Supplementing Neuro-Energy to Aid Cognition

Simultaneous PET/MR Imaging of Brain Glucose and Oxygen Metabolism to Assess Energy Deficits Related to Alzheimer's Disease and the Response to Intervention

It is projected that by 2030, one in every five Americans will be of retirement age, and this demographic shift is expected to result in more people suffering from dementia. A key feature of the brain is its need for a constant supply of glucose and oxygen to meet the high energy costs of mental activity. This study aims to develop clinically practical, noninvasive imaging methods based on combined positron emission tomography and magnetic resonance imaging to assess brain energy in order to better understand how this critical component of brain health is impacted by aging.

Study Overview

• Status: Not yet recruiting
• Conditions: Alzheimer Disease and Related Dementias (ADRD)
• Intervention / Treatment: Dietary supplement: Ketogenic Supplement; Other: Placebo Drink

Detailed Description

There are now close to six million people in the Unites States living with dementia and this number is only expected to grow as the population continues to age. The current lack of effective treatments for Alzheimer's disease (AD) speaks to the need to better understand the multiple factors that contribute to this complex disease. There is growing evidence that age-related metabolic dysfunction in the brain plays a role in the disease's etiology. This concept has led to treatments aimed at improving brain energy production. Notably, ketogenic dietary supplements have been shown to increase brain ketone metabolism and improve cognitive performance in AD patients. However, the overall benefits to brain metabolism in the AD brain are unknown given the complexity of imaging both oxygen and glucose metabolism in a single session by positron emission tomography (PET). Taking advantage of hybrid PET/MR imaging, this study will combine PET and MRI methods to investigate the effects of a ketogenic supplement on brain oxygen and glucose metabolism in AD patients.

• Study Type: Interventional
• Enrollment (Estimated): 17
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Keith St Lawrence, PhD; Phone Number: 65737 (519) 646-6100; Email: kstlawr@uwo.ca

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 4BQ
      • Lawson Research Institute
      • Contact: Keith St Lawrence, PhD; Phone Number: 65737 (519) 646-6100; Email: kstlawr@uwo.ca
      • Contact: Erain Pagana, NP; Phone Number: (519) 646-6100; Email: erin.pagana@sjhc.london.on.ca
      • Principal Investigator: Keith St Lawrence, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria - Healthy Participants: Males and females, Age 21 - 80 years, BMI of 18.5-30

Inclusion Criteria - Alzheimer's Disease Participants: Positive amyloid and tau biomarkers (as noted by PET imaging, cerebrospinal fluid or blood), Mild cognitive impairment or mild-to-moderate dementia, BMI of 18.5-30

Exclusion Criteria: Contraindications to MRI (claustrophobia, metal implants, pacemakers, etc.), Pregnant or breastfeeding women, Neurological disease (healthy participants only), Mental illness, Overt cardio- or neurovascular disease, Recent participation in any procedure(s) involving radioactive agents

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Alzheimer's Disease Patients - Treatment; Patients within the Alzheimer's continuum will be selected based on the National Institute of Aging - Alzheimer's Association Diagnostic Framework and be either classified as having mild cognitive impairment or mild-to-moderate dementia. Participants will undergo two PET/MR sessions in which CMRGlu and CMRO2 will be imaged simultaneously by PET and qBOLD MRI. For validation, CMRO2 will also be imaged by PMROx prior to FDG injection. The study will follow a crossover design in which participants will receive ketogenic supplement prior to imaging.	Dietary supplement: Ketogenic Supplement; Commercially available ketone ester drink; Other Names: Ketone-IQTM
Placebo Comparator: Alzheimer's Disease Patients - Placebo; Patients within the Alzheimer's continuum will be selected based on the National Institute of Aging - Alzheimer's Association Diagnostic Framework and be either classified as having mild cognitive impairment or mild-to-moderate dementia. Participants will undergo two PET/MR sessions in which CMRGlu and CMRO2 will be imaged simultaneously by PET and qBOLD MRI. For validation, CMRO2 will also be imaged by PMROx prior to FDG injection. The study will follow a crossover design in which participants will receive a placebo drink prior to imaging.	Other: Placebo Drink; Placebo drink containing sunflower oil.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cerebral Metabolic Rate of Oxygen (CMRO2)	Statistical analysis of imaging data sets under placebo and ketosis conditions will be used to investigate increases in regional CMRO2 caused by ketosis.	CMRO2 will be measured in both imaging sessions (placebo and ketosis)
Cerebral Metabolic Rate of Glucose (CMRGlu)	Statistical analysis of imaging data sets under palcebo and ketosis conditions will be used to investigate changes in regional CMRGlu caused by ketosis. Unlikek CMRO2, no difference in CMRGlu is expected between the two conditions for Alzheimer's patients.	CMRGlu will be measued in both imaging session (placebo and ketosis)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive Function	A psychometrist will assess baseline cognition using the Mini-Mental State Examination, the Montreal Cognitive Assessment, and the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog). The ADAS-cog will be repeated at the end of the second imaging session to test the potential cognitive benefits of the ketogenic supplement.	Baseline and 7 Days

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS); University of Western Ontario, Canada
• Investigators: Principal Investigator: Keith St Lawrence, PhD, Lawson Research Institute

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): February 29, 2028
• Study Completion (Estimated): March 31, 2028

Study Registration Dates

• First Submitted: January 6, 2025
• First Submitted That Met QC Criteria: January 6, 2025
• First Posted (Actual): January 9, 2025

Study Record Updates

• Last Update Posted (Estimated): October 14, 2025
• Last Update Submitted That Met QC Criteria: October 9, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: PET/MR, Keytone Supplement, Brain Energy Metabolism
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Alzheimer Disease
• Other Study ID Numbers: 126350; 1R01NS131235-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data sets to be shared include imaging data and participant demographics. Data will be made publicly available through the data sharing and archiving platform OpenNeuro.
• IPD Sharing Time Frame: Data release will follow a 36-month optional embargo to allow time for publication in a peer-reviewed journal.

IPD Sharing Access Criteria

Data submitted to OpenNeuro are first associated with metadata from the BIDS dataset and with submitter-provided metadata, then indexed for searching. Copies of absorbed content -- from each submitted dataset version -- are subsequently assigned persistent digital object identifiers (DOIs).

Datasets will be made publicly available through OpenNeuro with nominal restrictions using multiple open protocols. Prior to being made public, access to a dataset is controlled through strict authentication policies and an isolated storage backend to further guard against unintended access.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No