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

A.3
A.3 Study design
Although the intraindividual variation in response to glucose administration is substantial 599 ,
its value in epidemiologic studies has been demonstrated in several large-scale studies.
Major factors that may affect the test results can be largely excluded by following a strictly
standardized procedure. The standardized test conditions require a careful arrangement of
additional tests to be performed by the study participant. Due to insufficient evidence of possible
influences on other parameters, a feasibility study will be set up to explore this further
and to define measures that allow unbiased analyses of all aspects of the cohort study.
An oral glucose load of 75 g (in 300 ml water) is administerd to fasted subjects, and blood
sampling will be performed before and 30 min and 120 min after glucose load.
AGE reader
Recently, skin AF has emerged as a noninvasive and reproducible tool to estimate the AGE
level of skin tissue 600, 601 . Skin AF, as measured by AGE reader is associated with plasma
levels of advanced glycation endproducts and has been validated against skin levels of
several specific AGEs and a classic assay for AGEs – collagen-linked fluorescence – in different
populations (diabetics, subjects with renal failure, and controls) 600-602 .
Skin AF has a higher sensitivity than fasting glucose and HbA1c to detect impaired glucose
tolerance and diabetes and may be useful as a screening tool 603 . Lutgers et al. reported an
overall Altman error of 5% for repeated skin AF measurements in the same persons (diabetic
patients and controls) taken over a single day, and an error of 5.9% for the intraindividual
seasonal variance of skin AF among control participants and diabetic patients 604 .
Skin AF measurements by the AGE reader (DiagnOptics) are noninvasive, reliable, and
reproducible (good repeatability, low intraindividual variation, low measurement error at repeated
measurements) and are not affected by current glucose levels and thus not dependent
on fasting state during measurement 603 .
Procedure of measurement:
The tissue accumulation of AGEs will be determined with triple measurements by means
of fluorescent techniques, using the DiagnOptics AGE Reader. The total procedure takes 4
min and is noninvasive, easy to perform, and requires only a minimum of training.
A.3.3.4 Cognitive functioning tests
It is generally acknowledged that cognitive assessment must reflect several different cognitive
domains (e.g., memory, attention, reasoning, speed of processing, and excutive functions)
which may be specifically affected in certain diseases (e.g., Alzheimer’s disease,
stroke, Parkinson’s disease) and aging.
Cognitive ability and its decline in older age seems to be related to prior cognitive ability in
early or mid-life and to educational level, as subjects with higher education or social class
seem to be able to compensate longer for the age-related brain changes 605, 606 . Decline in
cognitive function and dementia may also be associated with general vascular risk factors,
such as physical inactivity 607, 608 , smoking 609, 610 , or diabetes 611 .
Procedure of measurement:
Cognitive function will be assessed by using different tests, performed during a face-to-face
interview or on a touch screen. Different domains of cognitive function will be covered with
the proposed tests: general cognitive ability (e.g., number series task), working (e.g., digit
span backward) and episodic memory (e.g., Hopkins-Verbal-Learning Test revised), verbal
92