Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2017 Dec 29;9(1):101.
doi: 10.1186/s13195-017-0328-9.

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

Isabelle Bos  1 , Frans R Verhey  2 , Inez H G B Ramakers  2 , Heidi I L Jacobs  2 , Hilkka Soininen  3   4 , Yvonne Freund-Levi  5 , Harald Hampel  6   7 , Magda Tsolaki  8 , Åsa K Wallin  9 , Mark A van Buchem  10 , Ania Oleksik  11 , Marcel M Verbeek  12 , Marcel Olde Rikkert  13 , Wiesje M van der Flier  14 , Philip Scheltens  14 , Pauline Aalten  2 , Pieter Jelle Visser  2   14 , Stephanie J B Vos  2
Affiliations
Multicenter Study

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

Isabelle Bos et al. Alzheimers Res Ther. .

Erratum in

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.

Keywords: Alzheimer’s disease; Amyloid; Cerebrospinal fluid; Cerebrovascular disease; Cognition; MRI; Medial temporal lobe atrophy; Neurodegeneration; Tau.

PubMed Disclaimer

Conflict of interest statement

Ethics approval and consent to participate

Written informed consent was obtained from all participants before inclusion in the study. The medical ethics committee at each site approved the study (Additional file 3).

Consent for publication

Not applicable.

Competing interests

IB receives research support from the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement number 115372 resources that are composed of financial contributions from EU FP7 (FP7/2007-2013) and in-kind contributions from EFPIA. HH serves as a senior associate editor for the journal Alzheimer’s & Dementia®. HH has been a scientific consultant and/or speaker and/or attended scientific advisory boards of Axovant Sciences, Anavex Life Sciences, Eli Lilly and Company, GE Healthcare Life Sciences, Cytox, Jung Diagnostics, Roche, Biogen Idec, Takeda-Zinfandel, and Oryzon Genomics; receives research support from the Association for Alzheimer Research (Paris), Pierre and Marie Curie University (Paris), Pfizer and Avid (paid to institution); and has patents as a coinventor but has received no related royalties. PS has acquired grant support (for the institution) from GE Healthcare Life Sciences, Danone Research, Piramal, and Merck. In the past 2 years, PS has received consultancy/speaker’s fees (paid to the institution) from Eli Lilly and Company, GE Healthcare Life Sciences, Janssen Pharmaceuticals, Probiodrug, Biogen, Roche, and EIP Pharma. PJV receives research support from the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement number 115372 and European Prevention of Alzheimer's Dementia grant agreement 115736, resources that are composed of financial contributions from EU FP7 (FP7/2007-2013) and in-kind contributions from EFPIA. SJBV receives research support from ZonMw and from the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement number 115372, resources that are composed of financial contributions from EU FP7 (FP7/2007-2013) and in-kind contributions from EFPIA. All other authors declare no conflict of interest.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Cognitive decline by amyloid-β/white matter hyperintensities (Aβ/WMH) group for global cognition, memory, and executive functioning. The graphs show mean scores and 95% CIs of cognitive decline over time for four different groups based on Aβ/WMH status. The left graph shows cognitive decline for global cognition (Mini Mental State Examination [MMSE]) after adjusting for demographics, study, and baseline diagnosis. The middle graph shows cognitive decline for memory (delayed recall of Rey Auditory Verbal Learning Test) after adjusting for study. The right graph shows cognitive decline for executive functioning (Trail Making Test part B) after adjusting for study
Fig. 2
Fig. 2
Risk of progression to dementia over time for amyloid-β/white matter hyperintensities (Aβ/WMH) groups, by baseline diagnosis. The graph shows the probability of surviving without dementia during a 4-year follow-up period for the four Aβ/WMH groups after adjusting for demographics and study, stratified by baseline diagnosis. MCI Mild cognitive impairment, SCD Subjective cognitive decline
See this image and copyright information in PMC

References

    1. Schneider JA, Aggarwal NT, Barnes L, Boyle P, Bennett DA. The neuropathology of older persons with and without dementia from community versus clinic cohorts. J Alzheimers Dis. 2009;18(3):691–701. doi: 10.3233/JAD-2009-1227. - DOI - PMC - PubMed
    1. Attems J, Jellinger KA. The overlap between vascular disease and Alzheimer’s disease - lessons from pathology. BMC Med. 2014;12:206. doi: 10.1186/s12916-014-0206-2. - DOI - PMC - PubMed
    1. Heyman A, Fillenbaum GG, Welsh-Bohmer KA, Gearing M, Mirra SS, Mohs RC, Peterson BL, Pieper CF. Cerebral infarcts in patients with autopsy-proven Alzheimer’s disease: CERAD, part XVIII. Consortium to Establish a Registry for Alzheimer’s Disease. Neurology. 1998;51(1):159–62. doi: 10.1212/WNL.51.1.159. - DOI - PubMed
    1. Zea-Sevilla MA, Fernandez-Blazquez MA, Calero M, Bermejo-Velasco P, Rabano A. Combined Alzheimer’s disease and cerebrovascular staging explains advanced dementia cognition. Alzheimers Dement. 2015;11(11):1358–66. doi: 10.1016/j.jalz.2015.01.004. - DOI - PubMed
    1. Jack CR, Jr, Wiste HJ, Vemuri P, Weigand SD, Senjem ML, Zeng G, Bernstein MA, Gunter JL, Pankratz VS, Aisen PS, et al. Brain β-amyloid measures and magnetic resonance imaging atrophy both predict time-to-progression from mild cognitive impairment to Alzheimer’s disease. Brain. 2010;133(11):3336–48. doi: 10.1093/brain/awq277. - DOI - PMC - PubMed

Publication types

MeSH terms