The distribution of the alpha7 nicotinic acetylcholine receptor in healthy aging: An in vivo positron emission tomography study with [18F]ASEM

Altered function of the alpha7 nicotinic acetylcholine receptor (alpha 7-nAChR) is implicated in several neuropsychiatric diseases. Nevertheless, studies of the human cerebral alpha 7-nAChR even in healthy aging are limited in number and to postmortem tissue. Methods: The distribution of the cerebral alpha 7-nAChR was estimated in nine brain regions in 25 healthy volunteers (ages 21-86 years; median 57 years, interquartile range 52 years) using [F-18]ASEM with positron emission tomography (PET) imaging. Regional total distribution volume (V-T) measurements were calculated using the Logan method from each subject's 90 min dynamic PET data and their metabolite-corrected plasma input function. Spearman's rank or Pearson's correlation analysis was used depending on the normality of the data. Correlation between age and regional 1) volume relative to intracranial volume (volume ratio) and 2) [F-18]ASEM V-T was tested. Correlation between regional volume ratio and [F-18]ASEM V-T was also evaluated. Finally, the relationship between [F-18]ASEM V-T and neuropsychological measures was investigated in a subpopulation of 15 elderly healthy participants (those 50 years of age and older). Bonferroni correction for multiple comparisons was applied to statistical analyses. Results: A negative correlation between tissue volume ratio and age was observed in six of the nine brain regions including striatum and five cortical (temporal, occipital, cingulate, frontal, or parietal) regions. A positive correlation between [F-18]ASEM V-T and age was observed in all nine brain regions of interest (ROIs). There was no correlation between [F-18]ASEM V-T and volume ratio in any ROI after controlling for age. Regional [F-18]ASEM V-T and neuropsychological performance on each of eight representative subtests were not correlated among the well-performing subpopulation of elderly healthy participants. Conclusions: Our results suggest an increase in cerebral alpha 7-nAChR distribution over the course of healthy aging that should be tested in future longitudinal studies. The preservation of the alpha 7-nAChR in the aging human brain supports the development of therapeutic agents that target this receptor for use in the elderly. Further study of the relationship between alpha 7-nAChR availability and cognitive impairment over aging is needed.