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

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 (Aβ 42 ,Aβ 40 ,Aβ 38 ), tau , phospho- tau Thr 181 , 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, Aβ 42 /Aβ 38 and Aβ 42 were lower, while tau /Aβ 42 and phospho- tau Thr 181 /Aβ 42 were higher; α-synuclein/Aβ 42 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 Thr 181 and tau /Aβ 42 , 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 Thr 181 /Aβ 42 and α-synuclein/Aβ 42 , and Severe MMSE inversely associated with tau /Aβ 42 and tau /phospho- tau Thr 181 . Conclusions Cerebrospinal fluid phospho- tau Thr 181 in DLB was similar to AD, but not Aβ 42 . In associations with test scores, biomarker ratios were superior to isolated biomarkers, while worse functionality was associated with axonal degeneration only in AD.