In vivo mapping of cholinergic terminals in normal aging, Alzheimer's disease, and Parkinson's disease

Abstract

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 [123I]iodobenzovesamicol (IBVM), an in vivo marker of the vesicular acetylcholine transporter. We used coregistered positron emission tomography with [18F]fluorodeoxyglucose 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 hippocampus (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 acetyltransferase activity (50-80%).

Heterogeneity of Cholinergic Denervation in Parkinson's Disease without Dementia

“…In vivo imaging studies have also shown that the presence of dementia in PD is associated with more severe and widespread cholinergic denervation compared with PD without dementia (Bohnen et al, 2003;Hilker et al, 2005;Kuhl et al, 1996;Shinotoh et al, 1999). These imaging results are consistent with post-mortem evidence that basal forebrain cholinergic system degeneration appears early in PD and worsens in parallel with the appearance of dementia (Ruberg et al, 1986).…”

Comparison of Noninvasive Quantification Methods of in Vivo Vesicular Acetylcholine Transporter Using [123I]-IBVM SPECT Imaging

“…In other studies, it was shown that as the disease progresses in AD patients, the levels of VAChT change in a similar fashion and magnitude to other cholinergic marker proteins, in particular choline acetyltransferase, supporting the interest in [ 123 I]-IBVM as an in vivo radioligand for imaging of neurodegenerative disease impairments, such as AD and DLB (Kuhl et al, 1996(Kuhl et al, , 1999. More recently, using […”

Basal forebrain integrity and cognitive memory profile in healthy aging

“…In the cholinergic system, neurons in the NBM are very prone to accumulate neurofibrillary tangles (Mesulam, 2004a,b), such that tangles in this region are also observed in healthy elderly people (Mesulam, 2004b;Sassin et al, 2000). Even in the absence of neuronal loss, the accumulation of such tangles in the NBM can be associated with a decrease in cholinergic neurotransmission as revealed by postmortem counts of cholinergic axons (Geula and Mesulam, 1989) and by in vivo SPECT mapping of cholinergic terminals (Kuhl et al, 1996). In animal studies (e.g., Weible et al, 2004;Woodruff-Pak et al, 2001) and in patients with Alzheimer's disease cognitive improvement can be achieved by nicotinergic as well as muscarinic receptor action (Oh et al, 2005;Raskind et al, 2000;Tariot et al, 2000).…”