Sture Eriksson

Donepezil in patients with severe Alzheimer's disease: double-blind, parallel-group, placebo-controlled study

BACKGROUND The cholinesterase inhibitor donepezil is used to treat mild-to-moderate Alzheimers disease. Its efficacy in severe dementia has not been assessed and is controversial. Our aim was to ascertain the effectiveness of donepezil in patients with severe Alzheimers disease, by focusing primarily on cognition and activities of daily living. METHODS We did a 6-month, double-blind, parallel-group, placebo-controlled study in 248 patients with severe Alzheimers disease (mini mental state examination score 1-10) who were living in assisted care nursing homes ran by trained staff in Sweden. We assigned patients oral donepezil (5 mg per day for 30 days then up to 10 mg per day thereafter, n=128) or matched placebo (n=120). Our primary endpoints were change from baseline to month 6 in the severe impairment battery (SIB) and modified Alzheimers Disease Cooperative Study activities of daily living inventory for severe Alzheimers disease (ADCS-ADL-severe). We analysed outcomes for patients with data at baseline and at one or more other timepoints (modified intent-to-treat population) with last observation carried forward used to replace missing data. FINDINGS 95 patients assigned donepezil and 99 patients assigned placebo completed the study. Patients treated with donepezil improved more in SIB scores and declined less in ADCS-ADL-severe scores at 6 months after initiation of treatment compared with baseline than did controls (least squares [LS] mean difference, 5.7, 95% CI 1.5-9.8; p=0.008, and 1.7, 0.2-3.2; p=0.03, respectively). The incidence of adverse events was comparable between groups (donepezil 82% [n=105] vs placebo 76% [n=91]), with most being transient and mild or moderate in severity. More patients discontinued treatment because of adverse events in the donepezil group (n=20) than in the placebo group (n=8). INTERPRETATION Donepezil improves cognition and preserves function in individuals with severe Alzheimers disease who live in nursing homes.

Incidence and Clinical Characterization of Unprovoked Seizures in Adults: A Prospective Population‐Based Study

In a population‐based prospective study of epileptic seizures in adults aged ≥17 years, we identified 563 patients with possible seizures in a period of 34 months. Seizures were unprovoked in 160 patients, an incidence of 56 in 100,000 person‐years. There was no difference in incidence between sexes. Age‐specific incidences of unprovoked seizures increased sharply in men from age 60 years and in women from age 70 years. The incidence of unprovoked seizures in those aged ≥65 years was 139 (men 166, women 116). The cumulative incidence of unprovoked seizures between the ages of 17 and 84 years was 4.6%. The proportion with an identified presumptive cause for unprovoked seizures increased with advancing age. A presumed etiology was identified in 77% of persons aged ≥60 years. Stroke was the most common etiology, detected in 30% (incidence 16) and in 45% at ages ≥60 years. Tumors were detected in 11% (incidence 6) and Alzheimers disease was detected in 7% (incidence 4). Eighteen percent of patients were demented. Unprovoked seizures were partial in 68% of cases (incidence 38), and generalized in 16% (incidence 9). Another 13% of patients had generalized seizures, but seizure onset was not witnessed (incidence 7). In 16%, there was a delay of ≥1 year from the first unprovoked seizure to initial diagnosis.

A non-intensive stroke unit reduces functional disability and the need for long-term hospitalization.

In a prospective controlled trial we compared the clinical outcome for unselected acute stroke patients in a non-intensive stroke unit (n = 110) and in general medical wards (n = 183). The patients were comparable in age, marital state and functional impairment on admission. Case fatality rates over the first year after the stroke were similar in the two groups. By three months after the stroke, 15% of the survivors initially admitted to the stroke unit and 39% of those admitted to general medical wards remained hospitalized (p less than 0.001). The corresponding figures by one year after the cerebrovascular accident were 12% and 28%, respectively (p less than 0.05). A greater proportion of surviving stroke unit patients was independent in walking (0.10 greater than p greater than 0.05), personal hygiene (p less than 0.05) and dressing (p less than 0.001). Essential features of the stroke unit are team work headed by a stroke nurse, staff, patient and family education and very early onset of rehabilitation. We conclude that this strategy improves functional outcome and reduces the need for long-term hospital care.

Developing the Concept of Moral Sensitivity in Health Care Practice

The aim of this Swedish study was to develop the concept of moral sensitivity in health care practice. This process began with an overview of relevant theories and perspectives on ethics with a focus on moral sensitivity and related concepts, in order to generate a theoretical framework. The second step was to construct a questionnaire based on this framework by generating a list of items from the theoretical framework. Nine items were finally selected as most appropriate and consistent with the research team’s understanding of the concept of moral sensitivity. The items were worded as assumptions related to patient care. The questionnaire was distributed to two groups of health care personnel on two separate occasions and a total of 278 completed questionnaires were returned. A factor analysis identified three factors: sense of moral burden, moral strength and moral responsibility. These seem to be conceptually interrelated yet indicate that moral sensitivity may involve more dimensions than simply a cognitive capacity, particularly, feelings, sentiments, moral knowledge and skills.

Development and Initial Validation of the Stress of Conscience Questionnaire

Stress in health care is affected by moral factors. When people are prevented from doing ‘good’ they may feel that they have not done what they ought to or that they have erred, thus giving rise to a troubled conscience. Empirical studies show that health care personnel sometimes refer to conscience when talking about being in ethically difficult everyday care situations. This study aimed to construct and validate the Stress of Conscience Questionnaire (SCQ), a nine-item instrument for assessing stressful situations and the degree to which they trouble the conscience. The items were based on situations previously documented as causing negative stress for health care workers. Content and face validity were established by expert panels and pilot studies that selected relevant items and modified or excluded ambiguous ones. A convenience sample of 444 health care personnel indicated that the SCQ had acceptable validity and internal consistency (Cronbach’s alpha exceeded 0.83 for the overall scale). Explorative factor analysis identified and labelled two factors: ‘internal demands’ and ‘external demands and restrictions’. The findings suggest that the SCQ is a concise and practical instrument for use in various health care contexts.

Cognitive Dysfunction, Hippocampal Atrophy and Glucocorticoid Feedback in Alzheimer’s Disease

BACKGROUND The hippocampal formation is damaged early in Alzheimers disease (AD). An association between temporal lobe volume and cognitive function has been shown in several studies. Increased limbic-hypothalamic-pituitary-adrenal (LHPA) axis function has been suggested to be related to hippocampal atrophy and cognitive impairment. Our hypothesis was that there is a clear link between hippocampal volume -- notably of the CA1 region -- memory (episodic and visuospatial) and decreased feedback sensitivity in the LHPA axis in AD. METHODS Sixteen medication-free outpatients with mild to moderate AD were included. Hippocampal volume was measured with magnetic resonance imaging. Dexamethasone suppression tests were performed using .5 mg and .25 mg dexamethasone. Three different components in the neuropsychological battery -- Rey 15 item memory test, Alzheimers Disease Assessment Scale (ADAS) word recall and spatial span from Wechsler Adult Intelligence Scale - Revised neuropsychological instrument (WAIS-R NI) -- were found to represent episodic and visuospatial memory. RESULTS Low hippocampal CA1 volume and high post-dexamethasone cortisol levels in combination were significantly associated with Rey 15 item memory and spatial span test outcomes. No association was found between LHPA feedback and hippocampal volume. CONCLUSIONS Low hippocampal volume and a disturbed negative feedback in the LHPA axis link to specific cognitive impairments in Alzheimers disease.

Atenolol in Secondary Prevention after Stroke

This study investigated the effect of 50 mg atenolol in reducing the risk of death, stroke and myocardial infarction after stroke and transient ischaemic attacks (TIA). The study was designed as a Swe

Prognosis after stroke in diabetic patients. A controlled prospective study.

SummaryCohorts of diabetic (n=121) and non-diabetic (n=584) patients were prospectively followed for up to ten years after having suffered from a stroke. All but six of the diabetic patients had Type 2 (non-insulin-dependent) diabetes mellitus. The diabetic patients had more risk factors associated with stroke: heart failure (p<0.001) and angina pectoris (p<0.001), than the non-diabetic patients. Neither body mass index nor blood pressure levels differed between the groups at admission. Haematocrit levels were higher in the diabetic group (p<0.01). The diabetic patients were more commonly afflicted by cerebral embolism and to a lesser extent by transient ischaemic attacks than the nondiabetic patients. When calculated by log-rank tests, the diabetic group had an increased risk of death (p<0.001), recurrent stroke (p=0.001), and of myocardial infarction (p=0.001) after the initial stroke. Autopsy-verified causes of death between the groups did not differ significantly, although half of all deaths during the period one to six months after stroke were caused by pulmonary embolism in the diabetic group. Thus, diabetes increases the risk of death after a stroke, and it also increases among stroke survivors the risk of recurrent stroke and myocardial infarction.

Motor and perceptual impairments in acute stroke patients: effects on self-care ability.

The relative importance of motor, perceptual, and some cognitive functions for self-care ability was analyzed in a representative sample of 109 subjects within 2 weeks of acute stroke. Forty-nine patients (45%) were dependent or partly dependent in self-care. Profound motor dysfunction was present in 39%, low-order perceptual deficits in 10%, high-order perceptual deficits in 60%, and disorientation in time and space in 13% of the patients. There was a significant covariation between motor function and self-care ability and between low-order perception and orientation function. Low-order and high-order perception covaried only weakly. Discriminant analyses showed that the actual level of self-care proficiency could be correctly predicted in 70% of the cases by the 4 indexes of motor function, low-order perception, high-order perception, and orientation. The dominating predictor was motor function, and the next highest was high-order perception. When a program for early training is designed with the aim to alleviate long-term self-care disability after stroke, correct assessment of motor and perceptual functions in the individual stroke patient is essential.

Acute Confusional States (Delirium) in Stroke Patients

Acute confusional states (ACS) were studied in 155 consecutive representative patients (mean age 73 years) with acute cerebrovascular disorders. Testing for ACS could be done in 94% of the patients. Sixty-nine of the 145 testable patients (48%) were acutely confused on admission or developed ACS within 7 days of admission. The mean age for the patients who developed ACS was 76 years compared with 69 years for patients without ACS (p