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Biomedical subjects

B Winblad

Publications and source records attributed to B Winblad.

At least 91 records · Page 5Linked to original sources

Discrimination of Alzheimer's disease and mild cognitive impairment by equivalent EEG sources: a cross-sectional and longitudinal study.

OBJECTIVES: The spatial aspects of brain electrical activity can be assessed by equivalent EEG frequency band generators. We aimed to describe alterations of these EEG generators in Alzheimer's disease (AD) and healthy aging and whether they could serve as predictive markers of AD in subjects at risk. METHODS: The amplitude and 3-dimensional localization of equivalent EEG sources were evaluated using FFT dipole approximation in 38 mild AD patients, 31 subjects with mild cognitive impairment (MCI) and 24 healthy control subjects. RESULTS: AD patients showed an increase of delta and theta global field power (GFP), which corresponds to the generalized EEG amplitude, as well as a reduction of alpha GFP when compared to the controls. A decrease of alpha and beta GFP was found in AD patients, as compared to the MCI subjects. With respect to topography in the antero-posterior direction, sources of alpha and beta activity shifted more anteriorly in AD patients compared to both the controls and MCI subjects. No significant difference was found between MCI and controls. Combined alpha and theta GFP were the best discriminating variables between AD patients and controls (84% correct classification) and AD and MCI subjects (78% correctly classified). MCI subjects were followed longitudinally (25 months on average) in order to compare differences in baseline EEG variables between MCI subjects who progressed to AD (PMCI) and those who remained stable (SMCI). Compared to SMCI, PMCI had decreased alpha GFP and a more anterior localization of sources of theta, alpha and beta frequency. In a linear discriminant analysis applied on baseline values of the two MCI subgroups, the best predictor of future development of AD was found to be antero-posterior localization of alpha frequency. CONCLUSIONS: FFT dipole approximation and frequency analysis performed by conventional FFT showed comparable classification accuracy between the studied groups. We conclude that localization and amplitude of equivalent EEG sources could be promising markers of early AD.

Aged↗

Cadmium concentration in blood in an elderly urban population.

Concentration of cadmium in blood in an elderly population with a mean age of 87 years was studied in relation to age, blood pressure, BMI, cognitive function, gender and smoking. This population-based study consisted of 804 subjects both men and women. Clinical examination included medical and social history, physical and neurologic examination, and assessment of cognitive functions with Mini-Mental State Examination (MMSE). Information on prescription and non-prescription drug use was collected. Anti-hypertensive drugs included all medicines potentially used for treating high blood pressure. Blood pressure was measured. Whole blood from 763 subjects was analysed for cadmium by atomic absorption spectrophotometry (GFAAS) with Zeeman background correction and with a graphite furnace using the L'vov platform technique including quality control. Differences in cadmium concentrations were related to non-smokers (3.9 nmol/l), previous smokers (4.4 nmol/l) and current smokers (7.5 nmol/l). There were no relations between cadmium and age, blood pressure or cognitive functions. In conclusion, increased cadmium levels were found in smokers. A possible contribution from previous occupational exposure needs to be further evaluated.

Aged↗

High suicidal ideation in persons testing for Huntington's disease.

This study examined the first participants who registered for the Huntington's disease predictive testing program 1990-1995 in Stockholm, Sweden. A psychosocial investigation was performed to evaluate potential effects of the presymptomatic testing. The results showed no significant differences between 13 gene carriers and 21 noncarriers in pretest attitudes, expectations, general well-being, life satisfaction and lifestyle, the need for support, estimated sense of wellbeing or degree of health. However, both groups showed high suicidal ideation and self-injurious behavior. Noncarriers had a very high frequency of attempted suicide, and both groups had similarly pronounced psychiatric dysfunction. Their relatives also had high frequencies of psychiatric diseases, suicide or suicidal attempts. Most of the participants had a desire to meet a psychologist or a social worker. The need for counseling, using a well designed protocol, and the importance of focusing on suicide risk of participants in predictive testing programs is emphasized.

Adult↗

The patient as 'teacher': learning in the care of elderly persons with dementia.

In 1996 HM Queen Silvia of Sweden started a non-governmental education programme with an integrated day-care unit devoted to elderly persons with dementia. A total of 18 Licensed Practical Nurses (LPN) from various parts of Sweden took part in the year theoretical and practical education in dementia care. The purpose was to develop specialized skills in the particular field and more generally to develop mentor capabilities. The aim of the study was to examine the experiences of the trainees, gained from following a single patient during their entire practical training period in the school's integrated day-care unit. The study was based on a combination of participant observations, interviews, diaries and recorded data and used an ethnographic approach. The results showed that themes such as 'personal guide', 'creating a relationship', 'reducing the working pace' and 'investigative mealtimes' were of major importance for the trainees' learning. In their role as 'personal guides', the trainees fell into six categories with different educational focuses. In their relationships with the patients, the trainees were able to form their own impressions of the patients' present and former lives. By training their ability to adapt the pace at which they worked, they had time to observe symptoms and be aware of the patients' needs, as well as the patients' signs of appreciation. The results also indicated that 'investigative mealtimes' can be an important element in the trainee's education in dementia care.

Aged↗

Mild cognitive impairment in the population and physical health: data on 1,435 individuals aged 75 to 95.

BACKGROUND: The physical health correlates of mild cognitive impairment (MCI) in the older individual are poorly known. The aim of this study was to investigate the relationship between physical health and MCI with population data. METHODS: Subjects were 1,435 nondemented 75- to 95-year-old subjects. MCI was defined as scoring one standard deviation below age- and education-specific means on the Mini-Mental State Examination. MCI was consistently associated with indicators of poorer health in logistic regression models with adjustment for potential confounders. RESULTS: The adjusted odds ratios for those with two, three, four, or more somatic symptoms compared with those with one or no symptoms were 1.3 (95% confidence intervals 1.0 to 1.9) and 2.1 (1.2 to 4.5; p for trend =.004); for those with poor self-rated health the odds ratio was 1.9 (1.4 to 2.6); for those with one, two, or more chronic diseases compared with those with no chronic diseases, the odds ratios were 1.3 (0.9 to 1.9) and 3.0 (1.2 to 7.6; p for trend =.02); and for those dying during the 3-year follow-up period the odds ratio was 1.5 (1.1 to 2.2). CONCLUSIONS: MCI is associated with poor physical health, leading to the hypothesis of a causal relationship between physical diseases and MCI in older populations.

Aged↗

The relationship between signs of cardiovascular deficiency and cognitive performance in old age: a population-based study.

The influence of cardiovascular signs (CVS) on cognitive performance was examined in 227 older adults not suffering from dementia between 75 and 96 years of age who were sampled from the community. Participants received a comprehensive physical examination that included specific evaluation of current CVS, including dyspnea, cardiac murmur, and edema in lower limbs. They were administered tests of digit span, episodic recall and recognition, verbal fluency, and visuospatial skill. CVS were found to predict performance on tests of episodic memory and visuospatial skill, after the effects of age, education, gender, relevant drug use, and mood symptoms were controlled for. Although CVS accounted for relatively little general performance variation, the findings are relevant to the understanding of normal variation in late-life cognitive performance. Finally, CVS increased with age and accounted for a sizable proportion of the age-related cognitive variation.

Age Factors↗

Ultrastructural analysis and TUNEL demonstrate motor neuron apoptosis in Werdnig-Hoffmann disease.

Werdnig-Hoffmann disease (WHD) is the most severe clinical type of spinal muscular atrophy characterized by loss of lower motor neurons and paralysis. We examined the hypothesis that disease pathogenesis is based on an inappropriate persistence of normally occurring motor neuron programmed cell death. The diagnosis of WHD was made on the basis of clinical findings, electromyoneurography, and biopsy, and further confirmed by mutation analysis of the survival motor neuron (SMN) and neuronal apoptosis inhibitory protein (NAIP) genes using PCR. We used ultrastructural analysis as well as TUNEL and ISEL methods to assess DNA fragmentation, and immunocytochemistry to identify expression of the apoptosis-related proteins bcl-2 and p53. A significant number of motor neurons in the spinal cord of children with WHD were shown to die by apoptosis. As revealed by TUNEL, dying neurons in WHD patients comprised 0.2%-6.4% of the neuron numbers counted. This finding contradicts earlier studies that failed to find such evidence and suggests that early blockade of prolonged motor neuron apoptosis may be a potential therapeutic strategy for WHD.

Apoptosis↗

Morbidity and comorbidity in relation to functional status: a community-based study of the oldest old (90+ years).

OBJECTIVES: To describe health and functional status in the oldest old; to explore the relationships of morbidity and functional status; and to verify whether this relationship was modified by gender. DESIGN AND SETTING: A community-based survey including all inhabitants aged > or = 90 living in central Stockholm, Sweden. All participants were clinically examined by physicians, cognitively assessed by psychologists, and interviewed by nurses. Diagnoses were made according to the International Classification of Diseases-Ninth Revision (ICD-9), the DSM-III-R criteria for dementia, and Katz index of activities of daily living. PARTICIPANTS: Of the 698 subjects in the study population, 99 (14%) had died and 29 (4%) moved before examination. Of the remaining subjects, 502 (88.1%) were examined, and the refusal rate was 11.9%. MEASUREMENTS: Age- and gender-specific prevalence figures, and age-, gender- and education-adjusted odds ratios (OR) were used. RESULTS: Of 502 examined subjects, 19% had no disease and 73% were functionally independent. Dementia was the most prevalent disease among women (42.2%), and cardio- and cerebrovascular diseases were the most frequent among men (42.4%). Women had higher prevalences of dementia (adjusted OR = 2.1, 95% confidence interval (CI) 1.2-3.7) and fractures and musculoskeletal diseases (adjusted OR = 2.8, 95% CI 1.1-7.3), whereas men had a higher prevalence of malignancy (OR = 0.2, 95% CI 0.1-0.7). Women were more disabled than men independent of age, education, and number of diseases (adjusted OR = 2.2, 95% CI 1.1-4.3). CONCLUSIONS: A great proportion of nonagenarians were functionally independent despite their advanced age. Further studies are needed to clarify the excess of disability among very old women.

Activities of Daily Living↗

Alzheimer's disease and vascular dementia. Some points of confluence.

The lack of biologic markers for Alzheimer's disease and vascular dementia, the controversy regarding the definition of vascular dementia, and the new evidence of vascular risk factors for Alzheimer's disease suggest that the traditional differentiation between Alzheimer's disease and vascular dementia is no longer very clear. We believe that both vascular and degenerative mechanisms contribute to the development of dementia, especially in very old age. The question of whether they are two independent parallel processes or interacting pathologies needs to be clarified.

Alzheimer Disease↗

Outcome measures in Alzheimer's disease: do they go far enough?

As the interest in Alzheimer's disease (AD) and its treatment has grown, so has the sophistication of clinical trials of potential drug therapies. In particular, interest has focused on outcomes used to assess the severity of the illness and the effectiveness of treatment. This paper reviews the assessments that are used frequently in trials of AD therapy and describes further measures that may be of value in determining effective treatments for the disease. The review concludes that it is important that evaluation of drug effects on AD is not confined solely to the assessment of cognitive function. To gain a true overview of the impact of AD on patients, carers and society, areas such as activities of daily living, caregiver burden, quality of life, behavioural symptoms and resource utilization need to be comprehensively determined.

Alzheimer Disease↗

Incidence of dementia in relation to stroke and the apolipoprotein E epsilon4 allele in the very old. Findings from a population-based longitudinal study.

BACKGROUND AND PURPOSE: Both stroke and the apolipoprotein E (APOE) epsilon4 allele increase the risk of dementia. However, the interaction between stroke and APOE on dementia is still unclear. We addressed this topic by using a longitudinal design. METHODS: We followed up a community cohort of 1301 subjects aged >/=75 years, who did not have dementia at baseline. Among them, 92 subjects had a history of stroke (from 3 months to 16 years before baseline interview). After the 3-year follow-up, 224 dementia cases had been diagnosed. During the period of follow-up, 91 subjects had a first occurrence of stroke (incident stroke). The APOE genotype was known for 985 subjects. Cox proportional hazards regression models were constructed to estimate the risk for dementia in terms of relative risks (RRs) for stroke and the APOE epsilon4 allele, with adjustment for age, sex, education, systolic blood pressure, antihypertensive medication use, and heart disease. RESULTS: In the entire study population, RRs for dementia related to history of stroke and incident stroke were 1.7 (95% CI, 1.1 to 2.6) and 2.4 (95% CI, 1.6 to 3.5), respectively, after adjustment for all potential confounders. Subjects with stroke that occurred within 3 years before baseline had RR of 2.4 (95% CI, 1.4 to 4.2), whereas those with stroke occurring >3 years before baseline had RR of dementia of 1.1 (95% CI, 0.6 to 2.3). Among those with APOE information, individuals with only history of stroke (that occurred within 3 years before baseline) had RR of 3.1 (95% CI, 1.4 to 6.6), individuals with only the APOE epsilon4 allele had RR of 1.7 (95% CI, 1.1 to 2.5), and individuals with both factors had RR of 5.3 (95% CI, 2.1 to 13.4). The corresponding figures when incident stroke was examined instead of history of stroke were 2.3 (95% CI, 1.3 to 4.1), 1.7 (95% CI, 1.1 to 2.4), and 4.6 (95% CI, 2.0 to 10.6), respectively. The RR of interaction term for history of stroke and APOE epsilon4 was 1.1 (95% CI, 0.3 to 3.8; P=0.8). The corresponding figure was 1.2 (95% CI, 0.4 to 4.4; P=0.7) for incident stroke and APOE epsilon4. Furthermore, the RRs of dementia without any stroke and dementia with stroke in relation to APOE epsilon4 were 1.6 (95% CI, 1.1 to 2.3) and 1.2 (95% CI, 0.6 to 2.4), respectively. In addition, the APOE epsilon4 allele was not significantly related to the occurrence of stroke (RR=0.8; 95% CI, 0.5 to 1.5). CONCLUSIONS: A relatively fresh stroke is a risk factor for dementia. APOE epsilon4 increases the risk of dementia without stroke but not dementia with stroke. Our data do not support a multiplicative effect of stroke and the APOE epsilon4 allele on the risk of dementia. However, both factors seem to have an additive effect on the risk of dementia. The APOE epsilon4 allele does not increase the risk of stroke in this Swedish elderly population.

Aged↗

Protective effect of Rolipram in experimental autoimmune neuritis: protection is associated with down-regulation of IFN-gamma and inflammatory chemokines as well as up-regulation of IL-4 in peripheral nervous system.

Rolipram, a phosphodiesterase type 4 inhibitor, is reported to have anti-inflammatory effects. It can markedly downregulate antigen-driven T cell proliferation and suppress TNF-(alpha and TNF-beta production in vitro and in vivo, which have led to its use in the treatment of a number of autoimmune disorders including experimental autoimmune encephalomyelitis (EAE) and experimental autoimmune neuritis (EAN). EAN is a CD4+ T cell-mediated demyelinating autoimmune disease of peripheral nervous system (PNS) that represents an animal model for the study of the immunopathogenesis and immunotherapy of Guillain-Barré syndrome (GBS) in human. In the previous study, we reported that suppression of EAN by Rolipram was associated with down-regulated myelin antigen-induced T cell responses as well as downregulated IFN-gamma and TNF-alpha production. Here we report that EAN induced in Lewis rats by inoculation with the PNS P2 protein peptide 57-81 and Freund's complete adjuvant (FCA), was strongly suppressed by Rolipram administered twice daily intraperitoneally from day 9 post immunization (p.i.), i.e. after onset of clinical EAN to day 18 p.i. This clinical effect was associated with dose-dependent down-regulated production of IFN-gamma and the chemokines macrophage inflammatory protein-1 alpha (MIP-1 alpha, MIP-2 and monocyte chemotactic protein-1(MCP-1) as well as up-regulated IL-4 production in sciatic nerve sections from Rolipram-treated EAN rats at maximum of clinical EAN, i.e. on day 14 p.i.. These findings suggest that Rolipram may be useful in certain T cell-dependent autoimmune diseases and inflammatory neuropathies. These observations call for further studies on the potential role of Rolipram in the treatment of autoimmune diseases.

Animals↗

Influencing aspects in nursing education on Swedish nursing students' choices of first work area as graduated nurses.

It is difficult to recruit RNs to positions in various areas of elder care. The aim of this study is to understand the meaning of Swedish nursing students' reasoning during education about where in the health care system they would like to work as RNs after graduation. The students were interviewed using the same guide at the end of each of their three academic years. In the second and the third year the students kept diaries about their clinical education. A phenomenological-hermeneutic method of analysis was used, and eight themes appeared vital for the students' choice of work area after graduation. The deeper interpretations of the results imply that the students received contradictory messages during the education in elder care. Students found that nurses working in this field were often isolated with no apparent support system, which in turn reinforced their own ambivalence and reluctance towards future work in elder care.

Attitude of Health Personnel↗

Tau gene polymorphisms and apolipoprotein E epsilon4 may interact to increase risk for Alzheimer's disease.

In an effort to analyze the genetic role of tau in Alzheimer's disease (AD), 17 polymorphisms were identified. Eleven of these polymorphisms were in complete linkage disequilibrium and segregated as two haplotypes, A and B. The A and B haplotypes were investigated in 269 AD cases and 238 controls from two different sources, a clinic-based group (mean age of onset 65+/-9 years), and a population-based group (mean age of onset 80+/-5 years). A synergistic effect between the common tau genotype AA and apolipoprotein E (APOE epsilon4) was found in the clinic-based AD group. Our study suggests that the common tau genotype AA may interact with APOE epsilon4 in increasing the risk of AD in a subgroup of the AD population.

Aged↗

Quantitative autoradiography of [3H]forskolin binding sites in post-mortem brain staged for Alzheimer's disease neurofibrillary changes and amyloid deposits.

Adenylyl cyclase (AC) signal transduction has been shown to be affected in Alzheimer's disease (AD). Deficits have been described in different components of the system, from the receptor to the effector level. [3H]forskolin is a diterpene that binds with high affinity to AC. In the present report, we used autoradiography to study [3H]forskolin binding to sections of entorhinal cortex and hippocampus from 23 cases staged for AD pathology according to Braak and Braak [Acta Neuropathol. 82 (1991) 239-259]. This protocol defines six stages according to neurofibrillary changes, which start in the entorhinal region (stages I-II), spread to the hippocampus (stages III-IV) and finally to the isocortical areas (stages V-VI). The amyloid classification includes three stages in which the basal isocortex is first affected (stage A), followed by other isocortical association areas (stage B) and finally the primary isocortical areas (stage C). We also studied the effects of the GTP-analogue Gpp[NH]p on binding, in order to detect changes in G-protein-AC coupling. We used two different concentrations of Gpp[NH]p, that were previously reported to inhibit and stimulate [3H]forskolin binding via Gi and Gs, respectively. Results showed that [3H]forskolin binding declined significantly with staging for neurofibrillary changes only in the entorhinal region (P < 0.05, ANOVA). In addition, the decrease in [3H]forskolin binding observed in the presence of 1 microM Gpp[NH]p diminished significantly with staging in the entorhinal region (P < 0.05, ANOVA). No significant changes were seen with amyloid staging, with the exception of the CA1 subfield of the hippocampus, where [3H]forskolin binding in the absence of Gpp[NH]p was significantly decreased at stage B compared with all other stages (P < 0.05, ANOVA). In conclusion, our results showed a very limited decrease in [3H]forskolin binding with the progression of AD pathology, suggesting that the AC levels may be largely preserved in the disease. The specific change in the effect of a low concentration of Gpp[NH]p on the binding could indicate the loss of Ca2+/calmodulin-sensitive AC isoforms in AD.

Adenylyl Cyclases↗

The occurrence of depressive symptoms in the preclinical phase of AD: a population-based study.

OBJECTIVE: To examine preclinical depressive symptoms 3 years before the diagnosis of AD. METHODS: The authors compared incident AD patients and nondemented individuals in terms of baseline mood- and motivation-related symptoms of depression, and assessed whether depressive symptoms in preclinical AD are related to self-perceived memory problems. Participants came from a population-based longitudinal study on aging and dementia in Stockholm, Sweden. The sample consisted of 222 persons older than 74 years who were followed for a 3-year interval. Thirty-four individuals had developed AD at follow-up, whereas 188 remained nondemented. Dementia diagnosis was made according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised. Depressive symptoms were assessed by the Comprehensive Psychopathological Rating Scale. RESULTS: The incident AD patients had more depressive symptoms than the nondemented persons at baseline. There was a dominance of motivation-related symptoms of depression (e.g., lack of interest, loss of energy, concentration difficulties) in preclinical AD. This association remained when adjusting for subjective memory complaints. CONCLUSIONS: Depressive symptoms are elevated preclinically in AD, and this elevation is not merely a by-product of self-perceived cognitive difficulties. Thus, depressive symptoms may be part of the preclinical phase in AD.

Aged↗

Ultrastructural analysis of the hippocampus of adult rats after long-term adrenalectomy.

Removal of adrenal steroids modulates various functions in the brain. However, adrenalectomy (ADX) induced cell death in the hippocampal formation of the adult rat is a recently described phenomenon. We undertook this ultrastructural study on long-term adrenalectomized (5 months) rats to investigate the mode of cell death in the hippocampus. Our results showed apoptotic changes in the hippocampus. In addition we have observed other types of degeneration in the hippocampal neurons. The novel finding in this study is that different morphological patterns of cell death were evident both in the dentate gyrus and in the pyramidal areas, which may reflect different stages of the same death process.

Adrenalectomy↗