National Initiative Brain and Cognition. Functional markers for cognitive deficits - dementia

There are many different forms of dementia. Two common forms are Alzheimer's
disease and frontotemporal lobar degeneration (FTLD). Until now, the diagnoses
are based on clinical criteria and neuropsychological testing. However, the
frequent overlap of the clinical syndromes associated with AD and FTLD poses
serious problems to a reliable diagnosis. Recently, more accurate techniques
like MRI have been developed. In the diagnostic work-up of dementia, MRI is
only used supplementary but provides valuable information. The conventional MRI
sequences and visual rating scales for MRI do not provide enough sensitivity
for an early and accurate diagnosis of AD, and even less so for FTLD. Hence,
there is a strong need for quantitative image analysis techniques and for
additional scan sequences, with which not only specific structures but the
whole brain and brain networks can be assessed. With this early, reliable
(differential) diagnoses kan be made.

The purpose of this study is the expansion of the conventional MRI sequences
for the diagnosis for patients with probable dementia. The focus is on
structural imaging, anatomical and functional connectivity. Patterns of change
in brain connectivity and -structure and the change over time are the focus of
attention to possibly develop a diagnostic tool for AD and FTLD.
Specific research goals:
1) How do patterns of atrophy, white matter tracts and functional connectivity
change in different brain regions in AD in comparison to FTLD and healthy
controls? How is functional connectivity related to the structure of the brain?
2) How do functional connectivity and brain structure change over a period of
one and two years in AD in comparison to FTLD and healthy controls and how can
this be linked to a specific diagnosis?
3) Do these changes between baseline and follow-up provide advantages as a
diagnostic biomarker over a one-time measurement at baseline?
4) Do changes in functional connectivity correlate with changes in anatomical
connectivity?
5) Is there a relationship between the severity/stage of dementia and regional
atrophy, anatomical connectivity between brain regions and/or functional
connectivity?

This project is a prospective longitudinal structural and functional MRI study
conducted in two medical centres (VU University medical center, Amsterdam and
Leiden university medical centre). Data from structural and functional MRI,
demographic, clinical and neuropsychological data will be obtained over a
period of 2 years. Clinical follow-up is scheduled after 12 and 24 months.
If the baseline scan of patients diagnosed with AD or FTLD does not include all
necessary sequences for our study, patients will be asked to return for the
missing MRI sequences (20 min) to complete the MRI protocol. At follow-up all
patients will undergo the repeated complete MRI scan (50 min) and
neuropsychological tests (1 hour). At baseline and at follow up age-matched
controls will undergo a complete MRI scan (50 min) a neuropsychological
screening (1 hour) and a physical examination by a medical doctor (30 min).
To examine the reproducibility of the MRI data between the two medical centres,
20 subjects will be asked to undergo a MRI scan at both centres.

MRI: participants are not exposed to invasive methods or other hazardous
circumstances.