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

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%).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50361/1/410400309_ftp.pd

Arterial/venous plasma nicotine concentrations following nicotine nasal spray

Background and objectives : Arterial (A) and venous (V) plasma nicotine and cotinine concentrations were measured after nasal nicotine spray in tobacco smokers of both genders. The hypothesis for this research was that a greater A/V difference in plasma nicotine would be present in males than females because males have greater skeletal muscle mass to bind nicotine.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42031/1/228-55-9-639_90550639.pd

Cerebral benzodiazepine receptor binding in vivo in patients with recurrent hepatic encephalopathy

Increased activation of the central benzodiazepine receptor (BZR) appears to play an important role in hepatic encephalopathy (HE). However, there is controversy regarding whether the density or affinity of BZRs is altered. A previous positron emission tomography (PET) study using the BZR antagonist [11C]flumazenil (FMZ) found two- to threefold greater cerebral cortical tracer uptake in recurrent HE, but did not account for impaired FMZ metabolism due to liver disease or assess the relative contributions of tracer delivery versus BZR binding. We hypothesized that correcting for these factors would affect estimations of BZR binding in HE. Nine patients with recurrent HE and 13 age-comparable controls were studied with [11C]FMZ PET. After intravenous administration of [11C]FMZ, arterial blood samples were collected, and PET images were acquired over 60 minutes. FMZ transport and binding maps were calculated for each subject by using a physiological tracer kinetic model. In agreement with the previous report, we found that FMZ reached a much higher level and was retained longer in the HE cerebral cortex despite similar total blood radioactivity levels in the two groups. However, the patients showed impaired hepatic metabolism of FMZ. After physiological modeling incorporating these data, significant increases in BZR binding were found in the thalamus (13%), cerebellum (20%), and pons (23%). There were minor, statistically insignificant increases in cerebral cortical (10%), putamen (12%), and whole brain (12%) BZR binding in patients with recurrent HE. These findings are in general agreement with results of autopsy studies, confirming a lack of major increases in cortical or basal ganglial BZR binding in HE. They emphasize that physiological tracer modeling should be used and altered peripheral radioligand metabolism considered in future PET studies of HE.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34769/1/510260204_ftp.pd