Disruption of cholinergic and serotonergic neurotransmitter systems is associated with cognitive, emotional and behavioural symptoms of Alzheimer's disease (AD). To investigate the responsiveness... Show moreDisruption of cholinergic and serotonergic neurotransmitter systems is associated with cognitive, emotional and behavioural symptoms of Alzheimer's disease (AD). To investigate the responsiveness of these systems in AD we measured the effects of a single-dose of the selective serotonin reuptake inhibitor citalopram and acetylcholinesterase inhibitor galantamine in 12 patients with AD and 12 age-matched controls on functional brain connectivity with resting state functional magnetic resonance imaging. In this randomized, double blind, placebo-controlled crossover study, functional magnetic resonance images were repeatedly obtained before and after dosing, resulting in a dataset of 432 scans. Connectivity maps of ten functional networks were extracted using a dual regression method and drug vs. placebo effects were compared between groups with a multivariate analysis with signals coming from cerebrospinal fluid and white matter as covariates at the subject level, and baseline and heart rate measurements as confound regressors in the higher-level analysis (at p < 0.05, corrected). A galantamine induced difference between groups was observed for the cerebellar network. Connectivity within the cerebellar network and between this network and the thalamus decreased after galantamine vs. placebo in AD patients, but not in controls. For citalopram, voxelwise network connectivity did not show significant group x treatment interaction effects. However, we found default mode network connectivity with the precuneus and posterior cingulate cortex to be increased in AD patients, which could not be detected within the control group. Further, in contrast to the AD patients, control subjects showed a consistent reduction in mean connectivity with all networks after administration of citalopram. Since AD has previously been characterized by reduced connectivity between the default mode network and the precuneus and posterior cingulate cortex, the effects of citalopram on the default mode network suggest a restoring potential of selective serotonin reuptake inhibitors in AD. The results of this study also confirm a change in cerebellar connections in AD, which is possibly related to cholinergic decline. Show less
Klaassens, B.L.; Gerven, J.M.A. van; Klaassen, E.S.; Grond, J. van der; Rombouts, S.A.R.B. 2019
Aging is accompanied by changes in neurotransmission. To advance our understanding of how aging modifies specific neural circuitries, we examined serotonergic and cholinergic stimulation with... Show moreAging is accompanied by changes in neurotransmission. To advance our understanding of how aging modifies specific neural circuitries, we examined serotonergic and cholinergic stimulation with resting state functional magnetic resonance imaging (RS-fMRI) in young and older adults. The instant response to the selective serotonin reuptake inhibitor citalopram (30 mg) and the acetylcholinesterase inhibitor galantamine (8 mg) was measured in 12 young and 17 older volunteers during a randomized, double blind, placebo-controlled, crossover study. A powerful dataset consisting of 522 RS-fMRI scans was obtained by acquiring multiple scans per subject before and after drug administration. Group x treatment interaction effects on voxelwise connectivity with ten functional networks were investigated (p < .05, FWE-corrected) using a non-parametric multivariate analysis technique with cerebrospinal fluid, white matter, heart rate and baseline measurements as covariates. Both groups showed a decrease in sensorimotor network connectivity after citalopram administration. The comparable findings after citalopram intake are possibly due to relatively similar serotonergic systems in the young and older subjects. Galantamine altered connectivity between the occipital visual network and regions that are implicated in learning and memory in the young subjects. The lack of a cholinergic response in the elderly might relate to the well-known association between cognitive and cholinergic deterioration at older age. Show less
Vos, F. de; Koini, M.; Schouten, T.M.; Seiler, S.; Grond, J. van der; Lechner, A.; ... ; Rombouts, S.A.R.B. 2018
The altered iron concentration in many neurodegenerative diseases such as Alzheimer's disease (AD) has led to the development of MRI sequences that are sensitive to the accompanying changes in the... Show moreThe altered iron concentration in many neurodegenerative diseases such as Alzheimer's disease (AD) has led to the development of MRI sequences that are sensitive to the accompanying changes in the transverse relaxation rate. Heavily T-2*-weighted imaging sequences at high magnetic field strength (7 T and above), in particular, show potential for detecting small changes in iron concentration. However, these sequences require a long echo time in combination with a long scanning time for high resolution and are therefore prone to image artifacts caused by physiological fluctuations, patient motion or system instabilities. Many groups have found that the high image quality that was obtained using high resolution T-2*-weighted sequences at 7 T in healthy volunteers, could not be obtained in AD patients. In this study the source of the image artifacts was investigated in phantom and in healthy volunteer experiments by incorporating movement parameters and resonance frequency (f0) variations which were measured in AD patients. It was found that image degradation caused by typical f0 variations was a factor-of-four times larger than artifacts caused by movement characteristic of AD patients in the scanner. In addition to respiratory induced f0 variations, large jumps in the f0 were observed in AD patients. By implementing a navigator echo technique to correct for f0 variations, the image quality of high resolution T-2*-weighted images increased considerably. This technique was successfully applied in five AD patients and in five subjective memory complainers. Visual scoring showed improvements in image quality in 9 out of 10 subjects. Ghosting levels were reduced by 24 +/- 13%. (C) 2010 Elsevier Inc. All rights reserved. Show less
