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

A.2 Scientific background and rationale for study elements
A.2.3.4 Intermediate stages of neurologic and psychiatric diseases
Mild cognitive impairment represents an intermediate state between normal cognitive function
and dementia, with the conversion rate to dementia being about three times higher than
in subjects without cognitive impairment. Older age, subjective memory impairment, impairment
in instrumental activities of daily living, and antecedent lower cognitive performance
have been found to be significantly associated with the development of future mild cognitive
impairment 191 . For the National Cohort, neuropsychological tests for cognitive impairment will
be used that include tests of episodic memory and executive function, as both have been
shown to predict time to progression from normal cognition to mild cognitive impairment as
well as from mild impairment to dementia 192 . Five-year follow-up testing, at the participants’
second visit, will then be used to assess intraindividual changes in cognitive function as a
major prospective study outcome. In addition to the cognitive tests, MRI-based examination
of the brain will be performed. It will thus be possible to couple specific morphologic changes
of brain structures associated with neurodegenerative processes to the assessments of prospective
change in cognitive function. Specific details about the methods and logistic organization
for MRI imaging are given in Sect. A.3.4.
The prevalence of olfactory dysfunction in the general population is a matter of debate.
Many authors reported frequencies of 1-5% of anosmia within the groups studied 193 , but
much higher prevalences can be found among older subjects 194, 195 . Causes of smell dysfunction
are manifold, the most important ones being aging, sinunasal disease, head trauma, or
infections of the upper respiratory tract. Loss of olfactory function is often accompanied by
depression 196-198 and is also related to neurodegenerative disease, as it has been shown to
be an early sign of Parkinson’s disease 197, 199 and Alzheimer’s disease 196, 198 , respectively. In
the National Cohort, a brief, standardized smell test will be applied.
Assessment of neurologic and psychiatric intermediate phenotypes:
Examinations and questionnaires (at baseline and during reassessment)
Level 1: Neuropsychological tests for cognitive impairment
Smell test
MRI program: Brain MRI
A.2.3.5 respiratory function and preclinical phenotype
Lung function embodies significant information regarding the state of the respiratory system
and can be used for diagnosis and staging of all major ventilatory disorders. Respiratory
symptoms and shortness of breath occur only when up to 50% of the lung capacity may
already be lost. According to data obtained in a large cohort study 200 it may be possible to detect
subclinical, mild to moderate airflow obstruction in up to 30,000 subjects (15%) in the National
Cohort. Apart from pulmonary conditions in COPD, asthma, and fibrotic lung disease,
reduced lung function has been found to be associated with many chronic medical conditions
such as ischemic and congestive heart failure, hypertension, obesity, and diabetes 201, 202 . In
addition, lung function is also a predictor of overall morbidity and mortality 203 and considered
to be one of the best noninvasive functional predictors of biological aging and longevity 204,
205 . Even in the absence of lung diseases, reduced forced expiratory volume in one second
(FEV1) is a marker of cardiovascular mortality, independent of smoking history 206 . Spirometry,
as the best established pulmonary function test, will be carried out in the National Cohort to
identify subclinical stages. It provides an integrative signal covering mechanistically relevant
aspects of lung volume loss and airway obstruction and can detect lung function decline or
deterioration over time in the longitudinal setting.
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A.2