Keto-Like Diet May Improve Cognition in MCI, Early Alzheimer's

Michelle E. Grady

July 03, 2019

A ketogenic diet may boost cognition in older adults who have early signs of dementia, preliminary research suggests.

Investigators at the Johns Hopkins University School of Medicine, Baltimore, Maryland, found that when older adults with mild cognitive impairment (MCI) switched their diet to a low-carbohydrate, high-fat ketogenic diet, they experienced modest improvement in memory, as measured by a standardized test.

"If we can confirm these preliminary findings, using dietary changes to mitigate cognitive loss in early-stage dementia would be a real game-changer. It's something that 400-plus experimental drugs haven't been able to do in clinical trials," principal investigator Jason Brandt, PhD, professor of psychiatry, behavioral sciences, and neurology, said in a release.

The study was published in the April issue of the Journal of Alzheimer's Disease.

"Dismal" Drug Development Record

Of the 413 clinical trials of new medications for Alzheimer disease (AD) conducted between 2002 and 2012, 99.6% of the drugs investigated yielded no significant benefit. "Given this dismal record of drug development and the devastating consequences of AD for patients and their families, the development of alternative approaches to treatment and prevention is essential," the investigators write.

"The possibility that changes in diet might improve cognitive or functional abilities of those afflicted, slow the rate of progression, or otherwise lessen its impact is promising and warrants investigation," they add.

To establish the feasibility of implementing the modified Atkins diet (MAD) in older adults who have early AD or MCI and to examine whether changes in participants' cognitive, behavioral, and emotional functioning are more favorable in those on the MAD vs a control diet, the investigators conducted a phase 1/2 randomized clinical trial.

The investigators note that normally, the brain uses glucose produced from the breakdown of carbohydrates as its primary fuel. However, for persons with early-stage AD, the ability to metabolize glucose is faulty, and glucose becomes inefficient as the primary energy source. Some experts, said Brandt, even refer to Alzheimer's as "type 3 diabetes."

The early findings suggest that by changing the diets of individuals who have MCI or early AD to a ketogenic diet rich in fats and low in sugars or starches, the brain and body begin to use ketones — produced during the metabolization of fat — as an alternative energy source.

Further Research Warranted

The 12-week study started with 27 participants, but owing to the difficulty of a complete diet overhaul and restrictive dietary measures, the number of active participants dropped to 14. The average age of the participants was 71 years. Half of the 14 participants were women, and all but one were white.

Participants were randomly assigned to consume one of two diets for the 12-week trial period. Nine participants followed the MAD, which restricted the amount of carbohydrates consumed to 20 grams per day or less. There was no restriction on calories. Prior to the study, these individuals were consuming on average 158 grams of carbohydrates per day.

The other five participants followed a National Institute of Aging (NIA) diet, which is similar to the Mediterranean diet. The NIA diet does not restrict carbohydrates and favors fruits, vegetables, low- or fat-free dairy, whole grains, and lean proteins. The five participants continued to eat well over 100 grams of carbohydrates per day.

Participants produced urine samples at the start of the study and every 3 weeks thereafter. The researchers used these samples to assess ketone levels. As expected, no ketones were detected in the urine samples of the participants who consumed the low-fat diet. For more than half of the participants on the MAD, at least some ketones were detected in urine from week 6 until the end of the study.

Participants completed the Montreal Cognitive Assessment, the Mini–Mental State Examination, and the Clinical Dementia Rating Scale at the start of the study.

Testing took place at baseline and at 6 and 12 weeks. At the 6-week mark, the researchers found a significant improvement in memory, which correlated with the highest levels of ketones and the lowest carbohydrate intakes.

When comparing the results of tests of delayed recall — the ability to recollect something they were told or shown a few minutes earlier — on average, those on the ketogenic diet improved by a couple of points (about 15% of the total score), whereas those who followed the NIA diet on average dropped a couple of points.

The researchers note that although these early results are far from proof that the high-fat diet can prevent cognitive decline, they are promising enough to warrant larger, longer-term studies of the impact of diet on brain function.

Growing Interest in Diet

Commenting on the findings for Medscape Medical News, Heather Snyder, PhD, senior director of medical and scientific operations at the Alzheimer's Association, who was not involved in the study, said the findings are interesting, if extremely preliminary.

"It's a small study with only 14 participants, so it certainly needs to be replicated in a larger study. But we've seen a growing number of studies that have looked at diet and nutrition, including a study published earlier this year that was a clinical trial using a keto drink and its impacts. We're seeing a number of groups around the world that are looking at keto-like interventions on brain health, and I don't think we completely understand it yet," she said.

Snyder emphasized that what works for one individual may not work for another. She compared dietary shifts to physical activity. She noted that individuals need to find something they enjoy and can keep doing. Otherwise, adherence to any intervention will falter.

"This underscores the importance of conducting multiple studies — the keto drink vs a keto diet," said Snyder. "But having a greater understanding of diet and nutrition will allow us to maximize our brain health as we age."

The study was supported by grants from the William and Ella Owens Medical Research Foundation, the BrightFocus Foundation, and the National Center for Advancing Translational Sciences. The authors' disclosures of relevant financial relationships are available on the journal's website.

J Alzheimers Dis. 2019;68:969-981. Abstract

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