NEUROcognitive fitness: Studying changes in Hippocampal Adult neurogenesis and cognition induced by Physical Exercise

Physical exercise is not only beneficial for general health, but has also been
shown to improve brain function (cognition) and influence brain structure
(increase brain volume, especially in the hippocampus). However, the underlying
neural mechanisms that cause this increase in volume are relatively unknown.
Animal studies have shown that physical exercise can increase the formation of
new neurons, a process called neurogenesis, and the survival of these neurons.
In addition, these new neurons have been demonstrated to be involved in
cognition, especially in hippocampal-dependent pattern separation. We
hypothesize that exercise could also increase neurogenesis in the human
hippocampus. The recently developed and validated non-invasive magnetic
resonance spectroscopy (MRS) now allows to reliably detect neurogenesis for the
first time in the live human brain.
Exercise has also been demonstrated to influence the formation of new blood
vessels (angiogenesis) in the hippocampus in rodents, a process which is
closely linked to neurogenesis. Angiogenesis can be measured in the human brain
by contrast-enhanced MRI, exploiting the leakiness of new vessels. In this
study, we aim to study the effect of exercise on neurogenesis and angiogenesis
and elucidate the link to brain function in the hippocampus.

Primary objective:
- To investigate if exercise can modulate neurogenesis and angiogenesis in
vivo, and whether this is associated with changes in hippocampal function, such
as pattern separation

Secondary objectives:
- To assess whether exercise-induced changes in VO2max correlate with changes
in neurogenesis and angiogenesis
- To assess whether BDNF levels in serum correlate with changes of VO2max,
neurogenesis and angiogenesis
- To assess exercise-induced changes in hippocampal volume
- To assess exercise-induced changes in neuropsychological functioning
- To assess exercise-induced changes in lifestyle and dietary patterns

Randomized controlled exercise intervention study.

Subjects will be randomized to either the exercise or control group. The
subjects in the exercise group will engage in 3x weekly sessions of aerobic
exercise, whereas the control group will engage in 3x weekly stretching
exercises.

Risk assessment:
- The placing of the IV cannula in our study for contrast administration can be
an unpleasant experience for the subjects. There is a low risk of phlebitis at
the IV injection sites, this is unpleasant, but not harmful, of temporary
nature and self-limiting. Adverse events to the contrast agent are rare.
- MRI is a non-invasive imaging modality. All volunteers will receive extensive
information about the MRI procedures beforehand. Volunteers suffering from
claustrophobia will be excluded.
- The CPET is routinely used in clinical practice to assess physical stamina.
Adverse effects as a consequence of this test are extremely rare
- The aerobic exercise intervention as well as the stretching and toning
intervention is considered to be safe for subjects this age. In case of adverse
effects caused by exercise, subjects will be examined by the supervising doctor
and advised to see the physiotherapist or general practitioner. If the subject
is willing to continue participation in the study, the medical specialist will
decide if continuing in the study is still safe for the subject.

Benefit
Subjects will engage in regular exercise. Exercise has several physical and
mental health benefits and is associated with a better quality of life.
Furthermore, the subjects in this study can contribute to the knowledge on how
exercise can be utilized to increase neurogenesis, better vascularization and
improved cognition * and be beneficial as (adjunctive) treatment for a number
of neuropsychiatric and neurodegenerative disorders.