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Biomedical subjects

B Winblad

Publications and source records attributed to B Winblad.

At least 217 records · Page 12Linked to original sources
PubMed1997

Apolipoprotein E epsilon4 allele decreases functional connectivity in Alzheimer's disease as measured by EEG coherence.

OBJECTIVES: The epsilon4 allele of apolipoprotein E (APOE) represents a major biological risk factor for late onset Alzheimer's disease. However, it is still not known whether the APOE genotype affects the progression of the disease, assessed by different functional methods. METHODS: The study sample included 41 patients with probable Alzheimer's disease. Subjects had similar severity of disease, age of onset, and duration of illness, and were subcategorised according to their APOE genotypes: 17 with no epsilon4 allele, 14 with one epsilon4 allele, and 10 with two epsilon4 alleles. The control group consisted of 18 healthy subjects comparable with the patients in age and education. Analysed quantitative EEG (qEEG) variables were the ratio of alpha and theta absolute power and EEG coherence in alpha frequency band, representing major cortical association pathways. RESULTS: There was pronounced EEG slowing in all three patient subgroups compared with the controls for the alpha/theta ratio, but there was no significant difference across the patient subgroups. Patients homozygous for the APOE epsilon4 allele had reduced right and left temporoparietal, right temporofrontal, and left occipitoparietal coherence. Patients without and with one epsilon4 allele showed an overlap between the control group and group with two epsilon4 alleles in coherence measures. CONCLUSIONS: APOE epsilon4 does not influence EEG slowing, an index which reflects severity of the disease in patients with Alzheimer's disease, but seems to be associated with selective decreases in functional connectivity as assessed by EEG coherence. This finding might be of clinical importance when considering different pathogenetic mechanisms.

Age of Onset↗
PubMed1997

Altered neurotransmission and signal transduction: targets for nicergoline treatment.

Although we do not yet have a complete understanding of the molecular mechanisms responsible for the pathophysiology of Alzheimer's disease, it is clear that a drug such as nicergoline, which may have both acute and longer-term effects on the disease, could offer a beneficial and worthwhile approach to treatment.

Adrenergic alpha-Antagonists↗
PubMed1997

Growth hormone stimulates production of interferon-gamma by human peripheral mononuclear cells.

There is substantial evidence for interactions between the immune and endocrine systems at different levels. In the present study we investigated whether human growth hormone (hGH) could stimulate proliferation of interferon-gamma-secreting cells (IFN-gamma-SC), and production of IFN-gamma. Human peripheral blood mononuclear cells (PBMC) taken from 15 normal subjects were incubated with varying doses (200,400,600 and 800 ng/ml) of recombinant hGH. Samples of cells were also incubated with PBS buffer (without hGH) to serve as controls. Effects of hGH were studied by enumerating IFN-gamma-SC and by measuring the concentration of IFN-gamma using an Immunospot assay and an enzyme-linked immunosorbent assay, respectively. The results showed that hGH significantly increased both the number of IFN-gamma-SC and the concentration of IFN-gamma in a dose-dependent manner. The maximum effects were obtained in the presence of (400 ng/ml) hGH (15 +/- .5 IFN-gamma-SC/10(6) PBMC and 300 +/- 55 U/ml IFN-gamma) compared to controls (4 +/- 2 IFN-gamma-SC/10(6) PBMC and 50 +/- 10 U/ml IFN-gamma). The results of the present study suggest that hGH might influence the immune system by stimulating the proliferation of IFN-gamma-SC and the production of IFN-gamma.

Human Growth Hormone↗
PubMed1997

Daughters and sons as caregivers for their demented and non-demented elderly parents. A part of a population-based study carried out in Sweden.

The study focuses on adult children (n = 81) having the main responsibility for parents with dementia (study group). They were compared with children (n = 102) of non-demented parents (reference group). The children were interviewed about burden experienced. The interviews also secured information about the children's co-operation with the informal and formal network and their willingness to remain as caregivers during the progression of the disease or ageing process. The results showed that the daughters reported feeling more affection in their caregiving role than the sons. About one third of the participants in the study could not get relief from someone else. Eighty-nine per cent of the children in the study group and 76% of the children in the reference group were not willing to care for their parents in the family home during the progression of the disease, even if they were employed as caregivers.

Adult↗
PubMed1997

Very old women at highest risk of dementia and Alzheimer's disease: incidence data from the Kungsholmen Project, Stockholm.

OBJECTIVE: To determine the incidence of different types of dementia in the very old, and to explore the relation with age and gender. DESIGN: A dementia-free cohort was followed for an average of three years in Stockholm, Sweden. At the end of the follow-up, the subjects were interviewed by nurses, clinically examined by physicians, and cognitively assessed by psychologists. Deceased cohort members were studied using death certificates, hospital clinical records, and discharge diagnoses. Dementia diagnoses were made according to the DSM-III-R criteria independently by two physicians. PARTICIPANTS: The cohort consisted of 1,473 subjects (75+ years old), of which 987 were clinically examined at follow-up, 314 died before the examination, and 172 refused to participate. RESULTS: During the follow-up, 148 subjects developed dementia. In the age-group 75 to 79, the incidence rates for dementia were 19.6 for women and 12.4 for men per 1,000 person-years, whereas for 90+ year-old subjects the corresponding figures were 86.7 and 15.0 per 1,000 person-years. A similar pattern of distribution by age and gender was seen for Alzheimer's disease. In each age stratum, the incidence rates of dementia and Alzheimer's disease were higher for women than for men. The age-adjusted odds ratio for women was 1.9 for dementia and 3.1 for Alzheimer's disease. CONCLUSIONS: (1) The incidence of dementia increases with age, even in the oldest age groups; (2) women have a higher risk of developing dementia than men, especially at very old ages; (3) this pattern is mainly due to the age and gender distribution of Alzheimer's disease, rather than vascular dementia.

Age Factors↗
PubMed1997

Low blood pressure and five-year mortality in a Stockholm cohort of the very old: possible confounding by cognitive impairment and other factors.

OBJECTIVES: Low blood pressure has often been reported to be related to excess mortality in people over the age of 75 years. This study examined whether other predictors may account for the association. METHODS: A community-based cohort of 1810 people who were aged 75 years and older was followed for 5 years. RESULTS: The relative risk of death was 1.39 (95% confidence interval [CI] = 1.11, 1.73) for people with systolic pressure lower than 130 mm Hg and 1.21 (95% CI = 1.02, 1.43) for those with diastolic pressure lower than 75 mm Hg, compared with corresponding reference groups, when all other variables were simultaneously considered in Cox proportional hazards models. The observed association was present mainly in subjects with at least two of the three conditions (cardiovascular disease, limitation in activities of daily living, or cognitive impairment). The effect of low diastolic pressure on mortality was also significant in those with only cognitive impairment. CONCLUSIONS: Preexisting cardiovascular disease, limitation in activities of daily living, and, more important, cognitive impairment may be responsible for the association of low blood pressure with increased mortality in the very old in that they cause both reductions in blood pressure and excess deaths.

Activities of Daily Living↗
PubMed1997

Dental management of Alzheimer patients. A predictive test of dental cooperation in individualized treatment planning.

The aim of the study was to investigate a possible relationship in Alzheimer patients between the stage of dementia, cognitive and functional capacity, and behavior as a dental patient. A special index for assessing behavior in the dental setting was used. The 40 participants were inmates of a nursing home and fulfilled the criteria for Alzheimer's disease in accordance with DSM-III-R. A deficiency in the dental behavior index (DBI) of 50% or less did not correlate with cognitive, functional, or graphic capacity. These subjects were generally aware of earlier regular dental treatment and behaved as if dental visits were familiar to them, although their cognitive, functional, and graphic capacities were more impaired than disclosed by the dental behavior index. A deficiency in the dental behavior index of 50% or more was more correlated with the other capacity assessments. Finding a proper treatment level for an Alzheimer patient is a delicate task in which it is essential to balance awareness of various aspects of impairment and realistic anticipation of benefit. The dental behavior index can be an appropriate instrument in this complex process.

Activities of Daily Living↗
PubMed1997

Costs of dementia and dementia care: a review.

Costs of dementia care constitute a great part of the total costs of care for elderly. Because the prevalence of dementia is linked to increasing age, and the number of the oldest old is rising, the costs of dementia care will increase considerably in the forthcoming decades. In this review, research describing costs of dementia care has been analysed and classified. The available database in this field is small, though expanding, and the methodological problems are obvious. Differences between countries, and between different periods of time, are difficult to analyse due to different methods of financing and organizing care. The main result of the present study is that the costs of dementia care differ considerably in the literature. One important reason for this variability is that the number of included cost categories vary, leading to a wide range of costs. Unpaid informal care forms a major part of the total costs, but the theory of costing informal care is complicated.

Aged↗
PubMed1997

Treatment of Alzheimer disease with tacrine: a cost-analysis model.

In a cost-analysis model, the effect on the costs of Alzheimer disease of tacrine (tetrahydroaminoacridine) treatment was studied. A model of the survival of the Swedish Alzheimer disease population was constructed in which the placement of patients with Alzheimer disease in care organization was assumed to be influenced by the use of tacrine. Based on this model, the cost analysis was performed. Fifty-two percent of the Alzheimer disease population with an initial Mini-Mental State Examination (MMSE) score of 10 to 24 points are in the main alternative of the model treated with 160 mg tacrine with an initial improvement in MMSE of 2.6 points. The benefit of tacrine was a cost reduction of 1.3% when the results were calculated for the entire Alzheimer disease population. This corresponds to a benefit of 1.3 billion Swedish kronor (SEK) (with 3% discount rate) for the entire estimated survival period. The annual benefit per patient was estimated as 2,900 SEK [approximately U.S. $320 (1993)]. In the sensitivity analysis, the range was between -0.6% and 5.2%. Beginning treatment in the early stages of Alzheimer disease results in lower costs than a later start. The main conclusion is that tacrine, according to the model, has beneficial but modest effects on the costs of Alzheimer disease in Sweden.

Alzheimer Disease↗
PubMed1997

Apolipoprotein E polymorphism in elderly east Africans.

Current advances have shown the apolipoprotein E (APOE)-epsilon 4 allele to be highly associated with late-onset familial and sporadic Alzheimer's disease (AD) in Western populations. The association of APOE allele frequencies and dementia remain unknown in populations from developing countries. We recently initiated a project to examine APOE frequencies in non-demented and demented elderly East Africans. Blood DNA collected from two hospital-based populations showed that the APOE allele frequencies in a group of non-demented 67 Tanzanians over the age of 65 years were found to be 14% for epsilon 2, 61% for epsilon 3 and 25% for epsilon 4. By comparison, the frequency of APOE-epsilon 4 in an age-matched demented group was also 25%. Assessment of APOE genotypes in the group of elderly Kenyan subjects from Nairobi also revealed high frequencies of the epsilon 4 allele with no clear difference in frequency between demented and non-demented subjects. Our preliminary observations suggest that elderly East Africans with no apparent clinical AD possess relatively high APOE-epsilon 4 allele frequencies compared to normal ageing subjects from Western countries including African-Americans. These results appear similar to those reported in a recent study in Nigerian Africans where a lack of correlation between APOE-epsilon 4 allele frequency and Alzheimer type of dementia was noted, and imply that APOE-epsilon 4 allele may not necessarily be a risk factor in some populations of Africa.

Aged↗
PubMed1996

Quantification of APP and APLP2 mRNA in APOE genotyped Alzheimer's disease brains.

Amyloid precursor protein (APP) is metabolised to produce A beta, a peptide found aggregated in Alzheimer's disease neuritic plaques. APP is a member of a multigene protein family which includes amyloid precursor-like protein 2 (APLP2). Since A beta accumulation can be triggered by factors acting up- or downstream of APP processing, we investigated whether APP mRNA expression was altered in Alzheimer's disease post-mortem cerebral cortex. In addition, we characterised cortical APLP2 mRNA levels. Quantitative RNA-RNA solution hybridisation-RNase protection was used to assay total APP. APP containing the Kunitz-type protease inhibitor (KPI) insert and APLP2 mRNA in mid-temporal and superior frontal cortices from apolipoprotein E-genotyped subjects with Alzheimer's disease, other neurological diseases and non-demented controls. Approximately 3 times more APP than APLP2 mRNA was detected and about 70% of total APP mRNA contained the KPI insert in the control subjects. Total APP and APLP2 mRNA levels were significantly reduced in Alzheimer's disease mid-temporal, but not superior frontal cortex, suggesting that regional reductions in these mRNA correlate with severity of disease pathology. A small significant increase in the proportion of APP KPI mRNA was seen in both cortical regions in Alzheimer's disease. Apolipoprotein E genotype did not influence cortical levels of total APP, APP KPI or APLP2 mRNA. Alzheimer's disease-related increases in tissue DNA content were seen in both regions studied, while tissue RNA levels were reduced in the positive disease controls. In summary, these results indicate that Alzheimer's disease is not associated with over-expression of either APP or APLP2 mRNA. Our findings reveal a disease-associated increase in the proportion of APP KPI-containing isoforms, and further investigation should clarify whether this predisposes affected individuals to A beta production and aggregation, or reflects later events such as gliosis and neuronal cell death.

Aged↗
PubMed1996

Expression of neurotrophin-3 mRNA in the rat visual cortex and hippocampus is influenced by environmental conditions.

Environmental enrichment results in structural changes in the brain. Recent findings indicate involvement of neurotrophins in neuronal plasticity. This study examined the effect of environmental complexity on the levels of neurotrophin-3 (NT-3) mRNA in the rat visual cortex and hippocampus, studied by in situ hybridization. Rats housed in groups in a complex, stimulating environment had significantly higher levels of NT-3 mRNA in the visual cortex and the hippocampus than rats housed in individual cages without stimulating objects. These results indicate a possible role for NT-3 in synaptic plasticity.

Animals↗
PubMed1996

Impaired G-protein-stimulated adenylyl cyclase activity in Alzheimer's disease brain is not accompanied by reduced cyclic-AMP-dependent protein kinase A activity.

Previous studies have shown that the regulation of adenylyl cyclase activity is disrupted in Alzheimer's disease postmortem brain. In the present study, we determined whether disrupted adenylyl cyclase is accompanied by altered cAMP-dependent protein kinase activity in Alzheimer's disease superior temporal cortex and cerebellum. GTP gamma S-stimulated adenylyl cyclase activity was significantly lower in Alzheimer's disease superior temporal cortex, but not cerebellum, compared to values from a series of matched control cases. Neither basal or forskolin-stimulated adenylyl cyclase activities were significantly different between the Alzheimer's disease and control brain regions. No significant differences were seen in either particulate or soluble fraction cAMP-dependent protein kinase activities between the Alzheimer's disease and control brain regions. It is concluded that disrupted adenylyl cyclase signalling in Alzheimer's disease brain occurs specifically at the level of Gs-protein-enzyme interactions and is not accompanied by an altered cAMP-dependent protein kinase activity.

Adenylyl Cyclases↗
PubMed1996

Abundance of the longer A beta 42 in neocortical and cerebrovascular amyloid beta deposits in Swedish familial Alzheimer's disease and Down's syndrome.

Recent studies have demonstrated the deposition of amyloid beta (A beta) protein with carboxyl- and aminoterminal heterogeneity in cortical and cerebrovascular deposits of Alzheimer's disease (AD). Using carboxyl end-terminal specific antibodies to A beta peptides, we examined the immunocytochemical distribution of A beta 40 and A beta 42 species in brain tissue from a Swedish subject with familial AD (FAD) bearing the double mutation at codons 670/671 in the amyloid beta precursor protein (A beta PP), and from subjects with Down's syndrome and sporadic AD. In the Swedish subject, we found profound parenchymal A beta deposits and cerebral amyloid angiopathy in all four cortical lobes and cerebellum. A beta 42 was evident in almost all parenchymal deposits as well as many vascular deposits. Although A beta 40 was present in meningeal and intraparenchymal vessels, deposits containing this shorter peptide reactivity were sparse. Surprisingly, our observations in Swedish FAD showing a remarkable abundance of A beta 42 in both parenchymal and vascular deposits were qualitatively similar to the Down's syndrome and most sporadic AD cases, and to previously published A beta PP717 FAD. While previous transfection studies in different cell cultures indicate substantially increased soluble A beta production and A beta 40 species to be predominant, it would appear that the double A beta PP mutations in Swedish FAD largely result in the deposition of the longer A beta 42 in vivo.

Adult↗
PubMed1996

Apolipoprotein E (apoE) levels in brains from Alzheimer disease patients and controls.

We measured apolipoprotein E (apoE) level in neutral and acidic pH extracts of the frontal, temporal and cerebellar cortices from patients with definite Alzheimer's disease (AD) and controls, and analyzed the relationship among apoE levels, clinical and neuropathological findings, and apoE genotype. Our data showed that the levels varied in different brain regions being lowest in the frontal cortex and highest in the cerebellum in Ad brains. ApoE levels in neutral pH extracts from the frontal cortex from AD patients were significantly lower than those of controls, and correlated negatively with the number of neurofibrillary tangles. ApoE genotype was not associated with the levels of apoE. There was no correlation between apoE levels and amyloid load or synaptophysin-immunoreactivity in the brain. We conclude that apoE levels are not increased in AD brains. However, apoE levels vary in different brain regions, and local factors related to the synthesis and metabolism of apoE may be crucial in the pathogenesis of AD.

Aged↗
PubMed1996

Low blood pressure and dementia in elderly people: the Kungsholmen project.

OBJECTIVE: To examine the relation between blood pressure and dementia in elderly people. DESIGN: Cross sectional, population based study. SETTING: Kungsholmen district of Stockholm, Sweden. SUBJECTS: 1642 subjects aged 75-101 years. MAIN OUTCOME MEASURES: Prevalence and adjusted odds ratio of dementia by blood pressure. RESULTS: People with systolic pressure < or = 140 mm Hg were more often diagnosed as demented than those with systolic pressure >140 mm Hg: odds ratios (95% confidence interval) adjusted for age, sex, and education were 2.98 (2.17 to 4.08) for all dementias, 2.91 (1.93 to 4.38) for Alzheimer's disease, 2.00 (1.09 to 3.65) for vascular dementia, and 5.07 (2.65 to 9.70) for other dementias. Similar results were seen in subjects with diastolic pressure < or = 75 mm Hg compared with those with higher diastolic pressure. When severity and duration of dementia were taken into account, only moderate and severe dementia were found to be significantly related to relatively low blood pressure, and the association was stronger in subjects with longer disease duration. Use of hypotensive drugs and comorbidity with cardiovascular disease did not modify the results for all dementias, Alzheimer's disease, and other dementias but slightly reduced the association between vascular dementia and diastolic blood pressure. CONCLUSIONS: Both systolic and diastolic blood pressure were inversely related to prevalence of dementia in elderly people. We think that relatively low blood pressure is probably a complication of the dementia process, particularly Alzheimer's disease, although it is possible that low blood pressure may predispose a subpopulation to developing dementia.

Aged↗