The effects of mood changes and antidepressants on the cognitive capacity of elderly depressed patients.
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Biomedical subjects
Publications and source records attributed to L F Jarvik.
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Alzheimer disease (AD) is a clinicopathologic syndrome of unknown etiology with numerous abnormalities in neuronal and nonneuronal cells. A review of the literature suggests that a common basic intracellular defect may underlie many of the reported abnormalities. We hypothesize impairment of the microtubule (MT) system as one explanation for the pathogenesis of AD. Evidence in support of the hypothesis includes the following: MTs are ubiquitous and vital cell components, unequally distributed, with the highest concentration in the brain; various abnormalities, including the key neuropathologic lesions, can be explained by impairments of the MT system; and experiments utilizing pharmacologic agents known to disrupt MTs have reproduced certain abnormalities observed in AD. The hypothesis provides a framework for systematic investigations of MTs at the cellular and molecular levels as well as the basis for in vivo diagnostic tests for AD.
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This review is based on 25 double-blind anti-depressant drug studies reported between 1964 and 1986 that focused on patients over 55 years of age. The number of studies located in the literature is appallingly small, particularly when we consider that we included experimental drugs as well as drugs not recommended for use with the elderly. In general, the results of our survey support clinical experience: the drugs are clearly superior to placebo; they show comparable therapeutic efficacy--about 50% improvement in Hamilton Psychiatric Rating Scale for Depression scores versus 20% to 25% on placebo; and all of them have undesirable side effects. Thus, the choice of drug is based on side effects profiles and potential drug-drug interactions rather than on degree of therapeutic efficacy. The review makes apparent the need for more substantial data on treatment outcome in patients over the age of 60 years. Beyond that, additional information is unlikely to change the 50% response rate or the potential for serious side effects with most of the currently available drugs. We clearly need better drugs.
There has been a dramatic increase in the incidence of dementia as the percentage of aging Americans has increased. Approximately half of these persons are living at home with their spouses or in the homes of their children. This increasing group of patients will be seeking care from community-based dentists. An understanding of the diagnosis, the treatment, the course, and the prognosis of the disease process will better prepare dentists to meet the unique needs of this group of patients.
Although relatives' retrospective reports are often used in characterizing the onset and progression of symptoms in dementia of the Alzheimer type (DAT), little is known about the accuracy of these accounts. The primary purpose of this paper is to summarize preliminary data obtained from relatives in an ongoing family study of DAT. Preliminary findings suggest there is rough reliability to relatives' recall of the progression of symptoms over time. This observation is discussed in relation to literature from other areas (e.g. child development, psychopathology) where the reliability of relatives' retrospection has been more thoroughly examined.
Elderly patients, just as younger ones, may suffer from the two extremes of affective disturbance known as mania and depression. Either may be secondary to underlying organic causes often requiring specific treatment. For primary disorders, treatment typically consists of pharmacotherapy and/or psychotherapy. Pharmacologic treatment of nonorganic conditions is essentially similar to that used in younger patients, although medication dosages are generally lower and side effects more common.
Longitudinal changes in cognitive functioning were examined for a sample of aging twins, some of whom developed dementia while others did not. Individuals who were judged to be demented at a mean age of eighty-five years had achieved lower scores on most tests twenty years prior to diagnosis, and experienced greater declines in vocabulary and forward digit span over time, than those surviving to a comparable age without dementia. These trends were observed for individuals with mild, as well as moderate-to-severe, dementia and were unrelated to physical health status or premorbid activity patterns. It is suggested that dementing illness may develop very slowly, and that the likelihood of exhibiting clinically significant dementia may vary with premorbid intellectual level.
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In Study 1, carefully screened elderly adults with primary degenerative dementia or major depression were compared to healthy aged control subjects on three tests of learning and memory: the Benton Visual Retention Test, Inglis Paired-Associate Learning Test, and the Fuld Object-Memory Evaluation (OME). The sharpest distinction in performance among the groups was observed on the OME, and discriminant equations based on this test correctly classified a high percentage (greater than or equal to 90%) of participants. Study 2 applied the classification rules derived in the first investigation to an unselected series of geropsychiatry inpatients referred for neuropsychological evaluation. There was agreement between memory test classification and general categories of clinical discharge diagnosis (organic vs. functional) for 21 of 25 patients, and with status at follow-up approximately 18 months later. Predictive value computations suggested that the OME is more accurate in confirming true dementia than in detecting dementia syndromes associated with functional disorders.
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Fear of possible cardiovascular side effects has prevented many physicians from treating older patients with antidepressants. However, we believe that it is the rare patient who cannot or should not be treated with some agent. Start with a low dose of desipramine, doxepin, or trazodone, depending upon the tolerance for sedation and anticholinergic side effects. Barring specific contraindications, the choice of drugs is usually based on the side-effect profile, rather than any differences in efficacy.
Blood pressure measurements were collected from 36 depressed geriatric outpatients (ages 55 to 81 years) enrolled in a double-blind, placebo-controlled study of the efficacy of doxepin and imipramine. Mean systolic postural changes were 25.9 mm Hg for imipramine, significantly higher than the 10.5 mm Hg for doxepin, and 12.4 mm Hg for placebo. The orthostatic drop in the imipramine group was only weakly related to dose and did not correlate with amount of pretreatment orthostatic hypotension or with duration of treatment. The increased orthostatic hypotension occurred early in treatment and at low doses of imipramine. Accordingly, caution is advised in the use of imipramine for the elderly.
The authors compared the frequencies of prior thyroid disease, thyroid medication use, and abnormal serum thyroxine levels in 61 patients with dementia of the Alzheimer type (DAT) with those of 38 control subjects. They found that the 33 women with DAT had a 24.2% frequency of prior thyroid disease, comparable with that found in a previous epidemiologic study. The 19 female controls, however, had a similar frequency, failing to support a previously reported association between DAT and thyroid disease.
Improvement in depressive symptoms was significantly related to a decrease in subjective memory complaints in 29 elderly depressed outpatients. Patients with substantial improvement in their depression showed similar reductions in memory complaints regardless of whether they received tricyclic antidepressants or group psychotherapy.