Journal
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
Volume 32, Issue 8, Pages 1609-1617Publisher
SAGE PUBLICATIONS INC
DOI: 10.1038/jcbfm.2012.60
Keywords
acetylcholinesterase; cognitive impairment; dopamine; motor; Parkinson's disease; PET
Categories
Funding
- Department of Veterans Affairs
- Michael J. Fox Foundation
- NIH [P01 NS015655, RO1 NS070856]
- NIH (NINDS, NIA)
- Bayer
- General Electric Medical Systems
- Avid Radiopharmaceuticals
- GE Healthcare
- AVID Radiopharmaceuticals (Eli Lilly)
Ask authors/readers for more resources
Parkinson's disease (PD) is a multisystem neurodegenerative disorder. Heterogeneous clinical features may reflect heterogeneous changes in different brain regions. In contrast to the pronounced nigrostriatal denervation characteristic of PD, cholinergic changes are less marked. We investigated cholinergic innervation activity in PD subjects relative to normal subjects. Nondemented PD subjects (n = 101, age 65.3 +/- 7.2 years) and normal subjects (n = 29, age 66.8 +/- 10.9 years) underwent clinical assessment and [C-11]methyl-4-piperidinyl propionate acetylcholinesterase and [C-11] dihydrotetrabenazine monoaminergic positron emission tomography (PET) imaging. Cholinergic projection changes were heterogeneous for 65 out of 101 PD subjects who had neocortical and thalamic acetylcholinesterase activity within the normal range. The remainder had combined neocortical and thalamic (13/101), isolated neocortical (18/101), or isolated thalamic (5/101) acetylcholinesterase activity below the normal range. The low neocortical acetylcholinesterase activity subgroup had significantly lower global cognitive performance compared with the normal range subgroup (F = 7.64, P = 0.0069) with an independent effect for nigrostriatal denervation (F = 7.60, P = 0.0074). The low thalamic acetylcholinesterase activity subgroup did not differ from the normal thalamic acetylcholinesterase activity subgroup in cognitive performance or motor impairments except for a history of falls (P = 0.0023). Cholinergic denervation is heterogeneous with reduced neocortical and/or thalamic acetylcholinesterase activity in 36% of nondemented PD subjects with corresponding clinical phenotypic variation. Results also show independent cognitive effects for both cholinergic and dopaminergic system changes in nondemented PD subjects. Journal of Cerebral Blood Flow & Metabolism (2012) 32, 1609-1617; doi: 10.1038/jcbfm.2012.60; published online 9 May 2012
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available