Effect of age on brain metabotropic glutamate receptor subtype 5 measured with [18F]FPEB PET
Adam P. Mecca,
Kelly Rogers,
Zachary Jacobs,
Julia W. McDonald,
Hannah R. Michalak,
Nicole DellaGioia,
Wenzhen Zhao,
Ansel T Hillmer,
Nabeel Nabulsi,
Keunpoong Lim,
Jim Ropchan,
Yiyun Huang,
David Matuskey,
Irina Esterlis,
Richard E. Carson,
Christopher H. van Dyck
Affiliations
Adam P. Mecca
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; Corresponding author.
Kelly Rogers
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
Zachary Jacobs
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
Julia W. McDonald
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
Hannah R. Michalak
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
Nicole DellaGioia
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
Wenzhen Zhao
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
Ansel T Hillmer
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
Nabeel Nabulsi
Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT, USA
Keunpoong Lim
Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT, USA
Jim Ropchan
Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT, USA
Yiyun Huang
Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT, USA
David Matuskey
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
Irina Esterlis
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
Richard E. Carson
Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT, USA
Christopher H. van Dyck
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
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.
