Rating‐Global (CDR‐G) scale ≤1 at initial clinical visit. The primary outcome of interest was Clinical Dementia Rating‐sum of boxes (CDR‐SB). Linear mixed models adjusted for baseline CDR‐SB, age, sex, education and APOEε4 status were used to evaluate longitudinal outcomes. Multiple imputations using fully conditional specification was performed to account for missing data in the multivariable modelsResult2422 Participants (1187 with ADP, 904 with ADP‐LRP and 331 with LRP) had a mean (SD) interval of 5.5 (2.8) years from initial visit to autopsy. Language symptoms had a consistently faster rate of decline per year than amnestic symptoms across all three pathologies (ADP, β 0.29, [95%CI, 0.16 to 0.41], p<0.001; LRP, β 0.69 [95%CI, 0.44 to 0.94], p<0.001;ADP‐LRP, β 0.40, [95%CI, 0.22 to 0.57], p<0.001). Executive symptoms had a faster rate of decline than amnestic symptoms in ADP, β 0.36, [95%CI, 0.21 to 0.51], p<0.001 and ADP‐LRP, β 0.25 [95%CI, 0.07 to 0.42], p = 0.008. Visuospatial symptoms had a faster rate of decline than amnestic symptoms in ADP‐LRP, β 0.38 [95%CI, 0.12 to 0.65], p = 0.013.ConclusionNon‐amnestic phenotypes have faster trajectories of clinical progression than amnestic across three pathology subgroups. Language phenotypes have the fastest progression.