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

Bos, Isabelle; Verhey, Frans R.; Ramakers, Inez H.G.B.; Jacobs, Heidi I.L.; Soininen, Hilkka; Freund-Levi, Yvonne; Hampel, Harald; Tsolaki, Magda; Wallin, Åsa K. LU and Van Buchem, Mark A., et al. (2017) In Alzheimer's Research and Therapy 9(1).
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... (More)

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.

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keywords
Alzheimer's disease, Amyloid, Cerebrospinal fluid, Cerebrovascular disease, Cognition, Medial temporal lobe atrophy, MRI, Neurodegeneration, Tau
in
Alzheimer's Research and Therapy
volume
9
issue
1
publisher
BioMed Central
external identifiers
  • scopus:85039756986
ISSN
1758-9193
DOI
10.1186/s13195-017-0328-9
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English
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yes
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eb91f57d-3c7e-4881-8ed8-cdb9505f781a
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2018-01-22 15:20:00
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2018-07-05 12:38:32
@article{eb91f57d-3c7e-4881-8ed8-cdb9505f781a,
  abstract     = {<p>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 Aβ<sub>1-42</sub> 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.</p>},
  articleno    = {101},
  author       = {Bos, Isabelle and Verhey, Frans R. and Ramakers, Inez H.G.B. and Jacobs, Heidi I.L. and Soininen, Hilkka and Freund-Levi, Yvonne and Hampel, Harald and Tsolaki, Magda and Wallin, Åsa K. and Van Buchem, Mark A. and Oleksik, Ania and Verbeek, Marcel M. and Olde Rikkert, Marcel and Van Der Flier, Wiesje M. and Scheltens, Philip and Aalten, Pauline and Visser, Pieter Jelle and Vos, Stephanie J.B.},
  issn         = {1758-9193},
  keyword      = {Alzheimer's disease,Amyloid,Cerebrospinal fluid,Cerebrovascular disease,Cognition,Medial temporal lobe atrophy,MRI,Neurodegeneration,Tau},
  language     = {eng},
  month        = {12},
  number       = {1},
  publisher    = {BioMed Central},
  series       = {Alzheimer's Research and Therapy},
  title        = {Cerebrovascular and amyloid pathology in predementia stages : The relationship with neurodegeneration and cognitive decline},
  url          = {http://dx.doi.org/10.1186/s13195-017-0328-9},
  volume       = {9},
  year         = {2017},
}