PhosphoRus, Proton Imaging and Amyloid BuRdEn (PREPARE) ON AMYLOID BURDEN AND COGNITION

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Neuroenergetic Adaptations in Alzheimer's Disease: Implications on Amyloid Burden and Cognition.

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Diagnostic Test: Measure of OxPhos upregulation
* Diagnostic Test: lactate (measured with 1H-MRSI)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: NL Group: Adults (male and female) aged >70 years in overall excellent health with normal cognition (CDR=0), and at least high school graduate level education. aMCI Group: Adults (male and female) aged >70 years, Clinical Dementia Rating (CDR)= 0.5 - 1 and Mini-Mental State Examination (MMSE): 20-25 English as first language or demonstrated proficiency in English for non-native speakers Exclusion Criteria: Any tumor, stroke, or trauma that would result in abnormal radiological findings History of bipolar disorder, schizophrenia, intellectual disability or substance abuse MRI scanner contraindications

Ages Eligible for Study
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Minimum Age: 70 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cognitively Normal<br>having 30 participants with normal cognition | Diagnostic Test: Measure of OxPhos upregulation<br>* 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<br>Diagnostic Test: lactate (measured with 1H-MRSI)<br>* PIB+ NL subjects will show increased levels of lactate (measured with 1H-MRSI) when compared to PIB- NL subjects in the PETAG mask.<br>|
| Amnesic MCI<br>aMCI Group having 15 participants with a CDR of 0.5-1 and a Mini-Mental State Examination (MMSE) of 20-25. | Diagnostic Test: Measure of OxPhos upregulation<br>* 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<br>Diagnostic Test: lactate (measured with 1H-MRSI)<br>* PIB+ NL subjects will show increased levels of lactate (measured with 1H-MRSI) when compared to PIB- NL subjects in the PETAG mask.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| (PCr)-to-ATP ratio levels | These 31P-MRSI data will differentiate PiB+ aMCI individuals from PiB+ NL individuals. | 1 Month |