Wake Forest Baptist Medical Center
Winston-Salem, North Carolina, 27157, United States
NCT Number: NCT03472664
The Brain Energy for Amyloid Transformation in AD (Alzheimer's disease) or BEAT-AD study will compare the effects of a ketogenic low-carbohydrate diet and a low-fat diet in adults with mild cognitive impairment. The data collected will help determine whether diet interventions induce changes in cognitive function, cerebral blood flow, and levels of certain proteins and hormones in body fluids.
The study will include volunteers who have mild cognitive impairment, who will be randomly assigned to receive either a ketogenic low-carbohydrate diet or a low-fat diet for 16-weeks, with follow-up assessment 8 weeks after diet completion. Study measures, clinic visits and phone sessions will occur at baseline and throughout the 24-week study.
Participant will follow either a low-carbohydrate or low-fat diet that will be individually planned with help from a study dietitian. After completing the study diet for 16 weeks, participants will resume their normal diet. The final visits will occur at week 24 (8 weeks after the completing the diet). At the end of the 24-week study, participants will be given the opportunity to meet with the study dietitian for education and assistance with planning a healthy diet.
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Notify Me55 year–85 year
All sexes
Interventional
Not applicable
Winston-Salem, North Carolina, 27157, United States
This study will examine the effects of a 4-month Modified Mediterranean-Ketogenic Diet compared with an American Heart Association Diet (AHAD - a regimen that has been shown to reduce the risk for cardiovascular disease). We will investigate diet effects on AD biomarkers, on cognition, and on neuroimaging measures of blood flow. Our study will extend previous findings in several important ways by: 1) using a Modified Mediterranean-Ketogenic Diet rather than a traditional Ketogenic Diet, which has the potential for greater long-term compliance and health benefits; 2) increasing the sample size and duration of the diet intervention; 3) examining potential mechanisms of diet effects that may result in new biomarkers and therapeutic targets; and 4) examining key treatment response variables such as Apolipoprotein E (ApoE) genotype, amyloid positivity and metabolic status that could inform precision medicine approaches to dietary prescription.
Adults with amnestic mild cognitive impairment (MCI) will be randomized on a 1:1 schedule to receive either a 4-month Modified Mediterranean-Ketogenic Diet (MMKD) or American Heart Association Diet (AHAD) intervention. Diet interventions will be equicaloric with participants' normal diets. Personalized nutritional guidance and menus will be provided, and compliance will be assessed by a registered dietitian. The principal investigator will be responsible for the overall monitoring of the data and safety of study participants, with assistance by members of the study staff, and the Data and Safety Monitoring Board (DSMB), which will be responsible for monitoring the safety of research participants.
Healthy volunteers accepted: No
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
Exclusion criteria
Modified Mediterranean-Ketogenic Diet is a low carbohydrate/high fat diet.
American Heart Association Diet is a low fat/high carbohydrate diet.
Time frame: baseline
Aβ42 is a a key Alzheimer's disease biomarker that reflects pathological aggregation of amyloid in the brain.
Time frame: week 16
Aβ42 is a a key Alzheimer's disease biomarker that reflects pathological aggregation of amyloid in the brain.
Time frame: baseline, week 16
Aβ40 is a peptide biomarker primarily used in the evaluation and diagnosis of Alzheimer's disease and other neurodegenerative conditions
Time frame: baseline, week 16
total tau is a general indicator of neuronal degeneration and injury
Time frame: baseline, week 16
ptau181 (phosphorylated tau 181) biomarker is a specialized protein used as a primary diagnostic indicator for Alzheimer's disease
Time frame: baseline, week 16
NfL (Neurofilament Light Chain) biomarker is a tool for diagnosing, monitoring, and predicting the progression of various neurodegenerative and neurological diseases
Time frame: baseline, week 16
Aβ42 is a a key Alzheimer's disease biomarker that reflects pathological aggregation of amyloid in the brain.
Time frame: baseline, week 16
Aβ40 is a peptide biomarker primarily used in the evaluation and diagnosis of Alzheimer's disease and other neurodegenerative conditions
Time frame: baseline, week 16
p-tau217 (phosphorylated tau at threonine 217) is a biomarker used to detect and predict the brain changes associated with Alzheimer's disease
Time frame: baseline, week 16
pTau181 (phosphorylated tau 181) is a biomarker that serves as a primary diagnostic indicator for Alzheimer's disease
Time frame: baseline, week 16
NfL (Neurofilament Light Chain) biomarker is a tool for diagnosing, monitoring, and predicting the progression of various neurodegenerative and neurological diseases
Time frame: baseline, week 16
Hemoglobin A1c measures your average blood sugar levels over the past 2 to 3 months. Below 5.7% is normal, 5.7-6.4% indicates prediabetes, 6.5% or higher indicates diabetes.
Time frame: baseline, week 16
The level of triglycerides (a type of fat) in blood with less than 150 mg/dL being normal.
Time frame: baseline, week 16
LDL (low-density lipoprotein) is the amount of "bad" cholesterol in the blood. The optimal level is less than 100 mg/dL.
Time frame: baseline, week 16
HDL (High-Density Lipoprotein) blood test measures the amount of "good" cholesterol in the blood. Optimal level is ≥ 60 mg/dL. Low HDL (<40 mg/dL for men, <50 mg/dL for women) indicates a higher risk for cardiovascular disease.
Time frame: baseline, week 16
Measure of overall amount of cholesterol in the blood, which includes both "bad" (LDL) and "good" (HDL) cholesterol. Desirable level is less than 200 mg/dL with higher levels indicating greater risk for heart attack and stroke.
Time frame: baseline, week 16
A blood ketone test specifically measures beta-hydroxybutyrate, the primary ketone in your blood. Under 0.6 mmol/L normal or negative. 0.6 to 1.5 mmol/L slightly elevated, body is in ketosis (burning fat for fuel). 1.6 to 3.0 mmol/L elevated, risk for diabetic ketoacidosis. Over 3.0 mmol/L high, indicates potentially dangerous levels that require emergency medical attention.
Time frame: baseline, week 16
Level of blood glucose with normal being less than 100 mg/dL while fasting. Fasting levels of 100 to 125 mg/dL indicate prediabetes. Fasting levels of 126 mg/dL or higher (on more than one occasion) indicate diabetes.
Time frame: baseline, week 16
Cerebral blood flow will be measured with pseudo continuous arterial spin labeling MRI and voxel based analyses will be conducted to determine diet-induced changes and their relationship to cognitive and biomarker outcomes. Healthy adult gray matter typically ranges between 50 to 70 ml/100g/min. Lower than typical range indicates reduced cerebral blood flow.
Time frame: baseline, week 16
Pseudo Continuous Arterial Spin Labeling measures regional cerebral blood flow. Meta-Region of Interest combines data from multiple predefined brain regions into a single composite uptake score. Higher values in mL/100g/min indicate greater tissue perfusion, while lower values reflect reduced blood flow. Normal gray matter perfusion in a healthy adult typically ranges between 50 and 60 mL/100g/min, while white matter generally measures around 20 mL/100g/min.
Time frame: baseline, week 16
NODDI-NDI measures the packing and density of neurites (axons and dendrites) in the hippocampal region of the brain. NDI values drop in the hippocampus as neurites degenerate during Alzheimer's disease or normal aging. NDI is expressed as a decimal value typically falling between 0 and 1. A value of 0 represents an area with no neurites (e.g., pure cerebrospinal fluid), while a value closer to 1 indicates a highly dense network of axons or dendrites.
Time frame: baseline, week 16
NODDI-NDI measures the packing and density of neurites in the region of interest in the brain. NDI values drop as neurites degenerate during Alzheimer's disease or normal aging. NDI is expressed as a decimal value typically falling between 0 and 1. A value of 0 represents an area with no neurites (e.g., pure cerebrospinal fluid), while a value closer to 1 indicates a highly dense network of axons or dendrites.
Time frame: baseline, week 16
ISOVF measures the proportion of water molecules that are diffusing freely and isotropically in the hippocampal region of the brain. Elevated ISOVF is frequently observed in Alzheimer's disease, cognitive decline, aging, and infection burdens, reflecting a breakdown of tissue structure. Expressed as a value between 0 and 1 with a higher number indicating a higher level of free, isotropic water.
Time frame: baseline, week 16
ISOVF Meta-ROI measures the proportion of water molecules that are diffusing freely and isotropically within a region of interests in the brain. Elevated ISOVF is frequently observed in Alzheimer's disease, cognitive decline, aging, and infection burdens, reflecting a breakdown of tissue structure. Expressed as a value between 0 and 1 with a higher number indicating a higher level of free, isotropic water.
Time frame: baseline, week 16
NODDI ODI (Orientation Dispersion Index) is used to quantify the spatial configuration and branching of neurites (axons and dendrites) in hippocampal region of the brain. It measures how widely the orientations of neurites spread out in space within a voxel. Low ODI indicates highly aligned or parallel fibers, typical of coherent white matter tracts. High ODI indicates highly dispersed or fanned-out fibers, typical of gray matter or areas with complex fiber crossings. ODI ranges from 0 to 1, where values closer to 0 represent fibers pointing in nearly the same direction (low dispersion).
Time frame: baseline, week 16
NODDI ODI (Orientation Dispersion Index) is used to quantify the spatial configuration and branching of neurites (axons and dendrites) in the region of interest in the brain. It measures how widely the orientations of neurites spread out in space within a voxel. Low ODI indicates highly aligned or parallel fibers, typical of coherent white matter tracts. High ODI indicates highly dispersed or fanned-out fibers, typical of gray matter or areas with complex fiber crossings. ODI ranges from 0 to 1, where values closer to 0 represent fibers pointing in nearly the same direction (low dispersion).
Time frame: Week 16
The modified Preclinical Alzheimer Cognitive Composite 5 (mPACC5) measures cognitive changes associated with Alzheimer's-related brain pathology. It aggregates z-scores from five specific cognitive tests across four domains: episodic memory (delayed recall tests), timed executive function (speed and processing tasks), semantic memory (verbal fluency tests), global cognition (overall mental status exams). Total Z-score range: healthy /unimpaired baseline -0.50 to +1.00, mild cognitive impairment -2.50 to -0.50, dementia -3.50 to -2.50. The central value of the mPACC5 is 0.
Time frame: baseline, week 16
The ADAS-Cog 12 is a psychometric instrument that evaluates memory, attention, reasoning, language, orientation, and praxis. A higher score indicates more impairment. Scores range from 0-85 with higher scores indicating greater cognitive impairment.
Time frame: baseline, week 16
The NPI-Q is widely used to assess the presence of mood disorders in geriatric populations. The NPI-Q measures 12 symptom categories and is scored on a scale of 0-36. A higher score indicates a higher burden of neuropsychiatric symptoms. A score of 0 indicates no symptoms are present.
Time frame: baseline, week 16
The Geriatric Depression Scale is a well-validated self-report questionnaire used frequently in clinical and research settings to assess mood in older adults. Total score range is 0-15 with 0-4 normal range (no risk of depression indicated), 5-8 mild depressive symptoms, 9-11 moderate depressive symptoms, 12-15 severe depressive symptoms.
Time frame: baseline, week 16
Pittsburgh Sleep Quality Index was inadvertently listed as a secondary outcome in the protocol but was actually an exploratory outcome.
Time frame: baseline, week 16
Epworth Sleepiness Scale was inadvertently listed as a secondary outcome in the protocol but was actually an exploratory outcome.
Time frame: baseline, week 16
WatchPAT sleep stage time was inadvertently listed as a secondary outcome in the protocol but was actually an exploratory outcome
Wake Forest University Health Sciences
Other
Brain Energy for Amyloid Transformation in AD (BEAT-AD) Study
Acronym: BEAT-AD
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