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Alzheimer DiseaseBEAT-ADNCT03472664

Brain Energy for Amyloid Transformation in Alzheimer's Disease Study

A study testing low carbohydrate/high fat diet and low fat/high carbohydrate diet in people with Alzheimer Disease and Mild Cognitive Impairment, run by Wake Forest University Health Sciences at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 55 to 85 years
Conditions the study is for
Alzheimer Disease, Mild Cognitive Impairment
What is being tested?
low carbohydrate/high fat diet and low fat/high carbohydrate diet
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
84 participants
Where
1 siteUnited States
Study dates
16 Jul 2018to 13 Sep 2024
Phase
Interventional
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 55 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosis of amnestic mild cognitive impairment
  • An informant (study partner) able to provide collateral information on the participant
  • Stable medical condition (generally 3 months prior to screening visit) at the discretion of study physician
  • Stable on medications (generally 4 weeks prior to screening visit) at the discretion of study physician
  • Able to complete baseline assessments

Who cannot join

  • Diagnosis of neurodegenerative illness (except for MCI);
  • History of a clinically significant stroke
  • Current evidence or history in past year of focal brain lesion, head injury with loss of consciousness or DSM-IV criteria for any major psychiatric disorder including psychosis, major depression, bipolar disorder, alcohol or substance abuse
  • Sensory impairment (i.e.: visual or auditory) that would preclude the participant from participating in the protocol
  • Diabetes that requires current use of diabetes medications
  • Clinically significant elevations in liver function tests
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  • Active neoplastic disease (stable prostate cancer and non-melanoma skin cancer is permissible)
  • History of epilepsy or seizure within past year
  • Contraindications for MRI (claustrophobia, craniofacial metal implants, pacemakers)
  • Significant medical illness or organ failure, such as uncontrolled hypertension or cardiovascular disease, chronic obstructive pulmonary disease, liver disease, or kidney disease

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Wake Forest Baptist Medical Center

    Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

Official title: Brain Energy for Amyloid Transformation in AD (BEAT-AD) Study

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.

Read the detailed description

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.

Being tested
low carbohydrate/high fat diet, low fat/high carbohydrate diet
Keywords
Memory, Diet, ketogenic
Medical subject headings
Alzheimer Disease, Cognitive Dysfunction

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • low carbohydrate/high fat dietOther

    Modified Mediterranean-Ketogenic Diet is a low carbohydrate/high fat diet.

  • low fat/high carbohydrate dietOther

    American Heart Association Diet is a low fat/high carbohydrate diet.

Study groups in NCT03472664
Study groupRoleWhat they receive
Modified Mediterranean Ketogenic DietExperimentalThe MMKD is a low carbohydrate/high fat diet aimed at inducing ketosis, as the experimental diet in the proposed study. Participants on the MMKD will keep their daily carbohydrate consumption below 20 grams per day throughout the 4 month intervention.The MMKD group will be supplied with extra virgin olive oil during their in person visits to use as a source of fat in their diet, and will be encouraged to eat plentiful fish, lean meats, and nutrient rich foods that meet the requirement of <20 grams total carbohydrates per day. Participants will receive a daily multivitamin (Centrum Silver) over the course of the study and instructed to take 1 tablet each day while on the diet.
Receives: Other: low carbohydrate/high fat diet
American Heart Association DietExperimentalThe American Heart Association Diet (AHAD), is a low fat/high carbohydrate diet (<40 grams/day) will be used as the control diet. Participants on the AHAD will be encouraged to limit their amount of fat intake to <40 grams/day, while eating plentiful fruits, vegetables, and carbohydrates containing adequate fiber. Participants will receive the same daily multivitamin supplement (Centrum Silver) over the course of the study and instructed to take 1 tablet each day while on the diet.
Receives: Other: low fat/high carbohydrate diet

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Cerebrospinal Fluid Abeta42

    Aβ42 is a a key Alzheimer's disease biomarker that reflects pathological aggregation of amyloid in the brain.

    Measured: baseline

  2. Cerebrospinal Fluid Abeta42

    Aβ42 is a a key Alzheimer's disease biomarker that reflects pathological aggregation of amyloid in the brain.

    Measured: week 16

Secondary outcomes (28)
  1. Cerebrospinal Fluid Aβ40

    Aβ40 is a peptide biomarker primarily used in the evaluation and diagnosis of Alzheimer's disease and other neurodegenerative conditions

    Measured: baseline, week 16

  2. Cerebrospinal Fluid Total Tau

    total tau is a general indicator of neuronal degeneration and injury

    Measured: baseline, week 16

  3. Cerebrospinal Fluid ptau181

    ptau181 (phosphorylated tau 181) biomarker is a specialized protein used as a primary diagnostic indicator for Alzheimer's disease

    Measured: baseline, week 16

  4. Cerebrospinal Fluid NfL

    NfL (Neurofilament Light Chain) biomarker is a tool for diagnosing, monitoring, and predicting the progression of various neurodegenerative and neurological diseases

    Measured: baseline, week 16

  5. Plasma Aβ42

    Aβ42 is a a key Alzheimer's disease biomarker that reflects pathological aggregation of amyloid in the brain.

    Measured: baseline, week 16

  6. Plasma Aβ40

    Aβ40 is a peptide biomarker primarily used in the evaluation and diagnosis of Alzheimer's disease and other neurodegenerative conditions

    Measured: baseline, week 16

  7. Plasma p-tau217

    p-tau217 (phosphorylated tau at threonine 217) is a biomarker used to detect and predict the brain changes associated with Alzheimer's disease

    Measured: baseline, week 16

  8. Plasma Phosphorylated Tau 181

    pTau181 (phosphorylated tau 181) is a biomarker that serves as a primary diagnostic indicator for Alzheimer's disease

    Measured: baseline, week 16

  9. Plasma NfL

    NfL (Neurofilament Light Chain) biomarker is a tool for diagnosing, monitoring, and predicting the progression of various neurodegenerative and neurological diseases

    Measured: baseline, week 16

  10. Hemoglobin A1c

    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.

    Measured: baseline, week 16

  11. Triglyceride Level

    The level of triglycerides (a type of fat) in blood with less than 150 mg/dL being normal.

    Measured: baseline, week 16

  12. LDL Level

    LDL (low-density lipoprotein) is the amount of "bad" cholesterol in the blood. The optimal level is less than 100 mg/dL.

    Measured: baseline, week 16

  13. HDL Level

    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.

    Measured: baseline, week 16

  14. Total Cholesterol Level

    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.

    Measured: baseline, week 16

  15. Ketones Level

    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.

    Measured: baseline, week 16

  16. Glucose Level

    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.

    Measured: baseline, week 16

  17. MRI Pseudo Continuous Arterial Spin Labeling Hippocampal Uptake

    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.

    Measured: baseline, week 16

  18. MRI Pseudo Continuous Arterial Spin Labeling Meta-Region of Interest Uptake

    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.

    Measured: baseline, week 16

  19. MRI Neurite Orientation Dispersion and Density Imaging-Neurite Density Index (NODDI-NDI) Hippocampal Uptake

    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.

    Measured: baseline, week 16

  20. MRI Neurite Orientation Dispersion and Density Imaging-Neurite Density Index (NODDI-NDI) Meta-Region of Interest Uptake

    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.

    Measured: baseline, week 16

  21. MRI Neurite Orientation Dispersion and Density Imaging-Isotropic Volume Fraction (NODDI-ISOVF) Hippocampal Uptake

    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.

    Measured: baseline, week 16

  22. MRI Neurite Orientation Dispersion and Density Imaging-Isotropic Volume Fraction (NODDI-ISOVF) Meta-Region of Interest (ROI) Uptake

    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.

    Measured: baseline, week 16

  23. MRI Neurite Orientation Dispersion and Density Imaging Orientation Dispersion Index (NODDI-ODI) Hippocampal Uptake

    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).

    Measured: baseline, week 16

  24. MRI Neurite Orientation Dispersion and Density Imaging Orientation Dispersion Index (NODDI-ODI) Meta-Region of Interest (ROI) Uptake

    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).

    Measured: baseline, week 16

  25. Modified Preclinical Alzheimer Cognitive Composite 5 (mPACC5) Score

    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.

    Measured: Week 16

  26. Alzheimer's Disease Assessment Scale-Cognitive 12 (ADAS-Cog 12) Score

    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.

    Measured: baseline, week 16

  27. Neuropsychiatric Inventory Questionnaire (NPI-Q) Score

    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.

    Measured: baseline, week 16

  28. Geriatric Depression Scale Score

    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.

    Measured: baseline, week 16

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Mar 2018
  2. Study start16 Jul 2018
  3. Primary completion19 Jul 2024
  4. Study completion13 Sep 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Adults with amnestic mild cognitive impairment will be randomized on a 1:1 schedule to receive either a 4-month Modified Mediterranean Ketogenic Diet or American Heart Association Diet 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. Amyloid positron emission tomography (PET) will be conducted at baseline. Blood collection and cognitive assessment will be conducted at baseline and after 2 and 4 months of diet. Lumbar puncture (LP) and MRI will be conducted at baseline and following the intervention for all participants.
Masking
Double blind
Who is masked
Investigator, Outcomes assessor
Enrolment
84 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03472664
Sponsor's protocol ID
IRB00049474
Other IDs
1R01AG055122-01
Acronym
BEAT-AD
Status last verified
May 2026
First submitted
12 Mar 2018
Last updated
3 Aug 2026
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Data sharing will follow guidelines and timeline recommended by the National Institute on Aging.

Questions about this trial

What is this clinical trial studying?

A study testing low carbohydrate/high fat diet and low fat/high carbohydrate diet in people with Alzheimer Disease and Mild Cognitive Impairment, run by Wake Forest University Health Sciences at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Aug 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cerebrospinal Fluid Abeta42 (time frame: baseline). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2026; AzTrials last refreshed its copy on 7 Nov 2026.

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