Adam P Mecca1, Kelly Rogers2, Zachary Jacobs2, Julia W McDonald2, Hannah R Michalak2, Nicole DellaGioia3, Wenzhen Zhao2, Ansel T Hillmer4, Nabeel Nabulsi5, Keunpoong Lim5, Jim Ropchan5, Yiyun Huang5, David Matuskey6, Irina Esterlis3, Richard E Carson5, Christopher H van Dyck7. 1. Alzheimer's Disease Research Unit, Yale University School of Medicine, One Church Street, 8th Floor, New Haven, CT, 06514, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA. Electronic address: adam.mecca@yale.edu. 2. Alzheimer's Disease Research Unit, Yale University School of Medicine, One Church Street, 8th Floor, New Haven, CT, 06514, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA. 3. Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA. 4. Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA; Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT, USA. 5. Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT, USA. 6. Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA; Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT, USA; Department of Neurology, Yale University School of Medicine, New Haven, CT, USA. 7. Alzheimer's Disease Research Unit, Yale University School of Medicine, One Church Street, 8th Floor, New Haven, CT, 06514, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA; Department of Neuroscience, Yale University School of Medicine, New Haven, CT, USA; Department of Neurology, Yale University School of Medicine, New Haven, CT, USA.
Abstract
OBJECTIVE: Metabotropic glutamate receptor subtype 5 (mGluR5) is integral to the brain glutamatergic system and cognitive function. This study investigated whether aging is associated with decreased brain mGluR5 availability. METHODS: Cognitively normal participants (n = 45), aged 18 to 84 years, underwent [18F]FPEB positron emission tomography scans to quantify brain mGluR5. Distribution volume (VT) was computed using a venous or arterial input function and equilibrium modeling from 90 to 120 min. In the primary analysis, the association between age and VT in the hippocampus and association cortex was evaluated using a linear mixed model. Exploratory analyses assessed the association between age and VT in multiple brain regions. The contribution of gray matter tissue alterations and partial volume effects to associations with age was also examined. RESULTS: In the primary analysis, older age was associated with lower [18F]FPEB binding to mGluR5 (P = 0.026), whereas this association was not significant after gray matter masking or partial volume correction to account for age-related tissue loss. Post hoc analyses revealed an age-related decline in mGluR5 availability in the hippocampus of 4.5% per decade (P = 0.007) and a non-significant trend in the association cortex (P = 0.085). An exploratory analysis of multiple brain regions revealed broader inverse associations of age with mGluR5 availability, but not after partial volume correction. CONCLUSION: Reductions in mGluR5 availability with age appear to be largely mediated by tissue loss. Quantification of [18F]FPEB binding to mGluR5 may expand our understanding of age-related molecular changes and the relationship with brain tissue loss.
OBJECTIVE: Metabotropic glutamate receptor subtype 5 (mGluR5) is integral to the brain glutamatergic system and cognitive function. This study investigated whether aging is associated with decreased brain mGluR5 availability. METHODS: Cognitively normal participants (n = 45), aged 18 to 84 years, underwent [18F]FPEB positron emission tomography scans to quantify brain mGluR5. Distribution volume (VT) was computed using a venous or arterial input function and equilibrium modeling from 90 to 120 min. In the primary analysis, the association between age and VT in the hippocampus and association cortex was evaluated using a linear mixed model. Exploratory analyses assessed the association between age and VT in multiple brain regions. The contribution of gray matter tissue alterations and partial volume effects to associations with age was also examined. RESULTS: In the primary analysis, older age was associated with lower [18F]FPEB binding to mGluR5 (P = 0.026), whereas this association was not significant after gray matter masking or partial volume correction to account for age-related tissue loss. Post hoc analyses revealed an age-related decline in mGluR5 availability in the hippocampus of 4.5% per decade (P = 0.007) and a non-significant trend in the association cortex (P = 0.085). An exploratory analysis of multiple brain regions revealed broader inverse associations of age with mGluR5 availability, but not after partial volume correction. CONCLUSION: Reductions in mGluR5 availability with age appear to be largely mediated by tissue loss. Quantification of [18F]FPEB binding to mGluR5 may expand our understanding of age-related molecular changes and the relationship with brain tissue loss.
Authors: Susan M Resnick; Dzung L Pham; Michael A Kraut; Alan B Zonderman; Christos Davatzikos Journal: J Neurosci Date: 2003-04-15 Impact factor: 6.167
Authors: H W Müller-Gärtner; J M Links; J L Prince; R N Bryan; E McVeigh; J P Leal; C Davatzikos; J J Frost Journal: J Cereb Blood Flow Metab Date: 1992-07 Impact factor: 6.200
Authors: Xiaotian T Fang; Jonas Eriksson; Gunnar Antoni; Ulrika Yngve; Linda Cato; Lars Lannfelt; Dag Sehlin; Stina Syvänen Journal: Neuropharmacology Date: 2016-10-12 Impact factor: 5.250
Authors: Laura Michiels; Aline Delva; June van Aalst; Jenny Ceccarini; Wim Vandenberghe; Mathieu Vandenbulcke; Michel Koole; Robin Lemmens; Koen Van Laere Journal: Neuroimage Date: 2021-02-24 Impact factor: 6.556
Authors: Adam P Mecca; Nicole M Barcelos; Shuo Wang; Anna Brück; Nabeel Nabulsi; Beata Planeta-Wilson; Jennifer Nadelmann; Amanda L Benincasa; Jim Ropchan; Yiyun Huang; Joel Gelernter; Peter H Van Ness; Richard E Carson; Christopher H van Dyck Journal: Neurobiol Aging Date: 2017-10-06 Impact factor: 4.673
Authors: Dean F Wong; Rikki Waterhouse; Hiroto Kuwabara; Jongho Kim; James R Brašić; Wichana Chamroonrat; Michael Stabins; Daniel P Holt; Robert F Dannals; Terence G Hamill; P David Mozley Journal: J Nucl Med Date: 2013-02-12 Impact factor: 10.057
Authors: Chadi G Abdallah; Jonas Hannestad; Graeme F Mason; Sophie E Holmes; Nicole DellaGioia; Gerard Sanacora; Lihong Jiang; David Matuskey; Ritvij Satodiya; Fabrizio Gasparini; Xin Lin; Jonathan Javitch; Beata Planeta; Nabeel Nabulsi; Richard E Carson; Irina Esterlis Journal: Biol Psychiatry Cogn Neurosci Neuroimaging Date: 2017-04-06
Authors: Mohamed Adil Shah Khoodoruth; Maria Anayali Estudillo-Guerra; Kevin Pacheco-Barrios; Azan Nyundo; Gina Chapa-Koloffon; Sami Ouanes Journal: Front Psychiatry Date: 2022-04-14 Impact factor: 5.435
Authors: James Robert Brašić; Jack Alexander Goodman; Ayon Nandi; David S Russell; Danna Jennings; Olivier Barret; Samuel D Martin; Keith Slifer; Thomas Sedlak; Anil Kumar Mathur; John P Seibyl; Elizabeth M Berry-Kravis; Dean F Wong; Dejan B Budimirovic Journal: Brain Sci Date: 2022-02-26