for the European-Dementia With Lewy Bodies (E-DLB) Consortium IMPORTANCE Plasma phosphorylated tau (p-tau) has proven to be an accurate biomarker for Alzheimer disease (AD) pathologic characteristics, offering a less expensive and less invasive alternative to cerebrospinal fluid (CSF) and positron emission tomography biomarkers for amyloid-β and tau. Alzheimer disease comorbid pathologic characteristics are common and are associated with more rapid cognitive decline in patients with dementia with Lewy bodies (DLB); therefore, it is anticipated that plasma p-tau concentrations may have utility in assessing cognitive impairment in individuals with this disorder. OBJECTIVE To measure the concentrations of plasma p-tau (p-tau181 and p-tau231) and evaluate their associations with cognitive decline in individuals with probable DLB.
DESIGN, SETTING, AND PARTICIPANTSThis multicenter longitudinal cohort study included participants from the European-DLB (E-DLB) Consortium cohort enrolled at 10 centers with harmonized diagnostic procedures from January 1, 2002, to December 31, 2020, with up to 5 years of follow-up. A total of 1122 participants with plasma samples were available. Participants with acute delirium or terminal illness and patients with other previous major psychiatric or neurologic disorders were excluded, leaving a cohort of 987 clinically diagnosed participants with probable DLB (n = 371), Parkinson disease (n = 204), AD (n = 207), as well as healthy controls (HCs) (n = 205).
MAIN OUTCOMES AND MEASURESThe main outcome was plasma p-tau181 and p-tau231 levels measured with in-house single molecule array assays. The Mini-Mental State Examination (MMSE) was used to measure cognition. RESULTS Among this cohort of 987 patients (512 men [51.9%]; mean [SD] age, 70.0 [8.8] years), patients with DLB did not differ significantly regarding age, sex, or years of education from those in the AD group, but the DLB group was older than the HC group and included more men than the AD and HC groups. Baseline concentrations of plasma p-tau181 and p-tau231 in patients with DLB were significantly higher than those in the HC group but lower than in the AD group and similar to the Parkinson disease group. Higher plasma concentrations of both p-tau markers were found in a subgroup of patients with DLB with abnormal CSF amyloid-β42 levels compared with those with normal levels (difference in the groups in p-tau181, −3.61 pg/mL; 95% CI, −5.43 to −1.79 pg/mL; P = .049; difference in the groups in p-tau231, −2.51 pg/mL; 95% CI, −3.63 to −1.39 pg/mL; P = .02). There was no difference between p-tau181 level and p-tau231 level across confirmed AD pathologic characteristcs based on reduced Aβ42 level in CSF in individuals with DLB. In DLB, a significant association was found between higher plasma p-tau181 and p-tau231 levels and lower MMSE scores at baseline (for p-tau181, −0.092 MMSE points; 95% CI, −0.12 to −0.06 MMSE points; P = .001; for p-tau231, −0.16 MMSE points; 95% CI, −0.21 to −0.12 MMSE points; P < .001), as well as more rapid MMSE...