If we have any chance of mitigating the rising tide of Alzheimer’s and other forms of dementia, it’s going to be via diet and lifestyle interventions, not expensive but minimally effective prescription drugs.

Fortunately, there is a swell of new data to support the notion that nutrition-based interventions can slow the progression of dementia, and may even be able to prevent it. The idea that holistic approaches can avert cognitive decline is no longer speculative. Increasingly, it is evidence-based.

Case in point, the June 2024 randomized, controlled study published by a multicenter team led by Dean Ornish, MD, founder of the Preventive Medicine Research Institute. The study involved 51 patients with mild cognitive impairment or early-stage Alzheimer’s (AD), randomized to usual care with no lifestyle changes (N=25), or a 20-week intensive diet and lifestyle intervention centered on a whole food vegan diet, with daily exercise, stress reduction, social activity, and a sizeable stack of nutraceuticals.  

Study participants ranged in age from 45-90 years, with a mean of 73. At baseline, there were no differences between the groups in terms of cognitive function, as measured by standardized, well-validated assessment tools.

Significant Impact

This is the first randomized trial to look at the impact of a multimodal lifestyle intervention for prevention of AD progression, and the results are impressive.

After 20 weeks, the intervention group showed statistically significant improvements on the Clinical Global Impression of Change (CGIC), Clinical Dementia Rating Global (CDR-G), Clinical Dementia Rating Global (CDR-G) scales, compared with their baseline scores. They also showed borderline significant improvement on the Alzheimer’s Disease Assessment Scale (ADAS-Cog).

These beneficial changes were corroborated by an increase in the Aβ42/40 ratio, a biomarker indicating the degree of amyloid-β transport out of the brain and into the bloodstream.  

The “usual care” control group had worse scores on all four cognitive function rating scales, and the Aβ42/40 ratio dropped, suggesting amyloid clearance was declining.

Comprehensive Lifestyle Change

The diet & lifestyle protocol in this trial was quite comprehensive. It consisted of:

• A whole foods minimally-processed vegan diet, high in fruits, vegetables, whole grains, legumes, soy, seeds and nuts, and low in harmful fats, sweeteners and refined carbs. Generally, the diet consisted of 14-18% of calories as fat,16-18% protein, and 63-68% mostly complex carbohydrates. Subjects received 21 meals per week along with snacks. Calories were unrestricted, and people with higher caloric needs got extra portions.
• Exercise & activity: Participants committed to walking at least 30 minutes per day, along with three physiologist-guided strength training sessions per week. Exercise was custom-tailored to each patient’s age and fitness level.
• Stress reduction: Patients participated in daily, hour-long sessions of meditation, yoga-based postures, stretching, breathing exercises and guided imagery, facilitated by a certified stress management specialist. They also had the option to use pulsed light (at a theta frequency of 7.83 Hz) glasses with relaxing music, as a sleep aid.
• Group social support: Patients and their spouses or study partners participated in thrice-weekly group support sessions, supervised by licensed mental health professionals. In-person sessions were augmented with Zoom sessions.
• Supplements: The study provided supplement packs consisting of:
  • Omega-3 fatty acids with Curcumin (1,680 mg omega-3 & 800 mg Curcumin, Nordic Naturals ProOmega CRP, 4 capsules/day).
  • Multivitamin and Minerals (Solgar VM-75 without iron, 1 tablet/day).
  • Coenzyme Q10 (200 mg, Nordic Naturals, 2 softgels/day).
  • Vitamin C (1 gram, Solgar, 1 tablet/day)
  • Vitamin B12 (500 mcg, Solgar, 1 tablet/day)
  • Magnesium L-Threonate (Mg) (144 mg, Magtein, 2 tablets/day)
  • Hericium erinaceus (Lion’s Mane mushroom) (Host Defense, 2 g/day):
  • Super Bifido Plus Probiotic (Flora, 1 tablet/day).

Cognitive Improvements

“Despite the inherent limitations of self-reported data, we found statistically significant correlations between the degree of lifestyle change from baseline to 20 weeks, and the degree of change in three of four measures of cognition and function,” the authors report.

On the CGIC scale, 10 of the 26 patients (38%) in the lifestyle group showed improvement at 20 weeks, versus none in the control group. Seven people in the intervention group showed a slight worsening of cognition on CGIC, versus 14 people among the control subjects. None of the lifestyle group showed moderate worsening versus 3 in the control group.

Mean CDR-Global scores improved in the intervention group, as indicated by a score reduction from 0.69 at baseline to 0.65. In contrast, the mean CDR-G score worsened in the usual care group, going from 0.66 to 0.74.

ADAS-Cog scores also improved in the lifestyle group, dropping from 21.6 at baseline to 20.5 at the 20-week mark. Among the control subjects, ADAS-Cog rose from 21.3 to 22.2, indicating progression of cognitive decline. CDR-SB scores worsened among the usual care subjects, going from 3.3 to 3.8. Among the lifestyle change subjects, there was minimal change on this measure.

Given the complexity of the lifestyle intervention, it is not surprising that compliance varied. Those who were most compliant definitely got the best results. The authors describe a “dose-response correlation.”  The more they changed their diets and lifestyle routines, the greater was the impact on their cognitive function.

Biomarkers Bolster Credibility

The difference in Aβ42/40 ratios between the two groups is one of the most important findings from this study. This ratio is clinically relevant, and indicative of AD progression. It increased by a mean of 6.4% in the lifestyle group, but decreased by 8.3% in the usual care group. Since it reflects clearance of amyloid from the brain, a decreasing Aβ42/40 ratio correlates with progression while an increase indicates improvement.

In a 2022 trial of the drug Lecanemab, there was a significant ratio increase among the treated patients after 18 months, while the control group showed a decrease. Ornish notes that his team’s lifestyle program gave similar results, but in a mere five months.

The lifestyle intervention also resulted in statistically-significant beneficial changes in several other biomarkers, including hemoglobin A1c, insulin, glycoprotein acetyls (GlycA), LDL, β-Hydroxybutyrate (ketone bodies), and pTau181.

“Improvement in these biomarkers provides more biological plausibility for the observed improvements in cognition and function, as well as more insight into the possible mechanisms of improvement.”

Microbiome Benefits

The intervention also led to beneficial microbiome changes. Organisms in the Blautia and Eubacterium genera both increased in the intervention group, but not in the controls. These genera are linked to lower risk of AD in prior studies. Moreover, there was a concomitant reduction in Prevotella and Turicibacter, both of which are associated with AD progression.

“These results support the hypothesis that the lifestyle intervention may beneficially modify specific microbial groups in the microbiome: increasing those that lower the risk of AD and decreasing those that increase the risk,” Ornish and colleagues report. It’s not possible to determine if the observed changes were due solely to the probiotic supplement, or if the plant-intensive diet also played a role.

The Ornish study is indeed good news at a time when new technologies have improved early AD detection, but conventional drug-based medicine still has little to offer.

“Many people do not want to know if they are likely to get AD if they do not believe they can do anything about it,” Ornish and colleagues say. If diet and lifestyle changes can improve cognition and AD-related biomarkers in people with early AD, it is reasonable to think the same approach would be effective in preventing the disease.

Since publication of the Ornish study, several other large trials have also confirmed the impact of dietary factors on the progression of dementia.

Med Diet Mitigates Genetic Risk

A recent Harvard study of genomic, metabolomic, and nutrition data from more than 5,700 subjects (4,215 women and 1,490 men), showed that a Mediterranean style diet is particularly effective in modulating dementia-related metabolic pathways. The strongest effect was in people homozygous for the APOE4 gene.

APOE4 confers a very high risk of developing AD, to the point where many people believe that the gene is practically a guarantee for dementia. This study, headed by epidemiologist Yuxi Liu, challenges that notion.

“A key distinction between metabolomics and genetics is that metabolites can be modified by exogenous factors and may serve as targets for intervention; in particular, diet significantly impacts the metabolome. We thus examined whether diet, specifically the MedDiet, which has been implicated in cognitive health, could modulate metabolite levels in individuals with different genetic predispositions to AD and AD-related dementias”

People who were most adherent to the Med diet had lower risk of dementia, and better cognitive function. “Greater adherence…was associated with higher levels of unsaturated glycerides and lower levels of saturated glycerides, lipid patterns potentially beneficial for cognitive health, as well as increased levels of established neuroprotective compounds, including piperine, betaine, and pantothenic acid.

The impact of the diet was greatest among those at highest genetic risk—the people who were homozygous for APOE4. In this subgroup, close adherence to the MedDiet mitigated AD risk by an estimated 35%. The finding pokes a big hole in the notion that AD is an inevitable consequence of certain genes.

Liu and colleagues note that specific components of the MedDiet–nuts, fruit and monounsaturated fats– were strongly associated with metabolomic improvements.

Keep This in MIND

The Harvard study augments and amplifies key findings from the US POINTER trial, presented at the 2025 Alzheimer’s Association International Conference, and published in late July in the Journal of the American Medical Association.

This study, officially called the US Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk, randomized 2,111 elders at risk for AD to either a structured and guided comprehensive lifestyle intervention based around the MIND diet and supervised exercise, or a less intensive self-guided program which included similar recommendations but fewer points of in-person engagement.

The MIND diet is a hybrid of the Mediterranean and DASH diets. It is plant-centric, emphasizing green vegetables, whole grains, berries, beans and legumes, but it also encourages consumption of fish and poultry.

After two years, both groups showed improved cognitive function, as indicated by a composite measure of executive function, episodic memory, and processing speed. But the change was greater among those in the structured intervention group. The composite score increased by a mean of 0.243 standard deviations per year in the structured group, and by 0.213 standard deviations in the self-guided group.

“Among older adults at risk of cognitive decline and dementia, a structured, higher-intensity intervention had a statistically significant greater benefit on global cognition compared with an unstructured, self-guided intervention,” wrote lead author Laura D. Baker, PhD, of Wake Forest University.

Protecting the Hippocampus

In another big win for the MIND diet, Rush University researchers showed that it can reduce the odds of developing hippocampal sclerosis (HS)—intensive neuronal loss and astrocyte overgrowth within the hippocampus. HS is a common feature in AD and other forms of age-related, limbic-predominant dementia.

The Rush team studied brain tissue from 809 deceased participants in the ongoing Rush Memory and Aging Project. They obtained validated food frequency data from questionnaires taken annually for up to 18 years prior to the participants’ deaths. They assessed the presence of HS using hematoxylin and eosin staining, and other histologic techniques, in 8 brain regions.

Higher adherence to a MIND diet pattern (based on the food questionnaire data) was associated with a 22% reduction in the odds of having HS, after controlling for age, gender, APOE-4 status, vascular disease, and other variables. A higher MIND diet score was associated with less hippocampal neuronal loss, and an estimated 21% reduction in severity of dementia at time of death.

This is the first study to document the impact of diet on hippocampal neuronal loss. “These findings support the role of the MIND diet for a common degenerative pathology of aging,” the authors state.

Speaking of the hippocampus, University of Michigan researchers showed that high consumption of fat and sugar had detrimental effects on hippocampus-dependent recognition memory and executive function, particularly in people between the ages of 50 and 65.

That conclusion was based on data from 472 subjects who filled out dietary fat and sugar questionnaires, and also completed a set of standardized pattern-separation recognition and face-name memory tasks.

Those at the highest self-reported fat and sugar consumption levels had more subjective memory complaints, after adjusting for other relevant variables. The impact of dietary fat and sugar on hippocampal function was affected somewhat by patient age, and by presence or absence of other comorbidities. High sugar and fat intake was associated with compromised memory performance only in those with no comorbidities. “Diet effects on cognition are more complex in older than younger adults,” the researchers concluded.

Animal studies suggest several different mechanisms by which high fat intake impairs hippocampal function. These are well-summarized in a thorough review article by Dr. Charles Plakin, and posted by the Center for Food as Medicine & Longevity. Fortunately, these studies also indicate that the damage associated with high fat consumption is reversible.

Lay Off the Sweet n’ Low

To preserve cognitive function, avoid artificial sweeteners. That’s the upshot of an 8-year study of 12,772 participants in the Brazilian Longitudinal Study of Adult Health. Reseachers at the Universidade de Sao Paolo studied the impact of self-reported sweetener consumption on cognitive function, as measured by 6 different standardized tests. The food intake questionnaire included questions on seven different low- and no-calorie artificial sweeteners–aka LNCS–such as aspartame, saccharin, acesulfame k, erythritol, xylitol, sorbitol, and tagatose.

Among people under age 60, those in the highest tertile for sweetener use showed declines in verbal fluency and overall global cognition compared with those in the lower tertiles. This pattern held for people with and without type 2 diabetes. Interestingly, the investigators saw no such effect in people over age 60.

“Our findings suggest the possibility of long-term harm from LNCS consumption, particularly artificial LNCSs and sugar alcohols, on cognitive function,” they concluded.

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