Last Month in Neurology Research: Some Ups, Some Downs

This transcript has been edited for clarity.

Dear colleagues, I'm Christoph Diener from the medical faculty of the University Duisburg-Essen in Germany. Today I'd like to review the published neurology research from October 2021, which was overall a frustrating month for news regarding the treatment of a number of diseases.

Losartan for Alzheimer's Disease

Preclinical mouse models of Alzheimer's disease have shown that angiotensin-converting enzyme (ACE) plays an important role in the deposition of both beta-amyloid and tau protein.

This was the basis on which a group in the United Kingdom performed a study in 211 patients with mild to moderate Alzheimer's disease. The patients were randomized to receive either the ACE inhibitor losartan or placebo. The primary endpoint was the change in brain volume at 1 year, as measured by MRI.

I don't think it will come as a big surprise to report that there was no benefit to losartan over placebo. Simply put, even if this therapy works, 211 patients are not enough to show a benefit in a study of Alzheimer's disease.

Mirtazapine for Agitation in Dementia

It is commonly known that many patients with dementia who get agitated cannot tolerate neuroleptics. Therefore, there is a need for alternative treatment.

In another study performed in the United Kingdom, investigators looked at the possible benefit of using the antidepressant mirtazapine to treat agitation in patients with dementia. Investigators randomized 204 patients to receive either mirtazapine or placebo, with a primary endpoint of a reduction in the Cohen-Mansfield Agitation Inventory score at 12 weeks.

Unfortunately, there was no benefit of mirtazapine over placebo. And there was even an increase in mortality with active drug over placebo.

The Best Anticoagulation Method for Reducing Dementia in Patients With Atrial Fibrillation

By now, we're all aware that atrial fibrillation represents an important risk factor for dementia. This is true for both vascular dementia and Alzheimer's disease. A number of studies have shown that there is a benefit in terms of preventing dementia if people with atrial fibrillation are anticoagulated with vitamin K antagonists.

A study published in Heart analyzed data from 39,200 people in the United Kingdom who, for the first time, were anticoagulated due to atrial fibrillation. Investigators compared vitamin K antagonists, which were used by 53% of patients, with direct oral anticoagulants (DOACs), which were used by 47% of patients. The endpoint was the development of all-cause dementia.

The risk of developing dementia was reduced by 16% in people who used DOACs, compared with the use of vitamin K antagonists.

Preventing Sepsis in the Intensive Care Unit

In 2017, a small study was published indicating that the combination of thiamine (vitamin B1), ascorbic acid, and hydrocortisone could possibly improve the prognosis of sepsis.

This combination has now been further studied in a meta-analysis published in Critical Care Medicine. Investigators included eight randomized controlled trials with a total of 1335 patients and assessed the primary endpoint of the Sequential Organ Failure Assessment (SOFA) score within 72 hours.

Unfortunately, there was no evident benefit to this combination for organ failure, mortality, and kidney function. As a result, we can infer that this very well-tolerated treatment is obviously not effective.

Choosing the Best Options for Preventing Chronic Migraine

When it comes to traditional migraine preventive drugs, we have scientific evidence supporting the benefit of topiramate and onabotulinumtoxinA. From the newer class of drugs in this indication, all four monoclonal antibodies against calcitonin gene-related peptide (CGRP) or the CGRP receptor are effective in patients with chronic migraine.

A study group in India conducted a double-blind controlled trial comparing propranolol with topiramate in chronic migraine. Ninety-five patients were randomized to either propranolol 160 mg/day or topiramate 100 mg/day, which was slowly titrated up over 1 month.

After following these patients for half a year, investigators found that both drugs were equally effective. The reduction in migraine days per month was between 5 and 7, with the numerical benefit favoring propranolol over topiramate. The rate of patients who tolerated this treatment was quite astonishing. Very few patients terminated treatment with either topiramate or propranolol.

This study offers important findings for those in the many countries where monoclonal antibodies are simply too expensive, who now have three established choices for treating chronic migraine: propranolol, topiramate, and onabotulinumtoxinA.

Dear colleagues, I hope you've found this discussion of five new studies published in October 2021 useful. Hopefully, I'll have more positive studies to report in November.

I am Christoph Diener from the Faculty of Medicine at the University of Duisburg-Essen in Germany. Thank you very much for listening and watching.

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