Biomedical subjects

B Winblad

Publications and source records attributed to B Winblad.

At least 127 records · Page 7Linked to original sources

PubMed1999

Early diagnosis of Alzheimer dementia based on clinical and biological factors.

Alzheimer's disease (AD) is common in elderly individuals; it causes distress for the patients and their relatives as well as large costs for the society. With the advent of symptomatic treatment at present and probable etiology-based cures in the future, it will be possible to relieve and put an end to these negative effects. Therefore, it is necessary to diagnose the disease as early as possible. In this review, we briefly summarize the state-of-the-art concerning various available clinical and biochemical methods for identifying AD. Increasing age, heritage, and presence of ApoE e4 allele have been confirmed as risk factors for AD as well as some putative factors (e.g., low education, hypertension, hypotension) based on epidemiological recent research. Selective impairment of episodic memory has been found to be a preclinical marker for future development of AD based on convergent data from asymptomatic AD-related mutation carriers, longitudinal studies of patients with mild cognitive impairment (MCI), and epidemiological studies of incident AD cases. Neurophysiological methods are inexpensive and useful for the identification of changes in brain dysfunction in AD and new promising methods are under development. Using magnetic resonance imaging (MRT), structural measurements of brain atrophy and specific brain structures such as the hippocampus have been reported to detect dementia development early in the course of disease. Similarly, functional measurements of brain activity (e.g., blood flow) have revealed that hypometabolism in bilateral parietotemporal brain areas early in the disease course. Finally, biochemical studies have demonstrated that certain proteins (e.g., tau the A beta 1-42/43 metabolite of the amyloid precursor protein) may be associated with the disease process in AD, although the specificity of these markers remains to be established. It is concluded that still no single marker of AD exists, which makes it necessary to rely on data from multiple sources in order to arrive at the best possible diagnosis of AD.

Age Factors↗

PubMed1999

The cost-effectiveness of donepezil therapy in Swedish patients with Alzheimer's disease: a Markov model.

This study compared the cost-effectiveness of donepezil, a new cholinesterase inhibitor indicated for the treatment of mild-to-moderate probable Alzheimer's disease (AD), with no treatment. A Markov state transition model was employed to simulate treatment costs based on Swedish epidemiologic data. The Markov states used in the model were defined according to cognitive function, as assessed by the Mini-Mental State Examination. Data on costs and baseline transition probabilities were taken from the Kungsholmen Project, an observational, population-based study of persons aged >75 years in Sweden. Data on the treatment effect were taken from a clinical trial comparing donepezil to placebo over 24 weeks and were applied to the baseline transition probabilities to assess the effect of treating the clinical manifestations of AD in Swedish patients. Also, a within-trial analysis was performed for comparison, using transition probabilities taken from the clinical study. Both models were run for 5 years in half-year cycles, and both demonstrated various degrees of cost savings and improved effectiveness, as measured by increased time in nonsevere disease states. Thus donepezil had superior cost-effectiveness compared with no treatment.

Aged↗

PubMed1999

Effects of environmental enrichment on cognitive function and hippocampal NGF in the non-handled rats.

In this study we examine whether exposure to differential housing after weaning would counteract the effects of postnatal handling (H) or nonhandling (NH) treatment by affecting learning and memory processes in young rats. In addition, we seek to determine if experience in enriched environment would alter hippocampal nerve growth factor (NGF) levels which is one of the factors known to be involved in the regulation of the survival and differentiation of developing basal forebrain neurones. Rats were either exposed to handling treatment, or left undisturbed starting day 1 after birth through day 21. After weaning on day 22, we exposed half of the H rats and half of the NH rats to environmental enrichment for 60 days. The other respective half of the rats was housed in isolated environmental condition (IC). Behavioural measures were taken in open field test, and spatial water maze test. Exposure to enriched environment following postnatal handling and nonhandling increased hippocampal NGF levels, and improved cognitive function in the both groups, with NH rats being more responsive to the effects of enrichment. Our results suggest that environmental enrichment has the potential to prevent or reduce the cognitive and neurochemical deficits in the adult animals associated with nonhandling.

Animals↗

PubMed1999

Nicergoline stimulates protein kinase C mediated alpha-secretase processing of the amyloid precursor protein in cultured human neuroblastoma SH-SY5Y cells.

We investigated the ability of the antidementia agents, nicergoline, aniracetam and hydergine to stimulate PKC mediated alpha-secretase amyloid precursor protein (APP) processing in cultured human neuroblastoma SH-SY5Y cells. Western immunoblotting of cell conditioned media using the Mabs 22C11 and 6E10 revealed the presence of 2 bands with molecular mass of 90 and 120 kDa, corresponding to possible alternatively glycosylated forms of secreted APP (APPs). Short-term (30 min and 2 h) treatment of cells with nicergoline gave an increased intensity of both bands, compared to non-treated cells. Maximal nicergoline effects, of the order of 150-200% over basal APPs release, were seen at concentrations between 1 and 10 microM. Under the same condition, 1 microM PdBu, used as a positive control, gave 500-1000% increases of basal APPs release. In contrast, aniracetam and hydergine, did not show any effect on APPs secretion. 2 h treatment with nicergoline had no effect on cellular full-length APP levels, as determined by immunoblotting of cell extracts with 22C11 and CT15 antibodies. Immunoblotting with PKC isoform specific antibodies of soluble and membrane fractions prepared from 2 h treated cells, showed that nicergoline (50 microM) and PdBu (1 microM) both induced translocation of PKC alpha, gamma and epsilon, but not PKC beta. The involvement of PKC in mediating nicergoline stimulated APPs release was also studied using specific inhibitors. 1 microM calphostin C, a broad range PKC inhibitor, significantly reduced both PdBu (1 microM) and nicergoline (10 microM) induced APPs release. In contrast, Go6976 (1 microM), a selective PKC alpha and beta1 inhibitor, as well as the cAMP-dependent protein kinase inhibitor, H89 (1 microM) were without effect. These results indicate that nicergoline can modulate alpha-secretase APP processing by a PKC dependent mechanism that is likely to involve the gamma and epsilon isoforms of this enzyme.

Amyloid Precursor Protein Secretases↗

PubMed1999

Co-localization of interleukin-1 receptor type I and interleukin-1 receptor antagonist with vasopressin in magnocellular neurons of the paraventricular and supraoptic nuclei of the rat hypothalamus.

Interleukin-1 receptor type I and interleukin-1 receptor antagonist were found in magnocellular neurons of the paraventricular and supraoptic nuclei of the rat hypothalamus by immunohistochemical detection. Double-labelling experiments revealed that both proteins occurred in vasopressin-containing neurons. A similar distribution pattern was observed in a group of vasopressin-positive accessory magnocellular neurons. Axons emanating from the interleukin-1 receptor type I- and interleukin-1 receptor antagonist-immunoreactive neuronal cell bodies could be seen within the hypothalamic nuclei, and varicosities expressing interleukin-1 receptor antagonist immunoreactivity were observed in the internal zone of the median eminence, as well as in the hypothalamo-pituitary projection. The co-localization of interleukin-1 receptor type I with vasopressin is in agreement with findings that interleukin-1 has a stimulatory effect on vasopressin synthesis and release. The hypothalamic neurons may serve as a source of interleukin-1 receptor antagonist to balance the effects of interleukin-1.

Animals↗

PubMed1999

Nucleus subputaminalis (Ayala): the still disregarded magnocellular component of the basal forebrain may be human specific and connected with the cortical speech area.

The small magnocellular group located within the rostrolateral extension of the basal forebrain was named and described as the nucleus subputaminalis in the human and chimpanzee brain by Ayala. Analysis of cytoarchitectonic and cytochemical characteristics of this cell group has been largely disregarded in both classical and more current studies. We examined the nucleus subputaminalis in 33 neurologically normal subjects (ranging from 15 weeks of gestation to 71 years-of-age) by using Nissl staining, choline acetyltransferase immunohistochemistry, acetyl cholinesterase histochemistry and nerve growth factor receptor immunocytochemistry. In addition, we applied reduced nicotinamide adenine dinucleotide phosphate-diaphorase histochemistry and calbindin-D28k immunocytochemistry in three neurologically normal subjects. At the most rostrolateral levels we describe the previously poorly characterized component of the lateral (periputaminal) subdivision of the subputaminal nucleus, which may be human specific since it is not described in non-human primates. Moreover, we find the human subputaminal nucleus best developed at the anterointermediate level, which is the part of the basal nucleus that is usually much smaller or missing in monkeys. The location of subputaminal cholinergic neurons within the frontal lobe, the ascension of their fibers through the external capsule towards the inferior frontal gyrus, the larger size of the subputaminal nucleus on the left side at the most rostral and anterointermediate levels and the most protracted development among all magnocellular aggregations within the basal forebrain strongly suggest that they may be connected with the cortical speech area. These findings give rise to many hypotheses about the possible role of the subputaminal nucleus in various neurodegenerative, neurological and psychiatric disorders, particularly Alzheimer's disease and primary progressive aphasia. Therefore, future studies on the basal forebrain should more carefully investigate this part of the basal nucleus.

Adolescent↗

PubMed1999

Immunohistochemical localization of interleukin-1beta, interleukin-1 receptor antagonist and interleukin-1beta converting enzyme/caspase-1 in the rat brain after peripheral administration of kainic acid.

The temporal and anatomical distribution of members of the interleukin-1 system in the rat brain following intraperitoneal kainic acid administration was studied in relation to neurodegeneration as detected with in situ end labelling. Kainic acid administration (10 mg/kg, i.p.) resulted in the induced expression of interleukin-1beta, interleukin- receptor antagonist and caspase-1p10 immunoreactivity in areas known to display neuronal and tissue damage upon excitotoxic lesions. The induction of these proteins was transient. Interleukin-1 immunoreactivity appeared at 5 h, and the interleukin-1 receptor antagonist-immunoreactive cells were first detected at 12 h, whereas the induction of caspase- 1p10 expression was first detected 24 h after kainic acid injection. Double labelling with the microglial marker Ox42 confirmed that both interleukin-1beta and interleukin-1 receptor antagonist were mainly localized in microglial cells. The regional distribution of in situ end-labelled neurons was similar to the distribution of cells expressing interleukin-1beta and interleukin-1 receptor antagonist, whereas the distribution of caspase-1 was more limited. The in situ end-labelled neurons, were, similarly to the interleukin-1beta-positive cells, first detected at 5 h, which is earlier than the induction of caspase-1. Our results show that the induction of IL-1beta and IL-1 receptor antagonist proteins after kainic acid are closely associated with the temporal as well as the anatomical distribution of in situ end-labelled neurons, whereas the induction of caspase-1 protein exhibited a delayed temporal profile and limited distribution. Since cytokine production occurs in activated microglial cells, the inflammatory component seems to be a strong mediator of this type of excitotoxic damage. The late onset of the caspase-1 expression would seem to indicate that this enzyme has no fundamental role in directly causing neuronal cell death induced by systemic kainic acid.

Animals↗

PubMed1999

Mortality from dementia in advanced age: a 5-year follow-up study of incident dementia cases.

Five-year follow-up of a community-based, 77+ old cohort including incident dementia cases was used to evaluate the impact of dementia on the risk of death, taking into account other chronic conditions potentially related to death, and contrasting Alzheimer's disease (AD), and vascular dementia (VaD). In this population, 70% of the dementia cases died during the five years after diagnosis, with a mortality rate specific for dementia of 2.4 per 100 person-years. After controlling for sociodemographic variables and comorbidity, 14% of all deaths could be attributed to dementia with a risk of death among demented subjects twice as high as that for non-demented people. Mortality risk ratios were 2.0 (95% confidence interval 1.5-2.7) for AD and 3.3 (95% confidence interval 2.0-5.3) for VaD. This study confirms that dementing disorders are a major risk factor for death. Even in the oldest old (85+), dementia shortens life, especially among women.

Aged↗

PubMed1999

Odor identification in normal aging and early Alzheimer's disease: effects of retrieval support.

Odor sensitivity and identification were examined in normal aging and early Alzheimer's disease (AD). The aims were to investigate AD as associated with lower odor sensitivity, odor identification as a function of retrieval support, and the relationship between global cognitive functioning (Mini-Mental State Exam [MMSE]; M. F. Folstein, S. E. Folstein, & P. R. McHugh, 1975) and olfactory performance. Results indicated intact odor sensitivity but deficient odor identification in AD. Both groups benefited from cues in identification, and the size of the gains was equally large in AD patients and controls. The finding of no selective benefit from retrieval support in AD suggests that a degradation of olfactory knowledge contributes to the odor identification deficits in these patients. MMSE and identification were positively related, whereas MMSE and olfactory sensitivity were unrelated. These findings suggest that the AD-related olfactory impairment stems from lesions in cortical rather than peripheral structures.

Aged↗

PubMed1999

CADASIL: hereditary disease of arteries causing brain infarcts and dementia.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) begins with migraine with aura in approximately one-third of the patients. More severe symptoms of recurrent strokes usually appear at 30-50 years of age. However, well before the first stroke, CADASIL may be diagnosed on the basis of characteristic hyperintensities in T2-weighted magnetic resonance images. Multiple lacunar infarcts located mainly in the basal ganglia and frontal white matter lead to a cognitive decline and finally to dementia. These infarcts result from a thickening and fibrosis of the walls of the small and medium-sized penetrating arteries with consequent obliteration and/or thrombosis. Although the symptoms are almost exclusively neurological, the arteriopathy is generalized. Thus, basophilic, periodic acid-Schiff-positive and, in electron microscopy, osmiophilic material accumulates between degenerating smooth muscle cells. This occurs even in dermal arteries, which renders skin a useful target for diagnostic biopsy. Presently, no specific therapy is available. CADASIL is caused by missense point mutations in the Notch3 gene, which encodes a transmembrane receptor protein. Each gene defect leads to either a gain or loss of a cysteine residue in the extracellular, N-terminal domain of the molecule, which most probably results in conformational alteration. The function of Notch3 in adults and the pathogenesis of CADASIL are still unknown.

Cerebral Arterial Diseases↗

PubMed1999

Change of outlook on elderly persons with dementia: a study of trainees during a year of special education.

In 1996 the Silvia Home Foundation started a non-governmental education programme with an integrated day-care unit devoted to patients with dementia: Working chairwoman of the foundation is HM Queen Silvia of Sweden. This study aims to describe the trainees' changed outlook on elderly people with dementia during a year of special education. Data were collected by interviews, informal discussions and participant observations during the lessons. The investigation focused on two questions: the trainees' outlook on the patients and their outlook on the work with the patients. At the beginning of their education, the trainees looked at the patients from a staff's perspective. During their education, this was gradually toned down and they changed to a disease perspective, and eventually to a human dignity perspective. After initially seeing dementia patients as a homogeneous group, the trainees went on to see them as unique human beings. Their outlook on their work also changed, from being task-oriented to a more humanitarian approach.

Adult↗

PubMed1999

Stroke patients ready for discharge from acute care--a multi-dimensional assessment of functions and further care.

PURPOSE: The aim of this study was to describe actual functions, performance of activities and needs of further care in patients with stroke in acute care wards at the time the physicians decided that the patients were ready for discharge, in relation to placement after discharge and the motives for the decision. METHOD: Thus 114 stroke patients in Stockholm County were assessed with the Resident Assessment Instrument, and the motives for further care were reviewed in the patients' case records. RESULTS: The results showed that the oldest, most severely impaired stroke patients had the shortest mean length of stay before the physician considered the patients ready for discharge to nursing homes, where resources for long-term rehabilitation and stroke care vary. CONCLUSION: It is important to secure continuing adequate care and rehabilitation for elderly severely impaired stroke patients being discharged early from acute care hospitals.

Aged↗

PubMed1999

Hypophysectomy enhances interleukin-1beta, tumor necrosis factor-alpha, and interleukin-10 mRNA expression in the rat brain.

Although the effects of various cytokines as regulators of hormone synthesis and production are well documented, the role for pituitary hormones as modulators of cytokine synthesis is not fully understood. In this study, we investigated the effect of pituitary hormones' depletion on cytokine synthesis after short- (21 days) and long- (35 days) term hypophysectomy (ST-HX and LT-HX, respectively). The expresssion of the proinflammatory cytokine interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) and the anti-inflammatory cytokines IL-10 and transforming growth factor-beta (TGF-beta) in the rat brain was studied using in situ hybridization. Our results indicate that IL-1beta mRNA-expressing cells were significantly upregulated at day 21 in hypophysectomized rats compared to sham-operated controls. This enhanced expression was also detected later at day 35 post hypophysectomy. However, TNF-alpha mRNA expression was significantly increased only at the later sampling interval. IL-10 mRNA-expressing cells were increased after long-term hypophysectomy compared to controls. TGF-beta mRNA-expressing cells were not increased after hypophysectomy. In conclusion, these results suggest a role for pituitary hormones in IL-1beta, TNF-alpha, and IL-10 synthesis.

Analysis of Variance↗

PubMed1999

Activity patterns in very old people: a survey of cognitively intact subjects aged 90 years or older.

AIM: to measure activity patterns in very old people, the factors related to this and the association of different types of activity with well-being. METHODS: a study of 105 people, aged 90 years or older, who were not cognitively impaired, living in Stockholm. The activities carried out during the previous day were recorded and each activity was rated. RESULTS AND CONCLUSIONS: the degrees of intellectual, social and physical activity are independent of each other. Very elderly people tended to have variable but relatively low activity levels over a day. Good health and not moving home were associated with greater intellectual activity. Extraversion and negative life events (such as death of close friend or family member) were associated with greater social activity, while relatively younger age and better health were associated with greater physical activity. There was positive association between physical activity and well-being.

Activities of Daily Living↗

PubMed1999

Distribution of active glycogen synthase kinase 3beta (GSK-3beta) in brains staged for Alzheimer disease neurofibrillary changes.

Accumulation of paired helical filaments (PHFs) in neurofibrillary tangles, neuropil threads, and dystrophic neurites is one of the major neuropathological hallmarks of Alzheimer disease (AD). The principal protein subunit of PHFs is the abnormally hyperphosphorylated tau. Glycogen synthase kinase 3beta (GSK-3beta) is one of the candidate kinases involved in PHF-tau formation. To play a role in PHF-tau formation, it would be expected that GSK-3beta is active in tangle bearing neurons. In the present study, we investigated the regional and intracellular distributions of active and inactive forms of GSK-3beta in brains staged for neurofibrillary changes. We found that neurons with tangle-like inclusions positive for active, but not inactive, GSK-3beta appear initially in the Pre-alpha layer of the entorhinal cortex and extend to other brain regions, coincident with the sequence of the development of neurofibrillary changes. Active, but not inactive, GSK-3beta was found to initially accumulate in the cytoplasm of pretangle neurons. These data provide direct in situ evidence that is consistent with the involvement of GSK-3beta in PHF-tau formation.

Adult↗

PubMed1999

Low blood pressure and incidence of dementia in a very old sample: dependent on initial cognition.

OBJECTIVE: To examine whether initially low blood pressure is related to the incidence of dementia. DESIGN: A population-based prospective study. SETTING: The Kungsholmen district of Stockholm, Sweden PARTICIPANTS: Three hundred four nondemented subjects aged 75 to 96 years at baseline. MEASUREMENTS AND MAIN RESULTS: After an average of 3 years, 81 dementia cases were identified (67 with Alzheimer's disease cases). Compared with individuals with baseline systolic pressure of 141 to 179 mm Hg, those with systolic pressure < or = 140 mm Hg had a significantly higher risk of dementia (relative risk (RR) = 1.9, 95% confidence interval (CI), 1.2-3.2) and Alzheimer's disease (RR = 2.2, 95% CI, 1.2-3.8). However, the RR in relation to systolic pressure < or = 140 mm Hg was 1.3 (0.8-2.2) for all dementia and 1.5 (0.8-2.6) for Alzheimer's disease, when the baseline Mini-Mental State Examination (MMSE) score was included in the model as a dichotomous variable (< 24 vs > or = 24). Baseline MMSE < 24 significantly predicted the occurrence of dementia (RR = 6.9; 95% CI, 4.3-11.1). Systolic pressure < or = 140 mm Hg was significantly related to MMSE score < 24 at baseline. CONCLUSIONS: These data suggest that low blood pressure may be an early correlate of a dementing process although a causative effect cannot be definitely ruled out.

Aged↗

PubMed1999

Prevalence and incidence of clinically diagnosed memory impairments in a geographically defined general population in Sweden. The Piteå Dementia Project.

In the Piteå River Valley all persons with memory impairment that interferes with normal life are referred to one hospital department for clinical workup and diagnosis. 619 patients were assessed in the department during the years 1990-1995. Of these, 36.9% had Alzheimer's disease (AD), 30.4% had vascular dementia (VaD), 3.0% had a mixed AD/VaD, 3.2% had frontotemporal dementia and 5.3% had other forms of dementia. Another 7% had memory impairment but no dementia. The overall mean annual incidence rate of clinically relevant dementia was 295/100,000 persons at risk and the mean prevalence rate was 755/100,000 persons. For persons 65 years and older the incidence and prevalence rates were 840 and 2,150/100,000 persons, respectively. This means that annually, approximately 300 persons/100,000 population over the age of 40 need medical attention or social services.

Adult↗

PubMed1999

Costs of Mini Mental State Examination-related cognitive impairment.

OBJECTIVE: To investigate the relationship between cognitive impairment, measured with the Mini Mental State Examination (MMSE), and the cost of care. DESIGN: The study uses data from the Kungsholmen project, a population-based study in Sweden in which people 75 years and older were observed over time. The initial study population (n = 1810) was divided into 4 health states based on the MMSE. A Markov model was constructed from the transition probabilities between different states between the first and second phases of the study. The expected cost of cognitive impairment for a period of 10 years was estimated for the cohort of patients studied. MAIN OUTCOME MEASURES AND RESULTS: There was a strong correlation between cognitive impairment in terms of the MMSE and the annual cost of care. A multivariate statistical analysis showed that a decrease in the MMSE by 1 point was associated with an increase in the cost of care of 15,000 Swedish kronor (SEK) [$US2000; 1995 values]. CONCLUSIONS: The results show that large savings are possible if the decline in cognitive functioning can be prevented. The model developed can be used to estimate the impact on cost of care of treatments which reduce the cognitive decline in patients with Alzheimer's disease.

Aged↗