Lithium Linked to Dementia Prevention

 Ask your doctor if this is a valid treatment to prevent your likely dementia or should you be doing this?

Stopping dementia at the nose with combination of rifampicin and resveratrol

January 2022 

Your doctor is required to have a solution. 

Your risks of dementia, has your doctor told you of this?

1. A documented 33% dementia chance post-stroke from an Australian study?   May 2012.

2. Then this study came out and seems to have a range from 17-66%. December 2013.`    

3. A 20% chance in this research.   July 2013.

4. Dementia Risk Doubled in Patients Following Stroke September 2018

Where are the  protocols to prevent your dementia?

The latest here:

Lithium Linked to Dementia Prevention

Study found lower risk of developing Alzheimer's, vascular dementia

by Kristen Monaco, Staff Writer, MedPage Today March 17, 2022

Treatment with lithium may be protective against dementia and its subtypes, a retrospective cohort study indicated.

Among patients receiving mental health care, those exposed to lithium at standard clinical dosages had a 44% lower risk of receiving a diagnosis of dementia versus those unexposed over an average follow-up of 4.8 years (HR 0.56, 95% CI 0.40-0.78), Shanquan Chen, PhD, of the University of Cambridge, England, and colleagues reported in PLoS Medicine.

Lithium use was tied to a significantly reduced risk for both dementia subtypes considered:

• Alzheimer's disease: HR 0.55 (95% CI 0.37-0.82)
• Vascular dementia: HR 0.36 (95% CI 0.19-0.69)

The researchers didn't measure risk for other dementia subtypes though, such as Lewy body or Parkinson disease dementia.

Of note, lithium use was protective both with 1 year or less of use and with long-term use of 5 or more years. However, medium-term exposures -- between 1 and 5 years of treatment -- weren't significantly protective, although Chen's group said this was likely just an effect of being statistically underpowered.

"The number of people with dementia continues to grow, which puts huge pressure on healthcare systems," Chen explained in a statement. "It's been estimated that delaying the onset of dementia by just five years could reduce its prevalence and economic impact by as much as 40 percent."

Not surprisingly, 73% of the patients in the lithium-treated group had mania or bipolar affective disorders -- one of the most common indications for lithium. Because of this, the researchers adjusted for this common comorbidity, as well as depression, age, sex, marital status, ethnicity, smoking status, alcohol disorders, antipsychotic use, hypertension, central vascular disease, diabetes mellitus, and hyperlipidemia.

"Bipolar disorder and depression are considered to put people at increased risk of dementia, so we had to make sure to account for this in our analysis," Chen noted.

For the analysis, the researchers used electronic health record data from 29,618 patients at a secondary care mental health service in the U.K. The cohort was exclusive to patients ages 50 and older (average 73.9) without a diagnosis of mild cognitive impairment or dementia at baseline.

Of these patients, only 548 had exposure to lithium. Patients treated with lithium were more likely to be married or in a civil partnership, be a former or current smoker, to have used antipsychotics, and have comorbid depression, mania/bipolar affective disorder, hypertension, central vascular disease, diabetes mellitus, or hyperlipidemia.

A total of 9.7% of the lithium-exposed patients were subsequently diagnosed with dementia, while 11.2% of the unexposed group were. "The frequency of dementia in our control cohort was higher than in the general population, as would be expected for a [mental health] service," the researchers pointed out.

Chen's group noted that lithium levels weren't consistently available throughout follow-up, but generally fell between in standard therapeutic range and well above the typical 0.00029 to 0.00386 mmol/L found in drinking water.

"The main unanswered question from this work is the dose-response association between lithium within its therapeutic range and the incidence of dementia," the researchers wrote. "The clinical context means that lithium levels primarily lay within its therapeutic range of 0.4 to 1.0 mmol/L...but at times, lithium levels in some patients may have been >1.0 mmol/L, with resultant potential for neurotoxicity, or subtherapeutic, either might alter the estimate of the protective effects of lithium, and the optimal level for any such protective effect is unknown."

The next steps to confirm a protective effect would involve large-scale dose and effect studies, particularly those that include the general population and measure outcomes for other types of dementia, Chen's group concluded. Also, randomized trials of lithium for the prevention of progression to dementia in those with mild cognitive impairment or early disease are warranted, they said.

• 

  Kristen Monaco is a staff writer, focusing on endocrinology, psychiatry, and nephrology news. Based out of the New York City office, she’s worked at the company since 2015.

Disclosures

The study was supported by grants from the Medical Research Council.

Chen reported no disclosures. Other co-authors did report relevant disclosures.

Primary Source

PLoS Medicine

Source Reference: Chen S, et al "Association between lithium use and the incidence of dementia and its subtypes: A retrospective cohort study" PLoS Med 2022; DOI: 10.1371/journal.pmed.1003941.

Stopping dementia at the nose with combination of rifampicin and resveratrol

Don't try to figure out how to nasally administer red wine, the amounts in a bottle of wine are miniscule. You'll just have to wait for appropriate research to occur and then get that translated to an intervention, maybe 50 years from now. With survivors in charge we could get it done much faster.

Stopping dementia at the nose with combination of rifampicin and resveratrol

Researchers from Osaka City University have shown in mice models of Alzheimer's disease, frontotemporal dementia, and dementia with Lewy bodies, that the intranasal administration of rifampicin and resveratrol in combination is safer and improves cognitive function more than rifampicin alone. The research results are expected to lead to the development of safe and effective nasal spray for the prevention of dementia.

Dementia is thought to occur when proteins called amyloid-β, tau, and α-synuclein accumulate in the brain and form oligomers. A research group from the Department of Translational Neuroscience, Osaka City University Graduate School of Medicine, had previously shown in a study using mice that the antibiotic rifampicin removes oligomers from the brain and improves cognitive function. However, the drug has been associated with side effects such as liver damage. Resveratrol, a naturally occurring antioxidant in plants, is used as a supplement in Europe and the United States. "To combat the negative side effects of the existing drug rifampicin, we thought of combining it with the hepatoprotective effects of resveratrol," illustrates Professor Takami Tomiyama, who acted as lead investigator for the current study.

This time, the research group administered a fixed dose combination of rifampicin and resveratrol intranasally five days a week for a total of four weeks to mice models of Alzheimer's disease, frontotemporal dementia, and dementia with Lewy bodies, and observed their cognitive functions and brain pathology. The results showed that the combination significantly improved the cognitive function of the mice, inhibited the accumulation of oligomers, and restored synaptophysin levels — presynaptic proteins that facilitate synapses. Additionally, blood levels of liver enzymes, a marker of hepatic damage that normally increases with rifampicin, remained normal in the fixed-dose combination. Furthermore, increased levels of brain-derived neurotrophic factor (BDNF) expression were observed in the hippocampus, which was not seen with rifampicin alone. These results indicate that this fixed-dose combination is superior to rifampicin alone in terms of both safety and efficacy.

The results of this study were published online in the Swiss scientific journal Frontiers in Neuroscience on December 13, 2021.

"The number of patients with dementia has been increasing all over the world, with some sources predicting a doubling of patients every 20 years. However, there is still no effective treatment for the disease," states Specially Appointed Lecturer Tomohiro Umeda, first author of the study. "Recent studies have shown that abnormalities begin to appear in the brains of dementia patients more than 20 years before the onset of the disease." By investigating new therapeutic purposes with existing drugs in a process called drug repositioning, the research team hopes to diagnose and prevent dementia before the neurons start dying.

Furthermore, based on the team's previous research experience, nasal administration of a fixed dose combination of rifampicin and resveratrol would increase drug transferability to the brain and further enhance both safety and medicinal effects. The dosage used in this study was 0.02 mg of rifampicin per mouse per day, or 1 mg/kg/day assuming a mouse weight of 20g. "Converted to a human dosage based on body surface area, it becomes 0.081 mg/kg/day," states Prof. Tomiyama, "currently, rifampicin is prescribed at 10 mg/kg/day as an antibiotic, and compared to this, we confirmed an effect at a much lower dosage."

The development of a fixed-dose combination of rifampicin and resveratrol nasal spray is currently being carried out by Medilabo RFP, a venture company originating from the research team's laboratory. Following the publication of this paper, Medilabo RFP has begun preparations for global clinical trials. In November 2021, with the support of the Japan External Trade Organization (JETRO), Medilabo RFP has established a subsidiary in Massachusetts, USA.

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