Introduction to the special issue of Neurobiology of Learning and Memory on memory impairment and disease.

This special issue of Neurobiology of Learning and Memory highlights current research into how various diseases impair memory in humans and animal models. Our goal for this issue was to appeal to investigators from a variety of fields that have a common interest in memory disorders. Although the issue reviews diseases for which memory dysfunction is well established (e.g., Alzheimer’s, chronic stress, sleep disorders), we intentionally solicited reviews on a wide range of diseases and conditions that have not historically been associated with memory loss (e.g., diabetes, metabolic disorders, Rett’s syndrome) to encourage a broader consideration of how disease states affect learning and memory. Authors with expertise in disease processes were asked to provide an overview of the disease’s effects on memory processes and brain function in humans and/or non-human animal models. Although the scope of this overview was determined by the authors, the articles were intended for a diverse audience of scientists interested in neural mechanisms of learning and memory. All manuscripts were peer reviewed by experts in each field and revised prior to publication. The resulting collection of papers provides readers with specific information about how each disease affects learning and memory processes, as well as a more general overview of the many ways in which disease states can affect learning and memory. Although seemingly disparate diseases are discussed in this issue, common themes emerged. One theme that ties together the first four papers is metabolic dysfunction. Although not a unitary central nervous system disease per se, alterations in metabolism have emerged as critically important in the etiology of several neurodegenerative diseases, particularly those that present with memory dysfunction. The issue starts quite generally with a discussion by Stranahan and Mattson of memory decline in the context of impaired energy metabolism associated with diabetes and obesity. Importantly from a public health perspective, these authors focus not only on the detrimental effects of dysfunctional metabolism, but also on the potential benefits of increasing metabolism through exercise and dietary restriction. The next article by McNay and Recknagel focuses on deficiencies in insulin signaling, with a specific emphasis on type 2 diabetes. The authors synthesize the literature demonstrating that insulin, particularly intrahippocampal insulin, is a critical modulator of learning and memory processes, and argue that impaired brain insulin signaling causes cognitive impairments, including those observed in type 2 diabetes. Interestingly, insulin dysregulation has recently been implicated in the