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Biomedical subjects

B Winblad

Publications and source records attributed to B Winblad.

At least 577 records · Page 32Linked to original sources
PubMedDate not supplied

Apolipoprotein E epsilon4 allele, skin vessel reactivity and vascular risk factors in Alzheimer's disease.

The apolipoprotein E (ApoE) epsilon4 allele is strongly associated with Alzheimer's disease (AD), and is, at the same time, a risk factor for cardiovascular disease. Recently, it has also been suggested that skin vessel reactivity is impaired in AD. The aim of this study was to assess the impact of the ApoE epsilon4 allele on the results of skin vessel reactivity tests and vascular risk factors such as cholesterol and blood pressure in AD. Fourteen non-smoking patients, who were in good general health and took no medicines, were tested. Three vasodilating substances with different modes of action, acetylcholine (ACh), isoprenaline and nitroprusside, were iontophoresed into the skin and the resultant vasodilation of the skin vessels was evaluated with the aid of a newly developed laser Doppler perfusion imager. The results of the tests did not differ significantly between the patient group with (n=10) and without (n=4) the ApoE epsilon4 allele, perhaps due to the small number of patients. The results of the skin vessel reactivity tests of the patient subgroups were also compared to those of healthy, non-smoking, non-medicating, age-matched controls. The findings of that comparison suggest, that the presence of the epsilon4 allele in AD might have an impact on skin vessel reactivity to the cholinergic agonist ACh.

Journal Article↗
PubMedDate not supplied

Levels of serum creatinine and estimated creatinine clearance over the age of 75: a study of an elderly Swedish population.

Serum creatinine was measured and creatinine clearance estimated using the Cockcroft-Gault (C-G) formula, in elderly people participating in a population study of the elderly, the Kungsholmen Project. This is an ongoing longitudinal study which was begun in 1987 and comprised all people in a district of Stockholm, born in 1912 or earlier. Out of 2368 people 1810 participated. In 1362 cases, serum creatinine and an estimation of the creatinine clearance could be obtained. The mean age of these elderly people was 81 years, and 92% were living in their own homes. A linear regression model showed that the weight of the elderly decreased by age, indicating a decrease in muscle mass. However, this was not accompanied by a decrease in serum creatinine levels. When creatinine clearance was estimated using the C-G formula, a significant decline with age was seen at an average rate of 1.2 ml/min per year. It declined from 52 ml/min at age 75 to 27 ml/min at age 95. The mean for the whole study group was 44.6 ml/min. Our data suggest that the glomerular filtration rate may be very low in the oldest old and that there is a continuing decline with increasing age, even in a population where a high number of the elderly are still living in their own homes. Furthermore, the lack of major changes in serum creatinine levels with age supports the idea that this parameter is not a reliable measure of renal function in the elderly.

Journal Article↗
PubMedDate not supplied

An integrative hypothesis concerning the pathogenesis and progression of Alzheimer's disease.

Observations, in Alzheimer's disease, in the pattern of nerve cell damage and loss, the pathology, microchemistry and immunology of senile plaques and neurofibrillary tangles and alterations in blood vessels are drawn together into a hypothesis that attempts to explain the pathogenesis and progression of the disorder. At the heart of this hypothesis lies a defect in blood brain barrier function and/or structure within the cerebral cortex and this defect may be the cause of the cerebral vessel amyloidosis common in many patients with Alzheimer's disease. Age-related alterations in blood brain barrier allow for damage to nerve terminals and limited formation of senile plaques within cerebral cortex; neurofibrillary tangles are formed within cortical and subcortical nerve cells which project to or near damaged vessels/senile plaques. Uptake of "neurotoxin" at affected terminals and retrograde transport to perikarya causes neurofibrillary tangles to be formed; their accumulation leads to perikaryal changes culminating in cell death and loss. Loss of cells in cortically projecting areas of subcortex such as nucleus basalis, locus caeruleus and dorsal raphe, which terminate on cerebral vessels, causes further blood brain barrier dysfunction, new plaque formation and continued cell loss in cortex and subcortex. Once started, such a process could be self-perpetuating and the initial site of damage could lie within the amygdala/hippocampus with putative pathogenic agent accessing the brain via the olfactory pathways.

Age Factors↗
PubMedDate not supplied

Divergent changes in D-1 and D-2 dopamine binding sites in human brain during aging.

The density of D-1 and D-2 dopamine receptors in human caudate nucleus and putamen, obtained postmortem, were studied throughout the adult lifespan using [3H]fluphenazine as the dopamine receptor ligand. The D-1 subtype increased progressively with age in both regions, while the D-2 subtype declined in caudate nucleus. The ratio of D-1/D-2 Bmax in both regions increased from approximately 1 at age 20 to 2 by age 75. The dopamine content in putamen declined with age and was inversely correlated with D-1 receptor density. We suggest that D-1 receptor density is up-regulated by loss of dopamine during aging. The D-2 receptor density in caudate nucleus was positively correlated with choline acetyltransferase activity, suggesting that loss of intrastriatal neurons with age may contribute to the decrease in D-2 sites. These divergent changes in dopamine receptor subtypes with age result in an altered complement of dopamine receptors in older humans and may provide a basis for selective pharmacotherapy in disorders of the basal ganglia.

Adolescent↗
PubMedDate not supplied

Skin vessel reactivity is impaired in Alzheimer's disease.

Fifteen patients with Alzheimer's disease (AD) and 16 age-matched controls underwent skin vessel reactivity tests employing three vasodilating substances with different modes of action: acetylcholine (ACh), nitroprusside, and isoprenaline. The substances were iontophoresed into the skin and the results were mapped through a newly developed laser Doppler perfusion imager. The skin vascular responses of the patients to ACh and isoprenaline but not nitroprusside were significantly attenuated compared to those of the controls. The differences between patient and control groups concerning skin vessel reactivity might be due to receptor/signal transduction abnormalities but might in addition indicate an attenuated endothelium-dependent vasodilation in AD. The results of this study support the hypothesis that AD might be a systemic disease. They suggest that tests of skin vessel reactivity might be of help in the antemortem diagnosis of AD.

Acetylcholine↗
PubMedDate not supplied

Economic impact of introducing propentofylline for the treatment of dementia in Sweden.

The purpose of this study was to estimate the impact of the introduction of propentofylline, a glial-cell modulator with neuroprotective properties, on the costs of dementia care in Sweden. To estimate the clinical effects of propentofylline treatment on dementia, we conducted a meta-analysis of four double-masked, placebo-controlled, randomized clinical trials and a simulation in a cohort of 57,000 patients with Alzheimer's disease (AD) or vascular dementia (VaD). This cohort represented the fraction of the total AD and VaD population in Sweden with mild-to-moderate disease, the target population for propentofylline treatment. The rate of progression of dementia was expressed in terms of the annual rate of change in score on the Mini-Mental State Examination (MMSE). The costs of care were estimated on the basis of a prospective population-based study. A regression model was used to quantify the costs of dementia care as a function of MMSE score. The estimates obtained were used to calculate and compare the costs of dementia care until death, with or without propentofylline treatment. The sensitivity of the results to a variety of model assumptions was also assessed. The total gross cost for 9 years under the current treatment strategy was SEK (Swedish kronor) 168.06 billion. Including propentofylline in the treatment strategy yielded net savings of SEK 0.8 billion, since the savings in the cost of patient care outweighed the drug acquisition costs. Over 9 years, this saving represents 3.8% of the costs of dementia care in the target population (MMSE score, 15-25 points) and 0.5% of the costs in the total AD and VaD population. The annual savings per patient ranged from SEK 5517 to 6387 during the first 4 years of propentofylline treatment. If an extended neuroprotective effect of propentofylline is assumed, savings increase to SEK 1.6 billion, equivalent to 7.6% of total care costs in the target population and 1.0% in the total population. Savings increase to SEK 14.6 billion if the extended neuro-protective effect is assumed to be effective in an extended target population (MMSE score, 0-25 points) without increased survival. In the sensitivity analysis, most scenarios yielded benefits in favor of propentofylline treatment. The clinical effects of propentofylline translate into meaningful economic effects. The drug acquisition costs are more than offset by the savings achieved in the cost of care. The inclusion of a broader range of outcomes may increase these savings.

Aged↗
PubMedDate not supplied

Musculoskeletal pain and analgesic therapy in a very old population.

The aim of this study was to examine the prevalence of musculoskeletal pain and use of analgesic drugs in a population of very old people. The investigation is based on data from the Kungsholmen project. Of the 2638 inhabitants aged 75 or more in a parish of central Stockholm 1800 were examined. Of the subjects. 60% reported trouble with pain at musculoskeletal locations, while only 40% of the pain reporting subjects used analgesics, one third of which were non-prescription minor analgesics. Prescription analgesics (non-steroidal antiinflammatory drugs or centrally acting drugs) were used by one fourth of the pain reporting subjects, and taken on a regular basis in only half of the cases. Potent opioids were used by less than 1% of the population. There was no increase in pain with increasing age, but an increase in use of minor analgesics with age >85. Women more often reported pain and had a higher consumption of analgesics. Light opioids were more often used by subjects with multifocal pain. Subjects living in sheltered accommodation used more analgesics, particularly light opioids, than did those living in their own homes or in institutions. Subjects with low or intermediate educational status more often reported pain and used light opioids to a larger extent than did the highly educated. These results indicate that musculoskeletal pain is relatively common among the very old, but does not seem to be a severe problem for the majority, considering the low proportion of subjects using prescription analgesics regularly. However, the very low use of potent opioids indicates that some of the elderly suffering from cancer and other severe pain causing diseases might be undertreated.

Journal Article↗
PubMedDate not supplied

The prevalence of functional disability in activities of daily living and instrumental activities of daily living among elderly Beijing Chinese.

In order to assess the prevalence of the functional disability defined by activity of daily living (ADL) and instrumental activity of daily living (IADL) and associated factors in elderly Chinese, a population-based cross-sectional study was performed in urban, plain rural and mountain rural regions of Beijing. Of the 3440 subjects, 1707 are males and 1733 are females, with mean age of 71.4+/-7.7 years. Demographic, socio-economic and health aspects were obtained by trained interviewers. The results showed functional disability prevalence was 6.5% on ADL and 7.9% on IADL. Among the three representative areas in Beijing, the plain rural had the highest disability rate, increasing with the progression of age. Bathing and doing heavy housework were the two most difficult functional tasks. The functional disabilities were associated with gender and marital status. Our data suggest that plain rural elderly are most likely to generate functional disability, and bathing and doing heavy housework are two promising predictors to monitor the development of functional disability in the elderly.

Journal Article↗
PubMedDate not supplied

Quantitative electroencephalography in mild cognitive impairment: longitudinal changes and possible prediction of Alzheimer's disease.

The present study evaluated the clinical course of patients with mild cognitive impairment (MCI), the pattern of electroencephalography (EEG) changes following cognitive deterioration, as well as the potential of neurophysiological measures in predicting dementia. Twenty-seven subjects with MCI were followed for a mean follow up period of 21 months. Fourteen subjects (52%) progressed (P MCI) to clinically manifest Alzheimer's disease (AD), and 13 (48%) remained stable (S MCI). The two MCI subgroups did not differ in baseline EEG measures between each other and the healthy controls (n = 16), but had significantly lower theta relative power at left temporal, temporo-occipital, centro-parietal, and right temporo-occipital derivation when compared to the reference AD group (n = 15). The P MCI baseline alpha band temporo-parietal coherence, alpha relative power values at left temporal and temporo-occipital derivations, theta relative power values at frontal derivations, and the mean frequency at centro-parietal and temporo-occipital derivations overlapped with those for AD and control groups. After the follow-up, the P MCI patients had significantly higher theta relative power and lower beta relative power and mean frequency at the temporal and temporo-occipital derivations. A logistic regression model of baseline EEG values adjusted for baseline Mini-Mental Test Examination showed that the important predictors were alpha and theta relative power and mean frequency from left temporo-occipital derivation (T5-O1), which classified 85% of MCI subjects correctly.

Adult↗
PubMedDate not supplied

Apolipoprotein E genotype and amyloid load in Alzheimer disease and control brains.

We investigated the effect of apolipoprotein E (apoE) genotype on amyloid load in the frontal and cerebellar cortices of 24 patients with definite Alzheimer disease (AD) and 19 controls. Amyloid load was examined by using two methods: 1) acid-extractable amyloid beta-protein (A beta) and insoluble A beta levels of frontal and cerebellar cortices were measured by using enzyme-linked immunosorbent assay, and 2) all types of amyloid plaques and neurofibrillary tangles (NFT) in the frontal cortices were counted after silver staining. Acid-extractable A beta and insoluble A beta levels were higher in AD brains than controls, although there was an overlap between the groups. Acid-extractable A beta and insoluble A beta levels were higher from AD and controls with the apoE epsilon 4 alleles than those without such alleles. However, the differences did not reach statistical significance in AD group. There was no correlation between acid-extractable A beta or insoluble A3 levels and the number of amyloid plaques in AD and control brains. However, insoluble A beta levels correlated positively with the number of NFT in AD brains. Our results show that although apoE epsilon 4 influences the accumulation of A beta, multiple processes may be involved in deposition of A beta in the brain.

Aged↗
PubMedDate not supplied

Intracellular inositol (1,4,5)-trisphosphate receptor levels are preserved in Alzheimer's disease platelets.

An increasing number of signal transduction disturbances have been reported in Alzheimer's disease. These changes are not restricted to histopathologically changed brain areas but are seen also in peripheral tissues. One of the most severe disturbances is a loss of calcium-mobilizing intracellular inositol(1,4,5)-trisphosphate receptors in Alzheimer cerebellar and cortical tissues. In the present study, the binding of [3H]inositol(1,4,5)trisphosphate ([3H]Ins(1,4,5)P3) to the calcium-mobilizing inositol(1,4,5)trisphosphate receptors in platelet membranes from eight Alzheimer's disease patients and eight control subjects were investigated to determine its possible role as a biological marker in Alzheimer's disease. It was found that there were no significant difference in [3H]Ins(1,4,5)P3 binding with respect to the number of sites measured at different protein concentrations or to the sensitivity of the binding to inhibition by nonradioactive Ins(1,4,5)P3 between Alzheimer disease platelets and controls. It is concluded that inositol(1,4,5)trisphosphate receptor levels are preserved in platelets from patients with Alzheimer's disease.

Aged↗
PubMedDate not supplied

IL-1beta and ICE mRNA are not altered upon beta-amyloid(25-35) induced neurotoxicity in human neuroblastoma cells.

The specific beta-amyloid(25-35) fragment induced cellular degradation of the human neuroblastoma cell line SH-SY5Y, but did not elicit an effect on the levels of interleukin-1beta and interleukin-1beta converting enzyme, as determined by semiquantitative reverse transcription-polymerase chain reaction and immunocytochemical analysis. The assays revealed constitutive expression of these proteins both at mRNA and protein level. It is conceivable that in the absence of glial elements, such as in the present neuroblastoma cell line, beta-amyloid triggers the toxicity through a direct action and/or through the production of other harmful molecules.

Amino Acid Chloromethyl Ketones↗
PubMedDate not supplied

Free recall and recognition of slowly and rapidly presented words in very old age: a community-based study.

This study addressed the effects of study time on episodic recall and recognition of words in a community-based sample of healthy older adults ranging from 75 to 96 years of age (N = 221). Results indicated a slight but reliable age-related deterioration of free-recall performance that was attributable to age deficits in secondary memory. The size of the age-related impairment in recognition was reduced relative to that in recall. As well, for all age groups, recall and recognition were higher when items were slowly as opposed to rapidly presented, indicating proficient utilization of study time in very old age. Finally, multiple regression analyses indicated that, although a variety of demographic (i.e., age and education), psychometric (i.e., Mini-Mental State Exam [MMSE] and Block Design scores), and biological (i.e., thyroid-stimulating hormone) variables were related to free-recall performance, only Block Design and MMSE scores made independent contributions to recognition performance.

Aged↗
PubMedDate not supplied

Epidemiology of vascular dementia: some results despite research limitations.

Vascular dementia, the second most common dementia after Alzheimer disease, has great potential for prevention and treatment. Epidemiological data provide the basis for planning primary prevention and clinical trials. Nevertheless, general consensus on disease definition and diagnostic criteria are still not well defined. Despite these limitations, some results from the Kungsholmen project, an epidemiological longitudinal study of people 75 years and older, are presented here.

Alzheimer Disease↗
PubMedDate not supplied

Second International Pharmacoeconomic Conference on Alzheimer' s Disease.

The Second International Pharmacoeconomic Conference on Alzheimer's Disease was held in Stockholm, Sweden, on April 4, 2000. The presentations focused on the role of cognition in pharmacoeconomic evaluations, the costs and consequences of behavioral disturbances, quality of life, disease progression models, and methods for valuing informal care. The results from individual studies will be published separately. Cognition has been used as the sole measure of disease severity in economic evaluations in dementia. However, behavioral disturbances are an important determinant of both cost and quality of life and should also be considered when appraising the effect of treatment. Quality-of-life assessment constitutes a single measure of the total impact of the disease, as well as a way of quantifying the benefits of treatment with antidementia drugs so that they can be compared with interventions in other disease areas. Measuring the quality of life of patients with dementia is associated with methodologic difficulties related to the difficulties for some patients in completing usual assessment processes. Disease progression models may be helpful in extrapolating the results from clinical trials to longer time periods and more representative populations. Modeling is an unavoidable part of the economic evaluation of antidementia drugs, and efforts should be made to increase transparency and comparability among models. Informal care constitutes a large percentage of the total care for patients with dementia, and the valuation of these services has a large impact on the results of pharmacoeconomic evaluations. Difficulties lie in quantifying the time spent on caring for the elderly and in attaching the correct price to each unit of time. The contingent valuation method is an alternative way of valuing informal care that so far has not been used in the field of dementia.

Alzheimer Disease↗
PubMedDate not supplied

The effects of phenytoin on serum and organ concentrations of zinc and copper in cat.

The effects of phenytoin (PHT) on zinc (Zn) and copper (Cu) concentrations in serum and different organs have been studied in cats. Five cats were treated with PHT 5 mg/kg body weight each day. Increased serum concentrations of Zn and Cu were found after 12 weeks of treatment. Increased Zn concentrations were found in the kidney and increased Cu concentrations in the liver and kidney. There wee signs of fatty degeneration of the liver. It is postulated that the drug acts as a chelator of the minerals and enhances their absorption from the intestine. A Cu accumulation may occur during PHT treatment.

Animals↗
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APOE polymorphism and clinical duration determine regional neuropathology in Swedish APP(670, 671) mutation carriers: implications for late-onset Alzheimer's disease.

Neurofibrillary changes throughout the brain were investigated for three relatives who carried the Swedish APP(670, 671) mutation which causes overproduction of Abeta40 and Abeta42. They differed in terms of APOE genotype, age at the onset of dementia, and disease duration (P1: epsilon2/3, age 57, 11 years; P2: epsilon2/3, age 61, 5 years; P3: epsilon4/4, age 44, 12 years). For each subject, paraffin-embedded sections from diverse anatomically and cytoarchitectonically well-preserved regions were stained using the modified Bielschowsky method. Neurofibrillary tangles (NFT) and neuritic plaques (NP) were counted, and the area occupied by plaque estimated (%NP). In addition, sections from the medial frontal gyrus were stained with monoclonal antibodies to APOE. The regional patterns of neurofibrillary changes were consistent with those for late-onset AD. Longer disease duration was associated with further accumulations in earlier-affected areas, with superficial cortical layers consistently containing higher %NP than deep layers. APOE epsilon4/4 was associated with deeper limbic and frontal NFT, with an excess of NP (especially in the outer parietal cortex) which stained heavily for APOE - as well as with very early onset. APP(670, 671) mutation carriers demonstrate regional brain neurofibrillary changes characteristic of late-onset Alzheimer's disease with evidence for more Abeta deposition for epsilon4/4 than epsilon2/3. This raises the possibility that early Braak Stage I-II lesions might also follow this pattern of promotion.

Adult↗