Plasma Amyloid-β Levels, Cerebral Small Vessel Disease, and Cognition: The Rotterdam Study

Article type: Research Article

Authors: Hilal, Saima^{a; b} | Akoudad, Saloua^{a; b; c} | van Duijn, Cornelia M.^d | Niessen, Wiro J.^e | Verbeek, Marcel M.^f | Vanderstichele, Hugo^g | Stoops, Erik^g | Ikram, M. Arfan^{a; b; c} | Vernooij, Meike W.^{a; b; *}

Affiliations: [a] Department of Radiology and Nuclear Medicine, Erasmus Medical Center, Rotterdam, The Netherlands | [b] Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands | [c] Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands | [d] Genetic Epidemiology Unit, Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands | [e] Departments of Radiology Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands | [f] Department of Neurology and Laboratory Medicine, Donders Institute for Brain, Cognition and Behaviour, Radboud Alzheimer Centre, Radboud University Medical Center, Nijmegen, The Netherlands | [g] ADx Neuro Sciences, Gent, Belgium

Correspondence: [*] Correspondence to: Meike W. Vernooij, MD, PhD, Erasmus Medical Center, office 2505, Wytemaweg 80, 3015 CNRotterdam, The Netherlands. Tel.: +31 10 703 09 44; E-mail: [email protected].

Abstract: Background:Plasma amyloid-β (Aβ) levels are increasingly studied as a potential, accessible marker of cognitive impairment and dementia. The most common plasma Aβ isoforms, i.e., Aβ1-40 and Aβ1-42 have been linked with risk of Alzheimer’s disease. However, it remains under-explored whether plasma Aβ levels including novel Aβ1-38 relate to vascular brain disease and cognition in a preclinical-phase of dementia Objective:To examine the association of plasma Aβ levels (i.e., Aβ1-38, Aβ1-40, and Aβ1-42) with markers of cerebral small vessel disease (SVD) and cognition in a large population-based setting. Methods:We analyzed plasma Aβ1 levels in 1201 subjects from two independent cohorts of the Rotterdam Study. Markers of SVD [lacunes, white matter hyperintensity (WMH) volume] were assessed on brain MRI (1.5T). Cognition was assessed by a detailed neuropsychological battery. In each cohort, the association of Aβ levels with SVD and cognition was performed using regression models. Estimates were then pooled across cohorts using inverse variance meta-analysis with fixed effects. Results:Higher levels of plasma Aβ1-38, Aβ1-40, Aβ1-42, and Aβ1-40/ Aβ1-42 ratio were associated with increasing lacunar and microbleeds counts. Moreover, higher levels of Aβ1-40 and Aβ1-40/ Aβ1-42 were significantly associated with larger WMH volumes. With regard to cognition, a higher level of Aβ1-38 Aβ1-40 and Aβ1-40/ Aβ1-42 was related to worse performance on cognitive test specifically in memory domain. Conclusion:Higher plasma levels of Aβ levels are associated with subclinical markers of vascular disease and poorer memory. Plasma Aβ levels thus mark the presence of vascular brain pathology.

Keywords: Cerebral small vessel disease, cognition, magnetic resonance imaging, plasma amyloid-β levels, population-based

DOI: 10.3233/JAD-170458

Journal: Journal of Alzheimer's Disease, vol. 60, no. 3, pp. 977-987, 2017