Jennifer M Coughlin1, Yong Du2, Hailey B Rosenthal2, Stephanie Slania3, Soo Min Koo2, Andrew Park2, Ghedem Solomon2, Melin Vranesic2, Inga Antonsdottir4, Caroline L Speck4, Kelly Rootes-Murdy4, Alexandria Lerner4, Steven P Rowe2, Yuchuan Wang2, Wojciech G Lesniak2, Il Minn2, Arnold Bakker4, Gwenn S Smith1, Robert F Dannals2, Hiroto Kuwabara2, Andrew Horti2, Dean F Wong5, Martin G Pomper6. 1. Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD, USA. 2. Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD, USA. 3. Department of Biomedical Engineering, Johns Hopkins Medical Institutions, Baltimore, MD, USA. 4. Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, MD, USA. 5. Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Department of Neuroscience, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Department of Neurology, Johns Hopkins Medical Institutions, Baltimore, MD, USA. 6. Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD, USA. Electronic address: mpomper@jhmi.edu.
Abstract
Altered function of the alpha7 nicotinic acetylcholine receptor (α7-nAChR) is implicated in several neuropsychiatric diseases. Nevertheless, studies of the human cerebral α7-nAChR even in healthy aging are limited in number and to postmortem tissue. METHODS: The distribution of the cerebral α7-nAChR was estimated in nine brain regions in 25 healthy volunteers (ages 21-86 years; median 57 years, interquartile range 52 years) using [18F]ASEM with positron emission tomography (PET) imaging. Regional total distribution volume (VT) 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) [18F]ASEM VT was tested. Correlation between regional volume ratio and [18F]ASEM VT was also evaluated. Finally, the relationship between [18F]ASEM VT 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 [18F]ASEM VT and age was observed in all nine brain regions of interest (ROIs). There was no correlation between [18F]ASEM VT and volume ratio in any ROI after controlling for age. Regional [18F]ASEM VT 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 α7-nAChR distribution over the course of healthy aging that should be tested in future longitudinal studies. The preservation of the α7-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 α7-nAChR availability and cognitive impairment over aging is needed.
Altered function of the alpha7 nicotinic acetylcholine receptor (α7-nAChR) is implicated in several neuropsychiatric diseases. Nevertheless, studies of the human cerebral α7-nAChR even in healthy aging are limited in number and to postmortem tissue. METHODS: The distribution of the cerebral α7-nAChR was estimated in nine brain regions in 25 healthy volunteers (ages 21-86 years; median 57 years, interquartile range 52 years) using [18F]ASEM with positron emission tomography (PET) imaging. Regional total distribution volume (VT) 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) [18F]ASEMVT was tested. Correlation between regional volume ratio and [18F]ASEMVT was also evaluated. Finally, the relationship between [18F]ASEMVT 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 [18F]ASEMVT and age was observed in all nine brain regions of interest (ROIs). There was no correlation between [18F]ASEMVT and volume ratio in any ROI after controlling for age. Regional [18F]ASEMVT 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 α7-nAChR distribution over the course of healthy aging that should be tested in future longitudinal studies. The preservation of the α7-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 α7-nAChR availability and cognitive impairment over aging is needed.
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