High-Fat Diet for Alzheimer's Disease

Overseen By Angela J Hanson, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Washington

Must not be taking: Diabetes meds, Hypertension meds, Statins, Dementia meds

Disqualifiers: Diabetes, Hypertension, Dementia, Psychiatric disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how a high-fat diet, specifically heavy cream, affects brain function in individuals with and without a gene linked to Alzheimer's disease (AD). Researchers seek to determine if this diet impacts blood flow in the brain, which relates to how the brain uses energy. Participants should be age 55 or older, able to undergo an MRI scan, and free from conditions like diabetes requiring medication or serious heart issues. This trial may suit those without significant medical issues who can consume dairy products and undergo brain imaging tests. As an unphased trial, it offers participants the chance to contribute to foundational research that could provide new insights into dietary impacts on brain health.

Will I have to stop taking my current medications?

The trial requires participants to stop taking certain medications. If you have hypertension, you must stop your medication for 2 weeks before the MRI visit, if safe. For significant lipid abnormalities, you need to stop medications like statins 4 weeks before the screening visit, unless they are for preventing heart attack or stroke.

What prior data suggests that this technique is safe for measuring cerebral blood flow?

Research has shown that dairy products, such as heavy cream, might be safer for brain health than previously thought. One study found that consuming more milk and dairy could lower the risk of dementia, including Alzheimer's disease, suggesting that heavy cream might be beneficial for brain health.

However, not all studies agree. Some research indicates that certain foods, possibly including heavy cream, could increase the risk of memory problems if consumed excessively. Therefore, while heavy cream might be safe in moderation, monitoring intake is important.

Overall, studies suggest that heavy cream can be safely consumed, but moderation is key. Participants in this trial will consume heavy cream under controlled conditions to manage any potential risks. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for Alzheimer's, which often involve medications that aim to manage symptoms or slow disease progression, this approach uses heavy cream as a dietary intervention. Researchers are excited about this treatment because it leverages the potential benefits of a high-fat diet to alter brain metabolism. The unique aspect here is the focus on dietary change to support brain health, which could offer a new, non-pharmaceutical avenue for managing Alzheimer's symptoms. This approach could provide more natural and potentially easier-to-access options for patients and caregivers.

What evidence suggests that this treatment might be an effective treatment for Alzheimer's?

Research has shown that high-fat diets can affect Alzheimer's disease in various ways. Some studies have found no clear link between dairy products, like milk, and Alzheimer's. However, other research suggests that certain fats, such as those in medium-chain triglycerides, might improve brain function. One important study found that people had better cognitive function after following a ketogenic diet, which is high in fats. This trial will investigate the effects of a high-fat diet using heavy cream as the intervention. While high-fat diets might generally increase the risk of Alzheimer's, specific fats could offer some brain benefits, especially for people with certain genetic traits. ^{1 3 4 6 7}

Who Is on the Research Team?

Angela Hanson, MD

Principal Investigator

University of Washington

Are You a Good Fit for This Trial?

This trial is for individuals aged 55 or older, both with and without the Alzheimer's risk gene E4. Participants must be post-menopausal women or men, able to consent, undergo an MRI, and ingest dairy. Exclusions include those on diabetes/hypertension medication (unless they can stop safely), with psychiatric disorders affecting study outcomes, metal implants incompatible with MRI, significant lipid abnormalities requiring medication (unless willing to stop), diagnosed dementia or severe cognitive impairment.

Inclusion Criteria

I am a woman who is post-menopausal for at least 1 year or have had a hysterectomy.

Able to read and understand English

My genetic test shows whether I have the APOE E4 gene.

Exclusion Criteria

I don't have severe lipid problems and can stop certain medications before the trial.

I have diabetes that needs medication, but diet control or past gestational diabetes is okay.

I can safely stop my hypertension medication for 2 weeks before the MRI.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Study Visit

Participants undergo MRI and oral triglyceride tolerance test (OTTT) after fasting

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the study visit

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Heavy Cream

Trial Overview The study investigates how a high-fat diet using heavy cream affects brain blood flow in people at risk of Alzheimer's disease. It focuses on differences between carriers and non-carriers of the APOE E4 gene by measuring cerebral blood flow through arterial spin labeling during an MRI scan.

How Is the Trial Designed?

Group I: Intervention Experimental Treatment 1 Intervention

All participants undergo the same intervention: Drinking heavy cream and undergoing MRI.

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

In a study using 5XFAD mice, a model for Alzheimer's disease, a high-fat diet significantly increased β-amyloid deposition and impaired cognitive function, highlighting its detrimental effects on AD pathology.

The high-fat diet also elevated oxidative stress in the brains of 5XFAD mice, suggesting that dietary fat can exacerbate Alzheimer's disease progression independently of metabolic disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Fat-Diet Intake Enhances Cerebral Amyloid Angiopathy and Cognitive Impairment in a Mouse Model of Alzheimer's Disease, Independently of Metabolic Disorders. Lin, B., Hasegawa, Y., Takane, K., et al.[2022]

In a study of 21 older adults, a triglyceride (TG) infusion significantly increased total lipid levels in cerebrospinal fluid (CSF), indicating that dietary lipids can influence CNS lipid profiles.

The lipid changes observed were affected by the presence of the APOE ε4 gene, suggesting that genetic factors may play a role in how the central nervous system processes lipids, which could be relevant to Alzheimer's disease risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebrospinal fluid lipidomics: effects of an intravenous triglyceride infusion and apoE status. Hanson, AJ., Banks, WA., Bettcher, LF., et al.[2023]

In a study of 2612 elderly participants over an average follow-up of 4.5 years, higher dietary intakes of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were linked to a significantly lower risk of developing Alzheimer's disease (AD).

Specifically, for each increase in DHA and EPA intake, the risk of AD decreased, with hazard ratios of 0.73 and 0.74 respectively, indicating that these long-chain polyunsaturated fatty acids may offer protective benefits against AD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary fatty acids and risk of Alzheimer's disease and related dementias: Observations from the Washington Heights-Hamilton Heights-Inwood Columbia Aging Project (WHICAP). Gustafson, DR., Bäckman, K., Scarmeas, N., et al.[2021]

In a randomized clinical trial involving 204 Alzheimer's disease patients, omega-3 supplementation did not show significant overall effects on neuropsychiatric symptoms or daily functioning, but did improve agitation in APOE4 carriers and depressive symptoms in non-APOE4 carriers.

The study highlights that while omega-3 fatty acids may not universally benefit all Alzheimer's patients, they could provide targeted improvements in specific symptoms based on genetic factors, suggesting a need for personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omega-3 supplementation in mild to moderate Alzheimer's disease: effects on neuropsychiatric symptoms. Freund-Levi, Y., Basun, H., Cederholm, T., et al.[2018]

In a study of 75 Alzheimer's patients over 3 months, the type of diet (normal, diabetic, or texture-modified) significantly influenced weight loss, with texture-modified diets being the most common among participants.

Non-malnourished patients showed notable differences in weight loss rates based on their diet type, highlighting the importance of tailored dietary approaches for managing weight in Alzheimer's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Impact of Diet Type on Weight Loss in Patients with Alzheimer's Disease. Nakamura, T.[2021]

In a randomized trial involving 204 patients with mild to moderate Alzheimer's disease, supplementation with Omega-3 fatty acids (DHA and EPA) for 6 months led to significant weight gain and improved appetite compared to a placebo group.

Patients who did not carry the APOEepsilon4 allele and had higher plasma DHA levels were more likely to experience weight gain, suggesting that genetic factors and DHA concentration may influence the effectiveness of Omega-3 supplementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omega-3 fatty acid supplementation effects on weight and appetite in patients with Alzheimer's disease: the omega-3 Alzheimer's disease study. Irving, GF., Freund-Levi, Y., Eriksdotter-Jönhagen, M., et al.[2015]

A prospective cohort study found that higher seafood consumption is linked to fewer brain plaques and tangles in elderly individuals, suggesting a potential protective effect against cognitive decline.

While some evidence supports the cognitive benefits of n-3 fatty acids in healthy older adults and those with mild cognitive impairment, a Cochrane review concluded that n-3 fatty acids do not provide significant benefits for patients with mild to moderate Alzheimer's disease over six months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fish consumption and omega-3 fatty acid supplementation for prevention or treatment of cognitive decline, dementia or Alzheimer's disease in older adults - any news? Cederholm, T.[2018]

In a study involving 53 Alzheimer's disease patients, a whole formula diet based on lyophilised foods led to a significant increase in body weight (2.06 kg) and improvements in nutritional markers like albumin and hemoglobin compared to a control group receiving nutritional advice.

While cognitive improvements measured by the Mini Nutritional Assessment and Pfeiffer tests were not significantly different between the two groups, the whole formula diet was well-tolerated and safe, with similar rates of serious adverse events in both groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of oral administration of a whole formula diet on nutritional and cognitive status in patients with Alzheimer's disease. Salas-Salvadó, J., Torres, M., Planas, M., et al.[2006]

In a study of 231 patients with cognitive dysfunction, a body mass index (BMI) of less than 23 was found in over half of the subjects and was associated with a threefold increased risk of mortality over seven years, regardless of age, gender, or type of dementia.

During a median hospital stay of three weeks, patients experienced an average weight gain and improvement in cognitive scores, but these changes were not correlated, suggesting that while nutritional interventions may have short-term benefits, they do not necessarily translate to long-term survival improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nutritional and cognitive relationships and long-term mortality in patients with various dementia disorders. Faxén-Irving, G., Basun, H., Cederholm, T.[2006]

A high saturated fat and low carbohydrate ketogenic diet significantly reduced brain amyloid-beta (Abeta) levels by about 25% in a transgenic mouse model of Alzheimer's disease, suggesting a potential dietary strategy for lowering Abeta accumulation.

Despite the reduction in Abeta levels and increased ketone body production, the ketogenic diet did not lead to improvements in behavioral measures, indicating that while the diet may affect biochemical markers, it does not necessarily translate to behavioral benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A ketogenic diet reduces amyloid beta 40 and 42 in a mouse model of Alzheimer's disease. Van der Auwera, I., Wera, S., Van Leuven, F., et al.[2020]

High intake of saturated and trans fatty acids is associated with an increased risk of developing dementia, while higher consumption of polyunsaturated and monounsaturated fatty acids may reduce this risk.

The review highlights the importance of dietary fat composition in maintaining blood-brain barrier function and cholesterol levels, both of which are crucial in the context of Alzheimer's disease, particularly for individuals with the apolipoprotein E-ε4 genetic risk factor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary fat composition and dementia risk. Morris, MC., Tangney, CC.[2021]

In a study involving 204 patients with mild to moderate Alzheimer's disease, omega-3 fatty acid supplementation did not significantly slow cognitive decline for the overall group over 6 months, as measured by standard cognitive tests.

However, a subgroup of 32 patients with very mild cognitive dysfunction showed a significant reduction in the rate of cognitive decline, suggesting potential benefits of omega-3s for early-stage Alzheimer's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study: a randomized double-blind trial. Freund-Levi, Y., Eriksdotter-Jönhagen, M., Cederholm, T., et al.[2022]

Higher intake of saturated fats is linked to an increased risk of Alzheimer's disease (AD) and cognitive decline, as shown in 3 out of 4 studies focused on AD and 2 out of 4 studies on cognitive decline.

The relationship between trans fat intake and dementia is less clear, with mixed results across the studies, indicating that more research is needed to understand its impact on cognitive disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Saturated and trans fats and dementia: a systematic review. Barnard, ND., Bunner, AE., Agarwal, U.[2018]

In a study involving 3,741 participants aged around 73 years, oral supplementation with long-chain polyunsaturated fatty acids (LCPUFAs) and lutein/zeaxanthin did not show any significant improvement in cognitive function compared to a placebo over a 5-year period.

The results indicate that these specific dietary supplements do not have a measurable effect on cognitive decline in older adults at risk for age-related macular degeneration, suggesting that other dietary factors may need to be explored for cognitive health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Omega-3 Fatty Acids, Lutein/Zeaxanthin, or Other Nutrient Supplementation on Cognitive Function: The AREDS2 Randomized Clinical Trial. Chew, EY., Clemons, TE., Agrón, E., et al.[2021]

Citations

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Effectiveness of dairy products to protect against cognitive ... There was no significant association between milk consumption and AD development. In contrast, in the other three prospective studies, increased milk ...

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The Effects of Medium Chain Triglyceride for Alzheimer's ... Meta-analysis showed cognitive improvements in general (SMD = 0.64; 95% CI [0.05, 1.24]), but not in memory, language, and attention domains ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1279770723008539

The Ketogenic Diet and Alzheimer's Disease Results showed a statistically significant 4.1-point increase in ADAS-Cog scores after the treatment period compared to baseline. After the washout period, the ...

4. nesr.usda.gov nesr.usda.gov/sites/default/files/2024-12/Dietary-patterns-neurocognitive-health-2025DGACSystematicReview.pdf

Dietary Patterns and Risk of Cognitive Decline, Dementia, ... not associated with cognitive outcomes (cognitive decline, dementia, Alzheimer's disease) in a majority-. Black (60%) cohort but was associated with better ...

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The Junk Foods That Harm Your Brain Most, Ranked by ... Individuals who consumed one or more extra servings of either of these foods showed a significantly increased risk of developing cognitive ...

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Preventive Effects of Dairy on Dementia & Mechanisms The investigation showed that a greater intake of milk and dairy products was associated with a reduced risk of dementia, especially Alzheimer's ...

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The Effects of Medium Chain Triglyceride for Alzheimer's ... This review provides some evidence that treatment with MCT could improve general cognitive function in APOE ɛ4 (−) cognitive impaired patients.