학술논문
Vascular risk burden is a key player in the early progression of Alzheimer's disease
Document Type
Author
Ferrari-Souza, Joao Pedro; Scheeren Brum, Wagner, 1997; Hauschild, Lucas A.; Da Ros, Lucas U.; Ferreira, Pamela C. L.; Bellaver, Bruna; Leffa, Douglas T.; Bieger, Andrei; Tissot, Cecile; Lussier, Firoza Z.; De Bastiani, Marco Antonio; Povala, Guilherme; Lessa Benedet, Andréa; Therriault, Joseph; Wang, Yi-Ting; Ashton, Nicholas J.; Zetterberg, Henrik, 1973; Blennow, Kaj, 1958; Martins, Sheila O.; Souza, Diogo O.; Rosa-Neto, Pedro; Karikari, Thomas; Pascoal, Tharick A.; Zimmer, Eduardo R.
Source
NEUROBIOLOGY OF AGING. 136:88-98
Subject
Language
English
ISSN
0197-4580
1558-1497
1558-1497
Abstract
Understanding whether vascular risk factors (VRFs) synergistically potentiate Alzheimer's disease (AD) progression is important in the context of emerging treatments for preclinical AD. In a group of 503 cognitively unimpaired individuals, we tested whether VRF burden interacts with AD pathophysiology to accelerate neurodegeneration and cognitive decline. Baseline VRF burden was calculated considering medical data and AD pathophysiology was assessed based on cerebrospinal fluid (CSF) amyloid-beta 1-42 (A beta 1-42) and tau phosphorylated at threonine 181 (p-tau181). Neurodegeneration was assessed with plasma neurofilament light (NfL) and global cognition with the modified version of the Preclinical Alzheimer's Cognitive Composite. The mean (SD) age of participants was 72.9 (6.1) years, and 220 (43.7%) were men. Linear mixed-effects models revealed that an elevated VRF burden synergistically interacted with AD pathophysiology to drive longitudinal plasma NfL increase and cognitive decline. Additionally, VRF burden was not associated with CSF A beta 1-42or p-tau181 changes over time. Our results suggest that VRF burden and AD pathophysiology are independent processes; however, they synergistically lead to neurodegeneration and cognitive deterioration. In preclinical stages, the combination of therapies targeting VRFs and AD pathophysiology might potentiate treatment outcomes.