“The Solvay Pharmaceuticals Conferences: where industry meets academia in a search for novel therapies”

A Disease of the Future: What Alois Alzheimer did not know?

When Alois Alzheimer admitted his 51 year old patient named Auguste Deker to the Städtische Anstallt für Irre und Epileptische in Frankfurt/Main in 1906, she did not know her last name. One month after her admission she lost memory of her first name, continued to deteriorate rapidly and died shortly thereafter. Auguste Deker was not an unusual case for Alois Alzheimer when categorized according to the medical standards of his time. “Greisenblödheit”, “schleichender Irrsinn” or “Gehirnerweichung” were the common diagnoses describing such cases. However, Alois Alzheimer recognized that this case was unusual. Therefore, he spoke to Auguste Deker almost every day, watching the progress of her disease. After her death, he opened her skull and sectioned her brain. He saw masses of proteins (called today “plaques”) in the cortex of her brain. Alois Alzeimer did not know that he was discovering the cause of one of the most devastating neurological diseases of human kind, called today after his name: Alzheimer's disease. He reported his observations in the lecture entitled “Über eine eigenartige Erkrankung der Hirnrinde” to the 37th Annual Meeting of German Psychiatrists (37. Versammlung Südwestdeutscher Irrenärzte) on November 2, 1906 at the University of Tübingen, suggesting that there might be an organic cause for memory loss [1], a breakthrough concept which has guided medicine for the last century in the search for therapy for Alzheimer's disease.

Today, neurological diseases and psychiatric disorders represent the largest and fastest growing unmet medical market with 2 billion affected people worldwide. Life expectancy of humans continues to increase, and the world population is aging. Advanced age may lead to deterioration of cognitive functions of the brain. The World Health Organization estimates that in the USA alone in 2030 more than 58 million adults will be aged 65 and more, and the fact that many of them will suffer from memory impairment is worrisome. The global incidence of Alzheimer's disease ranges between 15–18 million and is projected to double in the year 2025 to 34 million people. Thus, aging-associated memory impairment represents one of the major health problems of modern society. The reasons for a high propensity of humans to cognitive deterioration are not well understood. There seems to be consensus that on the background of aging, several factors may render humans prone to dementia. Psychiatric and neurological disorders such as schizophrenia, bipolar disorder or Parkinson's disease may contribute to development of dementia.

More people are looking today for help regarding their learning and memory capabilities. Although increasing knowledge on neuronal networks is transforming our view of the human brain and its function and we understand psychiatric and neurological diseases better today than ever before, novel therapies are needed to respond to the growing demand of patients for assistance with memory loss and learning impairment.

Building on decades of brain research and success in revealing how the human brain functions, we arrive at therapies improving the situation of humans suffering from dementia. In addition, progress in knowledge on learning and memory has contributed to the invention of pharmacological measures aiming to help humans improve impaired cognition. Acetylcholine esterase inhibitors such as donepezil, galantamine and rivastigmine and glutamate antagonists such as memantine were introduced to improve memory in dementia patients and have already changed therapy of cognitive impairment [2], reducing behavioral, functional and cognitive deterioration of the patients. However, the introduction of these drugs has not yet closed the gap for therapies improving cognition.

In fact, it is expected that novel therapies aiming at the processing of amyloid, or at activation of glutamatergic or nicotinergic systems, will demonstrate adequate efficacy in improving learning and memory disturbances enabling effective and safe long-term treatment and by doing so will minimize the impact of dementia on modern society.

The fifth Solvay Pharmaceuticals Conference entitled “Thinking about Cognition: Concepts, Targets and Therapeutics” was organized in Miami (Florida) from February 26 to 27, 2004. This conference attracted leaders in cognition research and provided state-of-the-art contributions on mechanisms and on therapy of cognitive disorders today.

The current volume stands as a comprehensive overview of the cellular and molecular mechanisms underlying the development of cognitive impairment. It integrates discoveries concerning dementia, such as mild cognitive impairment and Alzheimer's disease associated dementia, vascular dementia, retardation syndromes, and psychiatric and neurological disorders related cognitive impairments. This book will be useful to physicians, biologists, and those pursuing an interest or concerned with memory impairment.

W. Cautreels, C. Steinborn, L. Turski

References

[1] A. Alzheimer. Über eine eigenartige Erkrankung der Hirnrinde. University of Tübingen (1907). A. Alzheimer, R.A. Stelzmann, H.N. Schnitzlein and F.R. Murtagh. An English translation of Alzheimer's 1907 paper, “Uber eine eigenartige Erkankung der Hirnrinde”. Clin. Anat. 8 (1995) 429–431.

[2] M.S. Wolfe. Therapeutic strategies for Alzheimer's disease. Nat. Rev. Drug Discov. 1 (2002) 859–866.