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

Isabelle Bos; Frans R. Verhey; Inez H. G. B. Ramakers; Heidi I. L. Jacobs; Hilkka Soininen; Yvonne Freund-Levi; Harald Hampel; Magda Tsolaki; Asa 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

doi:10.1186/s13195-017-0328-9

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

Isabelle Bos^*, Frans R. Verhey, Inez H. G. B. Ramakers, Heidi I. L. Jacobs, Hilkka Soininen, Yvonne Freund-Levi, Harald Hampel, Magda Tsolaki, Asa 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

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background: Cerebrovascular disease (CVD) and amyloid-beta (A beta) often coexist, but their influence on neurodegeneration and cognition in predementia stages remains unclear. We investigated the association between CVD and A beta 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 A beta(1-42) and white matter hyperintensities (WMH) on magnetic resonance imaging (MRI) scans were used as measures of A beta and CVD, respectively. Individuals were classified into four groups based on the presence (+) or absence (-) of A beta 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 A beta - WMH+, A beta + WMH-, and A beta + WMH+ groups. MTA was most severe in the A beta + WMH + group compared with the groups with a single pathology. Both WMH and A beta 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 A beta 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.

Original language	English
Article number	101
Number of pages	10
Journal	Alzheimer's Research & Therapy
Volume	9
DOIs	https://doi.org/10.1186/s13195-017-0328-9
Publication status	Published - 29 Dec 2017

Keywords

Amyloid
Cerebrovascular disease
Alzheimer's disease
Cognition
Neurodegeneration
Medial temporal lobe atrophy
Tau
Cerebrospinal fluid
MRI
TEMPORAL-LOBE ATROPHY
WHITE-MATTER HYPERINTENSITIES
ALZHEIMERS-DISEASE
CEREBROSPINAL-FLUID
INTERNATIONAL WORKSHOP
DIAGNOSTIC-CRITERIA
VASCULAR DEMENTIA
TOTAL TAU
IMPAIRMENT

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1 Erratum / corrigendum / retractions

Correction to: Cerebrovascular and amyloid pathology in predementia stages: the relationship with neurodegeneration and cognitive decline (vol 9, 101, 2017)
Bos, I., Verhey, F. R., Ramakers, I. H. G. B., Jacobs, H. I. L., Soininen, H., Freund-Levi, Y., Hampel, H., Tsolaki, M., Wallin, A. K., van Buchem, M. A., Oleksik, A., Verbeek, M. M., Rikkert, M. O., van der Flier, W. M., Scheltens, P., Aalten, P., Visser, P. J. & Vos, S. J. B., 20 Jun 2018, In: Alzheimer's Research & Therapy. 10, 3 p., 56.
Research output: Contribution to journal › Erratum / corrigendum / retractions › Academic

Open Access

Cite this

Bos, I., Verhey, F. R., Ramakers, I. H. G. B., Jacobs, H. I. L., Soininen, H., Freund-Levi, Y., Hampel, H., Tsolaki, M., Wallin, A. K., van Buchem, M. A., Oleksik, A., Verbeek, M. M., Rikkert, M. O., van der Flier, W. M., Scheltens, P., Aalten, P., Visser, P. J., & Vos, S. J. B. (2017). Cerebrovascular and amyloid pathology in predementia stages: the relationship with neurodegeneration and cognitive decline. Alzheimer's Research & Therapy, 9, Article 101. https://doi.org/10.1186/s13195-017-0328-9

@article{8f654846e98244a18b722e68a309bab6,

title = "Cerebrovascular and amyloid pathology in predementia stages: the relationship with neurodegeneration and cognitive decline",

abstract = "Background: Cerebrovascular disease (CVD) and amyloid-beta (A beta) often coexist, but their influence on neurodegeneration and cognition in predementia stages remains unclear. We investigated the association between CVD and A beta 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 A beta(1-42) and white matter hyperintensities (WMH) on magnetic resonance imaging (MRI) scans were used as measures of A beta and CVD, respectively. Individuals were classified into four groups based on the presence (+) or absence (-) of A beta 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 A beta - WMH+, A beta + WMH-, and A beta + WMH+ groups. MTA was most severe in the A beta + WMH + group compared with the groups with a single pathology. Both WMH and A beta 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 A beta 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.",

keywords = "Amyloid, Cerebrovascular disease, Alzheimer's disease, Cognition, Neurodegeneration, Medial temporal lobe atrophy, Tau, Cerebrospinal fluid, MRI, TEMPORAL-LOBE ATROPHY, WHITE-MATTER HYPERINTENSITIES, ALZHEIMERS-DISEASE, CEREBROSPINAL-FLUID, INTERNATIONAL WORKSHOP, DIAGNOSTIC-CRITERIA, VASCULAR DEMENTIA, TOTAL TAU, IMPAIRMENT",

author = "Isabelle Bos and Verhey, {Frans R.} and Ramakers, {Inez H. G. B.} and Jacobs, {Heidi I. L.} and Hilkka Soininen and Yvonne Freund-Levi and Harald Hampel and Magda Tsolaki and Wallin, {Asa K.} and {van Buchem}, {Mark A.} and Ania Oleksik and Verbeek, {Marcel M.} and Rikkert, {Marcel Olde} and {van der Flier}, {Wiesje M.} and Philip Scheltens and Pauline Aalten and Visser, {Pieter Jelle} and Vos, {Stephanie J. B.}",

year = "2017",

month = dec,

day = "29",

doi = "10.1186/s13195-017-0328-9",

language = "English",

volume = "9",

journal = "Alzheimer's Research & Therapy",

issn = "1758-9193",

publisher = "BioMed Central Ltd",

}

Bos, I, Verhey, FR , Ramakers, IHGB , Jacobs, HIL, Soininen, H, Freund-Levi, Y, Hampel, H, Tsolaki, M, Wallin, AK, van Buchem, MA, Oleksik, A, Verbeek, MM, Rikkert, MO, van der Flier, WM, Scheltens, P, Aalten, P, Visser, PJ & Vos, SJB 2017, 'Cerebrovascular and amyloid pathology in predementia stages: the relationship with neurodegeneration and cognitive decline', Alzheimer's Research & Therapy, vol. 9, 101. https://doi.org/10.1186/s13195-017-0328-9

TY - JOUR

T1 - Cerebrovascular and amyloid pathology in predementia stages

T2 - the relationship with neurodegeneration and cognitive decline

AU - Bos, Isabelle

AU - Verhey, Frans R.

AU - Ramakers, Inez H. G. B.

AU - Jacobs, Heidi I. L.

AU - Soininen, Hilkka

AU - Freund-Levi, Yvonne

AU - Hampel, Harald

AU - Tsolaki, Magda

AU - Wallin, Asa K.

AU - van Buchem, Mark A.

AU - Oleksik, Ania

AU - Verbeek, Marcel M.

AU - Rikkert, Marcel Olde

AU - van der Flier, Wiesje M.

AU - Scheltens, Philip

AU - Aalten, Pauline

AU - Visser, Pieter Jelle

AU - Vos, Stephanie J. B.

PY - 2017/12/29

Y1 - 2017/12/29

N2 - Background: Cerebrovascular disease (CVD) and amyloid-beta (A beta) often coexist, but their influence on neurodegeneration and cognition in predementia stages remains unclear. We investigated the association between CVD and A beta 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 A beta(1-42) and white matter hyperintensities (WMH) on magnetic resonance imaging (MRI) scans were used as measures of A beta and CVD, respectively. Individuals were classified into four groups based on the presence (+) or absence (-) of A beta 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 A beta - WMH+, A beta + WMH-, and A beta + WMH+ groups. MTA was most severe in the A beta + WMH + group compared with the groups with a single pathology. Both WMH and A beta 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 A beta 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.

AB - Background: Cerebrovascular disease (CVD) and amyloid-beta (A beta) often coexist, but their influence on neurodegeneration and cognition in predementia stages remains unclear. We investigated the association between CVD and A beta 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 A beta(1-42) and white matter hyperintensities (WMH) on magnetic resonance imaging (MRI) scans were used as measures of A beta and CVD, respectively. Individuals were classified into four groups based on the presence (+) or absence (-) of A beta 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 A beta - WMH+, A beta + WMH-, and A beta + WMH+ groups. MTA was most severe in the A beta + WMH + group compared with the groups with a single pathology. Both WMH and A beta 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 A beta 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.

KW - Amyloid

KW - Cerebrovascular disease

KW - Alzheimer's disease

KW - Cognition

KW - Neurodegeneration

KW - Medial temporal lobe atrophy

KW - Tau

KW - Cerebrospinal fluid

KW - MRI

KW - TEMPORAL-LOBE ATROPHY

KW - WHITE-MATTER HYPERINTENSITIES

KW - ALZHEIMERS-DISEASE

KW - CEREBROSPINAL-FLUID

KW - INTERNATIONAL WORKSHOP

KW - DIAGNOSTIC-CRITERIA

KW - VASCULAR DEMENTIA

KW - TOTAL TAU

KW - IMPAIRMENT

U2 - 10.1186/s13195-017-0328-9

DO - 10.1186/s13195-017-0328-9

M3 - Article

C2 - 29284531

SN - 1758-9193

VL - 9

JO - Alzheimer's Research & Therapy

JF - Alzheimer's Research & Therapy

M1 - 101

ER -

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

Abstract

Keywords

Access to Document

Research output

Correction to: Cerebrovascular and amyloid pathology in predementia stages: the relationship with neurodegeneration and cognitive decline (vol 9, 101, 2017)

Cite this