Commentary on review by Veith and Raskind: the many faces of depression.

A range of different dysphoric symptomologies are subsumed under the general diagnostic label of depression. This may lead to problems with inter-laboratory reliability when reporting results of depression research. A partial list of a variety of "unhappiness" is submitted to encourage rigor of definitions and to stimulate discussion. Comments are made concerning the difficulty in drawing definitive conclusions about the possible influence of normal aging on CNS disturbances underlying depression. Also, the need is reinforced for in vivo baseline studies of the human nervous system as well as for creative experimentation using a variety of species. Finally, a plea is made for more openness and cooperation in the neurosciences regarding research activities and findings.

Vitamin E (tocopherols) in human cerebrospinal fluid.

Cerebrospinal fluid (CSF) and blood were obtained at the time of myelographic examinations from 40 adult, male, human subjects with no neurologic or metabolic abnormalities. Vitamin E (tocopherols) concentrations were determined by liquid chromatography. In subjects with normal concentrations of CSF protein (n = 22), the alpha- and gamma-tocopherol concentrations were 29.2 +/- 9.5 (mean +/- SD) and 6.5 +/- 3.6 nmol/L, respectively, in CSF and 26.0 +/- 8.1 and 6.0 +/- 3.6 mumol/L, respectively, in serum. The concentrations of alpha-tocopherol in CSF correlated significantly (P less than 0.001) with both total protein and albumin concentrations, suggesting that tocopherol transport into CSF is linked with that of plasma proteins. In vitro oxidation of vitamin E in CSF by the free-radical generator 2,2'-azobis-(2-amidinopropane) hydrochloride showed a measurable induction (lag) period. This is due to the presence of other antioxidants in human CSF.

The concept of "reversible" dementia. How nonreliable terminology may impair effective treatment.

Although good clinical and research information continually appears in the dementia literature, there is the disconcerting sense that, in some areas, a lack of clarity and rigor exists regarding terminology. Although definitions in the field of dementia initially seem reasonably straightforward, specific problem areas exist. This multidisciplinary field encompasses a variety of physician specialists, as well as other diverse professionals and brings not only the benefit of a rich mix of backgrounds, but also provides a medium for potential misunderstanding due to miscommunication. The variety of definitions of dementia, and especially the label, "reversible dementia," exemplifies this problem. Disease-specific dementias, pseudodementia, and delirium are three clinical situations that may or may not be classified as "reversible dementias," depending on individual training, custom, and jargon. Use of the term "reversible dementia" may cause misunderstanding and inefficiency and benefits neither patient nor caregiver. It is suggested that the term be replaced. Further, all diagnostic labels should be clearly understood and explained. Emphasis must be placed on promoting the fact that all patients with cognitive/functional decline, no matter how defined or what the cause, are eminently treatable individuals.

Management of behavior problems in elderly patients with Alzheimer's disease and other dementias.

The overall treatment and management of behavioral problems in Alzheimer's disease and other dementias is discussed. Three basic tenets of treatment are described. First, dementias should be considered as behavioral and functional disorders as well as cognitive ones. Second, treatment of these disorders must be multifaceted and utilize a variety of modalities. Third, optimum treatment must involve the caregiver as well as the patient.

Treatment considerations in dementing illness.

This issue focuses on the diagnosis and treatment of a variety of disorders that cause dementia. It emphasizes that all dementias, whatever their cause, are treatable. It is aimed at primary care physicians because they are likely to be the first physicians to see these complex patients and their caregivers. Each article is briefly introduced.

Medications to modify at-home behavior of Alzheimer's patients.

Benzodiazepines are used often in elderly, anxious patients with or without dementia. Clearly efficacious and relatively safe, benzodiazepines should be considered the first-line drugs of choice to treat anxiety associated with Alzheimer's disease. "Second-generation" antidepressants, although considerably more expensive than the tricyclics, are of significant benefit in the elderly, primarily because of extremely low anticholinergic side effects.

Helping families cope with Alzheimer's: the physician's role.

The physician's expressed approval of the caregiver's performance has much credibility with the caregiver, thus providing relief. No matter how many hours of devoted care are given, a caregiver almost never hears a "thank you" from a demented loved one. By listening closely to the caregiver, the physician will glean information decisive to the care of both the demented patient and the caregiver. This personal attention also affords the caregiver an outlet for stress.

Treatment of behavioral symptomatology of Alzheimer's disease, with emphasis on aggression: current clinical approaches.

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, carbamazepine, beta-blockers, and lithium. The most effective approach toward treating the psychiatric behavior disorders often combines both medication and nonmedication strategies.

Choline acetyltransferase activity and total protein content in selected optic areas of the rat after complete light-deprivation during CNS development.

Choline acetyltransferase (acetyl-CoA: choline O-acetyltransferase, I.U.B. 2.3.1.6) activity and total protein content in visual and extra-visual areas were compared in normal Long-Evans rats and in rats subjected to complete light-deprivation for 21 days from birth. The enzyme activity and the protein content in the superior colliculi, lateral geniculate bodies and visual cortex, as well as in the sensory-motor cortex, hypothalamus, brain stem and cerebellum, were measured in both mothers and progeny. By means of a radiochemical technique modified in this laboratory, a significant decline of ChAc activity was observed in the lateral geniculate bodies and superior colliculi, with no significant decline in the visual cortex of the experimental progeny. Total protein content, measured colorimetrically, was significantly decreased in the superior colliculi of the progeny. The biochemical data obtained from all other brain areas in the experimental animals (progeny and mothers) and controls demonstrated no marked differences. The enzymic alterations observed in the cholinergic system of progeny after complete light-deprivation during this critical period of CNS development can be specifically correlated with decreased functional maturation of the visual system. If it is accepted that ACh is a neuro-transmitter in some parts of the visual pathway, the data presented here suggest that complete light-deprivation from birth to 21 days of age in the rat has an effect on a biochemical system involved in synaptic transmission.

Relationship between nutrition and dementia in the elderly.

The complexities of physiologic interactions between the nutritional status of the aged and the incidence of dementia in the elderly should be obvious from this partial survey of the field. Investigations aimed at delineating the role of individual nutrients in mentation among the elderly are extremely difficult to design and perform. However, the potential for practical applications of the results is indeed very high. The studies discussed in this article permit the following conclusions. Although many attempts have been made to enhance average life expectancy through nutritional manipulation, no such panacea currently exists. There is a well-documented decrease in caloric intake among the elderly. However, this does not seem to put them at any higher risk of developing overt deficiencies of specific nutrients. The elderly population in this country has a strong tendency to consume nutritional supplements, with vitamins C and E being the most popular. It is unknown at present whether this practice has any health value. Several attempts have been made to alter the course of dementia in the elderly through nutritional means. Attempts to ameliorate the symptoms of Alzheimer's disease through use of choline and lecithin have been overwhelmingly unsuccessful. The postulate that aluminum toxicity is an etiologic factor in this disease remains unproven, and therapies with chelating agents are not now advisable. Vitamin B12 has to be seriously considered as a causative factor in dementia; it is hoped that methods to test vitamin B12 nutriture in humans that are both more reliable and more capable of revealing marginal deficiency states will emerge. Although folic acid is intimately related biochemically and nutritionally to vitamin B12, its potential role in normal mental function remains largely unknown. Clearly, when considering nutrition and dementia in the elderly, there are many areas that still require thorough scientific investigation. Hopefully, the future will see an increase in research activity, resulting in answers to many of the questions posed in this paper.

Progressive supranuclear palsy.

Progressive supranuclear palsy has been recognized as a distinct nosological entity for about three decades now. Typically, this progressive neurological disease manifests itself late in the sixth decade with a terminal course of approximately four to six years. Well over one hundred cases have been described in the literature and the heterogeneous nature of progressive supranuclear palsy includes the characteristic vertical ophthalmoplegia, frequent falling and a profound nuchal rigidity. Other features are similar in many respects to those found in Parkinson's disease. The present article reviews the literature on progressive supranuclear palsy with particular reference to its clinical manifestations including the ophthalmoplegia, characteristic sleep disturbances and unique dementia. Also addressed, are neuropathological and epidemiological findings. Finally, conclusions and recommendations for further investigation are offered especially with regard to the neuropsychological nature of this neurological disorder.

Latency and accuracy of word recognition in dementia of the Alzheimer type.

The sensitivity of reaction time (RT) measurement in assessing cognitive decline in dementia of the Alzheimer type (DAT) was evaluated. Sixteen DAT patients and 16 normal elderly controls, matched for age and education, read 50 stimulus words presented individually on a cathode-ray tube. DAT patients exhibited a significantly greater cognitive impairment as shown by multivariate analysis of variance (p less than 0.0001). Canonical variate correlations revealed RT (0.961) to be more sensitive to decline in cognitive functioning in dementia than the measure of number of reading errors (0.559). Results confirm that RT is a highly sensitive measure of central nervous system integrity, which allows for a more refined investigation of a patient's cognitive deficit than is obtainable with traditional test measures. These findings suggest that chronometric measures should be incorporated in clinical and research studies attempting to document the existence and severity of cognitive impairment in neurodegenerative disease.

Choice reaction time modifiability in dementia and depression.

The effects of cognitive impairment resulting from either dementia of the Alzheimer type (DAT) or major depression (pseudodementia) on choice reaction time were examined in two conditions hypothesized to influence group performance selectively. Elderly controls had shorter reaction times than depressed patients who, in turn, were faster than dementia patients in the standard choice reaction time test. Elderly control and depressed subjects responded more quickly under conditions designed to reduce task demands. However, no effect was detected for DAT patients, presumably due to the neural constraints imposed on cognitive functioning in dementia. These results highlight the different etiologies for the intellectual decline in dementia and pseudodementia.