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Cerebrovascular and amyloid pathology in predementia stages: the relationship with neurodegeneration and cognitive decline
Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, The Netherlands.
Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, The Netherlands.
Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, The Netherlands.
Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, The Netherlands.
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2017 (English)In: Alzheimer's Research & Therapy, E-ISSN 1758-9193, Vol. 9, no 1, article id 101Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
BioMed Central, 2017. Vol. 9, no 1, article id 101
Keywords [en]
Alzheimer’s disease, Amyloid, Cerebrospinal fluid, Cerebrovascular disease, Cognition, MRI, Medial temporal lobe atrophy, Neurodegeneration, Tau
National Category
Neurology
Identifiers
URN: urn:nbn:se:oru:diva-74040DOI: 10.1186/s13195-017-0328-9ISI: 000419007500001PubMedID: 29284531Scopus ID: 2-s2.0-85039756986OAI: oai:DiVA.org:oru-74040DiVA, id: diva2:1313787
Funder
EU, FP7, Seventh Framework Programme
Note

Funding agencies:

European Medical Information Framework Alzheimer’s disease (EMIF-AD) project - Innovative Medicines Initiative under EMIF

European Federation of Pharmaceutical Industries and Associations (EFPIA)

Center for Translational Molecular Medicine

European Commission, 5th framework program

Available from: 2019-05-06 Created: 2019-05-06 Last updated: 2019-06-18Bibliographically approved

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Freund-Levi, Yvonne

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