Acute Oral Ketone Monoester Supplementation and Resting-state Brain Connectivity

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