In vivo mapping of cholinergic terminals in normal aging, Alzheimer's disease, and Parkinson's disease
Open accessAbstract
To map presynaptic cholinergic terminal densities in normal aging (n = 36), Alzheimer's disease (AD) (n = 22), and Parkinson's disease (PD) (n = 15), we performed single‐photon emission computed tomography using [123 I]iodoben‐zovesamicol (IBVM), an in vivo marker of the vesicular acetylcholine transporter. We used coregistered positron emission tomography with [18 F]fluorodexyglucose for metabolic assessment and coregistered magnetic resonance imaging for atrophy assessment. In controls (age, 22–91 years), cortical IBVM binding declined only 3.7% per decade. In AD, cortical binding correlated inversely with dementia severity. In mild dementia, binding differed according to age of onset, but metabolism did not. With an onset age of less than 65 years, binding was reduced severely throughout the entire cerebral cortex and hippocapus (about 30%), but with an onset age of 65 years or more, binding reductions were restricted to temporal cortex and hippocampus. In PD without dementia, binding was reduced only in parietal and occipital cortex, but demented PD subjects had extensive cortical binding decreases similar to early‐onset AD. We conclude that cholinergic neuron integrity can be monitored in living AD and PD patients, and that it is not so devastated in vivo as suggested by postmortem choline acetylransferase activity (50–80%).
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The complex interaction between cholinergic and other transmitter systems participates in the pathophysiological mechanism of brain electricity slowing and cognitive decline in neurodegenerative diseases.
“Studies have shown that the complex interaction between cholinergic and other transmitter systems participates in the pathophysiological mechanism of brain electricity slowing and cognitive decline in neurodegenerative diseases [42-46].”
From QEEG Signatures are Associated with Nonmotor Dysfunctions in Parkinson's Disease and Atypical Parkinsonism: An Integrative Analysis (2023) · cites this paper as [42]
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- Authors
- Kuhl, D. E., Minoshima, S., Fessler, J. A., Ficaro, E. P., Wieland, D. M., Koeppe, R. A., Frey, K. A., & Foster, N. L.
- Affiliations
- Michigan Medicine (US)
- University of Michigan (US)
- Corresponding author
- Kuhl, D. E.
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 1996-09
- Volume
- 40
- Issue
- 3
- Pages
- 399-410
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W2087485448
- Cited by
- 426
- References
- 73
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 9 · 2023: 6 · 2022: 16 · 2021: 9 · 2020: 16 · 2019: 9 · 2018: 17 · 2017: 11 · 2016: 17 · 2015: 11 · 2014: 14 · 2013: 15 · 2012: 16
- FWCI
- 8.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- Funders
- University of Michigan
- National Institutes of Health (5r01ns024896-15)
- National Institute on Aging (P50AG008671, P50 AG08671)
- National Institute of Neurological Disorders and Stroke (R01 NS24896)
- National Center for Research Resources (M-O1-RR-00042, M01RR000042)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Keywords
- cholinergic nerve terminals, vesicular acetylcholine transporter, Alzheimer's disease, Parkinson's disease, normal aging, dementia severity, age of onset, hippocampus, brain glucose metabolism, brain atrophy, choline acetyltransferase
- MeSH terms
- Aged, Aged, 80 and over, Aging, Alzheimer Disease, Atrophy, Brain Mapping, Cerebral Cortex, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Nerve Endings, Parasympathetic Nervous System, Parkinson Disease, Radiography, Reference Values, Tomography, Emission-Computed, Tomography, Emission-Computed, Single-Photon
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