BACKGROUND: Treatment of Alzheimer's disease (AD) withcholinesterase inhibitors (ChEI) enhances cholinergic activity and alleviates clinical symptoms. However, there is variation in the clinical response as well as system level changes revealed by functional MRI (fMRI) studies. METHODS: We investigated 18 newly diagnosed mild AD patients with fMRI using a face recognition task after a single oral dose ofrivastigmine, a single dose of placebo and 1-month treatment with rivastigmine. The clinical follow-up took place at 6 and 12 months. RESULTS:MMSE score difference between baseline and the follow-ups showed a positive correlation with fMRI activation difference between treatment and placebo in the right prefrontal cortex. A negative correlation was found for the left prefrontal cortex and the left fusiform gyrus. In addition, greater signal intensity in the right versus the left fusiform gyrus predicted a response to ChEI with increasing MMSE scores during the follow-up with 77.8% sensitivity and 77.8% specificity. CONCLUSIONS: The increased fMRI activation by cholinergic stimulation in brain areas associated with the processing of the visual task reveals still functioning brain networks and a subsequent positive effect of ChEI on cognition. Thus, fMRI may be useful for identifying AD patients most likely to respond to treatment with ChEI.
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BACKGROUND: Treatment of Alzheimer's disease (AD) with cholinesterase inhibitors (ChEI) enhances cholinergic activity and alleviates clinical symptoms. However, there is variation in the clinical response as well as system level changes revealed by functional MRI (fMRI) studies. METHODS: We investigated 18 newly diagnosed mild ADpatients with fMRI using a face recognition task after a single oral dose of rivastigmine, a single dose of placebo and 1-month treatment with rivastigmine. The clinical follow-up took place at 6 and 12 months. RESULTS: MMSE score difference between baseline and the follow-ups showed a positive correlation with fMRI activation difference between treatment and placebo in the right prefrontal cortex. A negative correlation was found for the left prefrontal cortex and the left fusiform gyrus. In addition, greater signal intensity in the right versus the left fusiform gyrus predicted a response to ChEI with increasing MMSE scores during the follow-up with 77.8% sensitivity and 77.8% specificity. CONCLUSIONS: The increased fMRI activation by cholinergic stimulation in brain areas associated with the processing of the visual task reveals still functioning brain networks and a subsequent positive effect of ChEI on cognition. Thus, fMRI may be useful for identifying ADpatients most likely to respond to treatment with ChEI.
Authors: Matthew C Murphy; Ian P Conner; Cindy Y Teng; Jesse D Lawrence; Zaid Safiullah; Bo Wang; Richard A Bilonick; Seong-Gi Kim; Gadi Wollstein; Joel S Schuman; Kevin C Chan Journal: Sci Rep Date: 2016-08-11 Impact factor: 4.379