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 (Aβ42,Aβ40,Aβ38), tau, phospho-tauThr181, ubiquitin, α-synuclein and neurofilament light (NfL) with sleep duration, Schwab & England scale and MDS-UPDRS, adjusted for sex, age and APOE-ϵ4 alleles. RESULTS: Patients with DLB (APOE-ϵ4+:n=11, 76.64±9.0years; APOE-ϵ4-:n=16, 79.75±9.0years) were paired with patients with AD (APOE-ϵ4+:n=12, 80.17±5.7years; APOE-ϵ4-:n=15, 81.67±5.9years) and controls (APOE-ϵ4+:n=4, 82.00±6.4years; APOE-ϵ4-:n=23, 77.87±9.0years); two-thirds were women. APOE-ϵ4 carriers with dementia had more amyloidosis, higher phospho-tauThr181/Aβ42 and α-synuclein/Aβ42. In DLB, APOE-ϵ4 non-carriers had lower Schwab & England scores and higher MDS-UPDRS-I&II scores, lower tau/phospho-tauThr181 and higher ubiquitin and NfL than APOE-ϵ4 carriers. In controls, APOE-ϵ4 non-carriers had lower Aβ42 and Aβ42/Aβ38, higher phospho-tauThr181/Aβ42 and α-synuclein/Aβ42 than APOE-ϵ4 carriers. In DLB, sleep duration was associated with Aβ38 and α-synuclein and inversely associated with tau/phospho-tauThr181 and tau/ubiquitin; Schwab & England scores were associated with tau/ubiquitin and inversely associated with tau/phospho-tauThr181; MDS-UPDRS-I&II was associated with Aβ42/Aβ38; MDS-UPDRS-III was associated with tau/phospho-tauThr181; MDS-UPDRS-V ON was associated with Aβ42 and Aβ42/Aβ40, and MDS-UPDRS-V OFF was associated with Aβ42, Aβ42/Aβ40 and Aβ42/Aβ38. 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.