AGE/DOSE
Metabolism

Ketogenic Diet Restores Alzheimer’s Memory Deficits and Neurodegeneration, Study Shows 

Chinese scientists find that a high-fat, low-carbohydrate diet called the ketogenic diet restores memory deficits and neurodegeneration markers in mice modeling Alzheimer’s disease.

By Daniel R. Miranda, Ph.D.

Key Points: 

  • Alzheimer’s mice fed a ketogenic diet have improved spatial and short-term memory. 
  • The ketogenic diet largely restores the loss of neurons, neuronal connections, and neuron degeneration in Alzheimer’s mice. 
  • The effects of the ketogenic diet are mediated by reduced brain inflammation. 

When challenged with inflammation over a lifetime, our organs operate with declining efficiency. The brain, a reservoir of memories, is no different. When this organ declines, our memories are lost. Such is the case with Alzheimer’s disease (AD). Therefore, preventing or alleviating this condition, which can affect nearly anyone, is of grave value.

Now, scientists from the Chinese Academy of Sciences report in CNS Neuroscience & Therapeutics that dietary changes can alleviate cognitive impairment, neurodegeneration, and neuroinflammation in a mouse model for AD. Xu and colleagues show that spatial and short-term memory, as well as neuron degeneration, are restored in AD mice fed a ketogenic diet. The ketogenic diet also reduces brain inflammation and the beta-amyloid plaques characteristic of AD. 

Keto Diet Restores Memory and Prevents Neuron Degeneration 

To study the effects of the ketogenic diet on AD, Xu and colleagues fed a mouse model for AD a diet containing 76% plant-derived fat, 16% protein, 3% carbohydrates, and 5% dietary fiber. Feeding the AD mice this ketogenic diet resulted in the restoration of spatial learning and memory, as measured by the Barnes maze test, as well as restoration of short-term (working) memory, measured by the T maze test.

keto diet restores short-term memory
(Xu et al., 2021 | CNS Neurosci. Ther.) Keto Diet Corrects Alzheimer’s Memory Deficits. Normal mice (WT) and Alzheimer’s disease (AD) mice were fed either a standard diet (SD) or a ketogenic diet (KD). AD mice fed a KD (AD + KD) correctly remembered the location of food in the T maze as often as WT mice fed a SD (WT + SD), suggesting the restoration of short-term memory.

When the neurons of our brain lose connectivity, memory loss occurs. AD and other neurodegenerative diseases involve the loss of synapses and spines — the points at which neurons connect, as well as the loss of neurons themselves. Xu and colleagues found that feeding AD mice a ketogenic diet restored their neurons, synapses, and spines, suggesting prevention of neurodegeneration and improvements in neuronal connectivity. 

keto diet restores neuron degeneration
(Xu et al., 2021 | CNS Neurosci. Ther.) Keto Diet Corrects Alzheimer’s Neuron Degeneration. Normal mice (WT) and Alzheimer’s disease (AD) mice were fed either a standard diet (SD) or a ketogenic diet (KD). AD mice fed a KD (AD + KD) had neuron outgrowths (spines) similar to WT mice fed a SD (WT + SD), indicating restoration of neuron degeneration. 

Amyloid-beta plaques are protein aggregates that accumulate in AD brains. These plaques are associated with increased brain inflammation, which underlies the neurodegeneration and cognitive impairments seen with AD.  Xu and colleagues found that feeding AD mice a ketogenic diet reduced beta-amyloid plaques while at the same time reducing inflammation. 

The findings of Xu and colleagues suggest that the ketogenic diet can treat AD by reducing inflammation. The ketogenic diet promotes the genesis of what are called ketone bodies (mainly acetoacetate and β-hydroxybutyrate), which the brain can use as fuel in place of glucose. Abnormal glucose utilization has been observed in AD patients, so the ketogenic diet may provide the brain with more energy via ketone bodies. Additionally, a lack of glucose may reduce inflammation. 

The Keto Diet Improves Cognition in Alzheimer’s Patients

Several clinical trials have shown that the ketogenic diet improves the cognition, namely verbal memory and attention, of Alzheimer’s patients.  While less conclusive, some studies have shown that the keto diet can improve cognition in healthy older adults as well. Furthermore, the ketogenic diet may play a preventative role, as it improves the cognition of adults with mild cognitive impairment, a prerequisite to Alzheimer’s disease. While more studies are needed to come to definitive conclusions, the ketogenic diet seems to at least partially treat the cognitive deficits associated with aging.

Is the Keto Diet an Anti-Aging Therapy?

The ketogenic diet has been shown to extend the median lifespan of mice by 13.6% while preserving muscle mass, motor function, and memory. The diet has also been shown to mitigate heart aging and tumor growth in animal models. Other animal studies suggest that the ketogenic diet can also control obesity to prevent metabolic diseases like diabetes. Thus, with studies showing that the keto diet can treat multiple age-related diseases, it may only be a matter of time before the full anti-aging potential of the ketogenic diet is realized.

Model & Dosage

Model: 5XFAD mice, transgenic for five familial AD (FAD) mutations

Dosage: 76% fat, 16% protein, 3% carbohydrate, and 5% dietary fiber (by calories)

Source

Xu Y, Jiang C, Wu J, Liu P, Deng X, Zhang Y, Peng B, Zhu Y. Ketogenic diet ameliorates cognitive impairment and neuroinflammation in a mouse model of Alzheimer’s disease. CNS Neurosci Ther. 2022 Apr;28(4):580-592. doi: 10.1111/cns.13779. Epub 2021 Dec 10. PMID: 34889516; PMCID: PMC8928920.

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