Acute Oral Ketone Monoester Supplementation and Resting-state Brain Connectivity

The Impact of Acute Oral Ketone Monoester Supplementation on Resting-state Brain Connectivity in Adults With Cognitive Decline

The primary objectives of this pilot study are to test if a single dose of an oral ketone monoester supplement will increase blood flow and connectivity in the brain in adults with subjective cognitive decline (SCD) or mild cognitive impairment (MCI).

The main questions it aims to answer are:

Does a single dose of an oral ketone supplement increase global cerebral blood flow (CBF)?

Does a single dose of an oral ketone supplement improve resting-state functional connectivity in the Default Mode Network (DMN)?

Does the increase in CBF positively correlate with improved functional connectivity in the DMN?

Participants will:

• Attend one 2-hour session, which includes:
• Neurocognitive assessment
• MRI Scans (two, each 15 Minutes)
• Capillary blood ketone level measurements
• Hemodynamic assessment (blood pressure, heart rate)

In this non-randomized, single-arm study participants will undergo a baseline MRI scan to assess functional connectivity in the DMN and resting CBF without ketone supplementation. Participants will then consume 0.3 g/kg body weight of a ketone monoester supplement (∆G Tactical) and then rest for 70 minutes. Participants will then undergo a second MRI scan to evaluate changes in functional connectivity and CBF, with capillary β-OHB and blood pressure measured before and after each scan. The entire experimental visit, including scans and assessments, will last up to 2 hours.

Inclusion Criteria:

• Adults aged 55 years or older
• Subjective Cognitive Decline (SCD) or Mild Cognitive Impairment (MCI)

SCD CRITERIA:

• Self-experienced, persistent decline of cognitive abilities within the last 5 years in relation to a previously normal status
• Normal results on demographically adjusted standardized cognitive tests
• Accompanied by concerns associated with SCD and a feeling of worse performance than others in the same age group
• Decline must not be related to a specific event or explained by a specific disease, medical disorder, medication, or substance abuse

MCI CRITERIA

• Fulfils criteria of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5):
• Demographically adjusted performance between -1 and -2 SD below average in one or more cognitive domains on standardized cognitive tests
• Accompanied by concern from the individual, a knowledgeable informant, or clinician indicating mild cognitive decline
• Capacity for independent daily activities is maintained

Exclusion Criteria:

• Clinical diagnoses of psychiatric disorders (e.g., anxiety disorders, depression)
• Diagnosed major neurocognitive disorder (i.e., dementia)
• Association of SCD or MCI with delirium
• Diagnosed cardiometabolic disease (Uncontrolled hypertension (systolic blood pressure >160 mm Hg, and/or diastolic blood pressure >100 mm Hg, Type 2 diabetes)
• Substance use disorder
• History of heart attack or stroke requiring hospitalization in the past 3 years
• MRI contraindications, including implanted medical devices
• Experiencing residual fatigue, brain fog, or tiredness post-acute illness (i.e., long-COVID)
• Severe literacy, visual, hearing, and/or speech impairment that would make participation in the study difficult or impossible
• Individuals who are not fluent in Swiss German or German