In this Japanese PET study, acetylcholinesterase activity in the brain was measured in seven CBS patients, 12 PSP patients, and 8 FTD (frontotemporal dementia) patients.
Acetylcholine is a neurotransmitter that helps with cognition. By measuring “acetylcholinesterase activity, we can assess the integrity of the…cholinergic system.”
“Cerebral cortical acetylcholinesterase activity was moderately reduced in corticobasal syndrome and mildly reduced in progressive supranuclear palsy, while thalamic acetylcholinesterase activity was remarkably reduced only in progressive supranuclear palsy.”
The FTD group showed no decline in acetylcholinesterase activity. The authors make the point that acetylcholinesterase inhibitors (AChEIs include Aricept, Exelon, and Razadyne) are of no value in FTD.
The authors “found a correlation between MMSE scores and cortical acetylcholinesterase activity in the corticobasal syndrome group, suggesting that cognitive decline might be caused by cholinergic dysfunction in corticobasal syndrome.” From those in our local support group and on the CBD-related Yahoo!Group, it seems that AChEIs are of limited value in CBS.
Anecdotal evidence also indicates that AChEIs are of limited value in PSP. Further, the authors note: “In spite of the mounting evidence of cholinergic impairment in the brain of patients with progressive supranuclear palsy, a number of drug trial studies have failed to show beneficial effects of cholinergic stimulant therapy. … Other forms of acetylcholine modulating agent might be helpful for improving clinical symptoms in patients with progressive supranuclear palsy.” I’m not sure what “other forms” includes.
The authors compare the cholinergic deficits in CBS and PSP to those with Alzheimer’s Disease and other disorders. “We have studied brain acetylcholinesterase activity in other neurodegenerative diseases by PET and found that mean reduction of cortical acetylcholinesterase activity, compared with normal controls, was 13% in mild to moderate late-onset Alzheimer’s disease, 23% in mild to moderate early-onset Alzheimer’s disease, 12% in Parkinson’s disease without dementia, 27% in Parkinson’s disease with dementia and dementia with Lewy bodies, 21 and 36% in two patients with N279K FTDP-17 and 6% in a cerebellar variant of multiple system atrophy. Compared with the reduction of cortical acetylcholinesterase activities in these disorders, the reduction of cortical acetylcholinesterase was moderate [17.5%] in corticobasal syndrome and mild [9.4%] in progressive supranuclear palsy.”
I’ve copied the abstract below.
Robin
Brain. 2010 Jun 17. [Epub ahead of print]
Cholinergic imaging in corticobasal syndrome, progressive supranuclear palsy and frontotemporal dementia.
Hirano S, Shinotoh H, Shimada H, Aotsuka A, Tanaka N, Ota T, Sato K, Ito H, Kuwabara S, Fukushi K, Irie T, Suhara T.
Molecular Neuroimaging Group, Molecular Imaging Centre, National Institute of Radiological Sciences, Chiba, Japan.
Abstract
Corticobasal syndrome, progressive supranuclear palsy and frontotemporal dementia are all part of a disease spectrum that includes common cognitive impairment and movement disorders. The aim of this study was to characterize brain cholinergic deficits in these disorders.
We measured brain acetylcholinesterase activity by [(11)C] N-methylpiperidin-4-yl acetate and positron emission tomography in seven patients with corticobasal syndrome (67.6 +/- 5.9 years), 12 with progressive supranuclear palsy (68.5 +/- 4.1 years), eight with frontotemporal dementia (59.8 +/- 6.9 years) and 16 healthy controls (61.2 +/- 8.5 years).
Two-tissue compartment three-parameter model and non-linear least squares analysis with arterial input function were performed. k(3) value, an index of acetylcholinesterase activity, was calculated voxel-by-voxel in the brain of each subject. The k(3) images in each disease group were compared with the control group by using Statistical Parametric Mapping 2. Volume of interest analysis was performed on spatially normalized k(3) images.
The corticobasal syndrome group showed decreased acetylcholinesterase activity (k(3) values) in the paracentral region, frontal, parietal and occipital cortices (P < 0.05, cluster corrected).
The group with progressive supranuclear palsy had reduced acetylcholinesterase activity in the paracentral region and thalamus (P < 0.05, cluster corrected).
The frontotemporal dementia group showed no significant differences in acetylcholinesterase activity.
Volume of interest analysis showed mean cortical acetylcholinesterase activity to be reduced by 17.5% in corticobasal syndrome (P < 0.001), 9.4% in progressive supranuclear palsy (P < 0.05) and 4.4% in frontotemporal dementia (non-significant), when compared with the control group. Thalamic acetylcholinesterase activity was reduced by 6.4% in corticobasal syndrome (non-significant), 24.0% in progressive supranuclear palsy (P < 0.03) and increased by 3.3% in frontotemporal dementia (non-significant).
Both corticobasal syndrome and progressive supranuclear palsy showed brain cholinergic deficits, but their distribution differed somewhat. Significant brain cholinergic deficits were not seen in frontotemporal dementia, which may explain the unresponsiveness of this condition to cholinergic modulation therapy.
PubMed ID#: 20558417 (see pubmed.gov for this abstract only)