Effects of Exogenous Ketones on Cognitive Function in Older Adults With Prediabetes?

Summary

Brief Summary The goal of this clinical trial is to learn whether older adults with prediabetes, but no diagnosed cognitive impairment, show early changes in brain energy use and thinking speed compared to older adults with normal blood sugar levels. The study will also test whether a single dose of an exogenous ketone supplement can improve brain energy use and cognitive processing speed. The main questions it aims to answer are: Do older adults with prediabetes have lower brain glucose uptake and slower cognitive processing speed compared to those with normal glucose levels? Does a single dose of an exogenous ketone monoester supplement improve cognitive processing speed and brain glucose uptake? Researchers will compare older adults with prediabetes to older adults with normal glucose levels to determine whether differences exist in brain glucose metabolism and cognitive performance. In a subset of participants, researchers will also compare brain and cognitive outcomes before and after consuming a ketone monoester supplement (DeltaG, Oxford, England). Participants will: Complete metabolic testing to determine glucose status Undergo brain imaging using fluorodeoxyglucose positron emission tomography combined with magnetic resonance imaging (18FDG-PET/MRI) while performing a cognitive processing speed task Consume a single dose of a commercially available ketone monoester supplement during one study visit Complete cognitive testing during imaging to measure processing speed and brain activity The results of this study will help determine whether early metabolic dysfunction is linked to reduced brain energy use and whether ketones can temporarily support brain function in individuals at risk for dementia.

Eligibility

Inclusion Criteria:

* Age 60 to 75 years
* Able to provide written informed consent
* Fluent in English
* No diagnosed cognitive impairment or dementia

Classified as either:

* Prediabetes (based on American Diabetes Association criteria), or Normal glucose regulation (control group)
* Medically stable and cleared to undergo positron emission tomography and magnetic resonance imaging
* Willing to comply with study procedures, including metabolic testing, supplement ingestion, and neuroimaging

Exclusion Criteria:

* Diagnosis of mild cognitive impairment, dementia, or other neurodegenerative disorder
* Diagnosis of type 1 diabetes or type 2 diabetes
* Use of glucose-lowering medications (e.g., insulin, metformin, glucagon-like peptide-1 receptor agonists)
* History of major neurological disorder (e.g., stroke, traumatic brain injury with loss of consciousness \>30 minutes, epilepsy, multiple sclerosis)
* Major psychiatric disorder not stable on treatment
* Uncontrolled hypertension or significant cardiovascular disease
* Severe renal, hepatic, or gastrointestinal disease that may affect supplement metabolism
* Contraindications to magnetic resonance imaging (e.g., non-compatible implanted devices, severe claustrophobia)

Conditions3

Locations2 sites

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