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

A.2 Scientific background and rationale for study elements
Dementia and stroke are examples for this and illustrate two contrasting features of many of
these age-related neurologic diseases. They are either chronic conditions with slowly progressing
impairments over time, such as dementia, or can also have a sudden onset with
severe impairment, such as stroke.
While some neurologic or psychiatric conditions occur too rarely to study them even in a large
population such as the National Cohort (e.g., schizophrenia or Huntington’s disease), there
are conditions that primarily affect younger or middle-aged adults and cause considerable
health care costs, and health impairments. This group of conditions includes migraine and
other types of headache, restless legs syndrome, depression, and anxiety.
Cerebrovascular diseases are among the leading causes of death worldwide 55 , and survivors
often suffer from lifelong disabilities. The clinical syndrome “cerebrovascular disease” is
a heterogeneous term for different conditions to be further classified based on the duration
of clinical symptoms, underlying pathology, and underlying cause of ischemia 89 . The spectrum
of these conditions ranges from small diffuse changes in the fiber tracts of the white
matter, visible lesions in the white and gray matter, microbleeds, and lacunar infarcts to ischemic
stroke, hemorrhage, and post-stroke atrophy. The common denominator for the whole
spectrum is vascular brain changes. Therefore, cerebrovascular diseases will serve as an
ideal link pertaining to both research areas, “cerebrovascular diseases” and “neurologic and
psychiatric diseases”. Whereas ischemic stroke subtypes share a number of common risk
factors, including nonmodifiable (e.g., age, sex, genetic predisposition, lower socioeconomic
status, SES) and modifiable ones (e.g., hypertension, smoking, diabetes, smoking and high
alcohol consumption), other factors only increase the risk of specific pathological subtypes,
such as atrial fibrillation, carotid artery stenosis, or LDL cholesterol, and some might have a
divergent impact on some stroke subtypes, such as moderate alcohol consumption. Thus,
the impact of several risk factors on the occurrence of distinct pathological and etiological
subtypes still needs to be established.
The phenotyping within the National Cohort, e.g., characterization of the arterial system (ankle–brachial
index, arterial stiffness, left and right ventricular function, intima–media thickness
[CIMT]) combined with brain MRI data in 40,000 subjects will significantly contribute to
our understanding of risk factors for cerebrovascular diseases. In particular, by using MRI,
very early-stage vascular changes in the brain can be detected before the onset of any
clinical symptoms. In combination with the assessment of cognitive and emotional functions
(depression and anxiety scores), replicated over time, the natural course and progression of
subclinical cerebrovascular diseases can be explored based on prospective data.
Assessment of CVD:
Examinations and questionnaires (at baseline and during reassessment)
Level 1: Questionnaire
MRI program: Brain MRI
Active follow-up (and medical verification of self-reports):
Self-report or proxy report of physician-diagnosed stroke
Passive follow-up: Stroke registries, where available
Cognitive function, cognitive impairment, and dementia: Cognitive function represents
a continuum from normal function on one end through different stages of impairment to the
stage of dementia on the other end. For the latter it is estimated that in Germany currently
around 2 million people, especially women, suffer from Alzheimer’s disease or other forms
of dementia, and it is projected that this number will double over the coming two decades.
Current evidence suggests that vascular factors, such as midlife hypertension, diabetes, dietary
fat intake, high cholesterol, excessive smoking, alcohol misuse, and obesity contribute
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A.2