CHAPTER 10. DELIRIUM, DEMENTIA, AND AMNESTIC AND OTHER COGNITIVE DISORDERS Kaplan & Sadock’s Comprehensive Textbook of Psychiatry CHAPTER 10. DELIRIUM, DEMENTIA, AND AMNESTIC AND OTHER COGNITIVE DISORDERS ERIC D. CAINE, M.D. AND JEFFREY M. LYNESS, M.D. Definition History Comparative Nosology Diagnosis Pathology and Laboratory Examination Etiology and Differential Diagnosis Cognitive Disorders Diagnosis and Clinical Features Diagnosis and Clinical Features Psychiatry is in the midst of a profound transformation, at once struggling to incorporate a dynamic understanding of neuroscience and molecular biology while maintaining a view of unique persons or individuals as the central focus of therapeutic intervention. To date it has been beyond the scope of knowledge to effectively integrate research data regarding individual differences with more abstract findings regarding fundamental aspects of brain development or aging-related neurodegeneration. Discovering the bases for the major neuropsychiatric diseases can be expected to provide powerful clues for defining the nature of how neurobiological processes are expressed as emotions, thoughts, or actions, or how life events and daily experiences alter and shape brain growth and development. Since the late 1980s, a major conceptual transition has occurred in the way clinicians and researchers view the relation between mental disorders and brain function. For much of the past century psychiatry was trapped in an either-or dilemma—either a condition was viewed as a symptomatic manifestation of structural cerebral or systemic pathology (organic), or it was considered psychological or emotional in nature (functional). However, clinicians recognized that there are no behaviors that do not involve the brain, and that the transmission of culturally derived processes from individual to individual is influenced by each person's central nervous system (CNS). Behaviors defined by some cultures as abnormal may be mediated by normal neurophysiology; in contrast, patients with damaged brains may develop compensatory strategies reflective of CNS plasticity to ameliorate the effects of disordered neural systems. The same behavior (e.g., suicide) may reflect normal or abnormal physiology. For many diseases the CNS develops normally but acquires its dysfunction later in life whereas other diseases may reflect aberrant wiring patterns or connections that function in a neurochemically or neurophysiologically normal fashion. Despite such complexity, clinicians often depended on a single criterion for defining organic disorders—either the detection of a structural lesion or, less often, the diagnosis of a known disease process; however, such an approach is no longer satisfactory. Diagnostic decisions have depended largely on available technology. For more than a century gross postmortem examination and microscopic histopathological examination were the primary tools. Working in a tradition of clinical-pathological correlation, psychiatrists, neurologists, and others used a dichotomous approach to both diagnosis and classification—that is, a lesion was either present or absent. This approach proved heuristically limiting and became increasingly unrewarding. Indeed, histopathology is now no longer the gold standard for defining brain-based diseases. It was only marginally useful for psychiatry, and in the near future molecular biological methods will replace it for neurology. The advent of new technologies already has undermined the pseudocertainty of earlier years. Many patients with functional syndromes are found to have CNS abnormalities when studied with magnetic resonance imaging (MRI), positron emission tomography (PET), or single photon emission computed tomography (SPECT). Should these syndromes be reclassified as organic? Most would argue that such changes would be premature because the pathophysiological significance of newer findings remains obscure. Such arguments also are pertinent to the entire question of organic versus functional. The fourth edition of Diagnostic and Statistical Manual of Mental Disorder (DSM-IV) establishes a new approach to those questions. The categories of organic and functional have been abandoned. When a psychopathological syndrome is known to be a symptomatic manifestation of a systemic medical or cerebral disorder, it is designated as “due to . .” (secondary), with a designation of the specific disease process. When it is considered to be an idiopathic psychiatric disturbance, it is designated primary. A clinician should follow a careful process of case reasoning before settling on the primary or secondary status of a disorder. To appropriately diagnose a patient as having an idiopathic (i.e., primary) condition, the clinician must necessarily exclude all definable, potentially etiological disease processes. The clinician must exercise equal caution before diagnosing a disorder as secondary or symptomatic. To date there are no widely accepted guidelines for establishing probable causal relations between psychopathological conditions and detected cerebral abnormalities. Traditionally, such assignment of probable causality has been left to clinical judgment. DSM-IV outlines such guidelines; they have the effect of encouraging the clinician to undertake a thorough evaluation and to postulate causal connections conservatively. DEFINITION The primary-secondary classification, like similar classifications, reflects the thinking of its time. The change in terminology in DSM-IV from organic to due to . is more than cosmetic in that it captures the conceptual shift away from structure and lesion and toward active disease process and etiology. The broad group of cognitive disorders includes dementia, delirium, amnestic disorder, and other syndromes in which disordered cognition caused by known (or presumed) disease entities is the central characteristic featuret (Table 10-1). Specific secondary syndromes are scattered through the nosology, classified along with other phenomenologically similar clinical conditions (e.g., mood disorders due to general medical conditions are grouped among the mood disturbances). Such groupings are intended to foster differential diagnostic consideration; the changes in DSM-IV are intended to enhance rigorous clinical reasoning. Use of more specific designations (e.g., mood disorder due to thyroid deficiency, with major depressive-like episode) strengthens diagnostic specificity when contrasted to the previously used organic mood disorder and lays the foundation for more meaningful comparative research. Table 10-1 DSM-IV Cognitive Disorders Throughout this chapter the term “neuropsychiatry” is used in reference to the field of medicine that considers the brain bases of mental disorders. In the United Kingdom this field is sometimes called organic psychiatry. At one time nearly all of psychiatry was neuropsychiatry; at another time, few would have chosen that label. Considering the brain substrates of behavior necessarily forces clinicians and researchers also to recognize the experiential, psychological, social, and cultural aspects of the patients and the problems they encounter. HISTORY The development of neuropsychiatry and the growth of general psychiatry coincided with competition and ultimately cooperation between public psychiatric asylums (now called hospitals or centers) and clinical practice in universities and private offices. Different ideologies or dogmas developed, depending on whether the clinician was seeing principally institutionalized psychotic patients, for whom there was little hope for improvement or recovery, or ambulatory patients, whose apparent psychological accessibility gave rise to therapeutic optimism. Additionally, psychiatrists in the asylums (often called alienists) had different needs than the nerve doctors or neurointernists who saw the walking wounded in their offices. Table 10-2 presents a brief categorization of historical periods in neuropsychiatry. It is probably not presumptuous to state that Wilhelm Griesinger (1817–1868) created neuropsychiatry with the publication of his book in 1845, crafted after practicing 2 years in Winenthal, one of the leading German asylums. An advocate of physiological medicine, Griesinger attempted to steer German medical practice away from both the romantic and somatic schools of that time. He asserted that psychiatry was part of medicine and that “psychological diseases are diseases of the brain.” He also advocated knowing one's patients well, understanding their life course, and appreciating how their mental disease affected their overall functioning. He advanced a specific notion of the ego that attempted to explain all disease under a single conceptual view based on a gradual pathological erosion of ego integrity. He supported the idea of careful neuropathological observation, although he never pursued such work in the later fashion of Theodor H. Meynert, Karl Wernicke, or Alois Alzheimer. Table 10-2 Historical Periods in Neuropsychiatry Despite Griesinger's attempted integration, many of his notions now seem simplistic or misleading, especially the idea that all mental illnesses reflected one basic pathological process that could be divided into stages. The first of Griesinger's disease stages involved an assault on the ego by the basic disease, although no frank pathological disruption was apparent. In the second and third stages, ego disintegration was completed and permanent brain changes took place. Griesinger believed that therapeutic intervention would be successful