100-plus Study

About one third of people aged older than 85 suffer from the symptoms
associated with dementia. A large majority of
these patients suffer from Alzheimer*s Disease (AD) specifically, the most
common dementia subtype. Dementia
prevalence increases with age. However, some people reach ages well over 100
years enjoying great mental health.
This raises several questions: how can human neurons remain functionally
competent for more than 100 years? Do
neurons from these super-agers possess unique mechanisms for the repair of DNA
damage, protein damage and
protection against the toxic effects of AD pathology? How is the immune system
involved? The answers to these
questions are likely to provide new insights and directions for treating
neurodegenerative diseases. The combination of extreme old age with maintained
cognitive health is often observed in families, suggesting that
hereditary factors are involved in the protection against dementia. However, it
can be expected that *maintained
cognitive health during extreme aging* reflects the integrated outcome of
several underlying biochemical pathways.
Although these might be partly driven by a constellation of genetic variants,
our aim is to thoroughly phenotype a
comprehensive set of characteristics associated with maintained cognitive
health.

The aim of the 100-plus Study is to identify moleculair and environmental
constellations that maintain cognitive health
during extreme aging.

The 100-plus Study is a prospective longitudinal descriptive cohort study which
aims to collect and investigate the
genomes in combination with matching brain tissues, neuropsychological
assessments and further biological sampling
in cognitively healthy centenarians.
We will collect among other things , (i) data on medical and socio-economic
history, lifestyle and genealogy; (ii) we
measure grip strength and blood pressure; (iii) cognitive functioning is
measured with neuropsychological testing; (iv)
blood is collected for biomarker analyses and genotyping with NGS; (v) if
participants are willing, they can participate in the 90+ study to evaluate
Alzheimer-associated changes using in vivo brain imaging (vi) we inform
participants or a CHC-sibling about the
possibility for post-mortem brain donation (vii) plan follow-up visits to
evaluate changes in cognitive functioning and
general health.

There is no direct benefit for the participant. This study may lead to the
discovery of genetic and molecular
characteristics that are responsible for the protection against AD and will
learn us more about the processes that
maintain cognitive health during ageing. Ultimately, this might provide new
directions for AD research and druggable
targets to intervene in neurodegenerative processes. This will be a benefit for
future patients with AD.
For the largest part of the study, risks associated with participation are
negligible.
Blood collection is done with venipuncture, with associated risks.
Neuropsychological testing may induce fatigue.
Participants will be informed that they are free to withdraw at any time during
the study should they experience
excessive anxiety or malaise.