Panic disorder seems to be mediated by the neuronal circuitry and neurochemical systems that have evolved to respond to external threatening stimuli. Distant threats activate prefrontal cortex (involved in complex planning of avoidance strategies), while immediate threats activate midbrain structures (involved in fast reflexive behaviors). Panic disorder may, however, also involve more specific interoceptive mechanisms. For example, the association between respiratory dysfunction and panic disorder has bolstered a false suffocation alarm hypothesis. Genetic and environmental contributors to panic disorder are beginning to be delineated. Effective pharmacotherapy and psychotherapy are able to normalize the relevant psychobiology.

This review begins with a description of some problems that recently have beset an influential circuit model of fear conditioning and goes on to look at neuroanatomy that may subserve conditioning viewed in a broader perspective, including not only fear but also appetitive conditioning. The column will then focus on basal forebrain functional-anatomical systems, or macrosystems, as they have come to be called. Yet, more specific attention is then given to the relationships of the dorsal and ventral striatopallidal systems and extended amygdala with the dopaminergic mesotelencephalic projection systems, culminating with the hypothesis that all macrosystems contribute to behavioral conditioning.

Mild cognitive impairment (MCI) refers to the transitional state between the cognitive changes of normal aging and very early dementia. MCI has generated a great deal of research from both clinical and research perspectives. Several population- and community-based studies have documented an accelerated rate of progression to dementia and Alzheimer's disease in individuals diagnosed with MCI. Clinical subtypes of MCI have been proposed to broaden the concept and include prodromal forms of a variety of dementias. An algorithm is presented to assist the clinician in identifying subjects and subclassifying them into the various types of MCI. Progression factors, including genetic, neuroimaging, biomarker, and clinical characteristics, are discussed. Neuropathological studies indicating an intermediate state between normal aging and early dementia in subjects with MCI are presented. The recently completed clinical trials as well as neuropsychological and nutritional interventions are discussed. Finally, the clinical utility of MCI, and directions for future research are proposed.

Mild cognitive impairment (MCI) is a clinical diagnosis in which deficits in cognitive function are evident but not of sufficient severity to warrant a diagnosis of dementia. For the majority of patients, MCI represents a transitional state between normal aging and mild dementia, usually Alzheimer's disease. Multiple subtypes of MCI are now recognized. In addition to presentations featuring memory impairment, symptoms in other cognitive domains (eg, executive function, language, visuospatial) have been identified. Neuropsychological testing can be extremely useful in making the MCI diagnosis and tracking the evolution of cognitive symptoms over time. A comprehensive test battery includes measures of baseline intellectual ability, attention, executive function, memory, language, visuospatial skills, and mood. Informant-bassed measures of neuropsychiatric symptoms, behaviors, and competency in instrumental activity are also included. Careful assessment can identify subtle deficits that may otherwise elude detection, particularly in individuals of superior baseline intellectual ability. As we move closer to disease-modifying therapy for Alzheimer's disease, early identification becomes critical for identifying patients who have an opportunity to benefit from treatment.