Fluid Biomarkers of Motor and Non-Motor Experiences of Daily Living in Dementia with Lewy Bodies and Alzheimer’s Disease

Background: Associations of cerebrospinal fluid biomarkers with sleep, functionality and the MDS-UPDRS in dementia with Lewy bodies (DLB) and late-onset Alzheimer’s disease (AD) help elucidate their pathophysiological underpinnings. Methods: Consecutive outpatients with DLB and AD were matched by sex, cognitive scores and dementia stage, along with cognitively healthy controls matched by age and sex to investigate associations of cerebrospinal fluid amyloid- β (A β 42 ,A β 40 ,A β 38 ), tau , phospho- tau Thr 181 , ubiquitin, α -synuclein and neurofilament light (NfL) with sleep duration, Schwab & England scale and MDS-UPDRS, adjusted for sex, age and APOE - ϵ 4 alleles. Results: Patients with DLB ( APOE - ϵ 4+: n =11, 76.64±9.0years; APOE - ϵ 4-: n =16, 79.75±9.0years) were paired with patients with AD ( APOE - ϵ 4+: n =12, 80.17±5.7years; APOE - ϵ 4-: n =15, 81.67±5.9years) and controls ( APOE - ϵ 4+: n =4, 82.00±6.4years; APOE - ϵ 4-: n =23, 77.87±9.0years); two-thirds were women. APOE - ϵ 4 carriers with dementia had more amyloidosis, higher phospho- tau Thr 181 /A β 42 and α-synuclein/A β 42 . In DLB, APOE - ϵ 4 non-carriers had lower Schwab & England scores and higher MDS-UPDRS-I&II scores, lower tau /phospho- tau Thr 181 and higher ubiquitin and NfL than APOE - ϵ 4 carriers. In controls, APOE - ϵ 4 non-carriers had lower A β 42 and A β 42 /A β 38 , higher phospho- tau Thr 181 /A β 42 and α-synuclein/A β 42 than APOE - ϵ 4 carriers. In DLB, sleep duration was associated with A β 38 and α -synuclein and inversely associated with tau /phospho- tau Thr 181 and tau /ubiquitin; Schwab & England scores were associated with tau /ubiquitin and inversely associated with tau /phospho- tau Thr 181 ; MDS-UPDRS-I&II was associated with A β 42 /A β 38 ; MDS-UPDRS-III was associated with tau /phospho- tau Thr 181 ; MDS-UPDRS-V ON was associated with A β 42 and A β 42 /A β 40 , and MDS-UPDRS-V OFF was associated with A β 42 , A β 42 /A β 40 and A β 42 /A β 38 . In AD, MDS-UPDRS-III was associated with ubiquitin. Conclusion: Biomarker ratios were superior to isolated biomarkers in associations with motor and non-motor experiences in DLB, though not so prominently in AD due to less motor impairment.