TY  - JOUR
JF  - JAMA Neurology
N2  - 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-? 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 Participants: This 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 Measures: The 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-?42 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 A?42 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 decline over time. Plasma p-tau181 level was associated with a decrease of -0.094 MMSE points per year (95% CI, -0.144 to -0.052 MMSE points; P?=?.02), whereas plasma p-tau231 level was associated with an annual decrease of -0.130 MMSE points (95% CI, -0.201 to -0.071 MMSE points; P?=?.02), after adjusting for sex and age. Conclusions and Relevance: This study suggests that plasma p-tau181 and p-tau231 levels may be used as cost-effective and accessible biomarkers to assess cognitive decline in individuals with DLB.
UR  - https://doi.org/10.1001/jamaneurol.2021.4222
N1  - This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.
PB  - American Medical Association
SP  - 32
ID  - discovery10143515
A1  - Gonzalez, Maria C
A1  - Ashton, Nicholas J
A1  - Gomes, Bárbara Fernandes
A1  - Tovar-Rios, Diego Alejandro
A1  - Blanc, Frédéric
A1  - Karikari, Thomas K
A1  - Mollenhauer, Brit
A1  - Pilotto, Andrea
A1  - Lemstra, Afina
A1  - Paquet, Claire
A1  - Abdelnour, Carla
A1  - Kramberger, Milica G
A1  - Bonanni, Laura
A1  - Vandenberghe, Rik
A1  - Hye, Abdul
A1  - Blennow, Kaj
A1  - Zetterberg, Henrik
A1  - Aarsland, Dag
A1  - European?Dementia With Lewy Bodies (E-DLB) Consortium, .
EP  - 37
SN  - 2168-6157
AV  - restricted
VL  - 79
IS  - 1
TI  - Association of Plasma p-tau181 and p-tau231 Concentrations With Cognitive Decline in Patients With Probable Dementia With Lewy Bodies
Y1  - 2021/11/22/
ER  -