Cerebrovascular and amyloid pathology in predementia stages: The relationship with neurodegeneration and cognitive decline

Research output: Contribution to journalArticle

Abstract

Background: Cerebrovascular disease (CVD) and amyloid-β (Aβ) often coexist, but their influence on neurodegeneration and cognition in predementia stages remains unclear. We investigated the association between CVD and Aβ on neurodegenerative markers and cognition in patients without dementia. Methods: We included 271 memory clinic patients with subjective or objective cognitive deficits but without dementia from the BioBank Alzheimer Center Limburg cohort (n = 99) and the LeARN (n = 50) and DESCRIPA (n = 122) multicenter studies. CSF Aβ1-42 and white matter hyperintensities (WMH) on magnetic resonance imaging (MRI) scans were used as measures of Aβ and CVD, respectively. Individuals were classified into four groups based on the presence (+) or absence (-) of Aβ and WMH. We investigated differences in phosphorylated tau, total tau (t-tau), and medial temporal lobe atrophy (MTA) between groups using general linear models. We examined cognitive decline and progression to dementia using linear mixed models and Cox proportional hazards models. All analyses were adjusted for study and demographics. Results: MTA and t-tau were elevated in the Aβ - WMH+, Aβ + WMH-, and Aβ + WMH+ groups. MTA was most severe in the Aβ + WMH+ group compared with the groups with a single pathology. Both WMH and Aβ were associated with cognitive decline, but having both pathologies simultaneously was not associated with faster decline. Conclusions: In the present study, we found an additive association of Aβ and CVD pathology with baseline MTA but not with cognitive decline. Because our findings may have implications for diagnosis and prognosis of memory clinic patients and for future scientific research, they should be validated in a larger sample with longer follow-up.

Details

Authors
  • Isabelle Bos
  • Frans R. Verhey
  • Inez H.G.B. Ramakers
  • Heidi I.L. Jacobs
  • Hilkka Soininen
  • Yvonne Freund-Levi
  • Harald Hampel
  • Magda Tsolaki
  • Åsa K. Wallin
  • Mark A. Van Buchem
  • Ania Oleksik
  • Marcel M. Verbeek
  • Marcel Olde Rikkert
  • Wiesje M. Van Der Flier
  • Philip Scheltens
  • Pauline Aalten
  • Pieter Jelle Visser
  • Stephanie J.B. Vos
Organisations
External organisations
  • Maastricht University
  • University of Eastern Finland
  • Kuopio University Hospital
  • Karolinska University Hospital
  • Pitié-Salpêtrière University Hospital
  • Pitié Salpetriere University Paris
  • Aristotle University of Thessaloniki
  • Leiden University Medical Centre
  • Radboud University Nijmegen
  • VU University Medical Center
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurology

Keywords

  • Alzheimer's disease, Amyloid, Cerebrospinal fluid, Cerebrovascular disease, Cognition, Medial temporal lobe atrophy, MRI, Neurodegeneration, Tau
Original languageEnglish
Article number101
JournalAlzheimer's Research and Therapy
Volume9
Issue number1
Publication statusPublished - 2017 Dec 29
Publication categoryResearch
Peer-reviewedYes