To study associations of cerebrospinal fluid biomarkers with cognition and functionality in dementia with Lewy bodies (DLB) compared with Alzheimer’s dementia (AD) and cognitively healthy people.

Amyloidosis and neurodegeneration may correlate with cognition and functionality, reflecting degrees of neuropathology in dementia.

Consecutive outpatients with probable DLB (fourth consensus report of the DLB Consortium) were paired with outpatients with late-onset AD (NIA-AA criteria) by sex, Clinical Dementia Rating and Mini-Mental State Examination (MMSE) scores, and with healthy controls by sex and age to investigate associations of APOE-ε4-mediated cerebrospinal fluid concentrations of amyloid-β₄₂, amyloid-β₄₀, amyloid-β₃₈, tau, phospho-tau Thr₁₈₁, α-synuclein, ubiquitin and NfL with cognition and functionality. Genotyping for rs7412&rs429358 was undertaken with TaqMan® Real-Time PCR technology. Biomarkers were measured by enzyme-linked immunosorbent assays and correlated with scores on a clock drawing test, MMSE, Severe MMSE, digit span (forward&backward), the Index of Independence in Activities of Daily Living and Lawton’s Scale for Instrumental Activities of Daily Living. A linear model with post-hoc Bonferroni test was employed for clinical-biomarker associations adjusted for sex, schooling, age, length of dementia and number of APOE-ε4 alleles.

Overall, 27 patients with DLB (78.48±9.0years-old, eleven APOE-ε4+) were paired with 27 patients with AD (81.00±5.8years-old, twelve APOE-ε4+) and 27 controls (78.48±8.7years-old, four APOE-ε4+); two thirds were women. APOE-ε4 carrier status influenced biomarkers of amyloidosis, tau pathology and axonal degeneration in dementia. In DLB, digit span backward associated with amyloid-β₄₀ (p=0.041) and α-synuclein (p=0.002), instrumental activities of daily living inversely associated with tau (p=0.021) and the tau/phospho-tau ratio (p<0.001), and the Severe MMSE inversely associated with the tau/phospho-tau ratio (p=0.014). In AD, clock drawing test scores associated with amyloid-β₄₂ (p=0.044) and instrumental activities of daily living inversely associated with NfL (p=0.003).

Amyloidosis and neurodegeneration are modulated by APOE-ε4 carrier status and may differentially affect cognitive and functional phenotypes in dementia syndromes.