Spouse caregivers of Alzheimer patients: problem responses to caregiver burden.

This paper reports on comparisons of patterns of responses by 199 spouses of Alzheimer disease patients to stresses of functioning as caregivers. Focusing on gender and age of spouses, we examine effects of the total burden of caregiving and perceived patient problems on a set of emotional and social responses of caregivers. We also examine ways in which depressive symptoms and anxiety of spouse caregivers were associated with patterns of their responses to caregiving stresses. Total patient problem burden was most strongly associated positively with caregiver anger-resentment toward the patient, followed by caregiver concerns about personal time restriction and limitation of social life. Among individual areas of patient problems, emotional lability of the patient rather than cognitive impairment appeared strongest by far in affecting caregiver response measures. Negative impact of caregiving on their social life and associations appeared to have particularly marked effects on effects on caregiver depressive symptoms and anxiety scores. Spouse caregivers did not differ by age in clinically significant ways in their patterns of reaction to stresses of caregiving. The study suggests the importance of considering potential spouse caregiver reactions in such areas as anger and aggressive response to patients, the impact of feelings of social deprivation and personal sacrifice, as well as the implications of caregiving stresses for patient care and maintenance of family cohesion and quality of life.

Vulnerability of husband and wife caregivers of Alzheimer disease patients to caregiving stressors.

This study assessed relationships between problem behaviors in 199 Alzheimer Disease patients and vulnerability factors in the well being and emotional health of their spouse caregivers. Among caregiver wives and the younger caregiver husbands (64 years old and under) the volume of patient problem behavior was significantly negatively associated with total scores on a summary well being measure. The association was not found within the older husband caregiver group. Considering five subdimensions of the summary well being scale (Anxiety, Depressive Symptoms, Positive Well Being, Vitality and General Health), correlational analyses showed that the total patient problems measure appeared to have impact primarily among wife caregivers, particularly those 64 years old and under. Multiple regression analyses showed that one patient problem behavior category, Emotional Lability, was the single strongest predictor of impaired well being of the caregiver among all five subdimensions of the caregiver well being measure. Although Destructive Behavior of the patient was not significant by itself, an Age by Destructive Behavior interaction showed that high levels of patient Destructive Behavior predicted high levels of Depression, Anxiety, and low levels of Positive Well Being more among younger caregivers. Husband caregivers had significantly higher Anxiety scores than wife caregivers. These findings document how particular patient problem behaviors can affect caregivers. They point up as well how both gender and age may help target which caregivers are most vulnerable to the stress of specific Alzheimer patient behavior problems. They also suggest the utility of examining specific dimensions of well being rather than a total score alone for purposes of understanding the relationship of particular patient behavior problems to caregiver emotional and physical health.

Symptoms of depression in Alzheimer's disease, frontal lobe-type dementia, and subcortical dementia.

These findings support the hypothesis that a frontal-subcortical abnormality is necessary to produce symptoms of depression (e.g., mood-related signs, behavioral disturbances, neurovegetative signs) in dementia. Behavioral disturbances (e.g., disinhibition, agitation, social withdrawal) were more likely to occur in FLTD than in AD or SCD.

Memory self-report in Alzheimer's disease and in age-associated memory impairment.

We investigated memory self-report in Alzheimer's disease (AD) and age-associated memory impairment (AAMI). AD and AAMI patients and healthy elderly subjects were administered a self-report memory questionnaire, memory tests, a family-rated memory questionnaire, and a depression scale. The AD group reported worse memory than the control group, but many individual AD subjects reported normal memory. This finding confirms clinical observations that unawareness of memory loss is common in AD but variable across patients. Multiple regression analysis revealed that worse memory self-ratings were associated with greater dementia severity and higher depression scores. In the AAMI group, memory self-ratings were predicted by family ratings of memory ability but not by memory test scores. There was a nonsignificant trend for depression scores to predict memory self-ratings. Finally, level of self-reported memory ability did not differ for AD and AAMI, contradicting clinical lore that memory complaint is a useful diagnostic indicator.

Accelerated forgetting in Alzheimer-type dementia.

Accelerated forgetting of name-face associations and grocery list items within the first hour postpresentation is demonstrated in 80 persons with Alzheimer's disease (AD) compared to 80 control subjects matched on age, education, and gender. Differences in forgetting which exceeded statistical regression effects remained, even when AD and control subjects were matched on rate of acquisition during the learning trials of name-face associations. Results are discussed in relation to the neuropathology of AD, organic amnestic disorders, and methodological factors concerning previous research on forgetting in persons with AD.

A pilot clinical trial of the angiotensin-converting enzyme inhibitor ceranapril in Alzheimer disease.

This pilot clinical trial was a 15-week, double-blind, controlled, three-way crossover study evaluating cognitive effects of ceranapril in subjects with dementia of the Alzheimer type (age range 50-75 years). Computerized (CNTB) and noncomputerized cognitive test batteries revealed no significant results (p > 0.05). On further analysis of the data, however, a study of longer duration and/or higher dosages may be warranted.

Relation of hostility to medication adherence, symptom complaints, and blood pressure reduction in a clinical field trial of antihypertensive medication.

The impact of hostility was examined in relation to the conduct and results of a clinical field trial. Data were derived from a multi-center randomized double-blind study of the comparative effects of antihypertensive therapy (captopril, methyldopa and propranolol) on the quality of life of 620 hypertensive men. Hostility levels were higher in subjects reporting skipping medication dosages compared to those reporting they always complied with the medication schedule. Reporting of symptoms often associated with antihypertensive drug regimens was positively related to hostility scores throughout the study, even during the blinded placebo period. Persons with high hostility scores showed the greatest decline in blood pressure independent of type of antihypertensive medication. However, there was some limited evidence that hostility levels were significantly reduced by one antihypertensive medication. Overall, the present findings suggest that double-blind pharmacologic clinical trials may benefit from using reliable measures of hostility as covariates in the evaluation of symptom reports and amount of blood pressure reduction.

Self-reported side effects from antihypertensive drugs. A clinical trial. Quality of Life Research Group.

We report on the distress associated with physical symptoms in 761 male hypertensive patients enrolled in a clinical trial of the effects of captopril, methyldopa or propranolol on quality of life. Educational level at entry into the trial showed a negative association with a series of physical symptom distress items among patients not previously treated with antihypertensive medications but no association with symptoms among the previously treated. Over the 24 weeks of therapy captopril as monotherapy was associated with no change from baseline in distress in all symptoms examined. In contrast, distress increased in the methyldopa treated patients for dry mouth and blurred vision. Propranolol treated patients had increased "trouble getting breath," bradycardia, shortness of breath or wheezing, and blurred vision. Between group comparisons revealed significant differences favorably comparing captopril to both methyldopa and propranolol in regard to fatigue, and blurred vision, as well as to methyldopa alone for dry mouth and "feeling worn out." There were significant differences as well between captopril and propranolol with patients on propranolol worsening in bradycardia. Other comparisons of patients on propranolol and methyldopa monotherapy showed propranolol patients worsening in bradycardia and loss of taste, but methyldopa patients reported more dry mouth and feeling worn out than those on propranolol. The addition of hydrochlorothiazide to therapy worsened total physical symptom distress scores for methyldopa and propranolol patients. This study confirms the value of methods which assess the degree of distress associated with symptoms commonly reported by hypertensive patients receiving antihypertensive medications. This approach can be useful in establishing a treatment regimen least likely to cause distress and can be of value in preserving quality of life, preventing noncompliance, and withdrawal from treatment.

A double-blind, placebo-controlled study of adjunctive nadolol in the management of violent psychiatric patients.

We report a controlled 3-week study (n = 30) of adjunctive use of nadolol, 80 to 120 mg per day, vs. placebo for the management of violent psychiatric patients. There were no remarkable adverse cardiac effects at this dose. The active treatment group showed lower total Brief Psychiatric Rating Scale (BPRS) scores after the first week of treatment (analysis of covariance [ANCOVA], p less than .08) and similar trends for the activation factor and the hostility scale. There were parallel findings for measures of extrapyramidal symptoms (EPS) (Simpson-Angus Neurological Rating Scale), which were reliable after the second week (ANCOVA, p less than .02). A significant association between changes in EPS and BPRS scores was found by regression analysis, after the effects of baseline measures were removed. Given that nadolol does not penetrate the central nervous system well, the antiaggressive effects may be associated with sympathetic nervous system feedback mechanisms.

A short form for clinical assessment of quality of life among hypertensive patients.

Recently, medical research studies and clinical trials have included quality-of-life assessments, which measure the biomedical, behavioral, and social dimensions of living as a major therapeutic end point. Monitoring the quality of life in routine clinical practice also has the potential to aid clinicians to evaluate the impact of new therapies on the health status of their patients. However, because quality-of-life assessment techniques are quite lengthy and often require the aid of a trained interviewer, the research format is not practical for the typical clinical setting. This study describes the formulation, construction, and testing of an abbreviated quality-of-life questionnaire suitable for the clinical assessment of hypertensive patients. The initial formulation was based on analyses of data from a large-scale clinical trial (626 hypertensive male patients). Using the data at baseline for this group, items were selected such that the variance, internal consistency, and concurrent validity of the response scales were maintained by a reduced subset of items. The sensitivity of the reduced subsets was evaluated using treatment data and found to be as sensitive to treatment differentials as the original research instrument was. A subsequent field test of 87 volunteer subjects indicated that the new shortened version had the qualities of stable internal consistency and test-retest reliability over two successive trials. The questionnaire was self-administered and required less than 10 minutes to complete. It was given as an adjunct to the history and physical exam.(ABSTRACT TRUNCATED AT 250 WORDS)

Sexual symptoms in hypertensive patients. A clinical trial of antihypertensive medications.

The effects of captopril, methyldopa, and propranolol hydrochloride on reported distress over sexual symptoms over a 24-week treatment period were examined as part of a multicenter, randomized, double-blind clinical trial in which 626 men with mild to moderate hypertension participated. On entry into the clinical trial, 58% of patients taking antihypertensive medications and 44% of men not receiving antihypertensive drugs reported distress over one or more sexual symptoms. Among 304 patients treated with monotherapy who completed the trial, total symptoms distress scores of treatment groups did not differ from each other in change from baseline to week 24, but in particular, problems of maintaining an erection were significantly worsened with propranolol therapy. Among 177 patients treated with monotherapy plus a diuretic, total sexual symptoms distress scores worsened among the groups taking methyldopa or propranolol, with significant worsening in all individual symptoms among patients taking propranolol, and problems in maintaining an erection and in ejaculation among patients receiving methyldopa. Among patients treated with captopril plus a diuretic, no change from baseline appeared in scores for any of the sexual symptoms. The findings underline the importance of taking an adequate sexual history and document that selection of antihypertensive drugs may significantly affect the incidence of sexual symptoms.

Effects of antihypertensive medications on vitality and well-being.

The effects of captopril, methyldopa, and propranolol were assessed for sense of well-being and vitality among 626 men with mild to moderate hypertension in a multicenter, randomized, double-blind clinical trial. After a 24-week treatment period, patients taking captopril, compared with patients taking methyldopa and propranolol, scored significantly higher on measures of well-being and vitality. In addition, patients on captopril had more favorable results in being able to keep up with their work and in not feeling tired or sleepy at work. The effects of each of the drugs manifested themselves at different periods. For example, the negative effects of methyldopa on vitality were evident by week 8, whereas the negative effects did not become manifest for propranolol until week 24. On the other hand, a steady progressive improvement in vitality scores was evident at week 8 and at week 24 for patients on captopril. The findings of the study also suggest that the effects of the treatment drugs were most marked in patients who had had previous antihypertensive medications and who were on single-drug therapy during the course of the clinical trial. Further, the differences between patients taking captopril and those on methyldopa and propranolol appear to be obscured by the addition of a diuretic. The findings of the study may guide the physician in orienting his or her patient and in planning and implementing a therapeutic regimen.

Impact of antihypertensive therapy on quality of life: effect of hydrochlorothiazide.

Six hundred and twenty-six male patients with mild to moderate hypertension were enrolled in a multicentre randomized double-blind clinical trial to determine the effect of methyldopa, captopril and propranolol on the quality of life of these patients. During the 6-month trial hydrochlorothiazide was added to the treatment programme of those patients whose blood pressure was not normalized. More individuals in the captopril group (33%) required hydrochlorothiazide than in the propranolol group (22%). As a group, those individuals who required a diuretic were heavier and had higher basal and end-of-study blood pressure than those individuals requiring only monotherapy. However, the basal quality-of-life indices were similar in the six treatment subgroups. The withdrawal rate from the study was twice as high for those patients treated with propranolol and methyldopa as for those treated with captopril, whether a diuretic was added or not. More individuals requiring a diuretic experienced sexual dysfunction and a substantial worsening of their general well-being and of physical symptom indices over the 24 weeks of the study (P less than 0.01), particularly in the captopril and propranolol treatment subgroups. In summary, the present results suggest that diuretic therapy may have a greater negative impact on the quality of life of hypertensive patients than captopril, propranolol or methyldopa alone.

Work performance, absenteeism and antihypertensive medications.

Relationships between antihypertensive medications and selected aspects of work performance and absenteeism were explored in a multicentre, randomized, double-blind, clinical trial with 626 male hypertensive patients assigned to regimens of captopril, methyldopa or propranolol, either alone or supplemented as needed by a diuretic for blood pressure control. Patients previously on antihypertensive therapy did not differ from new patients in work absenteeism, both before and throughout the clinical trial. After a 24-week treatment period patients on captopril alone improved significantly over baseline in work-performance measures of mental acuity and job satisfaction-morale, while significant worsening in the methyldopa group and no change in the propranolol group occurred among patients given these drugs alone. When 24-week changes between groups not on diuretic were compared, significant differences in the measures appeared in favour of captopril. However, patients also taking a diuretic did not differ from baseline either within or between the three groups. Withdrawal from the trial because of lethargy and fatigue was significantly greater among patients on methyldopa and propranolol than among those receiving captopril. Absenteeism did not differ between the drug groups. The study shows that there are measurable differences in the impact of the antihypertensive drugs on aspects of work performance, and it underlines the importance of considering this factor in assigning patients to therapy.

Angiotensin converting enzyme and memory: preclinical and clinical data.

Results from both preclinical and clinical studies described here suggest that ACE may have a role in the modulation of cognitive memory processes in the rat and in humans. The finding of improved cognitive performance among patients treated with captopril relative to those treated with propranolol or methyldopa is consistent with other clinical and prec-clinical data. Clinical data derive primarily from quality of life measures based on interviews with patients in the same clinical trial from which our other cognitive data are drawn. For example, mental acuity in the workplace was reported to have improved significantly from baseline to week 24 in patients on captopril (p less than 0.05), although it did not change in patients treated with propranolol and worsened in those receiving methyldopa (Croog et al, 1987). The difference between captopril and methyldopa was significant (p less than 0.01). Pre-clinical data come primarily from studies demonstrating that inhibitors of ACE delay CAE in rats when compared not only with methyldopa, but also with saline (Sudilovsky et al, 1984, 1986). A fundamental question is how could inhibition of ACE improve cognitive functioning independent of blood pressure control. It is known that captopril exerts its antihypertensive effects primarily through inhibition of the ACE and that this is present in the brain as well as in non-neuronal tissues elsewhere (Ganten et al, 1982; Strittmatter et al, 1983, 1984). The activity of the enzyme has been found to be significantly increased in the caudate nucleus, the frontal cortex, parahyppocampal gyrus, and medial hippocampus of patients dying with Alzheimer's disease when compared to age-matched controls (Arregui et al, 1982). In addition, AII has been shown to impair performance on various learning and memory paradigms in animals (Melo and Graeff, 1975; Morgan and Routtenberg, 1977). Raising the level of endogenous AII by intravenous administration of its precursor renin has similar effects, and these are prevented if captopril is administered previously (Koller et al, 1979). Also, chronic oral treatment with captopril produces changes of brain renin angiotensin system parameters which suggest inhibition of AII biosyntheses in the brain (Scholkens et al, 1983). It is conceivable therefore, that our findings with prolonged administration of captopril are exerted through reduced formation of AII. Other possible mechanisms through which captopril may affect cognition include peptide-protein systems (Ganten et al, 1982, Sudilovsky et al, 1988) or the modulation of cerebral blood flow autoregulation mechanisms.(ABSTRACT TRUNCATED AT 400 WORDS)

Double blind controlled trials of cholecystokinin octapeptide in neuroleptic-refractory schizophrenia.

A group of 14 schizophrenics who remained symptomatic after neuroleptic treatment received either 0.02 mcg/kg CCK-8 or saline placebo intravenously. Thereafter, 13 received the alternative infusion as a crossover treatment. A second group of 16 such patients received 0.04 mcg/kg CCK-8 or saline intravenously and, thereafter, 14 of these received the alternative infusion as a crossover treatment. Psychopathology was rated prior to, 2-3 h post, and on days 3, 5 and 7 after each infusion. Ratings consisted of the BPRS, the Abrams and Taylor Scale for Emotional Blunting, the Hamilton Anxiety Scale and a Schneiderian "Positive" symptom scale abstracted from the President State Examination. Parallel groups and cross over design analyses failed to show efficacy for CCK-8.

Age-associated memory impairment: diagnostic criteria and treatment strategies.

In general, then, the term Age-Associated Memory Impairment (AAMI) has been adopted to describe healthy persons over 50 years of age who have experienced memory loss since early life, but who are not demented. Specific diagnostic criteria have been proposed for AAMI and these criteria are now being applied in clinical studies, including a number of pharmacologic treatment studies. Many of these latter studies are supported by evidence from preclinical studies suggesting that age-related memory deficits in animals can be pharmacologically altered. This evidence gives reason to hope that an important behavioral deficit associated with aging may be controlled or corrected through drug treatment. The development of such a treatment would be an accomplishment of immense clinical and scientific significance.

Evaluation of myelographic contrast-medium tolerance with psychometric testing.

Clinical tolerance to the myelographic contrast media metrizamide and iopamidol was evaluated in 26 and 30 patients, respectively, with a battery of neuropsychologic tests before and after myelography in a randomized, double-blind prospective study. Twenty hospitalized patients with chronic back pain were also studied before and after computed tomography to serve as controls relative to the groups administered contrast agents. Measures of conceptual reasoning and affect were sensitive tests of adverse reactions. These paralleled the incidence of somatic reactions and correlated with the dose of contrast medium. Methodologic problems included varying intervals between myelography and psychometric evaluation among subjects and use of a less-than-ideal control group. Neuropsychologic tests appear to be sensitive for detection of subtle adverse reactions and possibly predictive of their occurrence. Iopamidol was tolerated better than metrizamide, with somatic side effects occurring in 38% of patients receiving metrizamide and in 17% of patients receiving iopamidol.