TY - JOUR
T1 - The distribution of the alpha7 nicotinic acetylcholine receptor in healthy aging
T2 - An in vivo positron emission tomography study with [18F]ASEM
AU - Coughlin, Jennifer M.
AU - Du, Yong
AU - Rosenthal, Hailey B.
AU - Slania, Stephanie
AU - Min Koo, Soo
AU - Park, Andrew
AU - Solomon, Ghedem
AU - Vranesic, Melin
AU - Antonsdottir, Inga
AU - Speck, Caroline L.
AU - Rootes-Murdy, Kelly
AU - Lerner, Alexandria
AU - Rowe, Steven P.
AU - Wang, Yuchuan
AU - Lesniak, Wojciech G.
AU - Minn, Il
AU - Bakker, Arnold
AU - Smith, Gwenn S.
AU - Dannals, Robert F.
AU - Kuwabara, Hiroto
AU - Horti, Andrew
AU - Wong, Dean F.
AU - Pomper, Martin G.
N1 - Funding Information:
This work was supported by the Henry N. Wagner, Jr. Endowment (MGP), a Johns Hopkins Doris Duke Early Clinician Investigator Award (JC), the Alexander Wilson Schweizer Fellowship (JC), and the National Institutes of Health [R01 MH107197 (DFW and AH), AG038893 (GSS), AG041633 (GSS), Shared Instrument Grants S10RR023623 (DFW), S10RR017219 (DFW)]. The authors would also like to thank the Johns Hopkins PET Center for expert provision of [ 18 F]ASEM, with special thanks to Alimamy Kargbo for PET metabolite analyses. We thank Lorena Gapasin, BSN, MS who assisted in regulatory matters and Josh Roberts, PhD and Kelly Kitzmiller, BS who assisted in recruitment and characterization of some of the younger healthy subjects. We also give special thanks to Yukiko Lema for assistance in the figure design. Appendix A
Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2018/1/15
Y1 - 2018/1/15
N2 - 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.
AB - 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.
KW - Alpha7 nicotinic acetylcholine receptor
KW - Healthy aging
KW - PET imaging
KW - [ F]ASEM
UR - http://www.scopus.com/inward/record.url?scp=85032856764&partnerID=8YFLogxK
U2 - 10.1016/j.neuroimage.2017.10.009
DO - 10.1016/j.neuroimage.2017.10.009
M3 - Article
C2 - 28993233
AN - SCOPUS:85032856764
SN - 1053-8119
VL - 165
SP - 118
EP - 124
JO - NeuroImage
JF - NeuroImage
ER -