Differential associations of clinical features with cerebrospinal fluid biomarkers in dementia with Lewy bodies and Alzheimer's disease

Abstract

Aim: To explore associations of cerebrospinal fluid biomarkers of neurodegeneration and amyloidosis with caregiver burden, cognition and functionality in dementia with Lewy bodies (DLB) paired with late-onset Alzheimer's disease (AD) and healthy older people.

Methods: Consecutive outpatients with DLB were matched with outpatients with AD according to sex, cognitive scores and dementia stage, and with cognitively healthy controls according to age and sex to investigate associations of cerebrospinal fluid amyloid-β (Aβ₄₂,Aβ₄₀,Aβ₃₈), tau, phospho-tau Thr₁₈₁, ubiquitin, α-synuclein and neurofilament light with caregiver burden, functionality, reverse digit span, a clock drawing test, Mini-Mental State Examination (MMSE) and Severe MMSE, adjusted for sex, age, education, dementia duration and APOE-ε4 alleles.

Results: Overall, 27 patients with DLB (78.98 ± 9.0 years-old; eleven APOE-ε4 +) were paired with 27 patients with AD (81.50 ± 5.8 years-old; twelve APOE-ε4 +) and 27 controls (78.98 ± 8.7 years-old; four APOE-ε4 +); two-thirds were women. In AD, Aβ₄₂/Aβ₃₈ and Aβ₄₂ were lower, while tau/Aβ₄₂ and phospho-tau Thr₁₈₁/Aβ₄₂ were higher; α-synuclein/Aβ₄₂ was lower in DLB and higher in AD. The following corrected associations remained significant: in DLB, instrumental functionality was inversely associated with tau/phospho-tau Thr₁₈₁ and tau/Aβ₄₂, and reverse digit span associated with α-synuclein; in AD, instrumental functionality was inversely associated with neurofilament light, clock drawing test scores inversely associated with phospho-tau Thr₁₈₁/Aβ₄₂ and α-synuclein/Aβ₄₂, and Severe MMSE inversely associated with tau/Aβ₄₂ and tau/phospho-tau Thr₁₈₁.

Conclusions: Cerebrospinal fluid phospho-tau Thr₁₈₁ in DLB was similar to AD, but not Aβ₄₂. In associations with test scores, biomarker ratios were superior to isolated biomarkers, while worse functionality was associated with axonal degeneration only in AD.

Keywords: Activities of daily living; Alzheimer’s disease; ApoE; Cerebrospinal fluid; Cognitive disorders; Lewy body dementia.