MRI in neurodegenerative diseases

Sanneke van Rooden, Jeroen van der Grond, Mark van Buchem, Andrew Webb, Gerda Labadie, Madeline Redelijkheid, Annemarieke van Opstal, Marieke Wermer, Gisela Terwindt, Annette van den Berg-Huysmans, Huub Middelkoop, Jeske Damoiseaux, Serge Rombouts


Background
Neurodegenerative diseases we investigate are HCHWA-D (hereditary cerebral hemorrhage with amyloidosis – Dutch type or Katwijkse ziekte) and (early stages of) dementia (Alzheimer’s disease (AD)). Both diseases are characterized by deposition of amyloid-β in the brain. 


HCHWA-D is an hereditary variant of sporadic cerebral amyloid angiopathy (sCAA), which is a common cerebrovascular small vessel disease (SVD) of the elderly (1:4 above 60 years) that is caused by deposition of amyloid-β in small vessels. Symptoms of HCHWA-D and sCAA are hemorrhages and cognitive deterioration. A major problem with sCAA is the absence of reliable, non-invasive diagnostic tests which hampers the development of treatment. Because HCHWA-D is an autosomal dominant disease in which the chemical composition and underlying pathology of these amyloid deposits is similar to that in sCAA, it offers an unique opportunity to study early markers of CAA. 


AD is the most common form of dementia and its prevalence is increasing rapidly. It is estimated that 25 to 30 million people worldwide suffer from AD and this number will triple by 2040 as age is the most important risk factor for AD and life expectancy is increasing. AD is characterized by a long preclinical phase in which neuropathological changes (i.e. amyloid-β deposits) in the brain build up without apparent signs or symptoms of the disease. These early stages are called amnestic mild cognitive impairment (aMCI) and subjective cognitive decline (SCD).  

Aim
The general aim of our studies is to find early MRI markers in HCHWA-D and (early stages of) dementia using state-of-the art functional MRI, structural MRI and cognitive function methods to:

  • Develop early non-invasive markers of these diseases
  • Acquire new insights into the etiology of these diseases
  • Aid in the development of efficient therapies


Approach
HCHWA-D study (EDAN study)
A group of symptomatic and pre-symptomatic HCHWA-D patients and healthy controls are investigated with both 7T and 3T MRI using several MRI techniques and cognitive function was measured. Baseline and follow-up measurements are performed.
Dementia study
A group of memory clinic patients (from SCD to AD) are investigated with 3T MRI using several MRI techniques and cognitive function is measured. A part of this study contains both baseline and follow-up measurements. 


Selected publications

  • van Rooden S, van den Berg-Huysmans AA, Croll PH, Labadie G, Hayes JM, Viviano R, van der Grond J, Rombouts SARB, Damoiseaux JS (2018) Subjective cognitive decline is associated with greater white matter hyperintensity volume.  Journal of Alzheimer's disease.
  • Koemans EA, van Etten ES, van Opstal AM, Labadie G, Terwindt GM, Wermer MJH, Webb AG, Gurol EM, Greenberg SM, van Buchem MA, van der Grond J, van Rooden S (2018) Innovative Magnetic Resonance Imaging Markers of Hereditary Cerebral Amyloid Angiopathy at 7 Tesla. Stroke 49, 1518-1520.
  • van Opstal AM, van Rooden S, van Harten T, Ghariq E, Labadie G, Fotiadis P, Gurol ME, Terwindt GM, Wermer MJ, van Buchem MA, Greenberg SM, van der Grond J (2017) Cerebrovascular function in presymptomatic and symptomatic individuals with hereditary cerebral amyloid angiopathy: a case-control study. Lancet Neurol 16, 115-122.
  • van Rooden S, van Opstal AM, Labadie G, Terwindt GM, Wermer MJ, Webb AG, Middelkoop HA, Greenberg SM, van der Grond J, van Buchem MA (2016) Early Magnetic Resonance Imaging and Cognitive Markers of Hereditary Cerebral Amyloid Angiopathy. Stroke 47, 3041-3044.