We express our sincere gratitude to Barry Reisberg, M.D., and Gerald Oppenheim, M.B., B.S., F.R.A.N.Z.C.P., for their guest editorship in compiling a group of important papers on the clinical course of Alzheimer's disease, as well as the methodological implications of clinical changes in Alzheimer's disease for pharmacologic trials. The papers were presented initially at a special symposium of the IPA Fifth International Congress in Rome, Italy, August 18–23, 1991. This issue of International Psychogeriatrics is our second supplement within a year, derived from important presentations at IPA meetings and deemed worthy of dissemination to the wide IPA audience.

Alzheimer's disease (AD) is now recognized as a major cause of morbidity and mortality in elderly populations throughout the world. Tragically, no clearly effective treatment for this major illness entity has emerged. In part, the lack of an effective treatment is the result of an absence of fundamental knowledge regarding the etiology and pathogenesis of the illness. However, treatment implies the amelioration of symptoms, not cure. In other neuropsychiatric illnesses such as schizophrenia, major depression, and idiopathic Parkinson's disease, there is a similar absence of knowledge regarding etiology and, to a greater or lesser extent, regarding pathogenesis. Nevertheless, symptomatic treatment for these other neuropsychiatric illnesses is available. The same potential for symptomatic treatment exists in AD. The absence of consensus or systematic information regarding treatment in AD is in large part due to the failure to apply appropriate methodologies to symptomatic assessment and pharmacologic treatment.

Research on the nature of clinical symptomatology in AD indicates that two fundamentally different types of symptoms are identifiable. Symptoms within each of these two domains have common characteristics. The first symptomatic domain has been termed the “cognitive domain” and the second the “noncognitive behavioral domain.” Symptoms and losses in the cognitive domain occur invariably and progressively with the advance of AD over time. Symptoms in the behavioral domain do not invariably occur in AD and do not progress monotonically with the advance in AD over time. However, characteristic behavioral domain symptoms can be described over the course of AD.

The two symptomatic domains are likely to differ not only in nature and progression in AD, but also in underlying pathophysiology and in terms of possible treatment modalities. They also pose fundamentally different issues of assessment in AD. These distinct factors necessitate the separate assessment of the two Symptomatic domains in AD treatment trials. Judgments of efficacy and utility in remediating either symptomatic domain in AD should take into consideration the effects of treatment on both cognitive domain and behavioral domain symptoms separately and interactively. Appropriate assessment procedures are discussed.

Psychiatric symptoms and behavioral disturbances are of importance in dementia of the Alzheimer type (DAT) but have been relatively neglected by researchers. The main psychiatric symptoms are disorders of thought content (delusions and paranoid ideation), disorders of perception (hallucinations and misidentifications) and disorders of affect (depressed and elevated mood). They occur commonly in DAT, and there is evidence that they may indicate subtypes of the disorder in view of their demographic, structural, and prognostic correlates. Personality changes are very common, and these may be the earliest manifestation of dementia. Behavioral disturbances tend to be associated with advanced dementia and are particularly disruptive to caregivers. Structural correlates suggest that some behaviors are a direct result of brain damage. Psychiatric and behavioral features in DAT are important, as they may serve as a model for symptomatology in functional psychiatric disorders.

Evaluation of changes in functional performance and activities of daily living skills is an essential aspect of the assessment of elderly individuals with chronic illness. Although functional decrement is a central aspect of Alzheimer's disease (AD), many measures currently utilized to assess these changes have limitations. Empirical and systematic examination of the functional changes occurring in patients with AD has resulted in the development of an assessment measure termed Functional Assessment Staging (FAST) that allows for the specific evaluation of these changes throughout the entire course of AD. In this paper the results of three separate investigations regarding the reliability, validity, and progressive ordinality of FAST are described. The results indicate that FAST is a reliable and valid assessment technique for evaluating functional deterioration in AD patients throughout the entire course of the illness. Moreover, the results suggest that the FAST elucidates a characteristic pattern of progressive, ordinal, and functional decline in AD. Because the elements of functional capacity incorporated in FAST are relatively universal and readily ascertainable, as well as characteristic of the course of AD, FAST can serve as a strong diagnostic and differential diagnostic aid for clinicians. The sensitivity of FAST to the entire course of AD, even in its most severe stages, may be indicative of the potential value of this instrument for further investigation of the temporal longitudinal course of AD, and of the relationships between clinical pathology and neuropathology throughout the entire longitudinal course of AD.

Alzheimer's disease is characterized by loss of cells and synapses in specific neural systems. The development of more effective therapies will depend on understanding the relationships between this pathology and the cognitive and behavioral impairments. In this review, focusing primarily on work in our laboratory, we will examine both classic and neuropeptide neurotransmitter systems and will discuss conceptual and methodological problems in relating clinical and biological measures.

New findings on cognitive aging show that decline in brain functions is not part of a general decline of functioning in old age. We know now that with increasing age there is a differentiation of cognitive functions into two independent dimensions (fluid and crystallized functions).

This two-dimensional model allows a more precise description of the cognitive aging process and of pathological changes. While crystallized cognitive abilities can be improved by training till late in life, fluid cognitive functions are subject to a progressive decrease starting as early as age 30, becoming most evident in cases of organic mental disorders.

Thus, pathological aging is not necessarily accompanied by global loss of functions. Different abilities undergo changes in different ways, a fact taken into consideration by modern methods of psychometric evaluation. Beyond the aging processes mentioned previously, cognitive and behavioral changes in the elderly may be considered to be early indicators of organic mental disorders. The Nuremberg Self-Evaluation List seems to be a promising approach to diagnosis.

Nimodipine is a calcium antagonist which improves learning and memory in brain-lesioned or aged animals (LeVere & Sandin, 1989; Schuurman & Traber, 1989). It also accelerates the recovery of experimentally damaged sciatic nerves (van der Zee et al., 1987) and reduces age-associated gait abnormalities in aging rats (Schuurman et al., 1987). Selective action on cerebral vessels has also been proven. Vasoconstriction was prevented or reduced with nimodipine under experimental conditions (Toward, 1981) and cerebral blood flow could be increased (Kazda et al., 1982). The drug has been tested in subarachnoid hemorrhage, stroke, severe head injury, cerebral resuscitation after cardiac arrest, impaired brain function in old age, and dementia. Methodological aspects of clinical studies with this agent are examined in this paper.

Stake's concept of Responsive Evaluation is applied in evaluating the chain of psychogeriatric services of a general psychiatric hospital. Central to the approach presented are methodological considerations in describing individual treatment courses in their objective and subjective features. This can only be accomplished by establishing multidimensional strategies, incorporating biological, mental, psychological, and sociocultural aspects.

A scientific information base is developing which focuses on understanding and managing behavior problems in geriatric populations, especially those with dementing illnesses such as Alzheimer's disease. Many of these behavior problems occur in long-term care settings, which have a high prevalence of residents exhibiting emotional and behavioral disorders, often secondary to psychiatric illness. Prior to beginning treatment, behavior disorders must be systematically evaluated and understood to insure optimum care planning. One approach to effectively treating these disorders is to first separate them into two categories: those not amenable to psychotherapeutic medication treatment (nonpsychiatric disorders) and those that are amenable (psychiatric disorders). Specific nonpharmacological treatments may benefit those nonpsychiatric behavioral disorders and include behavioral and environmental paradigms. The psychiatric disorders, especially aggression and assaultive behavior, may be treated beneficially using a variety of psychopharmacological agents, including antianxiety agents, neuroleptics, carbamazapine, ß-blockers, and lithium. The most effective approach toward treating the psychiatric behavior disorders often combines both medication and nonmedication strategies.

As recently as five years ago, ideas about developing effective treatments for Alzheimer's disease were at a theoretical level. However, within a short period of time the scientific knowledge about neurobiology of this disease has advanced very rapidly. With this new knowledge many groups in academia as well as pharmaceutical companies have designed, developed, and tested several different types of compounds.