Alzheimer Disease and Related Dementias (ADRD)
Conditions
Keywords
PET/MR, Ketone Supplement, Brain Energy Metabolism
Brief summary
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.
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.
Interventions
DIETARY_SUPPLEMENTKetogenic Supplement
D-Beta-Hydroxybutyrate bonded to R-1,3 Butanediol
OTHERPlacebo Drink
Placebo drink containing flavored water.
Sponsors
University of Pennsylvania
National Institute of Neurological Disorders and Stroke (NINDS)
University of Western Ontario, Canada
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
Participants will not know if they have consumed the ketone monoester supplement drink or a placebo drink.
Intervention model description
Each patient receives a placebo and the active treatment on separate occasions undergoing the same imaging protocol.
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cerebral Metabolic Rate of Oxygen (CMRO2) | CMRO2 will be measured in both imaging sessions (placebo and ketosis) | Statistical analysis of imaging data sets under placebo and ketosis conditions will be used to investigate increases in regional CMRO2 caused by ketosis. |
| Cerebral Metabolic Rate of Glucose (CMRGlu) | CMRGlu will be measured in both imaging session (placebo and ketosis) | Statistical analysis of imaging data sets under placebo and ketosis conditions will be used to investigate changes in regional CMRGlu caused by ketosis. Unlike CMRO2, no difference in CMRGlu is expected between the two conditions for Alzheimer's patients. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cognitive Function | Baseline and 7 Days | 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. |
Countries
Canada
Contacts
CONTACTKeith St Lawrence, PhD
PRINCIPAL_INVESTIGATORKeith St Lawrence, PhD
Lawson Research Institute
Outcome results
None listed