Phosphorus metabolism in the brain of cognitively normal midlife individuals at risk for Alzheimer's disease
Background: Neurometabolic abnormalities and amyloid-beta plaque deposition are important early pathophysiologic changes in Alzheimer's disease (AD). This study investigated the relationship between high-energy phosphorus-containing metabolites, glucose uptake, and amyloid plaque using phosphor...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-12-01
|
| Series: | NeuroImage: Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666956022000459 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849315860241448960 |
|---|---|
| author | Prodromos Parasoglou Ricardo S. Osorio Oleksandr Khegai Zanetta Kovbasyuk Margo Miller Amanda Ho Seena Dehkharghani Thomas Wisniewski Antonio Convit Lisa Mosconi Ryan Brown |
| author_facet | Prodromos Parasoglou Ricardo S. Osorio Oleksandr Khegai Zanetta Kovbasyuk Margo Miller Amanda Ho Seena Dehkharghani Thomas Wisniewski Antonio Convit Lisa Mosconi Ryan Brown |
| author_sort | Prodromos Parasoglou |
| collection | DOAJ |
| description | Background: Neurometabolic abnormalities and amyloid-beta plaque deposition are important early pathophysiologic changes in Alzheimer's disease (AD). This study investigated the relationship between high-energy phosphorus-containing metabolites, glucose uptake, and amyloid plaque using phosphorus magnetic resonance spectroscopy (31P-MRS) and positron emission tomography (PET). Methods: We measured 31P-MRS, fluorodeoxyglucose (FDG)-PET, and Pittsburgh Compound B (PiB)-PET in a cohort of 20 cognitively normal middle-aged adults at risk for AD. We assessed 31P-MRS reliability by scanning a separate cohort of 13 healthy volunteers twice each. We calculated the coefficient-of-variation (CV) of metabolite ratios phosphocreatine-to-adenosine triphosphate (PCr/α-ATP), inorganic phosphate (Pi)-to-α-ATP, and phosphomonoesters-to-phosphodiesters (PME/PDE), and pH in pre-defined brain regions. We performed linear regression analysis to determine the relationship between 31P measurements and tracer uptake, and Dunn's multiple comparison tests to investigate regional differences in phosphorus metabolism. Finally, we performed linear regression analysis on 31P-MRS measurements in both cohorts to investigate the relationship of phosphorus metabolism with age. Results: Most regional 31P metabolite ratio and pH inter- and intra-day CVs were well below 10%. There was an inverse relationship between FDG-SUV levels and metabolite ratios PCr/α-ATP, Pi/α-ATP, and PME/PDE in several brain regions in the AD risk group. There were also several regional differences among 31P metabolites and pH in the AD risk group including elevated PCr/α-ATP, depressed PME/PDE, and elevated pH in the temporal cortices. Increased PCr/α-ATP throughout the brain was associated with aging. Conclusions: Phosphorus spectroscopy in the brain can be performed with high repeatability. Phosphorus metabolism varies with region and age, and is related to glucose uptake in adults at risk for AD. Phosphorus spectroscopy may be a valuable approach to study early changes in brain energetics in high-risk populations. |
| format | Article |
| id | doaj-art-bc6c712653d9421f8a3f831bf142d131 |
| institution | Kabale University |
| issn | 2666-9560 |
| language | English |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | NeuroImage: Reports |
| spelling | doaj-art-bc6c712653d9421f8a3f831bf142d1312025-08-20T03:52:02ZengElsevierNeuroImage: Reports2666-95602022-12-012410012110.1016/j.ynirp.2022.100121Phosphorus metabolism in the brain of cognitively normal midlife individuals at risk for Alzheimer's diseaseProdromos Parasoglou0Ricardo S. Osorio1Oleksandr Khegai2Zanetta Kovbasyuk3Margo Miller4Amanda Ho5Seena Dehkharghani6Thomas Wisniewski7Antonio Convit8Lisa Mosconi9Ryan Brown10Center for Advanced Imaging Innovation and Research, Department of Radiology, New York University Grossman School of Medicine, New York, NY, USADepartment of Psychiatry, New York University School of Medicine, New York, NY, USACenter for Advanced Imaging Innovation and Research, Department of Radiology, New York University Grossman School of Medicine, New York, NY, USADepartment of Psychiatry, New York University School of Medicine, New York, NY, USADepartment of Psychiatry, New York University School of Medicine, New York, NY, USACenter for Advanced Imaging Innovation and Research, Department of Radiology, New York University Grossman School of Medicine, New York, NY, USACenter for Advanced Imaging Innovation and Research, Department of Radiology, New York University Grossman School of Medicine, New York, NY, USA; Department of Neurology, Center for Cognitive Neurology, New York University Grossman School of Medicine, New York, NY, USADepartment of Psychiatry, New York University School of Medicine, New York, NY, USA; Department of Neurology, Center for Cognitive Neurology, New York University Grossman School of Medicine, New York, NY, USA; Department of Pathology, New York University Grossman School of Medicine, New York, NY, USADepartment of Psychiatry, New York University School of Medicine, New York, NY, USA; Nathan S Kline Institute for Psychiatric Research, Orangeburg, NY, USADepartment of Neurology, Weill Cornell Medical College, New York, NY, USA; Department of Radiology, Weill Cornell Medical College, New York, NY, USACenter for Advanced Imaging Innovation and Research, Department of Radiology, New York University Grossman School of Medicine, New York, NY, USA; Corresponding author. 660 First Ave, Room 404, New York, NY, 212-263-3396, USA.Background: Neurometabolic abnormalities and amyloid-beta plaque deposition are important early pathophysiologic changes in Alzheimer's disease (AD). This study investigated the relationship between high-energy phosphorus-containing metabolites, glucose uptake, and amyloid plaque using phosphorus magnetic resonance spectroscopy (31P-MRS) and positron emission tomography (PET). Methods: We measured 31P-MRS, fluorodeoxyglucose (FDG)-PET, and Pittsburgh Compound B (PiB)-PET in a cohort of 20 cognitively normal middle-aged adults at risk for AD. We assessed 31P-MRS reliability by scanning a separate cohort of 13 healthy volunteers twice each. We calculated the coefficient-of-variation (CV) of metabolite ratios phosphocreatine-to-adenosine triphosphate (PCr/α-ATP), inorganic phosphate (Pi)-to-α-ATP, and phosphomonoesters-to-phosphodiesters (PME/PDE), and pH in pre-defined brain regions. We performed linear regression analysis to determine the relationship between 31P measurements and tracer uptake, and Dunn's multiple comparison tests to investigate regional differences in phosphorus metabolism. Finally, we performed linear regression analysis on 31P-MRS measurements in both cohorts to investigate the relationship of phosphorus metabolism with age. Results: Most regional 31P metabolite ratio and pH inter- and intra-day CVs were well below 10%. There was an inverse relationship between FDG-SUV levels and metabolite ratios PCr/α-ATP, Pi/α-ATP, and PME/PDE in several brain regions in the AD risk group. There were also several regional differences among 31P metabolites and pH in the AD risk group including elevated PCr/α-ATP, depressed PME/PDE, and elevated pH in the temporal cortices. Increased PCr/α-ATP throughout the brain was associated with aging. Conclusions: Phosphorus spectroscopy in the brain can be performed with high repeatability. Phosphorus metabolism varies with region and age, and is related to glucose uptake in adults at risk for AD. Phosphorus spectroscopy may be a valuable approach to study early changes in brain energetics in high-risk populations.http://www.sciencedirect.com/science/article/pii/S2666956022000459Phosphorus magnetic resonance spectroscopyBrain energy metabolismPositron emission tomography |
| spellingShingle | Prodromos Parasoglou Ricardo S. Osorio Oleksandr Khegai Zanetta Kovbasyuk Margo Miller Amanda Ho Seena Dehkharghani Thomas Wisniewski Antonio Convit Lisa Mosconi Ryan Brown Phosphorus metabolism in the brain of cognitively normal midlife individuals at risk for Alzheimer's disease NeuroImage: Reports Phosphorus magnetic resonance spectroscopy Brain energy metabolism Positron emission tomography |
| title | Phosphorus metabolism in the brain of cognitively normal midlife individuals at risk for Alzheimer's disease |
| title_full | Phosphorus metabolism in the brain of cognitively normal midlife individuals at risk for Alzheimer's disease |
| title_fullStr | Phosphorus metabolism in the brain of cognitively normal midlife individuals at risk for Alzheimer's disease |
| title_full_unstemmed | Phosphorus metabolism in the brain of cognitively normal midlife individuals at risk for Alzheimer's disease |
| title_short | Phosphorus metabolism in the brain of cognitively normal midlife individuals at risk for Alzheimer's disease |
| title_sort | phosphorus metabolism in the brain of cognitively normal midlife individuals at risk for alzheimer s disease |
| topic | Phosphorus magnetic resonance spectroscopy Brain energy metabolism Positron emission tomography |
| url | http://www.sciencedirect.com/science/article/pii/S2666956022000459 |
| work_keys_str_mv | AT prodromosparasoglou phosphorusmetabolisminthebrainofcognitivelynormalmidlifeindividualsatriskforalzheimersdisease AT ricardososorio phosphorusmetabolisminthebrainofcognitivelynormalmidlifeindividualsatriskforalzheimersdisease AT oleksandrkhegai phosphorusmetabolisminthebrainofcognitivelynormalmidlifeindividualsatriskforalzheimersdisease AT zanettakovbasyuk phosphorusmetabolisminthebrainofcognitivelynormalmidlifeindividualsatriskforalzheimersdisease AT margomiller phosphorusmetabolisminthebrainofcognitivelynormalmidlifeindividualsatriskforalzheimersdisease AT amandaho phosphorusmetabolisminthebrainofcognitivelynormalmidlifeindividualsatriskforalzheimersdisease AT seenadehkharghani phosphorusmetabolisminthebrainofcognitivelynormalmidlifeindividualsatriskforalzheimersdisease AT thomaswisniewski phosphorusmetabolisminthebrainofcognitivelynormalmidlifeindividualsatriskforalzheimersdisease AT antonioconvit phosphorusmetabolisminthebrainofcognitivelynormalmidlifeindividualsatriskforalzheimersdisease AT lisamosconi phosphorusmetabolisminthebrainofcognitivelynormalmidlifeindividualsatriskforalzheimersdisease AT ryanbrown phosphorusmetabolisminthebrainofcognitivelynormalmidlifeindividualsatriskforalzheimersdisease |