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Biomedical subjects

B Winblad

Publications and source records attributed to B Winblad.

At least 181 records · Page 10Linked to original sources
PubMed1998

Cerebrospinal fluid tau protein as a biochemical marker for Alzheimer's disease: a community based follow up study.

OBJECTIVES: Biochemical markers for Alzheimer's disease would be of great value, especially to help in diagnosis early in the course of the disease. A pronounced increase in CSF tau protein (CSF-tau) is found in most patients with Alzheimer's disease. However, the specificity has to be further studied, as an increase in CSF-tau has also been found in other dementias, especially in vascular dementia. As most previous CSF studies have been based on selected inpatients, it was considered of special interest to examine the diagnostic potential of CSF-tau in a community population based sample of consecutive patients with dementia. Such patient material has been examined at the Piteå River Valley Hospital in Northern Sweden since 1986, and includes all those with memory disturbances in the community. The aim was also to study if an increase in CSF-tau is found early in the disease process, and whether CSF-tau changes during the progression of disease. METHODS PARTICIPANTS: Community population based sample of 75 demented patients (43 with Alzheimer's disease, 21 with vascular dementia, and 11 with mixed Alzheimer's disease/vascular dementia), 18 healthy subjects, and 18 neurological controls. A follow up investigation (including analysis of a new CSF sample) was performed in all patients after about one year. MAIN OUTCOME MEASURES: Concentrations of total (both normal tau and PHF-tau) tau in CSF, clinical measures (duration and severity of dementia), and apoE polymorphism. RESULTS: CSF-tau was markedly increased in Alzheimer's disease, 41/43 (95%) patients had values above the cut off level (mean+2 SD) in controls (306 pg/ml). High CSF-tau concentrations were also found in most patients with vascular dementia, preferentially in patients with vascular dementia without progressive leukoaraiosis on CT, whereas patients with vascular dementia with progressive leukoaraiosis had normal CSF-tau. Concentrations of CSF-tau were stable at one year follow up in both patients with Alzheimer's disease and patients with vascular dementia, and there was no correlation between CSF-tau and either duration or severity of dementia. CONCLUSIONS: The findings confirm the high sensitivity of CSF-tau for the diagnosis of Alzheimer's disease, but high CSF-tau was also found in vascular dementia, resulting in a lower specificity. However, high CSF-tau is preferentially found in patients with vascular dementia without progressive leukoaraiosis, which may constitute a group with concomitant Alzheimer's disease pathology. High CSF-tau may be present during the whole course of the disease in Alzheimer's disease. Possibly, therefore, the same high CSF-tau concentrations may be present before the onset of clinical dementia. Follow up studies on such patients will tell whether analysis of CSF-tau is useful as a biochemical marker for early Alzheimer's disease.

Aged↗
PubMed1998

Association of stroke with dementia, cognitive impairment, and functional disability in the very old: a population-based study.

BACKGROUND AND PURPOSE: Stroke is a major cause of disability in the elderly and is also related to the development of dementia, which is another important source of disability in old age. The aim of the present study was to examine the potential impact of stroke on cognitive and functional status in a community-based cohort of individuals aged 75 years and older. METHODS: The data were derived from a cross-sectional survey on aging and dementia that included all inhabitants of the Kungsholmen district in central Stockholm who were aged >/=75 years. Cases of stroke were identified through the computerized inpatient register system that has been widely used to study stroke in Sweden. Dementia was defined according to the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised. Dementia onset was considered the appearance, according to an informant, of the first symptom. Cognitive impairment without dementia was defined as the presence of a Mini-Mental State Examination score of <24 and the absence of dementia. Functional disability was assessed according to Katz Index of independence in activities of daily living. RESULTS: The prevalence of stroke was 10. 0% in men and 8.0% in women. One third of stroke survivors were diagnosed as demented, which was 3 times higher than those without stroke: adjusted odds ratio (OR) was 3.6 (95% confidence interval, 2. 5 to 5.8). Stroke was also significantly related to cognitive impairment without dementia (adjusted OR, 2.4 [95% confidence interval, 1.3 to 4.6]). The population-attributable risks of dementia and cognitive impairment in relation to stroke were 18.4% and 8.5%, respectively. Among the 49 stroke patients with dementia, 15 cases (30.6%) had missing information on dementia onset, 22 (44. 9%) had been reported by the informant to have dementia-related symptoms after or close to the occurrence of stroke, and 12 (24.5%) had symptoms before stroke occurrence. The prevalence rates of disability in activities of daily living were much higher among stroke patients than among stroke-free subjects, even after adjustment for age, sex, heart disease, hip fracture, and dementia: the corresponding adjusted ORs for bathing, dressing, toileting, transfer, and continence were 3.5 (2.4 to 5.3), 2.2 (1.4 to 3.3), 3. 0 (2.0 to 4.5), 3.3 (1.9 to 5.7), and 2.1 (1.3 to 3.3), respectively. After dementia and hip fracture, stroke was the third largest contributor to disability in bathing, dressing, and transfer. Stroke was the second contributor to disability in toileting. CONCLUSIONS: Stroke is strongly associated with dementia, although it may relate to dementia in different ways: it can be the main cause or a precipitating factor of dementia, or they may share common etiological bases. Together with dementia and hip fracture, stroke is a major contributor to disability in most aspects of activities of daily living in very old people.

Activities of Daily Living↗
PubMed1998

Preclinical symptoms of major depression in very old age: a prospective longitudinal study.

OBJECTIVE: The authors' goal was to examine whether individuals diagnosed as having major depression experienced greater levels of depressive symptoms and cognitive dysfunction up to 3 years before the clinical diagnosis was rendered. METHOD: The study included 185 subjects 75 years old or older who participated in a population-based longitudinal survey in Stockholm. Ten of the subjects were diagnosed as depressed up to 3 years after initial screening, and these individuals were compared with the 175 subjects who were not depressed at 3-year follow-up. Depression was diagnosed according to DSM-III-R and DSM-IV criteria. Psychiatric signs and symptoms were assessed by physicians using a structured interview. Cognitive functioning was assessed with the Mini-Mental State. RESULTS: At the initial screening, the patients later diagnosed as depressed had a greater number of depressive symptoms, such as dysphoria and appetite disturbance, and their symptoms were also more severe than those of the nondepressed subjects. Moreover, the depressed subjects suffered from a more severe lack of interest and psychomotor disturbance and had lower Mini-Mental State scores. CONCLUSIONS: There are preclinical markers for individuals who will become depressed after a 3-year interval. Major depression may have a more chronic nature in very old age, in contrast to the relatively short clinical onset of depression seen in younger adults. The authors conclude that standard diagnostic instruments such as DSM-IV may have to take this lengthy course of impairment into consideration when dealing with very old adults.

Adult↗
PubMed1998

Dementia is the major cause of functional dependence in the elderly: 3-year follow-up data from a population-based study.

OBJECTIVES: The purpose of this investigation was to study the role of dementia and other common age-related diseases as determinants of dependence in activities of daily living (ADL) in the elderly. METHODS: The study population consisted of 1745 persons, aged 75 years and older, living in a district of Stockholm. They were examined at baseline and after a 3-year follow-up interval. Katz's index was used to measure functional status. Functional dependence at baseline, functional decline, and development of functional dependence at follow-up were examined in relation to sociodemographic characteristics and chronic conditions. RESULTS: At baseline, factors associated with functional dependence were age, dementia, cerebrovascular disease, heart disease, and hip fracture. However, only age and dementia were associated with the development of functional dependence and decline after 3 years. In a similar analysis, including only nondemented subjects. Mini-Mental State Examination scores emerged as one of the strongest determinants. The population attributable risk percentage of dementia in the development of functional dependence was 49%. CONCLUSIONS: In a very old population, dementia and cognitive impairment make the strongest contribution to both the development of long-term functional dependence and decline in function.

Activities of Daily Living↗
PubMed1997

Reactions to predictive testing in Huntington disease: case reports of coping with a new genetic status.

A predictive testing program for Huntington disease has been available in Stockholm, Sweden since October 1990. Psychosocial assessments were performed throughout the testing program to evaluate the impact of the risk situation itself and the effect of predictive testing, and to identify those individuals who were most vulnerable to severe stress and anxiety reactions. All subjects underwent neurological, neuropsychological, and psychiatric examinations. Individuals undergoing predictive testing were assessed twice by a genetic counsellor before receiving their results, and at 10 days (gene carriers only) and then 2, 6, 12, and 24 months after receiving the results. The process of coping with the test results and the psychological adjustment to knowledge about new genetic status have been shown to vary considerably. In this report, we describe the results obtained from two gene carriers and two noncarriers. The four persons chosen represent different ways of coping with the outcome of the test and of integrating knowledge about their genetic status into everyday life. These cases illustrate common themes and recurrent problems often surfacing during the counselling and testing process. The longitudinal evaluations provide information about the impact, adaptation, and long-term effects of living with a new genetic status.

Adaptation, Psychological↗
PubMed1997

Depression and dementia in relation to apolipoprotein E polymorphism in a population sample age 75+.

The aim of this study was to define the co-occurrence of depression and dementia in relation to apolipoprotein E (APOE) polymorphism. Physicians extensively examined 806 persons aged 78 years and over. DNA was extracted from peripheral white blood cells, and APOE genotype was determined using a microsequencing method on microtiter plates. The prevalence of dementia was 22.8% and was found to increase with the number of epsilon 4 alleles present. Depression was found in 11.4% of the demented subjects compared to 3.5% of the nondemented subjects. The overrepresentation of depression in demented subjects was found for each of the common genotypes. Depression was not strongly associated with APOE polymorphism. In spite of the association between dementia and APOE polymorphism, as well as dementia and depression, there was no association between APOE polymorphism and depression.

Aged↗
PubMed1997

Progesterone, 5alpha-pregnane-3,20-dione and 3alpha-hydroxy-5alpha-pregnane-20-one in specific regions of the human female brain in different endocrine states.

Post-mortem concentrations of progesterone, 5alpha-pregnane-3,20-dione (5alpha-DHP) and 3alpha-hydroxy-5alpha-pregnane-20-one (allopregnanolone) were measured in 17 brain areas and serum in five fertile and five postmenopausal women. Steroid concentrations were measured with radioimmunoassay after extraction of brain tissue with ethanol and purification with celite chromatography. There were regional differences in brain concentrations of all three steroids. The highest progesterone levels were noted in the amygdala, cerebellum and hypothalamus and the highest levels of 5alpha-DHP and allopregnanolone were seen in the substantia nigra and basal hypothalamus. Brain concentrations of all three steroids were significantly higher in the fertile women in luteal phase compared to their postmenopausal controls (P < 0.01). In general, the study showed that there is a variation in brain concentrations depending on ovarian steroid production, indicating that the secretion pattern during the menstrual cycle is reflected in the brain. However, regional differences in brain steroid levels imply local mechanisms for steroid uptake and binding as well. Investigations of gonadal steroid distributions in the human brain might be of importance considering the actions of these steroids in the central nervous system. Such studies could provide information about physiological mechanisms, such as the ovulation, and also form a baseline for comparative studies of normal and pathological conditions involving steroids, for instance, catamenial epilepsy and the premenstrual tension syndrome.

5-alpha-Dihydroprogesterone↗
PubMed1997

Autoradiographic characterization of [3H]cGMP binding sites in the rat brain.

Quantitative autoradiography was used to characterize and localize [3H]cGMP binding sites in the rat brain. [3H]cGMP binding was found to be pH-sensitive (with two optima at 7.4 and 5.0) and Mg2+-dependent. At pH 7.4, the binding was dependent on inclusion of the phosphodiesterase inhibitor IBMX. In contrast, at pH 5.0, IBMX had little effect on binding. The binding of [3H]cGMP was reversible and saturable with a Kd of 22 nM at pH 7.4 and 36 nM at pH 5.0. Bmax values were 172 fmol/mg at pH 7.4 and 462 fmol/mg at pH 5.0. [3H]cGMP binding was inhibited by cGMP and its analogues, with cGMP and cAMP being the most potent at pH 7.4 and cGMP and 8-Br-cGMP being the most potent at pH 5.0. Using an extracellular pH 7.4 buffer, the selective cGMP-dependent protein kinase (PKG) inhibitor Rp-8pCPT-cGMPS had very little effect on [3H]cGMP binding. In contrast, with a cytosolic pH 5.0 buffer, Rp-8pCPT-cGMPS displaced binding in the cerebellum. This indicates that PKG is localized in the cerebellum, and that the binding to PKG is favored under cytosolic conditions. Autoradiographic localization of [3H]cGMP binding sites revealed a heterogeneous distribution with the highest densities in the substantia nigra and interpeduncular nucleus. High densities were also observed in the basal ganglia, the medial habenular nucleus, the frontoparietal cortex, the lateral amygdaloid nucleus and the subiculum. It is concluded that the nature of [3H]cGMP binding is complex, with one site probably being related to cytosolic PKG mainly found in the cerebellum, and one site probably representing cGMP-stimulated phosphodiesterase mainly located in the forebrain.

1-Methyl-3-isobutylxanthine↗
PubMed1997

Blood pressure and performance on the Mini-Mental State Examination in the very old. Cross-sectional and longitudinal data from the Kungsholmen Project.

The authors examined the association of blood pressure with cognitive function as assessed by the Mini-Mental State Examination (MMSE) in a community-based Swedish cohort of 1,736 people aged 75-101 years. Age, sex, education, antihypertensive medication use, heart disease, and stroke were considered as covariates. Multiple linear regression analysis indicated that both systolic and diastolic blood pressure, measured in 1987-1989, were positively and significantly related to baseline MMSE score; baseline systolic pressure was also positively and significantly related to follow-up MMSE score, measured after an average period of 40.5 months among subjects who were not taking antihypertensive medication at baseline. Furthermore, in the nontreated group, multiple logistic regression showed that individuals with a baseline systolic pressure less than 130 mmHg had an odds ratio of 1.88 (p = 0.05) for follow-up cognitive impairment (MMSE score < 24) compared with those whose systolic pressure was 130-159 mmHg. An increased but not statistically significant risk of cognitive impairment was associated with high blood pressure (systolic pressure > or = 180 mmHg or diastolic pressure > or = 95 mmHg) only in persons taking antihypertensive medication at baseline. Subjects with systolic pressure of 160-179 mmHg tended to be at lower risk of cognitive impairment. These results may support the view that a certain blood pressure level, particularly a systolic pressure of at least 130 mmHg, is important to the maintenance of cognitive functioning in the very old. They also suggest that severe hypertension that is not well controlled (systolic pressure > or = 180 mmHg or diastolic pressure > or = 95 mmHg) is still a threat to cognitive function in this age group. However, the use of blood pressure measurements made at a single visit and the relatively short follow-up period should be considered when interpreting these results.

Aged↗
PubMed1997

Decreased beta-adrenoceptor-stimulated adenylyl cyclase activity in lymphocytes from Alzheimer's disease patients.

Previous studies have shown that in Alzheimer's disease post-mortem brain there are disruptions of both beta1-adrenoceptor-G-protein coupling and G-protein stimulation of adenylyl cyclase activity. Decreased beta-adrenoceptor stimulated adenylyl cyclase activity has also been shown in Alzheimer's disease primary skin fibroblasts. In the present study, we determined the regulation of adenylyl cyclase in Alzheimer's disease patients using an easily accessible tissue source, namely peripheral blood lymphocytes. beta-Adrenoceptor- and forskolin-stimulated adenylyl cyclase activities were investigated in lymphocytes from 12 Alzheimer's disease and 12 carefully matched and selected control subjects. No significant differences were found in basal or forskolin-stimulated enzyme activities between Alzheimer's disease and control lymphocytes. In contrast, isoprenaline-stimulated adenylyl cyclase activities were significantly lower in the Alzheimer's disease groups, as compared to controls. These results indicate that there is a widespread disruption of beta-adrenoceptor-G-protein-enzyme coupling in different tissues from Alzheimer's disease patients, and that adenylyl cyclase disturbances previously reported in Alzheimer's disease brain do not occur as a consequence of disease pathology or of terminal illness.

Adenylyl Cyclases↗
PubMed1997

Volume and number of neurons of the human hippocampal formation in normal aging and Alzheimer's disease.

In order to observe changes owing to aging and Alzheimer's disease (AD) in the volumes of subdivisions of the hippocampus and the number of neurons of the hippocampal formation, 18 normal brains from subjects who died of nonneurological causes and had no history of long-term illness or dementia (ten of these brains comprised the aged control group) and 13 AD brains were analyzed. An optimized design for sampling, measuring volume by using the Cavalieri principle, and counting the number of neurons by using the optical disector was implemented on 50 microns-thick cresyl-violet sections. The mean total volume of the principal subdivisions of the hippocampal formation (fascia dentata, hilus, CA3-2, CA1, and subiculum) showed a negative correlation with age in normal subjects (r = -0.56, 2P < 0.05), and a 32% mean reduction in the AD group compared with controls (P < 0.001). This finding supports the measurement of the coronal cross-sectional area and the volume of the hippocampal formation in the clinical diagnosis of AD. There was an inverse relationship between the age of normal subjects and the number of neurons in CA1 (r = -0.84, 2P < 0.0001) and subiculum (r = -0.49, 2P < 0.05) but not in other subdivisions. Pronounced AD-related reductions in neuron number were found only in the subiculum and the fascia dentata. Compared with controls, both losses represented 23% of neurons (P < 0.05). These results 1) confirm that AD is a qualitatively different process from normal aging and 2) reveal the regional selectivity of neuron loss within the hippocampal formation in aging and AD, which may be relevant to understanding the mechanisms involved in the neuron loss associated with the two processes.

Adolescent↗
PubMed1997

Expression of MHC class II CD4+ and ED1 molecules in association with selective hippocampal neuronal degeneration after long-term adrenalectomy.

The neuroendocrine and the immune systems are interconnected. Monoclonal antibodies against major histocompatibility complex (MHC) class I, class II, CD4, CD8, pan T cells, and macrophages were used for immunostaining brains from adrenalectomized (ADX) and shamoperated rats to investigate the potential involvement of the immune/inflammatory mechanisms in the neurodegeneration of hippocampus after ADX. Our results demonstrate upregulation of MHC class II, CD4 antigens and activated microglial marker-ED1 expression selectively in the hippocampus after ADX. The absence of CD5 reactivity precludes that these activated cells were T lymphocytes. The activated microglial cells may either be instrumental in the hippocampal neuronal loss or activated secondarily to the neuronal degeneration after long-term adrenalectomy.

Adrenalectomy↗
PubMed1997

No difference in cerebral glucose metabolism in patients with Alzheimer disease and differing apolipoprotein E genotypes.

BACKGROUND: Recent findings of a reduced cerebral metabolic rate of glucose (CMRGlu) in at-risk relatives of patients with Alzheimer disease (AD) who carry the apolipoprotein E (APOE) epsilon 4 allele suggest a causative role for the E4 isoform in cognitive changes that lead to AD. It is not known whether epsilon 4 allele-associated deficits exist in patients with clinical AD. OBJECTIVE: To determine whether distinct patterns of cerebral hypometabolism exist in patients who carry the epsilon 4 allele. PATIENTS AND METHODS: Information on the CMRGlu and APOE genotype was available for 46 patients at a memory disorders clinic: 31 patients were diagnosed as having probable AD, 3 demented patients did not meet criteria for AD, and 12 patients had mild memory complaints. Positron emission tomography with the use of 18F-fludeoxyglucose was used to calculate the CMRGlu in the frontal and temporoparietal regions of the cortex. Estimates were standardized to the sensorimotor area of the cortex. Linear regression models were constructed to relate the APOE genotype to the CMRGlu, adjusting for cognitive status (ie, the Mini-Mental State Examination score). RESULTS: Distinct patterns of the CMRGlu did not emerge for patients with different APOE genotypes. Bilateral deficits in the CMRGlu were found in the patients with AD. Left-right asymmetry was found in 8 of 12 patients with mild memory complaints: 7 of 8 had CMRGlu ratio less than 0.85 in the left side of the temporoparietal region of the cortex. CONCLUSIONS: The APOE epsilon 4 allele does not appear to be associated with specific deficits in brain metabolism in patients with AD despite evidence that the epsilon 4 allele is associated with preclinical alterations. This finding is consistent with previous epidemiologic results that have demonstrated a higher risk for AD in carriers of the epsilon 4 allele, but no change in the rate of progression of AD.

Adult↗