The relationship between donepezil and behavioral disturbances in patients with Alzheimer's disease.

The authors tested the hypothesis that behavioral disturbances are reported at significantly lower rates by caregivers of Alzheimer's disease (AD) patients receiving the antidementia drug donepezil, compared with a group of patients receiving no antidementia drug treatment. Patients administered donepezilfor 6 months (n=84) were compared with patients not on donepezil (n=248). Patients taking donepezil had significantly lower levels of behavioral disturbances than patients not receiving this agent (P< or =0.011). Specifically, donepezil patients were described as significantly (P< or =0.05) less likely to be threatening, destroy property, and talk loudly. Also, significantly fewer patients receiving donepezil were treated with sedatives (P< or =0.005). These findings support the growing body of evidence that cholinesterase inhibitors have psychotropic properties and reduce behavioral disturbances in patients with AD.

Patterns of care in the early stages of Alzheimer's disease: impediments to timely diagnosis.

OBJECTIVE: Description of factors associated with delay in diagnosis of Alzheimer's disease (AD). DESIGN: A self-administered mail questionnaire. SETTING: Households including someone with AD identified through a nationwide marketing database. PARTICIPANTS: A total of 1480 caregivers of patients diagnosed with AD. MEASUREMENTS: There were two measures of delay examined through caregiver reports: (1) duration in years from first AD signs until determination of a definite problem, and (2) duration from problem recognition to first physician consultation. Also, caregivers were categorized by time since patient's diagnosis and relationship to patient. Within-group analyses examined the impact of these characteristics on delay measures. RESULTS: Mean lag in years from observation of first symptoms to problem recognition for those diagnosed in the past 12 months, the past 13 to 48 months, and the past 49 months or more was, respectively, 1.20, 1.56, and 2.25 (P < .001). The timing of diagnosis also influenced lag from problem recognition to first physician consultation so that subgroups with recent, less recent, and distant diagnosis reported delays in years of .82, .84, and 1.31 (P < .001). Caregiver relationship was not significantly related to these lags. Correct diagnosis of AD was reported by caregivers in only 38% of cases at initial physician consultation. CONCLUSIONS: These results suggest that both caregivers and physicians lack ready understanding of the difference between memory processes in aging and AD. Ongoing public and professional education is needed to convey the basics of the diagnosis of AD. In addition, routine screening for dementia should be considered to surmount attitudinal and logistical barriers.

An economic evaluation of donepezil in the treatment of Alzheimer's disease.

Using data from a longitudinal survey of caregivers of Alzheimer's disease patients, we calculated the average per-patient direct medical costs over a 6-month period for a matched sample of patients (N = 376). A group of patients receiving donepezil for 6 months was compared with a group not receiving this form of drug therapy. The groups were matched by disease severity, age, sex, and comorbidity. The average age in the two groups was 74 years, with 50% female and 90% white. Patients in both groups had a mean of 1.6 comorbid conditions. No patients in either group were institutionalized at the beginning of the 6-month period, and all patients were taking at least one prescription drug, including donepezil. Mean 6-month direct medical expenses for a patient receiving donepezil were $3443, including the cost of the drug, whereas the per-patient mean expenses for the comparison group were $3476. Although the patients receiving donepezil had greater expenditures for prescription drugs, these costs were offset by a slower rate of institutionalization. At the end of the 6-month period, 5% of donepezil patients were institutionalized, compared with 10% of the nondonepezil patients. The cost of receiving donepezil treatment for 6 months did not result in a significantly higher per-patient mean direct cost.

Case study: neurofibromatosis.

Neurofibromatosis (Von Recklinghausen disease) is a genetically transmitted, multisystemic disorder characterized by abnormalities of the skin, peripheral nerves, bone, and soft tissue. Symptoms appear early in life and vary with the type and severity of the disease. Care of patients with neurofibromatosis (NF) presents a complex challenge for nursing, the multidisciplinary team, and the family. This article profiles the progression of neurofibromatosis in one girl from birth through adolescence. The author emphasizes that while health care workers ably provide expertise and assistance, the ultimate responsibility for decision making rests with the child and her family.

Alterations in responses to bradykinin, angiotensin I, and angiotensin II during the induction phase of one-kidney, one-wrapped hypertension and associated arterial disease in rabbits.

During the induction phase of low-renin, one-kidney, one-wrapped hypertension in rabbits,serum angiotensin converting enzyme (ACE) activity is depressed and correlates inversely with the degree of necrotic arterial disease that develops. Responses to the vasoactive polypeptides, bradykinin (BK), angiotensin I (AI), angiotensin II (AII), the ACE blocker teprotide, and the AII antagonist 1-sar-8-ile AII were studied. Responses to BK, AII, and AI showed significant changes in both magnitude and duration (recovery time). Recovery time for depressor responses to BK in hypertensive rabbits was approximately three times that in the control period. One-wrapped, two-kidney control rabbits without hypertension-associated arterial disease showed no change in BK recovery time, although serum ACE activity was significantly depressed. In the experimental period BK recovery time correlated directly with the degree of arterial disease and indirectly with the final serum ACE activity. Duration of the pressor responses after AII correlated directly with the degree of arterial disease and indirectly with final serum ACE activity. In untreated hypertensive rabbits the percentage of increases in blood pressure after AI relative to control animals were decreased, and for all hypertensive rabbits' the increase in blood pressure correlated directly with the final serum ACE activity. Long-term treatment with teprotide moderated the hypertension but had little effect on serum ACE activity or the responses to BK, AII, and AI. Short-term infusions of 1-sar-8-ile AII and teprotide caused significant decreases in blood pressure in both the control and experimental periods, although no change in response to either polypeptide occurred. These studies support other evidence that pressor components of the renin-angiotensin system do not sustain the elevation of blood pressure in this form of experimental hypertension. Alterations in response patterns following AII and AI suggest that a vasodepressor system may be altered. In addition, part of the altered response to BK, and possibly AII, appears related to the development of the hypertension-associated arterial disease.

Serum angiotensin converting enzyme activity and the capacity to develop hypertention-associated arterial disease. Studies during the induction phase of one-kidney perinephritis hypertension in rabbits.

Serum angiotensin converting enzyme (ACE) activity and plasma renin activity (PRA) were studied during the development of the widespread necrotic arterial disease that occurs in the induction phase of one-kidney perinephritis hypertension. Control serum ACE activity was significantly higher in rabbits developing many arterial lesions than it was in rabbits developing relatively few arterial lesions. Serum ACE decreased 7 days after the production of unilateral perinephritis in all rabbits. Following contralateral nephrectomy, serum ACE decreased further in rabbits devloping many arterial lesions but returned toward control values in rabbits developing relatively few arterial lesions. Significant inverse correlations were demonstrated for the total number of arterial lesions that developed relative to a) the decrease in serum ACE activity 7 days after the production of unilateral perinephritis, b) the lowest or the average serum ACE activity during the period of development of the arterial lesions after contralateral nephrectomy, and c) the change in serum ACE activity during the period of development of the arterial lesions. Chronic treatment with SQ 20,881, a synthetic nonapeptide inhibitor of ACE activity, during the period of development of the hypertension and the arterial lesions significantly reduced the serum ACE activity and the hypertension but did not change interrelationships between serum ACE activity and the number of arterial lesions that developed. PRA significantly decreased after the production of perinephritis and decreased somewhat further during the induction period of the hypertension after contralateral nephrectomy. No relationships were demonstrated between PRA, or changes in PRA, and the development of arterial lesions. The increase in blood pressure during the incubation period of the hypertension did not correlate with the number of arterial lesions that developed. These finding indicate that serum ACE activity reflects importantly on the capacity to develop necrotic arterial lesions during the induction phase of one-kidney perinephritis hypertention and on functional events relating to their pathogenesis.