Lipophilic Statin use Linked to Increased Risk of Dementia

Significant metabolic decline in the posterior cingulate cortex in lipophilic statin users

Reston, VA (Embargoed until 7:30 p.m. EDT, Monday, June 14, 2021)–In patients with mild cognitive impairment, taking lipophilic statins more than doubles their risk of developing dementia compared to those who do not take statins. According to research presented at the Society of Nuclear Medicine and Molecular Imaging 2021 Annual Meeting, positron emission tomography (PET) scans of lipophilic statin users revealed a highly significant decline in metabolism in the area of the brain that is first impacted by Alzheimer’s disease.

Statins are medications used to lower cholesterol and reduce the risk of heart attack or stroke. They are the most commonly used drugs in the developed world, and nearly 50 percent of Americans over age 75 use a statin. Different types of statins are available based on a patient’s health needs, including hydrophilic statins that focus on the liver and lipophilic statins that are distributed to tissues throughout the body.

“There have been many conflicting studies on the effects of statin drugs on cognition,” said Prasanna Padmanabham, project head, statins and cognition in the molecular and medical pharmacology student research program at the University of California, Los Angeles in Los Angeles, California. “While some claim that satins protect users against dementia, others assert that they accelerate the development of dementia. Our study aimed to clarify the relationship between statin use and subject’s long-term cognitive trajectory.”

Researchers separated study participants into groups based on three parameters: baseline cognitive status, baseline cholesterol levels and type of statin used. Participants underwent 18F-FDG PET imaging to identify any regions of declining cerebral metabolism within each statin group. Eight years of subject clinical data was analyzed.

Patients with mild cognitive impairment or normal cognition who used lipophilic statins were found to have more than double the risk of developing dementia compared to statin non-users. Over time, PET imaging of lipophilic statin users also showed a substantial decline in metabolism in the posterior cingulate cortex, the region of the brain known to decline the most significantly in the earliest stages of Alzheimer’s disease. In contrast, no clinical or metabolic decline was found for users of other statins or for statin users with higher baseline serum cholesterol levels.

“By characterizing the metabolic effects associated with statin use, we are providing a new application of PET to further our understanding of the relationship between one of the most commonly used classes of drugs and one of the most common afflictions of the aging brain,” noted Padmanabham. “Findings from these scans could be used to inform patients’ decisions regarding which statin would be most optimal to use with respect to preservation of their cognition and ability to function independently.”

About the Society of Nuclear Medicine and Molecular Imaging

The Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and medical organization dedicated to advancing nuclear medicine and molecular imaging, vital elements of precision medicine that allow diagnosis and treatment to be tailored to individual patients in order to achieve the best possible outcomes.

SNMMI’s members set the standard for molecular imaging and nuclear medicine practice by creating guidelines, sharing information through journals and meetings and leading advocacy on key issues that affect molecular imaging and therapy research and practice. For more information, visit http://www.snmmi.org


JOURNAL


The BEST Veggie Burger ever!

Veggie Burgers

Makes 6

Veggie Burger with Gluten Free Bun

Years ago when my Meal Delivery Service was vegetarian I served veggie burgers made with rice and kidney beans. They sold well but I was never completely thrilled with the recipe.  I couldn’t get them to be crispy enough and over the years I stopped eating beans. I found I couldn’t get them crispy enough and I thought they were just too heavy. 

THESE are the veggie burgers I always wanted.

2 tablespoons extra-virgin olive oil, more for drizzling
1 onion, diced, caramelized and drained
16 ounces mushrooms, mix of shiitake + Portobello, de-stemmed and diced
2 tablespoons tamari
¼ cup balsamic vinegar
1 tablespoon mirin
2 garlic cloves, minced
½ teaspoon smoked paprika
2 teaspoons siracha, more if desired
½ cup crushed walnuts
¼ cup ground flaxseed
2 cups cooked short-grain brown rice, freshly cooked so that it’s sticky*
1 cup gluten-free panko bread crumbs, divided
Worcestershire sauce, for brushing (I make my own)
Ghee to pan fry
Sea salt and freshly ground black pepper

 

Heat the olive oil in a medium skillet over medium heat.  Add the mushrooms, a generous pinch of salt, and sauté until soft and browned, 6 to 9 minutes, turning down the heat slightly, as needed. Add the caramelized onion and stir well

Stir in the tamari, vinegar, and mirin. Stir, reduce the heat, and then add the garlic, and smoked paprika, and siracha. Remove the pan from the heat and let cool slightly.

In a food processor, combine the sautéed mushrooms, walnuts, flaxseed, brown rice, and ½ cup of the panko. Pulse until well combined.

Transfer to a large bowl and stir in the remaining panko.

425° for about 9 minutes per side, or broiled for 5-7 minutes per side.


Junk Food Linked to Gut Inflammation

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The impact of diet on health is really a no-brainer – even leading to calls for GPs to prescribe fruit and vegetables before writing out a drug prescription.

Now, US researchers report in the journal Cell Host & Microbe that they’ve found a mechanism to explain how obesity caused by junk food and an unhealthy diet can induce inflammation in the gut.

“Our research showed that long-term consumption of a Western-style diet high in fat and sugar impairs the function of immune cells in the gut in ways that could promote inflammatory bowel disease or increase the risk of intestinal infections,” says lead author Ta-Chiang Liu, from Washington University.

This has particular relevance for Crohn’s disease – a debilitating condition that has been increasing worldwide and causes abdominal pain, diarrhoea, anaemia and fatigue.

A key feature of the disease is impaired function of Paneth cells, immune cells found in the intestines that help maintain a healthy balance of gut microbes and ward off infectious pathogens.

When exploring a database of 400 adults with and without Crohn’s disease, the researchers discovered that higher body mass index (BMI) was associated with progressively more abnormal looking Paneth cells, captured under a microscope.

Armed with their discovery, they studied two strains of mice genetically predisposed to obesity and were surprised to find that the animals’ Paneth cells looked normal.

To dig deeper, the researchers fed normal mice a diet in which 40% of the calories came from fat or sugar, typical of a Western diet.

After two months the mice became obese – and their Paneth cells became abnormal. They also had associated problems such as increased gut permeability, a key feature of chronic inflammation that allows harmful bacteria and toxins to cross the intestinal lining.

“Obesity wasn’t the problem per se,” says Lui. “Eating too much of a healthy diet didn’t affect the Paneth cells. It was the high-fat, high-sugar diet that was the problem.”

Importantly, switching from junk food back to a standard diet completely reversed the Paneth cell dysfunction.

Further experiments revealed that a bile acid molecule known as deoxycholic acid, formed as a by-product of gut bacteria metabolism, increased the activity of immune molecules that inhibit Paneth cell function.

Liu and colleagues are now comparing the individual impact of fat and sugar on Paneth cells.

Whether the damaged cells respond to a healthy diet in humans remains to be seen, but preliminary evidence suggests diet can alter the balance of gut bacteria and alleviate symptoms of Crohn’s disease.