Supplementing Neuro-Energy to Aid Cognition

University of Pennsylvania

Status: Begins enrollment in 2 months

Conditions: Alzheimer Disease and Related Dementias (ADRD)

Treatments: Dietary Supplement: Ketogenic Supplement; Other: Placebo Drink

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT06767124

1R01NS131235-01A1 (U.S. NIH Grant/Contract)

126350

Details and patient eligibility

About

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.

Full 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.

Enrollment: 17 estimated patients

Sex: All

Ages: 21+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Single Blind

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17 participants in 2 patient groups, including a placebo group

Alzheimer's Disease Patients - Treatment

Active Comparator group

Description:

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.

Treatment:

Dietary Supplement: Ketogenic Supplement

Alzheimer's Disease Patients - Placebo

Placebo Comparator group

Description:

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.

Treatment:

Other: Placebo Drink