Scientific Concept of the National Cohort (status ... - Nationale Kohorte

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A.3 Study design
cal cerebrovascular disorders, including gliosis, microbleeds, and angiopathy and carotid
and intracranial plaque burden, for the development of cerebrovascular and cardiovascular
events can be evaluated.
Gliosis is a proliferation of astrocytes in damaged areas of the central nervous system.
Gliosis and neuronal loss in brain regions are seen in various neurodegenerative disorders,
such as Alzheimer's disease, Korsakoff's syndrome, and Parkinson’s disease and following
acute episodes of multiple sclerosis. Although gliosis belongs to the neurodegenerative disease
category and some other diseases in this category are caused by vascular disorders,
there is uncertainty as to the possible relation between gliosis and atherosclerotic diseases.
Microbleeds and amyloid angiopathy are accurately detected by brain MRI and share common
risk factors. Particularly, hypertension is related to an increased risk of both 709 . The role
of further atherosclerotic risk factors including smoking, diabetes, and obesity is less clear.
We hypothesize that the risk factor profiles for incident carotid artery plaques, intracranial
vascular plaques, and microbleeds are different. In addition, we assume that carotid atherosclerosis
is not associated with amyloid angiopathy. Rather, genetic factors and gene-to-environment
interactions predispose individuals to specific subclinical cerebrovascular disorders.
Neurodegeneration
MRI in a population setting offers various research options for assessing prevalence and incidence
of neurodegenerative changes of the brain, which include measuring brain volume
(total volume, gray and white matter volume), alterations in microstructural integrity (through
diffusion tension imaging), vascular brain lesions (white and gray matter lesions, lacunar
infarcts, microbleeds), subclinical atherosclerosis (lacunar infarcts, white matter lesions, carotid
plaques), and functional connectivity networks and their role in cognitive impairment,
emotional functioning, and dementia. On the one hand, information on neurodegenerative
changes at baseline will serve as exposure to assess the future risk of incident MI, stroke,
mild cognitive impairment, and dementia. On the other hand, by performing follow-up MRI
examinations incident neurodegenerative disorders can be defined for incidence and risk
factor analyses. Finally, the changes in neurodegenerative disorders will be analyzed in relation
to incident fatal and nonfatal cardiovascular events that have occurred after follow-up
MRI examinations.
Cardiovascular system
Cardiac function
MRI is the most accurate noninvasive and nonradiation-based method to determine left
ventricular mass. Using this technique left ventricular diastolic and systolic function can be
accurately assessed globally and regionally. In addition, morphology and function of the
right ventricle can be evaluated. While there is clear evidence that impaired systolic function
of the left ventricle is one of the strongest predictors of cardiac mortality, only older studies
indicate that right ventricular dilation and dysfunction may add predictive value to this association
710 . Follow-up examinations of cardiac MRI will form the basis for identifying risk
factors for incident cardiac hypertrophy and dysfunction and for associating the change in
these cardiac parameters with incident cardiac morbidity and mortality.
vascular morphology and stiffness
Recent technologies have substantially improved the use of non-contrast-enhanced MRI
for detecting and quantifying impaired vascular structure and function. Thus, in the National
Cohort MRI will also be used to determine the prevalence, cross-sectional and longitudinal
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