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

Alzheimer Disease Clinical Trial

— PREPARE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03999879
• Other study ID #: 18-01919
• Status: Completed
• Start date: May 1, 2019
• Est. completion date: February 24, 2023

Study information

• Verified date: June 2023
• Source: NYU Langone Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: February 24, 2023
• Est. primary completion date: February 24, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 70 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

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
• 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.

Locations

Country	Name	City	State
United States	New York University School of Medicine	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
NYU Langone Health

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	(PCr)-to-ATP ratio levels	These 31P-MRSI data will differentiate PiB+ aMCI individuals from PiB+ NL individuals.	1 Month