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

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

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.

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease
• Intervention / Treatment: Diagnostic test: Measure of OxPhos upregulation; Diagnostic test: lactate (measured with 1H-MRSI)

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 37

Contacts and Locations

• Study Contact: Name: Katherine Medina; Phone Number: 212-263-5053; Email: katherine.medina@nyulangone.org

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • New York University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years to 85 years (Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adults (male and female) aged >70 years in overall excellent health with normal cognition (CDR=0), and at least high school graduate level education.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cognitively Normal; having 30 participants with normal cognition	Diagnostic test: Measure of OxPhos upregulation; 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; Diagnostic test: lactate (measured with 1H-MRSI); PIB+ NL subjects will show increased levels of lactate (measured with 1H-MRSI) when compared to PIB- NL subjects in the PETAG mask.
Amnesic MCI; 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; 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; Diagnostic test: lactate (measured with 1H-MRSI); PIB+ NL subjects will show increased levels of lactate (measured with 1H-MRSI) when compared to PIB- NL subjects in the PETAG mask.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Investigators: Principal Investigator: Ryan Brown, MD, New York Langone Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2019
• Primary Completion (Actual): February 24, 2023
• Study Completion (Actual): February 24, 2023

Study Registration Dates

• First Submitted: June 25, 2019
• First Submitted That Met QC Criteria: June 25, 2019
• First Posted (Actual): June 27, 2019

Study Record Updates

• Last Update Posted (Actual): July 3, 2023
• Last Update Submitted That Met QC Criteria: June 29, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: 18-01919

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No