There is no need to restate the impact of dementia on families, institutions, and the social fabric. Adult-onset dementia is typically diagnosed as Alzheimer’s when one of two conditions is present:
- Amyloid-beta plaques (amyloidosis; first observed by Alois Alzheimer in 1907 and biochemically profiled by George Glenner in 1984)
- Hippocampal atrophy in disproportion to global cortical atrophy
The vast majority of research funding to date has been directed at the theory that amyloid-beta plaque and tau tangle formation, consisting respectively of misfolded amyloid-beta and tau proteins, is the root cause of the observable neurodegeneration (neuron death) and symptomatic presentation of dementia.
Two alternative mechanisms to produce misfolded proteins are proposed in this theory: glutamate excitotoxicity, and attacks by reactive oxidative species. The hypothesis is then that the disease can be stopped by preventing the misfolding from occurring.
I will not address this disease model or hypothesis of treatment as both have been and continue to be thoroughly explored in the literature. However, as no actionable solutions have yet arisen from the depths of this research, and it does not even attempt to address dementias with a non-Alzheimer’s pathology (i.e.: no amyloidosis) I will attempt to redraw the picture on a blank canvas.
(The following is pure conjecture and subject to revision and feedback)
Inflammation and oxidation
Free radicals (molecules which readily oxidize materials with which they come into contact) can be consumed in contaminated or toxic foods, and they can also be produced by the gut flora. Free radicals are directly toxic to cells through oxidation attacks that produce reactive oxidative species. Inflammatory cytokines are produced by the actions of free radicals, as well as directly by hostile periodontal and gut bacteria. Free radicals directly attack the gut lining, while at the same time inflammatory cytokines induce an autoimmune response that misidentifies the gut lining as the source of inflammation and destroys it, causing gut permeability with respect to the blood and to the vagus nerve.
Inflammation and metabolic diseases are linked to Alzheimer’s. The gut microbiome can contain pathogens which are a source of inflammation. Fecal transplantation is used in Europe to treat metabolic syndrome. Intestinal inflammation is linked to the development of Parkinson’s disease, with the vagus nerve as the suspect vector. In Parkinson’s, aromatic compounds are excreted in sebum that can be used to identify sufferers with 100% accuracy.
Excess iron is a major contributor to free radical formation. An elevated body iron level has been linked to heart attack, stroke, cancer, diabetes, and Alzheimer’s. Cannabidiol was shown to restore memory and mitochondrial function as well as inhibit apoptosis in the brains of iron-overloaded rats.
While the immediate neurodegeneration during a stroke event is likely due to glutamate excitotoxicity, a process which is also involved in epileptic seizures and is entirely deactivated by cannabidiol, it seems that the ongoing neurodegeneration and cognitive impairment subsequent to a stroke is actually caused by central nervous system inflammation, possibly due to dormant bacterial infection. Perispinal etanercept administration scavenges the inflammatory cytokine TNF from the central nervous system and produces rapid improvement in stroke victims.
While steroids have been used to suppress inflammation in Alzheimer’s victims, scavenging of the TNF cytokine itself by perispinal etanercept administration produces rapid improvement in aged dementia victims, documented on video, for whom chronic inflammation rather than neurodegeneration is presumably the immediate cause of cognitive impairment — although TNF itself has also been shown to produce cognitive impairment even in the absence of neurodegeneration. One could surmise that this could be because mitochondria switch from producing energy to producing toxins during inflammation. Cannabidiol has a potent anti-inflammatory (including anti-TNF) and immunosuppressive effect as well.
TNF has been proposed as the culprit in chronic cognitive dysfunction. Despite persuasive clinical evidence that eliminating TNF and thus TNF-triggered inflammation restores lost cognitive performance, the theory itself remains unsatisfying because it does not propose a causal mechanism for the overproduction of TNF itself.
Vagal nerve stimulation has been shown to inhibit the production of inflammatory cytokines.
Chronic inflammation is suspected to be the cause of depression and anxiety disorders.
Studies have shown that blueberry powder and blueberry vinegar relieve mild cognitive impairment. One anecdote further demonstrated that a strict berry, greens, and sweet potato diet initiated a complete recovery of dementia. Blueberries, as well as blackberries, raspberries, and blackcurrants, contain anthocyanins that have antioxidant effects through mechanisms that are not fully understood. However, one thing that is known is that blueberries inhibit the production of TNF. Pomegranate extract and juice were independently shown to aid in stroke recovery and to reverse mild cognitive impairment. One serving of tart cherry juice per day improved sleep and reduced inflammation in only a few days. Individuals in a study who ate approximately one serving of leafy greens per day performed on average as if they were 11 years younger on a standard cognitive assessment test. A number of flavonoids have demonstrated suppression of TNF and TNF secretion at extremely low doses. Sulforaphane, a flavonoid that can be produced in quantity from broccoli sprouts through an enzymatic process, showed an ability to inhibit amlyoid-beta formation, inflammation, and cognitive deficits in separate Chinese and Korean mouse studies. Sterubin, the main constituent in Yerba santa, was found to have potent anti-inflammatory and neuroprotective effect in vitro. Fisein, a flavonoid found in strawberries, apples, grapes, and onions, was found to reduce cognitive deficits and inflammation in mice, to induce autophagy of p-tau as well as to cross the blood-brain barrier effectively.
Sulforaphane, a phytochemical found in broccoli, cabbages and related vegetables, was claimed in a Chinese study to have triggered neural stem cell proliferation and differentiation into new neurons with no toxicity. Sulforaphane also inhibits secretion of TNF.
The experimental drug J147, a pyrazole derivative of curcumin, was found to prevent and reverse Alzheimer’s in mice genetically engineered to express amyloid-beta. In mice genetically engineered to rapidly age, J147 was able to halt many aging markers and maintain cognitive and motor performance. The patent covering J147 and a related curcumin derivative, CNB-001, describes many anti-inflammatory, anti-aging, and anti-Alzheimer’s properties. J147’s anti-aging and antioxidant properties appear to be due to its ability to bind to and downregulate the mitochondrial ATP synthase complex. J147 is currently in a phase I FDA trial.
B vitamin supplementation slowed AD-typical brain atrophy in patients diagnosed with mild cognitive impairment. Gingko biloba extract was found to be as effective as Aricept in slowing the progression of mild cognitive impairment.
An anti-inflammatory medical diet fed to mice genetically engineered to develop Alzheimer’s disease completely eliminated the cognitive symptoms while reducing amyloid-beta levels.
Metabolic factors and autophagy
Autophagy impairment is characteristic of Alzheimer’s and other neurodegenerative disorders. Intermittent fasting has been shown to induce neuronal autophagy.
Insulin resistance is strongly associated with Alzheimer’s and with the underlying amyloid-beta and tau anomalies. Insulin sensitivity (inverse resistance) is increased with high-intensity interval training. Tying these threads together, as of 2018 regular exercise is officially recommended and drugs considered ineffective in the treatment of cognitive impairment. A study showed that simply restoring impaired hearing and eyesight significantly slowed the rate of cognitive decline.
Alzheimer’s has recently been unofficially dubbed “type 3 diabetes“. Alzheimer’s and type 2 diabetes have both been linked to chronic spirochete infection. Simple carbohydrates such as sugars are the key dietary factors in the insulin resistance model, and it happens that sugars are also the only energy source for most spirochete bacteria. There is only one spirochete species, Spirochaeta isovalerica which does not use sugars but rather uses the proteinogenic branched-chain amino acids leucine, isoleucine, and valine for food. In this context, it may be of interest to note that athletic supplementation with branched-chain amino acids is suspected to cause an ALS-like syndrome and that individuals diagnosed with ALS have subsequently died of Lyme disease.
Periodontitis
Since the early 20th century, periodontal pathogens have been implicated in heart disease, originally due to the observations of dentist Weston Price of heart attacks occurring shortly after root canal work. Since then, periodontitis has been linked to high blood pressure, chronic back pain, and, yes, Alzheimer’s disease. A C-reactive protein (CRP) test can reveal systemic inflammation rooted in periodontitis.
What’s the connection? Common periodontal bacteria emit inflammatory cytokines which cause autoimmune destruction of gum and bone tissue and subsequent tooth detachment. Among those periodontal bacteria are spirochetes. Oral spirochetes have been shown to migrate through gum tissue into the body. Spirochetes are a key suspect in an infectious model of dementia.
Finally, P. gingivalis, the bacterium that causes periodontitis, has been separately implicated in multiple in vitro studies as a cause of Alzheimer’s. Recently, P. gingivalis has been directly implicated in Alzheimer’s in vivo, with targeted protease inhibitors introduced to eliminate its toxic effects.
Pathogens
Viruses in the herpes simplex family are implicated in recent research as a root cause of dementia, using mice. Separately, the HSV1 virus was shown to induce Alzheimer’s-typical plaques and tangles in neural tissue, and the plaques and tangles contained viral DNA; subsequent research showed that untreated herpes simplex (HSV1) and varicella zoster (VZV) infections were associated with a significantly greater risk of later senile dementia. In the HSV hypothesis, the formation of amyloid-beta plaques is a reactive, protective mechanism, rather than an independent pathological mechanism. It has been known for decades that herpes simplex viruses are unable to replicate in the presence of the cannabinoid THC. The outcome of utilizing cannabinoids seems to depend on whether inflammation is beneficial or pathogenic in a specific case.
Separately, increased loads of the human herpesviruses HHV-6 and HHV-7 have been confirmed in the brains of deceased Alzheimer’s patients. Immune systems of Alzheimer’s patients showed a decreased response to HHV-6. For various reasons, active HHV-6 brain infection is very difficult to test for.
A controlled study found evidence of fungal infection in the entorhinal cortex/hippocampus (ERH) region of the brains of Alzheimer’s patients.
Influenza infection was linked to the development of Parkinson’s in birds and mice. HIV brain infection causes the same biological markers implicated in Alzheimer’s.
A new theory divides Alzheimer’s victims into three categories, and identifies inhalational mycotoxins as the cause of neurodegeneration in the third category. Patients in this category are typically younger and healthier and may comprise as much as 10% of the patient population. A treatment protocol is available to halt the neurodegeneration and reverse the cognitive decline.
Lyme disease, which is caused by the spirochete borrelia burgdorferi, commonly causes a variety of cognitive impairments, and causes severe dementia in a small number of cases – including that associated with cerebral infarct (global cortical atrophy), which is reversible by clearing the pathogen. Spirochete infection has been characterized as a parasitic symbiotic relationship, in contrast to typical pathogenic bacterial infections.
It should be noted that Lyme disease is notoriously difficult to diagnose because in dormancy it produces false negatives with PCR-based assay, and because many people without active infections carry Lyme antibodies, so the presence of Lyme antibodies in blood serum is also inconclusive.
A new theory of Alzheimer’s pathology is that Lyme and periodontal spirochetes infect the central nervous system and cause the symptoms of Alzheimer’s. In this theory, these spirochetes are able to hide themselves in neural tissue under a protective biofilm while producing the inflammation and autoimmune response that causes amyloid-beta plaque formation and neurodegeneration. Lyme biofilms and cystic/granular spirochete configurations were directly observed inside amyloid-beta plaques in 100 out of 100 Alzheimer’s postmortem brain tissue samples. The presence of microbe biofilms in Alzheimer’s plaques was independently confirmed through staining. Alzheimer’s plaques were found to contain both human-derived and spirochete-derived amyloid-beta proteins. Interestingly, the cannabinoid THC both destroys the amlyoid-beta plaques and inhibits the associated inflammatory response, due to THC’s selective anti-TNF activity. It is worth noting that TNF suppression has been shown to interfere with anti-spirochete antibiotic therapy (another report here); however, that could be a useful property to exploit in identifying a concealed and/or unknown pathogen, as spirochetes are notoriously difficult to culture outside of host tissue. That is, one might conduct an anti-inflammatory protocol with drugs or anti-inflammatory herbs as a ruse to entice the spirochete out of dormancy so that the pathogen could be identified. New testing protocols continue to be developed to meet the diagnostic challenge spirochetes present.
Even when the spirochete is eradicated, inflammation can persist long afterwards. Eradication of spirochetes poses two more problems: animals whose spirochete infections were measurably eradicated were still able to pass active infections to ticks (1, 2, 3), and material from destroyed spirochetes is still able to trigger inflammation. However, levels of inflammatory cytokines are lower in chronically infected individuals (>6 mo.). This may be because the biofilm morphology of spirochetes allows the bacteria to persist in a state that does not activate the host immune system, nor respond to typical long-term antibiotic treatment often utilized against “chronic Lyme”. An antibiotic protocol based on daptomycin has been found to destroy biofilms in vitro. Traditional herbal medicine such as cinnamon oil, clove bud oil, oregano/thyme oil, ethyl alcohol tinctures of stevia leaf (and — one might surmise — agents which are capable of dissolving amyloid-beta plaques such as cannabinoids) are demonstrated to be capable of destroying spirochete biofilms in vitro and in tissue samples. Agents which are known to destroy other microbial biofilms may be of particular service: cinnamon oil was found to destroy Candida and MRSA (1, 2) biofilms, while thyme oil was also found to destroy MRSA biofilms. Epsilon-polylysine, a peptide that is used as a natural food preservative, was found to destroy Pseudomonas aeruginosa and aspergillosis biofilms. While liposomal encapsulations of oils are typically required to cross the blood-brain barrier, oregano oil has psychoactive effects in its default state. A universal protocol remains elusive; however, Alzheimer’s plaques have been attacked with varying success with the antibiotics clioquinol (2001), doxycycline and rifampin (2003), ceftriaxone (2016), and an antibiotic cocktail (2016).
There is a hypothesis that the root cause of the devastating immune syndrome known as AIDS is actually the spirochete that causes syphilis, and that HIV is merely comorbid. The syphilis spirochete is also capable of causing neurodegeneration and dementia that mimics Alzheimer’s. Treatment with the antibiotic doxycycline reduced the number of Alzheimer’s plaques and relieved cognitive impairment in mice. The Lyme spirochete is present in semen and vaginal secretions, raising implications for non-tick-centric epidemiology. Intestinal spirochete infection is endemic in homosexual men and HIV-infected individuals.
Celebrity Kris Kristofferson suffered dementia for years and was misdiagnosed with Alzheimer’s before the root cause was found to be Lyme disease. Commentators rejected the diagnosis of chronic Lyme as facially invalid, but failed to propose an alternative (non-iatrogenic) pathogenesis that fit the same facts. Several cases of reversible dementia rooted in Lyme infection have been documented.
To weave an even more intriguing web, Lyme-infected tick-borne nematode parasites have been found in the brains of multiple sclerosis, brain cancer, and Lewy body dementia victims. Doxycycline, which is also the primary antibiotic used in treating Lyme disease, kills filarial nematodes by killing the symbiotic bacterium generally required in their reproduction. A filarial Acanthocheilonema nematode infects around 30% of lone star ticks; however, Acanthocheilonema is one of the few filarial nematodes lacking the symbiont.
Schizophrenia has been linked to endogenous retrovirus infection. Intriguingly, treatment with the antibiotic minocycline was found to reverse schizophrenic symptoms in multiple studies in 2010, 2014, and 2017. Minocycline was also found to halt the progression of multiple sclerosis. Although minocycline is most commonly used as an acne medication, it is in the same tetracycline family as doxycycline, the most commonly used antibiotic in treating Lyme disease. For some reason, the theorized mechanism of effect of minocycline is primarily anti-inflammatory rather than primarily anti-microbial, even though spirochetes have been stained and cultured from the cerebrospinal fluid of MS patients for nearly a century. Numerous cases of patients suffering from various mental illnesses and subsequently making a full recovery after an infection with a high fever, or after a bone marrow transplant, have been documented. Common spirochetes cannot survive above 105.8 degrees Fahrenheit, with optimal reproduction occurring at significantly lower temperatures, and induced hyperthermia/’pyrotherapy’ continues to be utilized in management of persistent spirochete infections.
The Lyme spirochete has been documented to cause new-onset panic disorder (1, 2). Panic disorder comorbidity with schizophrenia has enough distinct features from other schizophrenia manifestations that it has been suggested this comorbidity should be recharacterized. Moderate to severe cognitive impairment is characteristic of schizophrenia, while schizophrenia medications are implicated in brain atrophy. However, recent research demonstrates that at-risk individuals who later develop full psychosis have a steeper rate of gray matter loss; the authors posit that the missing link between schizophrenia and brain atrophy is neuroinflammation rather than medication. As it happens, a single 600mg daily dose of the cannabinoid cannabidiol given over 40 months eradicated structural brain differences associated with a high risk of psychosis.
A presentation of stroke which turns out to be rooted in infection with the Lyme spirochete is documented again and again in the literature (1, 2, 3).
(Is there further evidence for spirochete-viral coinfections in various chronic neurological diseases?)
A pathogen ensemble could explain the “mixed pathology” often observed in brain tissue autopsies of dementia patients.
Stem cell neurogenesis
A stem cell treatment has been approved in Japan for Alzheimer’s. A phase I trial is underway in the U.S. with observed restoration of cognitive performance and hippocampal volume subsequent to injection with neural stem cells derived from waist fat.
However, neuroplasticity and mitochrondrial health may be important factors limiting the success of these treatments.
Neuroplasticity and mitochondria
Neuroplasticity refers to the generation of new synapses, the connections between neurons in the brain’s neural network. A synapse requires a physical point of contact between two neurons. A typical synapse occurs at the point where a dendrite of one neuron contacts the dendrite of another neuron. When neuroplastic conditions are present, new connections are being made through a combination of neurogenesis (increasing neuron density) and dendritic outgrowth. Neuroplasticity has demonstrated an incredible ability to compensate for tissue loss, as in the case of children who had an entire hemisphere removed to control epilepsy and who developed completely normally despite their enormous volumes of missing cerebral tissue.
While neuroplasticity is known to decrease with age, loss of existing dendritic spines is characteristic in Alzheimer’s. Dendrite loss may be an effect of out-of-control synaptic pruning – an otherwise normal process that is mediated by inflammatory cytokines ‘tagging’ a synapse for destruction. Loss of dendrites does not necessarily destroy memories embedded in the neural network, but rather prevents access to them, which can be restored. It has been found that serotonergic psychedelic drugs, commonly referred to as entheogens, stimulate dendritic outgrowth. Ketamine, a NMDA receptor antagonist with fast-acting antidepressant qualities, stimulates dendritic spine outgrowth and regrowth of spines damaged by chronic stress in mice.
Entheogens as a family are non-specific serotonin receptor agonists, but primarily bind to 5-HT2 receptors. 5-HT2 receptor loss is characteristic of Alzheimer’s patients and is implicated in the behavioral and psychological symptoms of dementia. However, 5-HT2 receptor loss precedes the associated neurodegeneration. The 5-HT2 receptor loss could be due to downregulation subsequent to serotonin misregulation by a third factor. One study posits a connection between chronic stress and hyperserotonism which then causes the development of a serotonin resistance. Another study showed that low levels of serotonin transporter protein (SERT) is correlated with dementia, implying that impaired serotonin transport is associated with serotonin receptor loss. If impaired serotonin transport and subsequent serotonin resistance is the mechanism by which 5-HT2 receptor loss follows, a supportive therapy is conceivable in which natural serotonin production is suppressed and simultaneously, a non-monoamine 5-HT2 agonist such as LSD is administered to activate 5-HT2 receptors in its place.
Since the sensory-altering effects of entheogens are caused by their binding to the 5-HT2A serotonin receptor, if psychoactive side effects of entheogen administration are too severe, the side effects can be selectively attenuated with a 5-HT2A blocker. Curiously, it has been shown that activation of the same 5-HT2A receptor with microdose quantities of a drug similar to LSD potently blocks TNF-alpha induced inflammation in the whole body. The activation of 5-HT2A receptors and not the particular agent that activates them seems to be the key process, as other non-psychoactive 5-HT2A agonists have been shown to block TNF-induced inflammation. Chronic inflammation is suspected to be the root cause of anxiety and depression disorders. LSD itself is currently being studied as a treatment for anxiety and depression pursuant to the quantity of anecdotes indicating its efficacy in those diseases.
Where synaptic paths are present, proper synaptic function is dependent on healthy mitochondria. Mitochondrial dysfunction is a precursor to Alzheimer’s. The vitamin NR (nicotinamide riboside) has been shown to restore neural mitochrondria function, destroy amyloid plaques, and restore cognitive performance.
Mitochondrial transplants have been effective in reviving degenerated muscle tissue; the healthy mitochondria need not even be injected directly into the degenerated tissue to find their ‘home’. One could surmise that neural mitochondrial transplant would have a similar safety profile.
Meditation has been shown to increase the proportion of the hippocampus and areas of the frontal cortex relative to other brain regions. One could surmise that neurons can thus be recruited to different networks according to utilization, important in the context of mental illness.
Mental illness and sleep quality
Moderate to severe anxiety, depression, and chronic stress are independent risk factors for dementia. Pseudodementia is cognitive impairment that is caused by such mental illness rather than an organic process. Pseudodementia can be treated. However, it is unclear whether pseudodementia is a separate process from the observable organic processes in dementia. What we know is that depression and anxiety are comorbid with dementia, with 54% of dementia patients exhibiting both depression and anxiety. While cause and effect is unclear, untreated anxiety and depression is detrimental to quality of life, whether or not dementia is present or would otherwise follow. As with various forms of dementia, harmful gut bacteria are increasingly implicated in mental illnesses as varied as anxiety and schizophrenia. Schizophrenia could be predicted from the microbiome of patients’ stool samples in one study.
One could surmise that the ineffectiveness of SSRIs in reversing dementia-related depression and anxiety is due to the aforementioned low levels of serotonin transporter protein (SERT) and serotonin receptor loss that are implicated in dementia, and the resulting inference that serotonin itself is critically low or absent such that the SSRI has no effect.
Furthermore, SSRIs are known to disrupt sleep in the elderly, and poor sleep quality is a risk factor for dementia. The latter study inexplicably excluded REM sleep as an object of study. A later study found that REM sleep anomalies are indeed a predictor of dementia. While several mechanisms for the connection of sleep quality to dementia have been explored, the most promising link is an observed increased flow of cerebrospinal fluid (CSF) due to neuron contraction during sleep.
If SSRIs are inappropriate for people experiencing dementia, what else could terminate anxiety and depression?
Transcranial magnetic stimulation has been demonstrated to halt Alzheimer’s-related cognitive decline and is currently in a FDA trial. While TMS is known to alleviate depression and anxiety in non-Alzheimer’s patients, whether that effect maps to Alzheimer’s patients with their differing serotonin configuration is unknown.
The dissociative anesthetic ketamine has recently been shown to be the most powerful and fastest-acting antidepressant yet known, confirming widespread anecdotes of its efficacy against treatment-resistant depression and relatively minor side effects. In mice, an immediate antidepressant effect is followed by dendritic spine outgrowth accompanying persisting antidepressant effects. Interestingly, ketamine is also a NMDA calcium channel blocker; under the glutamate excitotoxicity theory of dementia, it therefore serves the same purpose as the widely prescribed Alzheimer’s drug, memantine, in blocking the calcium ion channel that – the theory holds – excessive levels of glutamate would otherwise overactivate. However, cannabidiol prevents glutamate excitotoxicity with a much better safety profile and fewer side effects than agents acting on NMDA receptors.
The serotonergic psychedelics psilocybin, LSD, and MDMA have all been shown to alleviate treatment-resistent depression and/or PTSD. Since they bind directly to serotonin receptors, they can be effective even in individuals with low and/or misregulated serotonin.
Nicotine has been shown to control depression, and its use is widely observed in mentally ill populations as a suspected form of self-medication. Nicotine use has been shown to be preventive of Alzheimer’s and Parkinson’s and improves cognitive performance, with studies still ongoing in the area. Nicotine is also a known anti-inflammatory and immunosuppressant. One could surmise that since an autoimmune process triggered by chronic inflammation is implicated in various forms of dementia, nicotine’s benefits are in that it is suppressive of the autoimmune reaction as well as the underlying inflammatory cytokines.
Delivery problems
While several agents like curcumin, resveratrol, cannabidiol, and the steroid etanercept are known to have, variously, effective amyloid-beta destruction and inflammatory cytokine scavenging effects as well as anti-oxidant effects, delivering those agents to the central nervous system poses a challenge because of intestinal absorption, conversion in the liver, and the blood-brain barrier (BBB). While active systemic inflammation increases the permeability of the blood-brain barrier, and an agent can be engineered to cross a healthy blood-brain barrier, an ingested agent still has to be either properly absorbed by the gut or leak through the gut lining to enter the blood in the first place.
The “Longvida” formulation of curcumin is an example of a liposomal encapsulation. It is able to deliver curcumin, a powerful antioxidant, anti-inflammatory, amyloid-beta plaque inhibitor, and autophagic stimulator, to the central nervous system via the BBB. Liposomal encapsulation is also used with resveratrol, a polyphenol found in red wine. When delivered to the central nervous system across the BBB, liposomal resveratrol is a potent antioxidant and amyloid-beta scavenger.
The vagus nerve is an important nerve that connects the brain stem to the heart, lungs, and gut in order to exercise control of involuntary body functions such as bowel motility. Constipation is extremely common in older individuals and dementia patients, and one could surmise that neurodegeneration of the vagus nerve or the brain stem is the root cause. The carotid sheath is a conduit for the vagus nerve. Topical application of essential oils to the ganglia of the vagus nerve behind the ears is anecdotally effective in delivery of those oils to the nerve. Since the vagus nerve connection to the gut is also implicated in the development of Parkinson’s disease, with direct observation of Parkinson’s proteins being transported from the gut to the brain, one could reason that beneficial agents could traverse the vagus nerve as well, perhaps via the carotid sheath as a conduit. A study showed via fluorescent analysis that the cells of the intestinal lining are connected directly to vagal neurons via synapse-like structures. Laser stimulation of the gut lining stimulated the release of brain dopamine in mice, further illustrating a direct gut-brain connection.
As discussed above, etanercept is a steroid, immunosuppressant, and potent TNF scavenger. Perispinal administration of etanercept is performed via injection into the external vertebral venous plexus, after which it diffuses through the cerebrospinal venous system. Historically, cocaine was administered in a similar manner. Perispinal administration can be roughly considered a lower-risk and less complicated form of an epidural injection.
Aromatherapy has seen a variety of applications, with mostly anecdotal results and not much in the way of peer-reviewed, double-blind studies. However, a plausible mechanism for the delivery of aromatherapy agents to the central nervous system comes in the unlikely form of the brain-eating amoeba, a freshwater pathogen that enters the central nervous system via the nasal olfactory nervous passageways. One could reason that a vaporized aromatherapy agent could enter the central nervous system in the same manner.