A new study out this week and published in iScience found that fat cells play a major role in advancing brain aging and cognitive decline through Na,K+ATPase signaling. Recent studies have suggested that this pathway is also responsible for conditions that accelerate cardiovascular disease risk including, metabolic syndrome and fatty liver (nonalcoholic steatohepatitis).
The new study was conducted in mice that were genetically modified to release the peptide, NaKtide, in fat cells. NaKtide is a direct inhibitor of Na,K+ATPase signaling. The authors found that compared to a control diet, a Western diet (greater than 40% of calories derived from fat) resulted in Na,K+ATPase -mediated cellular inflammation and altered levels of brain biomarkers that affect memory and cognition. These proinflammatory effects were abolished when NaKtide was activated, thereby resulting in improved function of regions that include the brain’s memory center (hippocampus).
The bottom line is that in a mouse model, Na,K+ATPase signaling in fat cells promotes memory loss and neurodegenerative changes. They raise the possibility that a similarly operative signaling -pathway in humans might lead to adverse long-term neurologic consequences under certain conditions (such as repeated exposure to a high fat diet). Finally, they suggest that effective therapies directed against this proinflammatory signaling pathway could offset cognitive decline.
Of course, the most effective and currently available approach to reduce cognitive decline as related to this pathway would consist of reducing daily intake of highly saturated, processed and deep-fried foods!
Listed below are additional features related to diet, physical activity, obesity and brain health.
- Obesity promotes inflammation within the brain leading to cognitive decline and progression of neurodegenerative disorders.
- Significant and rapid weight loss as a consequence of bariatric surgery has been associated with improvements in cognitive function including memory and executive function.
- Adherence to the Mediterranean diet – high in vegetables, whole grains, fish, and olive oil – correlates with higher cognitive function.
- Compared to a high fat, Atkins Diet, a low fat Ornish Diet is associated with low levels of TMAO, a gut metabolite predictive of increased cardiovascular disease risk and reduced cognitive function.
- Replacement of saturated fat by polyunsaturated or monounsaturated fat is associated with lower rates of neurodegenerative disease.
- Higher levels of physical activity are associated with a 35% reduced risk of cognitive decline and 14% reduced risk of dementia.
- A diet containing at least one serving of green leafy vegetables each day is associated with slower age-related cognitive decline by approximately 10 years.
- Metabolic Syndrome is associated with increased risk of developing cognitive impairment and premature dementia.
- Chronic exposure to stress confers a higher risk of developing neurodegenerative disorders including Alzheimer’s disease.
- Chronic insomnia is associated with a 30-35% increased risk of progressive dementia.
- Musicians are 64% less likely to develop mild cognitive impairment or dementia, even after adjusting for physical activity and education.
- Drinking 3-5 cups of coffee per day at midlife was associated with a decreased risk of dementia and Alzheimer’s Disease by about 65% at late-life.
- Speaking at least 2 languages has been shown to delay the onset of dementia by 4-5 years.
Dr. Michael Miller is Professor of Cardiovascular Medicine at the University of Maryland School of Medicine in Baltimore, Maryland. Check him out on twitter: @mmillermd1