The Locus coeruleus hits the bull's eye: stress-vulnerability as a predictor for cognitive decline.

Stress is an intricate part of modern life, and the high demands of the current
society puts people under more stress constituting a risk for cognitive decline
in later years. Stress activates the brains noradrenergic system and the
hypothalamic pituitary adrenal (HPA) axis. In younger adults, this
noradrenergic activation predicts memory performance following an inverted
U-curve. However, advanced age is associated with changes in activation of the
HPA axis and the adrenergic system. Noradrenergic brain activity is commonly
measured by monitoring pupil dilation during arousing conditions. The locus
coeruleus, a small nucleus in the brainstem, is the main source of
noradrenalin. This property puts the locus coeruleus at the forefront of the
stress-cognition association. Interestingly, neuropathological studies suggest
that the locus coeruleus, is affected early on in life and might be the site of
the initial accumulation of Alzheimer Disease pathology. Therefore, it can be
hypothesized that stress-vulnerability at a younger age may be a predictor for
incipient cognitive decline and potentially development of prodromal
Alzheimer*s disease.

Objective: Main outcome measures are: brain activity, pupil dilation,
noradrenergic network activity and memory performance.
We aim:
i) To investigate risk and protective factors for cognitive decline in high and
low stress vulnerable persons across the adult lifespan.
ii) To investigate whether individuals with higher stress vulnerability show
patterns of noradrenergic network integrity that is similar to the patterns of
MCI patients as compared to individuals with lower stress vulnerability.
iii) How stress vulnerability as well as subjective stress about cognitive
performance relates to cognitive decline over time.

This study entails a longitudinal study with 2 measurement days at baseline and
3 follow ups.
There is also a cross-sectional variant of the study for prospective new
participants.

The expected risks and burden are expected to be minimal, since strict
inclusion and exclusion criteria for participation in the MRI procedure are
maintained. Participants will complete a standard medical questionnaire that
screens for contraindications. When included in the longitudinal study, the
burden and risks associated with this study are restricted to the testing days.
At baseline, day one will consist of administration of several
neuropsychological tests and questionnaires, a behavioral stress measurement
with pupil measurements. The behavioral stress measurement contributes to the
burden of participating in the study. However, the stress-induction will only
occur once and there have been no reports of long-term conditions attributable
to exposure to the task. Day two will consist of a short scan session, and
blood drawing. At follow-up sessions for healthy participants cognitive
performance will be retested by administration of neuropsychological tests and
questionnaires, and pupil dilations will be measured. For the cross-sectional
observational study, on day one participants will undergo several
neuropsychological tests and questionnaires. On the second day, patients will
be scanned in the MRI scanner for 1 hour including an emotional memory task and
pupil dilation measurements. MRI is a non-invasive method and the risks are
negligible (temporary dizziness in some individuals).