Licensed Anti-Microbial Drugs Logical for Clinical Trials against Pathogens Currently Suspected in Alzheimer's Disease.

There is now considerable evidence that several infectious agents (viruses, bacteria, or parasites) may play a contributing role in the development of Alzheimer's disease (AD). The six primary suspects are herpes viruses, spirochetal bacteria, Chlamydia pneumoniae, Porphyromonas gingivalis, mycobacteria, and toxoplasma parasites. Also, some of the antimicrobial and antiviral agents that are used to treat them have shown promise for AD interventions. I describe this evidence and assert it is now time to accelerate clinical trials of these existing drugs, already federally approved, to determine if such treatments can delay, halt, or reverse AD.

Repurposing Licensed Drugs for Use Against Alzheimer's Disease.

Substantial evidence, composed of drug mechanisms of action, in vivo testing, and epidemiological data, exists to support clinical testing of FDA-approved drugs for repurposing to the treatment of Alzheimer's disease (AD). Licensed compound investigation can often proceed at a faster and more cost-effective manner than un-approved compounds moving through the drug pipeline. As the prevalence of AD increases with life expectancy, the current rise in life expectancy amalgamated with the lack of an effective drug for the treatment of AD unnecessarily burdens our medical system and is an urgent public health concern. The unfounded reluctance to examine repurposing existing drugs for possible AD therapy further impedes the possibility of improving the quality of patient lives with a terminal disease. This review summarizes some evidence which exists to suggest certain already-approved drugs may be considered for the treatment of AD and will perhaps encourage physicians to off-label prescribe these safe therapeutics.

Predicted economic damage from a quick, simple Alzheimer's disease cure.

The estimated 5.8 million Alzheimer's disease patients in the U.S. require an enormous share of national healthcare expenditures. Other nations face similar economic burdens. There have been great efforts, thus far unsuccessful, to discover an effective therapeutic, with 1081 Alzheimer's disease drug trials completed as of May 2019. The pessimism thus engendered has forestalled contingency planning for the potential major economic repercussions of a simple, quick cure. Yet, promising new research spotlighting the possible "trigger" role of infectious agents might allow some or all cases of Alzheimer's disease to be halted, reversed, or prevented with an antibiotic or antiviral compound, possibly even one already approved by drug regulators for other uses. The sudden advent of such an unexpected therapy would theoretically have dramatic impacts, both detrimental and beneficial, on the American economy. The damages would include a $414 billion shrinkage of Medicaid, Medicare and other revenues to all six sectors comprising the healthcare provider category. Nursing homes and skilled nursing facilities are projected to suffer the greatest loss of annual revenue: $51 billion and $16 billion, respectively. This would cause the loss of an estimated 654,000 jobs. Facility mortgage and commercial loan repayments could stop. Other adverse consequences would include detrimental effects on reserves for Social Security and pensions, cutbacks in dementia research funding, and reduced donations to Alzheimer's disease advocacy groups. Insurance company reserves for fixed payment annuities already sold could be jeopardized. However, an Alzheimer's disease cure would also create economic beneficiaries. Medicare and Medicaid would save up to a projected $195 billion annually. Life insurance companies and unpaid caregivers would also benefit financially. By identifying the healthcare sectors likely to be detrimentally impacted by a simple, quick Alzheimer's disease cure, contingency plans can be made in the U.S. and other countries to assist the foreseeable painful transitions for staff and facilities.

The Beehive Theory: Role of microorganisms in late sequelae of traumatic brain injury and chronic traumatic encephalopathy.

Traumatic brain injury and chronic traumatic encephalopathy are both major health problems, well-publicized for the severe delayed effects attributed to them, including cognitive decline, psychiatric disorders, seizures, impaired motor function, and personality changes. For convenience, the two afflictions are considered together under the rubric traumatic brain injury. Despite the need for neuroprotective agents, no substances have shown efficacy in clinical studies. Thus, a deeper understanding of the neuropathological mechanism of such injury is still needed. Proposed here is a theory that microorganisms from within the brain and elsewhere in the body contribute to the long-term neurological deterioration characteristic of traumatic brain injury. The label, "The Beehive Theory", is drawn from the well-known fact that disturbing a tranquil beehive with a blow can cause a swarm of angry bees to exit their dwelling place and attack nearby humans. Similarly, an impact to the head can initiate dislocations and disruptions in the microbiota present in the brain and body. First, since the normal human brain is not sterile, but is host to a variety of microorganisms, blows to the skull may dislodge them from their accustomed local environments, in which they have been living in quiet equilibrium with neighboring brain cells. Deleterious substances may be released by the displaced microbes, including metabolic products and antigens. Second, upon impact commensal microbes already resident on surfaces of the nose, mouth, and eyes, and potentially harmful organisms from the environment, may gain access to the brain through the distal ends of the olfactory and optic nerves or even a disrupted blood-brain barrier. Third, microbes dwelling in more distant parts of the body may be propelled through the walls of local blood vessels into the bloodstream, and then leak out into damaged areas of the brain that have increased blood-brain barrier permeability. Fourth, the impact may cause dysbiosis in the gastrointestinal microbiome, thereby disrupting signaling via the gut-brain axis. Possible preventatives or therapeutics that would address the adverse contributions of microbes to the late sequelae of traumatic brain injury include anti-inflammatories, antibacterials, antivirals, and probiotics.