Alzheimer Disease: Current Challenges, Emerging Treatments: ORIGINAL ARTICLETherapeutic Strategies for Alzheimer Disease: Focus on Neuronal Reactivation of Metabolically Impaired NeuronsSwaab, D. F.*; Dubelaar, E. J. G.*; Scherder, E. J. A.†; van Someren, E. J. W.*; Verwer, R. W. H.*Author Information From the *Netherlands Institute for Brain Research and the †Department of Clinical Psychology, Free University, Amsterdam, The Netherlands. Supported by the Research Institute for Diseases in the Elderly and funded by the Ministry of Education & Science and the Ministry of Health, Welfare and Sports, through the Netherlands Organization for Scientific Research (NWO), Internationale Stichting Alzheimer Onderzoek en Alzheimer Nederland. Reprints: Dr. D. F. Swaab, Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ Amsterdam, The Netherlands (e-mail: [email protected]). Alzheimer Disease & Associated Disorders: July-September 2003 - Volume 17 - Issue - p S114-S122 Buy Abstract Based on several lines of evidence, it has been hypothesized that decreased neuronal metabolic rate may precede cognitive impairment, contributing to neuronal atrophy as well as reduced neuronal function in Alzheimer disease (AD). Additionally, studies have shown that stimulation of neurons through different mechanisms may protect those cells from the deleterious effects of aging and AD, a phenomenon we paraphrased as “use it or lose it.” Therefore, it is attractive to direct the development of therapeutic strategies toward stimulation of metabolic rate/neuronal activity to improve cognition and other symptoms in AD. A number of pharmacological and nonpharmacological approaches discussed here support the concept that stimulation of the brain has beneficial effects and may, to a certain degree, restore several aspects of cognition and other central functions. For instance, the circadian system, which controls the sleep/wake cycle, may be stimulated in AD patients by exposing them to more light or transcutaneous nerve stimulation. We will also discuss a procedure that has been developed to culture human postmortem brain tissue, which allows testing of the efficacy of putative stimulatory compounds. © 2003 Lippincott Williams & Wilkins, Inc.