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Biomedical subjects

B Winblad

Publications and source records attributed to B Winblad.

At least 109 records · Page 6Linked to original sources
PubMed1999

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↗
PubMed1999

Mortality in nondemented subjects with cognitive impairment: the influence of health-related factors.

Nondemented older subjects with cognitive impairment are at higher risk of death than are mentally intact persons. It is unknown whether the effect of cognitive impairment on mortality is independent or mediated by poorer health or other factors. To address this issue, the authors used a prospective population-based cohort study with 8 years of follow-up started in 1987 in the urban district of Kungsholmen, Stockholm, Sweden. Subjects were all 75- to 95-year-old subjects nondemented at baseline (n = 1,435). Data on cognition, health (mental and subjective health, physical diseases and comorbidity, nutritional status, and disability), and apolipoprotein E genotype were collected at baseline as was time of death at follow-up. Cognitive impairment was defined on the basis of age- and education-specific cutoffs on the Mini-Mental State Examination. When compared with cognitively unimpaired subjects (n = 1,210), those cognitively impaired (n = 225) had poorer health conditions, were more frequently apolipoprotein E epsilon4 carriers, and had greater mortality risk (hazard ratio = 1.7; 95% confidence interval: 1.5, 2.1). Neither health nor apolipoprotein E genotype accounted for the association of cognitive impairment with mortality (adjusted hazard ratio = 1.6; 95% confidence interval: 1.3, 1.9). The functional and behavioral consequences associated with the progression of cognitive impairment may mediate the increased mortality risk.

Aged↗
PubMed1999

Sensitivity, specificity, and stability of CSF-tau in AD in a community-based patient sample.

OBJECTIVE: To evaluate the sensitivity and specificity of CSF-tau in clinical practice as a diagnostic marker for AD compared with normal aging and depression, to study the stability of CSF-tau in longitudinal samples, and to determine whether CSF-tau levels are influenced by different covariates such as gender, age, duration or severity of disease, or possession of the APOE-epsilon4 allele. METHODS: Consecutive AD patients from a community-based sample were studied, including 407 patients with AD (274 with probable AD and 133 with possible AD), 28 patients with depression, and 65 healthy elderly control subjects. A follow-up lumbar puncture was performed in 192 AD patients after approximately 1 year. CSF-tau was determined using a sandwich ELISA, which was run as a routine clinical neurochemical analysis. RESULTS: CSF-tau was increased in probable (690+/-341 pg/mL; p < 0.0001) and possible (661+/-447 pg/mL; p < 0.0001) AD, but not in depression (231+/-110 pg/mL) compared with control subjects (227+/-101 pg/mL). Receiver operating characteristics analysis showed that a cutoff level of 302 pg/mL resulted in a sensitivity of 93% (95% CI, 90-96%) and a specificity of 86% (95% CI, 75-94%), with an area under the curve of 0.95 to discriminate AD from control subjects. Within the AD group, CSF-tau did not differ significantly between baseline and follow-up investigations, and was relatively stable between baseline and 1-year follow-up levels, with a coefficient of variation of 21.0%. High CSF-tau levels were also found in most AD patients with very short duration of dementia, and with Mini-Mental State Examination scores >23 (n = 205). In total, 193 of 205 patients (sensitivity, 94%) had a CSF-tau level higher than 302 pg/mL. CONCLUSIONS: CSF-tau has a high sensitivity and specificity to differentiate AD from normal aging and depression, as demonstrated in a large community-based series of consecutive AD patients during which analyses were run continually in a clinical neurochemical laboratory. The increase in CSF-tau is found very early in the disease process in AD, is stable over time, and has a low interindividual variation on repeated sampling. Although high CSF-tau is found in some neurologic conditions (e.g., stroke), these findings suggest that CSF-tau may be of use to help in differentiating AD from normal aging and depression, especially early in the course of the disease, when the symptoms are vague and the diagnosis is especially difficult.

Aged↗
PubMed1999

Cerebrospinal fluid tau and Abeta42 as predictors of development of Alzheimer's disease in patients with mild cognitive impairment.

We studied CSF-tau and CSF-Abeta42 in 16 patients with mild cognitive impairment (MCI) who at follow-up investigations 6-27 months later had progressed to Alzheimer's disease (AD) with dementia. For comparison, we studied 15 age-matched healthy individuals. At baseline, 14/16 (88%) of MCI patients had high CSF-tau and/or low CSF-Abeta42 levels. These findings show that these CSF-markers are abnormal before the onset of clinical dementia and that they may help to identify MCI patients that will develop AD. This is especially important when drugs with potential effects on the progression of AD will reach the clinical phase.

Aged↗
PubMed1999

Dynamics of production of MIP-1alpha, MCP-1 and MIP-2 and potential role of neutralization of these chemokines in the regulation of immune responses during experimental autoimmune neuritis in Lewis rats.

Experimental autoimmune neuritis (EAN) is an inflammatory autoimmune demyelinating disease of the peripheral nervous system (PNS) and represents an animal model of Guillain-Barré syndrome (GBS), which is a major inflammatory demyelinating disease of the PNS in humans. In the present study, the dynamics of the expression of the chemokines macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-2 and monocyte chemotactic protein-1 (MCP-1) were determined in the sciatic nerves of EAN rats. Additionally, the effect of neutralizing antibodies against MIP-1alpha, MIP-2 and MCP-1 on the clinical course of EAN and the chemokine expression was investigated. The maximum of MIP-1alpha positive cells in the sciatic nerves was seen on day 14 post immunization (p.i.) correlating with the development of severe clinical signs. Administration of an anti-MIP-1alpha antibody suppressed the clinical signs of EAN and inhibited inflammation and demyelination in the sciatic nerve. Peak numbers of MCP-1 positive cells in the sciatic nerves were detected on day 7 p.i. Administration of an anti-MCP-1 antibody caused a delay of onset of EAN. However, 4 of the 6 EAN rats receiving the anti-MCP-antibody showed the same degree of inflammatory cell infiltration and demyelination in the sciatic nerves as sham-treated EAN rats, whereas only 2 EAN rats had less inflammation and demyelination. The numbers of MIP-2 positive cells reached a maximum on day 21 p.i. Anti-MIP-2 antibody failed to suppress the clinical signs of EAN and the inflammation and demyelination in the sciatic nerves. Only administration of the anti-MIP-1alpha antibody resulted in a significant reduction in the number of chemokine (MIP-1alpha)-positive cells and ED1-positive macrophages in the sciatic nerves. The present results demonstrate that MIP-1alpha and MCP-1 may play a role in the immunopathogenesis of EAN, and that MIP-1alpha induced trafficking of inflammatory cells can be inhibited by immunoneutralization. Further elucidation of the regulation and coordination of MIP-1alpha and MCP-1 production may lead to new therapeutic approaches to GBS in humans.

Animals↗
PubMed1999

Inhibition of [3H]forskolin binding by Gpp[NH]p may reflect adenylate cyclase coupling to Gi.

The effect of the GTP analogue guanylyl-5'-imidodiphosphate (Gpp[NH]p) on [3H]forskolin binding was studied in rat brain using autoradiography. In the striatum the presence of 100 microM Gpp[NH]p produced a 40% increase in binding, whereas a decrease of about 30% was observed with low Gpp[NH]p concentrations (0.1 microM). In the molecular layer of the cerebellum all concentrations of Gpp[NH]p decreased [3H]forskolin binding. The decrease in binding disappeared in both striatum and the molecular layer of cerebellum in sections pretreated with 100 microM N-ethylmaleimide (NEM) for 10 min. NEM pretreatment did not significantly affect the stimulation of [3H]forskolin binding by micromolar concentrations of Gpp[NH]p in the striatum, but reversed the decrease observed in the molecular layer of the cerebellum, to an increase. Based on these data we suggest that the effects of Gpp[NH]p on [3H]forskolin binding may involve both Gs and Gi, where stimulation produces an increase and decrease in binding, respectively. The regional effects of Gpp[NH]p may reflect differences in the responsiveness of adenylate cyclase to Gs- and Gi-mediated effects.

Adenylyl Cyclases↗
PubMed1999

Brain regions associated with episodic retrieval in normal aging and Alzheimer's disease.

OBJECTIVE: To examine patterns of brain activation during verbal episodic retrieval in normal elderly subjects and patients in an early phase of AD. BACKGROUND: It is established that 1) a profound episodic memory impairment is a cardinal symptom of AD; and 2) some of the earliest brain changes in this disease occur in regions critical to episodic memory, such as the hippocampus and neighboring regions. Yet, it remains largely unknown whether the episodic memory deficit seen in AD is paralleled by concomitant alterations in brain activity during actual task performance in these or other brain areas. METHODS: Using PET, blood flow was assessed in normal elderly subjects and patients with early AD during two retrieval conditions involving completion of word stems: baseline and cued recall. RESULTS: The patients with AD showed a marked performance deficit in cued recall, although the two groups were indistinguishable in the baseline task condition. Both groups showed bilateral activity in orbital and dorsolateral prefrontal cortex, left precuneus, and right cerebellum, as well as decreased activity in distinct left temporal regions during cued recall. The normal elderly alone activated the left parietal cortex and the left hippocampal formation during episodic retrieval. By contrast, AD-related increases in activity during cued recall were observed in the left orbital prefrontal cortex and left cerebellum. CONCLUSIONS: The similar patterns of activations in the two groups suggest that a large distributed network involved in episodic memory retrieval functions relatively normally in early AD. Those retrieval activations seen in the normal elderly, as opposed to the patients, may reflect AD-related failures in semantic processing and successful recollection of the target information, respectively. Finally, the AD-related increases in activity were interpreted in terms of compensatory reactions to the difficulties in performing the episodic memory task.

Aged↗
PubMed1999

Further evidence on the effects of vitamin B12 and folate levels on episodic memory functioning: a population-based study of healthy very old adults.

BACKGROUND: The relationship between vitamin status and cognitive functioning has been addressed in several recent studies with inconclusive results. The purpose of this study was to examine separate and combined effects of serum vitamin B12 and folic acid on episodic memory functioning in very old age. METHODS: Four study groups were selected from a population-based sample of healthy very old adults (90-101 years of age): normal B12/normal folic acid, low B12/normal folic acid, normal B12/low folic acid, and low B12/low folic acid. Cutoff levels were set at 180 pmol/L for vitamin B12 and at 13 nmol/L for folic acid. Subjects completed two episodic recall tasks (objects and words) and two episodic recognition tasks (faces and words). RESULTS: Neither vitamin affected recognition or primary memory. Most interesting, although B12 was unrelated to recall performance, subjects with low folic acid levels showed impairment in both word recall and object recall. CONCLUSIONS: These results replicate and extend previous findings that folic acid may be more critical than B12 to memory functioning in late life. The selective effects of folic acid on episodic recall were discussed in terms of encoding and retrieval mechanisms, as well as in relation to brain protein synthesis.

Aged↗
PubMed1999

Smoking and the occurrence of Alzheimer's disease: cross-sectional and longitudinal data in a population-based study.

The authors tested the hypothesis that smoking exerts a protective effect on Alzheimer's disease or dementia in a population-based cohort of 668 people aged 75-101 years (Sweden). Smoking was negatively associated with prevalent Alzheimer's disease (adjusted odds ratio = 0.6, 95% confidence interval 0.4-1.1) and dementia (adjusted odds ratio = 0.6, 95% confidence interval 0.4-1.0). Over 3-year follow-up (1989-1992), the hazard ratios of incident Alzheimer's disease and dementia due to smoking were 1.1 (95% confidence interval 0.5-2.4) and 1.4 (95% confidence interval 0.8-2.7). Mortality over 5-year follow-up was greater among smokers in demented (hazard ratio = 3.4) than nondemented (hazard ratio = 0.8) subjects. Smoking does not seem protective against Alzheimer's disease or dementia, and the cross-sectional association might be due to differential mortality.

Aged↗
PubMed1999

Aging and the occurrence of dementia: findings from a population-based cohort with a large sample of nonagenarians.

CONTEXT: In spite of numerous studies on the occurrence of dementia, many questions remain, such as the relation between age, aging, and dementing disorders. This question is relevant both for understanding the pathogenetic mechanism of the dementias and for the public health prospective because of the increasing number of 85-year-old or older persons in our population. OBJECTIVE: To estimate the occurrence of dementia in the very old, including nonagenarians, in relation to age, gender, and different dementia types. DESIGN: An epidemiological survey where all participants were clinically examined by physicians, assessed by psychologists, and interviewed by nurses. The Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R) criteria for dementia were followed. A category of "questionable dementia" was added when all criteria were not fulfilled. A double diagnostic procedure was used for all subjects. SETTING: Community-based population, including all inhabitants of 2 areas in central Stockholm, Sweden (N = 1848). PARTICIPANTS: Of the 1848 subjects in the study population, 168 (9.1%) had died and 56 (3%) moved before examination. Of the remaining subjects, 1424 (87.7%) were examined, and the refusal rate was 12.3%. MAIN OUTCOME MEASURES: Age- and gender-specific prevalence figures, and gender- and education-adjusted odds ratios were used. RESULTS: At the end of the diagnostic procedure, 358 clinically definite cases of dementia and 101 questionable cases of dementia were identified. Alzheimer disease (AD) contributed to 76.5%, and vascular dementia (VaD) to 17.9%. The prevalence of dementia increases from 13% in the 77- to 84-year-old subjects to 48% among persons 95 years and older (from 18% to 61% when questionable cases were included). The odds ratio for subjects 90 to 94 years and 95 years and older in comparison with 77- to 84-year-old subjects was 3.7 (95% confidence interval [CI], 2.7-5.1) and 6.5 (95% CI, 3.9-10.8) for dementia, 4.8 (95% CI, 3.3-7.0) and 8.0 (95% CI, 4.6-14.0) for persons with AD, 2.3 (95% CI, 1.3-4.2) and 4.6 (95% CI, 1.9-11.2) for VaD, respectively. CONCLUSIONS: Dementia prevalence continues to increase even in the most advanced ages. This increase is especially evident among women and is more clear for AD. We believe that our prevalence data reflect the differential distribution of dementia risk.

Age Factors↗
PubMed1999

Cerebrospinal fluid beta-amyloid(1-42) in Alzheimer disease: differences between early- and late-onset Alzheimer disease and stability during the course of disease.

OBJECTIVES: To study the diagnostic potential of the 42 amino acid form of beta-amyloid (beta-amyloid(1-42)) in cerebrospinal fluid (CSF) as a biochemical marker for Alzheimer disease (AD), the intra-individual biological variation of CSF-beta-amyloid(1-42) level in patients with AD, and the possible effects of differential binding between beta-amyloid and apolipoprotein E isoforms on CSF-beta-amyloid(1-42) levels. DESIGN: A 20-month prospective follow-up study. SETTING: Community population-based sample of consecutive patients with AD referred to the Piteå River Valley Hospital, Piteå, Sweden. PATIENTS: Fifty-three patients with AD (mean +/- SD age, 71.4 +/- 7.4 years) diagnosed according to the National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association criteria and 21 healthy, age-matched (mean +/- SD age, 68.8 +/- 8.0 years) control subjects. MAIN OUTCOME MEASURES: Cerebrospinal fluid beta-amyloid(1-42) level--analyzed using enzyme-linked immunosorbent assay--and severity of dementia--analyzed using the Mini-Mental State Examination. RESULTS: Mean +/- SD levels of CSF-beta-amyloid(1-42) were decreased (P<.001) in patients with AD (709 +/- 304 pg/mL) compared with controls (1678 +/- 436 pg/mL). Most patients with AD (49 [92%] of 53 patients) had reduced levels (<1130 pg/mL). A highly significant correlation (r = 0.90; P<.001) between baseline and 1-year follow-up CSF-beta-amyloid(1-42) levels was found. There were no significant correlations between CSF-beta-amyloid(1-42) level and duration (r = -0.16) or severity (r = -0.02) of dementia. Low levels were also found in patients with mild dementia (Mini-Mental State Examination score, >25). CONCLUSIONS: The sensitivity of CSF-beta-amyloid(1-42) level as a diagnostic marker for AD is high. The intra-individual biological variation in CSF-beta-amyloid(1-42) level is low. Low CSF-beta-amyloid(1-42) levels are also found in the earlier stages of dementia in patients with AD. These findings suggest that CSF-beta-amyloid(1-42) analyses may be of value in the clinical diagnosis of AD, especially in the early course of the disease, when drug therapy may have the greatest potential of being effective but clinical diagnosis is particularly difficult.

Aged↗
PubMed1999

Occurrence and progression of dementia in a community population aged 75 years and older: relationship of antihypertensive medication use.

OBJECTIVE: To examine whether antihypertensive medication use can affect the occurrence and progression of dementia. SUBJECTS AND METHODS: In a community cohort of 1810 persons aged 75 years and older, 225 prevalent cases of dementia were detected. Among the 1301 persons without dementia, 224 incident cases of dementia were identified during an average period of 3 years. Among the 225 prevalent cases of dementia, 79 were suitable for the analysis of cognitive decline. Information on drug use was collected for the 2 weeks preceding the baseline interview. RESULTS: Subjects taking antihypertensive medication (n = 651, 83.9% of whom took diuretics) had a lower prevalence of dementia than those not taking antihypertensive medication (P<.001). Subjects without dementia who were taking antihypertensive medication at baseline (n = 584) had a reduced incidence of dementia (adjusted relative risk, 0.7; 95% confidence interval, 0.6-1.0; P = .03). Furthermore, subjects taking diuretics (n = 484) had an adjusted relative risk of 0.7 (95% confidence interval, 0.5-1.0; P = .02) for all dementia, and subjects taking diuretic monotherapy (n = 345) had an adjusted relative risk of 0.6 (95% confidence interval, 0.4-0.9; P = .006). The use of other antihypertensive medication (calcium antagonists or beta-blockers), however, was related to a reduced risk of Alzheimer disease (adjusted relative risk, 0.6; 95% confidence interval, 0.3-1.2) only in the subpopulation with a higher baseline blood pressure (n = 458). Patients with dementia at baseline who were not taking diuretics had a 2-fold faster rate of decline in the score on the Mini-Mental State Examination than those taking diuretics. CONCLUSION: The use of diuretics may protect against dementia in elderly persons.

Aged↗
PubMed1999

Memantine in severe dementia: results of the 9M-Best Study (Benefit and efficacy in severely demented patients during treatment with memantine).

OBJECTIVES: To assess clinical efficacy and safety of memantine--an uncompetitive N-methyl-D-aspartate (NMDA) antagonist--in moderately severe to severe primary dementia. MATERIALS AND METHODS: Dementia was defined by DSM-III-R criteria and severity was assessed by the Global Deterioration Scale (stages 5-7) and the Mini-Mental State Examination (< 10 points). Primary endpoints were the Clinical Global Impression of Change (CGI-C) rated by the physician, and the Behavioural Rating Scale for Geriatric Patients (BGP), subscore 'care dependence', rated by the nursing staff. Secondary endpoints included the modified D-Scale (Arnold/Ferm). RESULTS: The ITT sample comprised 166 patients and 151 patients were treated per protocol. At 12-week ITT endpoint analysis, 82 received memantine 10 mg per day, 84 placebo. Dementia was in 49% of the Alzheimer type and in 51% of the vascular type (CT, Hachinski score). A positive response in the CGI-C was seen in 73% versus 45% in favour of memantine (stratified Wilcoxon p < 0.001), independent of the etiology of dementia. The results in the BGP subscore 'care dependence' were 3.1 points improvement under memantine and 1.1 points under placebo (p = 0.016). A coincident response of the two independent target variables was observed in 61.3% (memantine) versus 31.6% (placebo). Secondary endpoint analysis of the D-Scale assessing basic ADL functions support the primary results. Regarding the safety profile, no significant differences between treatment groups were observed. CONCLUSIONS: The results of this trial support the hypothesis that memantine treatment leads to functional improvement and reduces care dependence in severely demented patients.

Activities of Daily Living↗
PubMed1999

The social consequences for families with Alzheimer's disease patients: potential impact of new drug treatment.

The social consequences of Alzheimer's disease are highlighted in this review with regard to impact on family situation, a changing treatment context caused by demographic changes, reorganization of long-term care, a financial crisis in the public health systems and the introduction of antidementia drugs. In the early phase of dementia there may be significant consequences for the patients and the family members which are largely unrecognized by the healthcare system. As the disease progresses, the impact on caregivers in terms of physical and emotional burden, financial and employment status may be enormous. The current care provision in Sweden, the UK and The Netherlands is described. Innovative care alternatives and strategies may improve the situation. The introduction of antidementia drugs such as the acetylcholine esterase inhibitors may also contribute to improved circumstances for patients and caregivers. There is still a great need for further research in this field.

Activities of Daily Living↗
PubMed1999

Incidence of major depression in a very elderly population.

BACKGROUND: Depression is considered to be a major health problem in the elderly. Due to methodological problems, there are few studies on the incidence of depression in old age. The present study examines the prevalence of depression in a 3-year follow-up study of a non-depressed very elderly population, thus estimating the incidence. METHODS: 875 non-depressed persons with a mean age of 85 years were extensively examined by physicians twice with a 3-year interval. Depression diagnosis was made according to DSM-IV. All persons with a history of depression or a current depression were excluded in order to estimate the first incidence. RESULTS: 4.1% of the population was diagnosed as having a depression at the follow-up examination. The estimated first incidence was 1.4% per person year (0.8% in males and 1.5% in females). Characteristics at baseline correlated with the onset of depression were: having a dementia, insufficient social network and having more than two depressive symptoms. CONCLUSIONS: The incidence of depression was slightly lower in this very elderly population than for younger age groups, but followed the same female to male ratio.

Age Distribution↗