Rate of clinical progression in mixed Limbic‐Predominant Age‐Related TDP‐43 Encephalopathy (LATE) and Alzheimer disease

Abstract

AbstractBackgroundLimbic predominant age‐related encephalopathy neuropathologic change (LATE‐NC) is associated with amnestic type dementia. LATE‐NC frequently coexists with Alzheimer disease neuropathologic change (ADNC). It is unclear whether LATE and Alzheimer disease neuropathologic change interact or independently affect clinical disease progression.MethodsData was from 80 autopsied participants with TDP‐43 immunohistochemical studies from the Wisconsin Alzheimer’s Disease Research Center and Wisconsin Registry for Alzheimer’s Prevention. We used linear mixed effects models to estimate associations of ADNC and LATE‐NC with rate of progression of Clinical Dementia Rating Sum of Boxes (CDR‐SB) and investigated whether co‐occurrence of these two pathologies would modify these trends.ResultsParticipants in our sample were 42% female with mean age at death of 77.8 years (SD 9.6). Neuropathologic diagnoses were low/intermediate ADNC in 20 (25%), high ADNC in 29 (36%), LATE‐NC in 8 (10%), and LATE‐NC + high ADNC in 23 (29%) participants. Clinical progression of cognitive impairment was faster in participants with high ADNC than in those LATE‐NC (Slopes:1.82 units/year [95% CI: 0.93‐2.71] vs 1.33 units/year [95% CI: 0.29‐2.38]) (Figure). Co‐occurrence of LATE‐NC + high ADNC predicted similar progression than high ADNC alone (Slope: 1.83 units/year [95% CI: ‐0.45 – 4.12]) demonstrating interaction (p = 0.013) between LATE‐NC and high ADNC.ConclusionLATE‐NC and ADNC are independently associated with clinical progression of cognitive impairment. Co‐occurrence of LATE‐NC and high ADNC is expected to have similar clinical progression than ADNC alone. Research is ongoing to examine differences among these groups using T1‐weighted volumetric imaging and CSF glial activation biomarkers.