Metabolic and Environmental Biomarkers in Mild Cognitive Impairment and Dementia: An Exploratory Study.

Objective: To determine the frequency with which suspected pathogenic factors, including metals and metabolites that might contribute to Alzheimer's disease (AD), may be found in patients with cognitive impairment through commonly available blood tests. Methods: A variety of serum studies, including metals, ammonia, homocysteine, vitamin B12, folate, thyroid tests, metabolic products, and inflammatory markers, were measured in two cohorts: one meeting mild cognitive impairment (MCI) criteria and the other meeting mild-to-moderate dementia (DE) criteria. Medications these patients received were reviewed. Results: Metal abnormalities were detected in over half the subjects, including evidence of mercury, lead, and arsenic elevation as well as instances of excessive essential metals, iron (Fe), and copper. Some metal aberration was detected in 64% of the DE group and 66% of the MCI group. Females were more likely to have elevated copper, consistent with hormonal effects on copper excretion. Homocysteinemia was the most common abnormality, detected in 71% with DE and 67% with MCI, while methylmalonic acid was not elevated. Slight hyperammonemia was moderately common (38%) suggesting a hepatic factor in this subset. Findings of moderate insulin resistance were present in nearly half (44% DE, 52% MCI). Sixty of 65 (92%) had at least one abnormal biomarker and 60% had two or more. The most common drug taken by the total cohort was proton pump inhibitors at 22% DE and 38% MCI. Conclusions: This study suggests that both toxic metals and excessive vital metals such as copper and iron, as well as common metabolic and hepatic factors are detectable at both stages of MCI and DE. There appears to be a multiplicity of provocative factors leading to DE. Individualized interventions based on these parameters may be a means to reduce cognitive decline leading to DE. A more comprehensive prospective study of these environmental and metabolic factors with corrective early interventions appears warranted.

Environmentally Mediated Health Disparities.

We describe important settings where environmental exposure leads to disease disparities. Lead exposure in urban settings disproportionately impacts the urban Black poor. Native Americans have been forcibly relocated to areas of the West that have arsenic-contaminated groundwater or exposure to radionuclides near mines and nuclear development. Latino farm workers are disproportionately exposed to pesticides and herbicides. These chemicals are associated with cancer, neuropsychiatric disorders, renal failure, and respiratory disorders. The rural poor, both white and of color, are disproportionately impacted by hydraulic fracturing, exposing residents to volatile organic compounds such as toluene and benzene and heavy metals such as lead and arsenic. The urban and rural poor are both exposed to air pollution that significantly impact health. Short- and long-term ambient air pollution exposure has been associated with all-cause cardiovascular disease, stroke, blood pressure, and ischemic heart disease. Cancer due to air pollution has disproportionately impacted poor communities like "Cancer Alley" where numerous industrial sources are geographically clustered. Understanding local environmental hazards and available resources to address them can enhance the quality of medical care.

Alzheimer's Disease Is a Multi-Organ Disorder: It May Already Be Preventable.

In this commentary, we offer an overview of the several environmental and metabolic factors that have been identified as contributing to the development of Alzheimer's disease (AD). Many of these factors involve extracranial organ systems including immune system dysfunction accompanied by neuroinflammation (inflammaging), gastrointestinal dysbiosis, insulin resistance, and hepatic dysfunction. A variety of microbial factors including mouth flora, viruses, and fungi appear to play a significant role. There is a role for the colonic microbiome becoming dysbiotic and producing toxic metabolites. Declining hepatic function contributes diminished neuronal precursors and reduces toxin elimination. Environmental toxins especially metals play an important role in impairing the blood-brain barrier and acting synergistically with biotoxins and other toxic chemicals. Prevention and treatment of AD appears to require measuring several of these biomarkers and implementing corrective actions regarding such toxicants and correcting metabolic dysfunction at early or preclinical stages of this disorder.

Extra-cranial factors in the development of Alzheimer's disease.

The development of Alzheimer's Disease (AD) likely involves dysfunction in more than one extra-cranial organ system. AD appears to depend on several functional organ impairments that develops frequently during aging: lack of normal hepatic synthesis, defective detoxification of ammonia, gut microbiome dysbiosis, the development of insulin resistance, diminished adrenal production of dehydroepiandrosterone, nutrient depletion, impaired immune processes with persistent chronic neuro-inflammation, and persistent infectious processes are important components of this system-wide disorder. By reviewing these abnormalities in different organ systems, this review intends to suggest that clinical research into the prevention of dementia needs to take this interplay of organ system dysfunction into account. The design of therapeutic interventions needs to address dysfunction in more than one system at a time. We have singled out one aberrant signaling pathway, NF-kB, that seems common to several of the dysfunctional organ systems and suggest some potential interventions that may be effective when combined with others. Clinical research may need to shift from single factor interventions to studies that include multiple simultaneous interventions that restore health in multiple impaired organ systems in the aging human in order to avert future epidemics of AD.

Putting the "Informed" in the informed consent process for implantable cardioverter-defibrillators: Addressing the needs of the elderly patient.

Implantable cardioverter defibrillator (ICD) management complexities challenge the ethos of fully informed consent, particularly for the typically multimorbid elderly patient considering the device for primary prevention. The Heart Rhythm Society recommends providers include discussion on the potential need for later device deactivation or nonreplacement at the time of first implant, and to revisit this at appropriate intervals. The initial consent procedure could meet this standard by incorporating the future need to discuss further such issues when the recipient's clinical condition changes to such an extent that defibrillation would no longer be beneficial. At the time of obtaining consent, some patients may lack the will or capacity to make medically complex decisions when it would be necessary for healthcare surrogate decision-makers to contribute to this process. Ensuring an appropriate level of understanding and response may be enhanced by the use of information and decision aids. With improved communication regarding the nuances of ICD therapy, device eligible patients, and those close to them, will be empowered with a better understanding of the nature, benefits, and risks of ICD implantation, allowing them to make treatment decisions consistent with their values.

Why does Finland have the highest dementia mortality rate? Environmental factors may be generalizable.

Finland has the highest death rate from dementia in the world and its environmental features can be instructive in understanding hidden causes of dementia. Environmental factors there include: 1) a climate that is both very cold and humid resulting in housing frequently harboring molds that are capable of producing a neurotoxic mycotoxin 2) the Gulf of Finland as well as Finnish lakes harbor cyanobacteria that produce the neurotoxin, beta-N-methyl amino-L-alanine, known to cause dementia and related disorders 3) the aforementioned toxins can be potentiated by the presence of mercury and methyl mercury which can be found in Finnish waters 4) soil in Finland is naturally low in selenium and selenium deficiency may reduce the quantity and effectiveness of glutathione's ability to protect against neurotoxins. A high rate of fatal dementia could be the consequence of these environmental factors. Studies that can support or disprove this hypothesis are suggested. Such environmental toxins are likely to promote Alzheimer's disease elsewhere in the world where such a combination of neurotoxins may also occur.

HOW PHYSICIAN LEADERS CAN SUCCESSFULLY RESOLVE TEAM CONFLICTS.

Examine how physician leaders can become more knowledgeable about assessing the nature of health care team conflicts and intervening with teams to improve their collaboration skills.

Postmodern Stress Disorder (PMSD): A Possible New Disorder.

The murder of cardiovascular surgeon, Michael Davidson, MD, suggests the existence of a new disorder, postmodern stress disorder. This disorder is characterized by repetitive exposure to digital images of violence in a variety of electronic media, including films, television, video games, music videos, and other online sources. This disorder appears to be a variant of posttraumatic stress disorder, and shares with it excessive stimulation of the amygdala and loss of the normal inhibitory inputs from the orbitofrontal cingulate cortical gyrus. In postmodern stress disorder, repetitive digital microtraumas appear to have an effect similar to that of macrotraumas of warfare or civilian assaults. Other elements of the disorder include the development of fixed ideas of bullying or public shaming, access to weapons, and loss of impulse control. This syndrome could explain a number of previously inexplicable murders/suicides. Violence against health care professionals is a profound concern for the medical profession, as are assaults on nonclinicians. The recommendation is made to change forensic procedures to include obtaining historic information concerning the use of digital media during investigations of violent crimes and murders so that the disorder may be further characterized. Gaining an understanding of this disorder will require a multidisciplinary approach to this life-threatening public health problem. Research should also focus on the development and evaluation of possible antidotes to postmodern toxicities.

Integrating quality improvement into continuing medical education activities within a community hospital system.

The integration of the Mercy Health System's quality improvement (QI) and continuing medical educational (CME) activities is described. With the implementation of computerized medical data, the opportunities for QI-focused CME are growing. The authors reviewed their regularly scheduled series and special CME programs to assess their impact on quality care processes. Clinical improvements were affected by combining national guidelines and advancements with local clinical data and interactions with physicians within interdisciplinary as well as specialty conferences. Case-based, multidisciplinary conferences lent themselves to this process to a greater extent than didactic conferences. The latter also could lead to QI when the topics were focused on specific quality initiatives that often are part of a national QI initiative. Although the authors consider these efforts to be at an intermediate stage of development, they have observed several QI/patient safety process improvements.