Alzheimer's disease: An emerging public health problem

Impact

Epidemiology According to different estimates, between 2% and 10% of all cases of dementia start before the age of 65 and the prevalence doubles every five-years following this age. Alzheimer's disease is the sixth leading cause of all deaths in the United States, and the fifth leading cause of death in Americans aged 65 and older. Whereas other major causes of death are decreasing, deaths due to AD are dramatically are increasing. Between 2000 and 2006, a 47% increase in the number of deaths attributable to AD was observed. The total number of patients with dementia worldwide is estimated at 35.6 million and is expected to nearly double every 20 years, to reach 65.7 million in 2030 and 115.4 million in 2050. The total number of new cases of dementia each year worldwide is nearly 7.7 million, implying one new case every four seconds. Dementia: a public health priority. WHO, WM 200. Alzheimer's disease represents an emerging public health problem in Europe as well. Based on demographic data, in Switzerland, the number of patients suffering from Alzheimer's disease is 100'000 and this number is expected to triple by 2050. The total estimated worldwide costs of dementia were around 604 billion per year at present and is expected to increase even more quickly than the prevalence.
The challenges to governments to respond to the growing numbers of people with dementia are substantial. If the cause of Alzheimer’s disease is not defined, and treatments to delay or prevent the disease are not provided, the world will face an unprecedented health-care problem by the middle of the century. 

Alzheimer's disease is the most frequent cause of dementia

Accumulation of senile plaques and neurofibrillary tangles are the characteristic lesions, which leads to neuronal damage and brain atrophy. Alzheimer's disease is slowly progressive. It starts several years or decades before the diagnosis of dementia is made and the patients can survive in an advanced stage of dementia, necessitating continuous care for years or decades.Alzheimer's disease causes the suffering of the patients and those also of caring family members and affects the dignity of the patients. 

Growing number of epidemiological studies in the U.S. and Europe indicate that dementia will be the most intractable problem to confront by our health system in the next decades. Around 5.3 million Americans are diagnosed with Alzheimer's disease today and the estimated prevalence for 2050 is expected to approach 11 to 16 million. The annual direct and indirect costs related to Alzheimer's disease and other dementias are an estimated 148 billion dollars, without the inclusion of an annual 94 billion dollars of unpaid services provided by 10 million caregivers.

In Europe these direct and indirect costs are estimated to correspond to 87 billion Euros. It is also expected to double or even triple by 2050. Alzheimer's disease represents a public health emergency problem around the world, including Switzerland. Based on demographic data the number of patients with Alzheimer's disease is around 100'000 today and similarly to other countries a two or three fold increase is expected during the next decades. Unless treatments to delay or prevent the disease are developed, the world will face an unsustainable care bill by the middle of this century. Prompt action is needed! In addition to support health care needs, investing heavily in research on Alzheimer's disease and other chronic disorders (e.g. vascular disorders, diabetes etc…) is critical. The goal of the foundation is to prevent Alzheimer's disease and other devastating chronic disorders in the framework of an international effort.

The realization that pathogens can evade from destruction by the host immune system and produce slowly progressive chronic diseases has resulted in a new concept of infectious diseases and opened a new avenue for the treatment and prevention of these chronic disorders.

This "health revolution" started by the studies of Warren and Marshall who following 25 years of continuous research have finally received the Noble prize for their discovery that stomach ulcer is caused by the slightly curved bacterium, called Helicobacter pylori. Increasing number of recent observations show the involvement of bacteria and viruses in various chronic inflammatory disorders, including atherosclerosis, cardio- and cerebro-vascular disorders, diabetes, neurodegenerative disorders and Alzheimer's disease. Activated macrophages and microglial cells are the principal players in this pathogen chronic infection, which leads to slowly progressive parenchymal damage and tissue atrophy.

The fact that pathogens may suppress, subvert or evade host defenses and establish chronic or latent infection has received little attention in the past. During infection, active oxygen and nitrogen species generated by inflammatory cells can cause DNA damage, induce apoptosis, and modulate enzyme activities and gene expression. Depending upon the biology of the pathogen and the host defense mechanisms the microorganisms can persist in the infected tissues and cause chronic, persistent inflammation and slowly progressive tissue damage. The outcome of infection is as much determined by the genetic predisposition of the patient as by the virulence and biology of the infecting agent. Environmental factors, including stress and nutrition are critical determinants of disease expression as well. Further research in this direction is essential as these chronic inflammatory disorders affect a large part of the population up to 50 years and represent an enormous socio-economical charge.

The possibility that microorganisms may play a role in senile plaque formation has been discussed by Fischer, Alzheimer and their colleagues more than a century ago. It has also been known from more than a century that chronic bacterial infection can cause dementia. The spirochete Treponema pallidum in syphilis, can cause slowly progressive dementia, cortical atrophy and amyloid deposition, which revealed to be beta-amyloid. Recently it was shown that other types of spirochetes, including Borrelia burgdorferi, the causative agent of Lyme disease are also able to persist in the brain, and cause dementia, brain atrophy and beta-amyloid deposition. Bacteria, including spirochetes, are powerful stimulators of inflammation and are amyloidogenic and they can initiate and sustain chronic inflammation and amyloid deposition in Alzheimer’s disease. Recent observations also revealed that beta-amyloid, which is the most important biological marker of Alzheimer's disease belongs to the family of antimicrobial peptides (AMP). 

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