Novel functional markers of dementia using pharmacological resting state FMRI
07 / 2011 - 06 / 2015
In dementia research, aimed at finding specific biological markers for Alzheimers disease (AD), frontotemporal lobe dementia (FTLD) and Lewy body disease (DLB), there is a strong need for an early specific marker of each dementia type, before atrophy can be observed on MRI scans. Although measures of brain function (FMRI) are expected to be more sensitive to early neuropathological brain changes than measures of brain structure (MRI), development of FMRI for this purpose has not been successful so far. The applicants and collaborators have recently developed a new technique, called pharmacological RS-FMRI (Ph-RS-FMRI). With this technique, using different pharmacological interventions, they have demonstrated specific drug-induced RS-FMRI-observable changes in brain connectivity in healthy volunteers, reflecting alterations in neurotransmitter activity. The cholinergic and the serotonergic neurotransmitter systems are (differentially) targeted in AD, FTLD and DLB dementia. Therefore challenging these systems with a pharmacological agent is expected to enhance patterns of brain dysfunctions that may currently not be observed with functional brain imaging techniques. Hence, this new Ph-RS-FMRI technique may provide new opportunities to develop sensitive early markers of dementia. Here we propose to apply the newly developed Ph-RS-FMRI technique with specific pharmacologic challenges in AD, FTLD and DLB patients, and matched controls, to investigate the sensitivity and specificity of this technique to differentiate between dementias and between dementia and controls.