Saima Hilal1,2, Saloua Akoudad1,2,3, Cornelia M van Duijn4, Wiro J Niessen5, Marcel M Verbeek6, Hugo Vanderstichele7, Erik Stoops7, M Arfan Ikram1,2,3, Meike W Vernooij1,2. 1. Department of Radiology and Nuclear Medicine, Erasmus Medical Center, Rotterdam, The Netherlands. 2. Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands. 3. Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands. 4. Genetic Epidemiology Unit, Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands. 5. Departments of Radiology Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands. 6. Department of Neurology and Laboratory Medicine, Donders Institute for Brain, Cognition and Behaviour, Radboud Alzheimer Centre, Radboud University Medical Center, Nijmegen, The Netherlands. 7. ADx Neuro Sciences, Gent, Belgium.
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 dementiaObjective: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.
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 dementiaObjective: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.
Entities:
Keywords:
Cerebral small vessel disease; cognition; magnetic resonance imaging; plasma amyloid-β levels; population-based
Authors: Nira Cedres; Daniel Ferreira; Milan Nemy; Alejandra Machado; Joana B Pereira; Sara Shams; Lars-Olof Wahlund; Anna Zettergren; Olga Stepankova; Lenka Vyslouzilova; Maria Eriksdotter; Stefan Teipel; Michel J Grothe; Kaj Blennow; Henrik Zetterberg; Michael Schöll; Silke Kern; Ingmar Skoog; Eric Westman Journal: Neurology Date: 2022-08-02 Impact factor: 11.800
Authors: Nicholas M Pajewski; Fanny M Elahi; Manjula Kurella Tamura; Jason D Hinman; Ilya M Nasrallah; Joachim H Ix; Lindsay M Miller; Lenore J Launer; Clinton B Wright; Mark A Supiano; Alan J Lerner; Tiffany L Sudduth; Anthony A Killeen; Alfred K Cheung; David M Reboussin; Donna M Wilcock; Jeff D Williamson Journal: Alzheimers Dement Date: 2021-11-17 Impact factor: 16.655
Authors: Stuart J McCarter; Timothy G Lesnick; Val J Lowe; Alejandro A Rabinstein; Scott A Przybelski; Alicia Algeciras-Schimnich; Vijay K Ramanan; Clifford R Jack; Ronald C Petersen; David S Knopman; Bradley F Boeve; Kejal Kantarci; Prashanthi Vemuri; Michelle M Mielke; Jonathan Graff-Radford Journal: J Alzheimers Dis Date: 2022 Impact factor: 4.160
Authors: Harald Hampel; Sid E O'Bryant; José L Molinuevo; Henrik Zetterberg; Colin L Masters; Simone Lista; Steven J Kiddle; Richard Batrla; Kaj Blennow Journal: Nat Rev Neurol Date: 2018-11 Impact factor: 42.937
Authors: Oscar L Lopez; William E Klunk; Chester A Mathis; Beth E Snitz; Yuefang Chang; Russell P Tracy; Lewis H Kuller Journal: Brain Commun Date: 2019-11-27
Authors: Saima Hilal; Frank J Wolters; Marcel M Verbeek; Hugo Vanderstichele; M Kamran Ikram; Erik Stoops; M Arfan Ikram; Meike W Vernooij Journal: Alzheimers Res Ther Date: 2018-06-30 Impact factor: 6.982