An group of research mavericks contend that the slow progress toward finding a disease-related cure for Alzheimer’s is the result of an erroneous perception and some false assumptions by mainstream investigators.
Ming Chen, Ph.D., Huey T. Nguyen, B.S., and Darrell R. Sawmiller, Ph.D., of the Aging Research Laboratory, R&D Service, Bay Pines VA Healthcare System and University of South Florida, undertook an independent and systematic analysis of the underlying research assumptions associated with Alzheimer’s.
In an article scheduled for publication in the December issue of the Journal of Alzheimer’s Disease the authors suggest that when the National Institutes of Health separated out dementia from other senile conditions and redefined it as a distinct and “curable” disease — Alzheimer’s — in the 1970s, it opened a Pandora’s box and may have misdirected research for decades.
The study authors believe the definition and carve-out of the disease by National Institutes of Health has lead researchers to search for pathogenic factors and cures. In doing so, investigators have minimized the role of demographic change and its diverse end results in the elderly.
Senile disorders are considered diseases occurring after age 60, with many of them eventually affect the majority of the elderly. However, not all such disorders are life threatening — such as tooth, hearing or memory loss.
In the new study, researchers argue that these senile disorders are fundamentally different from other diseases because they are caused by the aging process — a process still not entirely understood. Therefore researchers have been designing studies and formulating interventions for these kinds of disorders that may not be the most appropriate or effective.
Moreover, the authors contend that a central regulator in cognition –the Ca2+ signaling system — has been misconceived by institutional thinking that favors a “cure” for senile dementia. The dominant hypothesis, still unproven, is that Ca2+ levels rise throughout the aging process, leading to cell death. Research to-date has therefore often focused on calcium antagonists, in hopes of lowering those levels.
In the new study, authors say that this viewpoint has been promoted by policy makers and has been the subject of a number of high profile clinical trials. But even after decades of research, the researchers find that no positive results have emerged.
In contrast, the authors propose that declining functionality of Ca2+ signaling as a result of the aging process, among a myriad of other age-related changes, leads to cognitive decline. Therefore interventions for senile dementia should attempt to activate Ca2+ function by promoting energy metabolism and use of Ca2+ agonists such as caffeine and nicotine.
At the same time, risk factors play a key role.
“Aging and Ca2+ deficits set the stage for senile dementia, but do not always lead to senile dementia in real life,” said Chen. “Lifestyles and other risk factors are the key. So we think that senile dementia may be explained by ‘advanced aging plus risk factors.'”
Chen said this model points to a new direction for prevention including promoting healthy lifestyles in the elderly. “And we should develop medications to extend the lifespan of old neurons, rather than looking for ways to inhibit far-fetched ‘pathogenic’ factors,” he said.
“The model implies that senile dementia is, by and large, a lifestyle disease,” says Dr. Chen.
“This view, in fact, has been shared by many in the medical and clinical community, but contrasts sharply with current dominant theories in the Alzheimer research field, which assume a linear and ’cause and effect’ mechanism.
“Since they have not taken into account the fundamental roles of aging and risk factors, it is clear that these theories, though highly appealing to the public and researchers alike, are of little relevance to the scientific nature of senile dementia.”
“The two overwhelming concepts, senile dementia as a distinct disease and the Ca2+ overload hypothesis, have effectively blocked any meaningful progress in senile dementia research, and have inhibited the self-correcting mechanism of science,” Chen said. “An independent scrutiny of the field may be helpful.”
Still, Chen is optimistic even while conceding that dementia is incurable.
“Our research, if guided by correct theories, will produce medications to help delay dementia to a certain extent − similar to the drugs that delay or ameliorate atherosclerosis and osteoporosis today.”
Source: IOS Press