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Normal cells primarily produce energy with the help of the "mitochondria". These "small organs" are also called the "powerhouses of the cell" turn the sugars, fats and proteins that is eaten into forms of chemical energy that the body can use to carry on living. This process is called oxidative phosphorylation. In addition to the help from the mitochondria and oxidative phosphorylation, most cells can produce energy by lactic acid fermentation. This process is less energy efficient but faster and used by the brain, muscle or other organs under specific circumstances and energy demands, even in the presence of abundant oxygen. It is also called aerobic glycolysis. Aerobic glycolysis and oxidative phosphorylation are the two major mechanisms involved in brain energetics.
The consequences of Alzheimer's disease (AD) (deposition of amyloid plaques and neurofibrillary tangles) are known. The cause of these deposition of proteins is not. Some scientist argue that an increase in oxidative phosphorylation activity and a lack of ability to shift to aerobic glycolysis are the underlying source of these changes. The purpose of this study is to test whether there is a correlation between neuroenergetic levels of aerobic glycolysis/oxidative phosphorylation and risk for Alzheimer's disease. The study will examine these neuroenergetic adaptations in a group of 15 elderly participants (age range: 70-85 y/o) with amnestic mild cognitive impairment (aMCI) and 30 cognitively normal controls (NL). Multimodal (MR/PET) and multinuclear (31P/1H) neuroimaging will allow us to gain access to a uniquely comprehensive and highly consistent view of neuroenergetic adaptations in both the clinical and preclinical stages of Alzheimer's disease.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cognitively Normal | having 30 participants with normal cognition |
| |
| Amnesic MCI | aMCI Group having 15 participants with a CDR of 0.5-1 and a Mini-Mental State Examination (MMSE) of 20-25. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Measure of OxPhos upregulation | Diagnostic Test | OxPhos upregulation [i.e., lower phosphocreatine (PCr)-to-ATP ratio levels] in the PET AG mask. PIB+ NL subjects will show OxPhos downregulation (i.e. increased PCr/ATP ratio that indicate the presence of metabolically inert PCr that cannot be used as ATP) when compared to PIB- NL subjects in the PETAG mask |
| Measure | Description | Time Frame |
|---|---|---|
| (PCr)-to-ATP ratio levels | These 31P-MRSI data will differentiate PiB+ aMCI individuals from PiB+ NL individuals. | 1 Month |
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Inclusion Criteria:
Exclusion Criteria:
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Adults (male and female) aged >70 years in overall excellent health with normal cognition (CDR=0), and at least high school graduate level education.
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| Name | Affiliation | Role |
|---|---|---|
| Ryan Brown, MD | New York Langone Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| New York University School of Medicine | New York | New York | 10016 | United States |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| ICF | No | No | Yes | Informed Consent Form | May 9, 2022 | Jun 28, 2023 | ICF_000.pdf |
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| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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|
| lactate (measured with 1H-MRSI) | Diagnostic Test | PIB+ NL subjects will show increased levels of lactate (measured with 1H-MRSI) when compared to PIB- NL subjects in the PETAG mask. |
|
| D024801 |
| Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |