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
. 2024 Nov;20(11):7518-7528.
doi: 10.1002/alz.14171. Epub 2024 Oct 10.

Cognition in (pre)symptomatic Dutch-type hereditary and sporadic cerebral amyloid angiopathy

Rosemarie van Dort  1 , Kanishk Kaushik  1 , Ingeborg Rasing  1 , Reinier G J van der Zwet  1 , Manon R Schipper  2 , Jeroen van der Grond  2 , Sanneke van Rooden  2   3 , Erik W van Zwet  4 , Gisela M Terwindt  1 , Huub A M Middelkoop  1 , Ellen P Hart  5 , Matthias J P van Osch  2 , Marianne A A van Walderveen  2 , Marieke J H Wermer  1   6
Affiliations

Cognition in (pre)symptomatic Dutch-type hereditary and sporadic cerebral amyloid angiopathy

Rosemarie van Dort et al. Alzheimers Dement. 2024 Nov.

Abstract

Introduction: Cerebral amyloid angiopathy (CAA) is a main cause of cognitive dysfunction in the elderly. We investigated specific cognitive profiles, cognitive function in the stage before intracerebral hemorrhage (ICH), and the association between magnetic resonance imaging (MRI) based cerebral small vessel disease (cSVD) burden in CAA because data on these topics are limited.

Methods: We included Dutch-type hereditary CAA (D-CAA) mutation carriers with and without ICH, patients with sporadic CAA (sCAA), and age-matched controls. Cognition was measured with a standardized test battery. Linear regression was performed to assess the association between MRI-cSVD burden and cognition.

Results: D-CAA ICH- mutation carriers exhibited poorer global cognition and executive function compared to age-matched controls. Patients with sCAA performed worse across all cognitive domains compared to D-CAA ICH+ mutation carriers and age-matched controls. MRI-cSVD burden is associated with decreased processing speed.

Discussion: CAA is associated with dysfunction in multiple cognitive domains, even before ICH, with increased MRI-cSVD burden being associated with slower processing speed.

Highlights: Cognitive dysfunction is present in early disease stages of cerebral amyloid angiopathy (CAA) before the occurrence of symptomatic intracerebral hemorrhage (sICH). Presymptomatic Dutch-type CAA (D-CAA) mutation carriers show worse cognition than age-matched controls. More early awareness of cognitive dysfunction in CAA before first sICH is needed. Increased cerebral small vessel disease CAA-burden on magnetic resonance imaging is linked to a decrease in processing speed.

Keywords: Dutch‐type hereditary cerebral amyloid angiopathy; cerebral amyloid angiopathy; cerebral small vessel disease burden; cognitive dysfunction; hereditary cerebral amyloid angiopathy; intracerebral hemorrhage; magnetic resonance imaging; presymptomatic mutation carriers.

PubMed Disclaimer

Conflict of interest statement

Marieke J.H. Wermer reports independent support from the Dutch Research Council (NWO), ZonMw (VIDI grant 91717337), the Dutch Heart Foundation (Dekker grant 2016T086), and the Dutch CAA foundation.

Matthias J. P. van Osch reports independent support from NWO (VICI grant 016.160.351) and ZonMw.

Gisela M. Terwindt reports independent support from the NWO, European Community, the Dutch Heart Foundation, the Dutch Brain Foundation, and the Dutch CAA foundation.

Sanneke van Rooden reports independent support from the National Institutes of Health (NIH) (R01 NS070834) and ZonMW/NWO (VENI grant 016.196.118) and Alzheimer Nederland (WE.03‐2018‐12).

Jeroen van der Grond reports independent support from the NIH (R01 NS070834).

All other authors report no disclosures in the manuscript. Author disclosures are available in the supporting information.

Figures

FIGURE 1
FIGURE 1
Cognitive performance in D‐CAA and sCAA.
FIGURE 2
FIGURE 2
Association between cognitive performance and cSVD CAA burden.
See this image and copyright information in PMC

References

    1. Natté R, Maat‐Schieman MLC, Haan J, Bornebroek M, Roos RAC, Van Duinen SG. Dementia in hereditary cerebral hemorrhage with amyloidosis‐dutch type is associated with cerebral amyloid angiopathy but is independent of plaques and neurofibrillary tangles. Ann Neurol. 2001;50:765‐772. - PubMed
    1. Van Rooden S, Van Opstal AM, Labadie G, et al. Early magnetic resonance imaging and cognitive markers of hereditary cerebral amyloid angiopathy. Stroke. 2016;47(12):3041‐3044. - PMC - PubMed
    1. Wermer MJH, Greenberg SM. The growing clinical spectrum of cerebral amyloid angiopathy. Curr Opin Neurol. 2018;31(1):28‐35. - PubMed
    1. Koemans EA, Chhatwal JP, van Veluw SJ, et al. Progression of cerebral amyloid angiopathy: a pathophysiological framework. Lancet Neurol. 2023;22(7):632‐642. - PubMed
    1. Gahr M, Nowak DA, Connemann BJ, Schönfeldt‐Lecuona C. Cerebral amyloidal angiopathy—A disease with implications for neurology and psychiatry. Brain Res. 2013;1519:19‐30. - PubMed

MeSH terms