Prevention of Dementia by Intensive Vascular Care - MRI sub-study

The vast majority of patients with old-age dementia suffer from what is called
'mixed dementia'. In addition to neurodegenerative changes, typical for
Alzheimer's disease, there is often concomitant cerebrovascular disease in the
form of white matter lesions or cerebral infarcts. The importance of a vascular
component in old-age dementia has repeatedly been shown in epidemiological,
neuroradiological and neuropathological research.

In spite of all the evidence of observational studies, it is currently unlcear
whether treatment aimed at vascular risk factors can slow down progression of
cerebrovascular lesions in non-demented elderly subjects and if this could lead
to prevention or slowing of cognitive decline. In the ongoing preDIVA trial
elderly non-demented participants are randomized to standard care according to
current guidelines or intensive vascular care. The primary outcome of the
preDIVA-trial is incident dementia. In the preDIVA-M study, the effect of this
intervention on the progression of cerebrovascular lesions on MRI will be
studied in a sub-population of subjects partcipating in the preDIVA-trial.

Primary objective:
- To investigate whether a multi-component intervention strategy aimed at
several vascular risk factors can prevent the occurrence of new cerebrovascular
lesions in elderly non-demented subjects and if this correlates with prevention
of cognitive decline and dementia.

Secondary objectives:
- To evaluate which subject characteristics influence this effect, to
eventually delineate a profile of subjects who can benefit from intensive
vascular care to prevent or delay cognitive decline and dementia.

- To do exploratory analyses on which vascular risk factor is most associated
with progression of cerebrovascular lesions and which component of the
intensive vascular care has most effect on the radiological progression.

- To pave the way for better individualized treatment strategies aimed at the
vascular component of dementia, with currently readily available and easy to
implement intervention strategies.

PreDIVA-M is a diagnostic study designed as a nested case-control study within
the ongoing cluster-randomized controlled preDIVA-trial. As such, no new
interventions will take place. The only procedure involved is that participants
will undergo an MRI-scan without intravenous contrast at the Academic Medical
Centre twice, over a period of 4 years. The MRI scans will be analyzed by a
rater who is blinded to any clinical information of the participant.

No direct benefit for an individual participant can be expected. The burden of
participation is limited . Participants have to undergo an MRI-scan of the
brain without intravenous contrast twice over a 4-year period at the AMC.
Subjects for whom the MRI is too large of a burden, e.g. in case of
claustrophobia, are not eligible for the study and will not be invited to
undergo an MRI-scan.
There are no known health risks involved in MRI-scanning of the brain without
intravenous contrast.
There is the potential of an unexpected finding on the MRI scan, whether with
or without clinical consequences. Participants are explicitly made aware of
this possibility, which is also clearly described in the patient information.
If unexpected abnormalities on the MRI-scan are found, this will be
communicated to the participant by one of the researchers (E.Richard or W.A.
van Gool, both neurologist).