Clinical trials: new opportunities

Abstract

Human cognitive aging has been too long neglected and underappreciated for its critical importance to quality of life in old age. The articles in this session present novel approaches to improving cognitive function in normal aging persons with drugs and interventions that are based on findings in epidemiology, studies in aged animals, and in vitro research. In addition, since aging is the primary risk factor for Alzheimer's disease, these studies also have implications as interventions for prevention and treatment. As a field of research, new knowledge regarding the causes and mechanisms of cognitive aging are ripe for translation into human studies, with the application of this knowledge leading the development of interventions and therapeutics for the prevention of cognitive decline in old age and Alzheimer's disease.

Figure 1.

Working model of intracellular signaling events that regulate the strength of PFC network connections. A. In the aged PFC, increased cAMP opens K⁺ channels on spines, which weakens network connections. Examples of K⁺ channels: HCN= Hyperpolarization-activated Cyclic Nucleotide-gated channels; KCNQ=Kv.7_2/3/5. B. Guanfacine treatment inhibits cAMP production, which strengthens network connections. (Adapted from Reference 17.)

Figure 2.

Electrophysiological studies of PFC network firing in monkeys. A. Working memory-related PFC neuronal firing is markedly reduced with advancing age. Examples show representative individual neurons from young adult, middle-aged, and aged monkeys. B. Delay-related PFC neuronal firing rate as a function of age in monkeys. There is a highly significant decline in firing rate with advancing age. C. Iontophoresis of guanfacine (bottom graph) onto PFC neurons restores memory-related firing in aged monkeys compared to control conditions (top graph). (Adapted from Reference 17.)