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G Waldemar

Publications and source records attributed to G Waldemar.

At least 19 recordsLinked to original sources
PubMed2001

A 1-year, randomized, placebo-controlled study of donepezil in patients with mild to moderate AD.

OBJECTIVE: To evaluate the long-term clinical efficacy and safety of donepezil versus placebo over 1 year in patients with mild to moderate AD. METHODS: Patients (n = 286; mean age, 72.5 years) with possible or probable AD from five Northern European countries were randomized to receive either donepezil (n = 142; 5 mg/day for 28 days, followed by 10 mg/day) or placebo (n = 144) for 1 year. RESULTS: The study was completed by 66.9% of the donepezil- and 67.4% of the placebo-treated patients. The benefit of donepezil over placebo was demonstrated by the Gottfries-Bråne-Steen (a global assessment for rating dementia symptoms) total score at weeks 24, 36, and 52 (p < 0.05) and at the study end point (week 52, last observation carried forward; p = 0.054). Advantages of donepezil over placebo were also observed in cognition and activities of daily living (ADL) assessed by the Mini-Mental State Examination at weeks 24, 36, and 52, and the end point (p < 0.02) and by the Progressive Deterioration Scale at week 52 and the end point (p < 0.05). Adverse events (AE) were recorded for 81.7% of donepezil- and 75.7% of placebo-treated patients, with 7% of donepezil- and 6.3% of placebo-treated patients discontinuing because of AE. Treatment response to donepezil was not predicted by APOE genotype or sex in this population. CONCLUSION: As the first 1-year, multinational, double-blinded, placebo-controlled study of a cholinesterase inhibitor in AD, these data support donepezil as a well tolerated and effective long-term treatment for patients with AD, with benefits over placebo on global assessment, cognition, and ADL.

Aged↗
PubMed2001

Management of dementia in primary health care: the experiences of collaboration between the GP and the district nurse.

OBJECTIVE: The objective of this study was to explore the context and experiences of collaboration between the GP and the district nurse (DN) in diagnosing dementia, in order to identify possible procedures to improve care. METHODS: Two group interviews were conducted with four DNs and five GPs, respectively, working in the municipality of Copenhagen. RESULTS: The group interviews revealed that the suboptimized collaboration could be due to different inter-professional diagnostic strategies and a lack of understanding of the importance of early, shared, decision making. This could create conflicts between the groups. CONCLUSIONS: This study indicates a possibility for improved collaboration between the two professional groups in diagnosing dementia. Possible approaches for improved care should focus on an inter-professional understanding of the importance of early, shared, decision making, emphasizing early identification and care of diagnosed demented patients. Establishing a shared collaboration model including out-patient memory clinics, GPs and DNs could be a first step. This model should also take into account an evaluation of possible consequences for the diagnosed demented patients in terms of treatment and care and consider the indication for referrals to a comprehensive diagnostic evaluation. We are at present planning a study to address these aspects.

Adult↗
PubMed2001

Single photon emission computed tomography and apolipoprotein E in Alzheimer's disease: impact of the epsilon4 allele on regional cerebral blood flow.

The aim of this study was to examine the impact of the apolipoprotein E (APOE) epsilon4 allele on semiquantitative regional cerebral blood flow (rCBF) in Alzheimer's disease. Single photon emission computed tomography technetium (SPECT) with (99m)Tc d,l-hexamethyl propylenamine oxine was used to determine rCBF in 41 consecutive patients (18 males/23 females) with probable Alzheimer's disease according to the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria (mean age 71.0 years; range 54-85). The mean Mini-Mental State Examination (MMSE) score was 20.4 (range 10-30). After normalization of CBF to mean blood flow in the cerebellum, values for rCBF in several cortical regions of interest, side-to-side asymmetry indices, and anterior-posterior ratios were calculated. Determination of the APOE genotype from blood samples was performed using restriction enzyme polymerase chain reaction technique. Multivariate regression analyses and the Wilcoxon rank-sum test for unpaired data (Mann-Whitney) were used for statistical analysis. The patients comprised 27APOE epsilon4-positive and 14APOE epsilon4-negative individuals. Five patients were APOE epsilon4 homozygotes. APOE epsilon4-positive patients had significantly reduced rCBF in the right frontal and left occipital lobes. On nonparametric analysis, the most prominent differences between epsilon4-negative and epsilon4-positive patients were demonstrated in subregions representing the frontal association cortex (Mann-Whitney, P < .01). Age-stratified analysis suggested that these findings could be demonstrated predominantly in the elderly patients. The results of this study suggest that the APOE genotype in itself may have an impact on the pattern of rCBF deficits in Alzheimer's disease. The more pronounced reduction of rCBF in frontal association cortex observed in elderly APOE epsilon4-positive patients might predict clinical progression.

Age Factors↗
PubMed2000

Diagnosis and management of Alzheimer's disease and other disorders associated with dementia. The role of neurologists in Europe. European Federation of Neurological Societies.

In 1998 a task force to develop guidelines for diagnostic evaluation and treatment of dementia was initiated by the European Federation of Neurological Societies (EFNS) scientist panel on dementia. The aims of the task force were to provide evidence-based recommendations and to highlight the role of the neurologist in the management of patients with Alzheimer's disease and other disorders associated with dementia. We based our recommendations on a review of available evidence-based guidelines supplemented with further literature reviews. The recommendations were derived from consensus meetings and relate to individual patient management, as there are inadequate data on the cost-effectiveness of different diagnostic evaluations and treatments for dementia. Their specific applications will depend upon available resources. The particular contributions of the neurologist include: early identification and differential diagnosis of rare and common brain disorders causing cognitive and behavioural symptoms, referral for and interpretation of ancillary investigations, and identification and treatment of vascular and other concurrent diseases. A review of the management of dementia in Europe revealed considerable variation. In some countries neurologists have taken the lead in the management of patients with dementia, while in other countries the neurologist is rarely involved. We recommend that neurologists should have a clear role in the management of dementia in the whole of Europe. They should be involved in the diagnostic evaluation of dementia and facilitate the development of multidisciplinary teams for evaluation and management of patients with cognitive disturbances. The increasing role of neurology in the management of patients with dementia has important implications for training and education.

Alzheimer Disease↗
PubMed1999

[Behavioral disorders in nursing home residents. 147 consecutive referrals to an interdisciplinary team of consulting specialists].

During a period of 22 months 147 consecutive residents with behavioural disturbances from 80% of the Copenhagen nursing homes were referred to a visiting team of consulting specialists. Each resident was evaluated clinically, and data were recorded in a database. The conditions thought to represent the underlying etiologies were dementia (79%), delirium (28%) and depression (35%). The most commonly observed behavioural symptoms were aggressiveness, vocally disruptive behavior and non-aggressive psychomotor symptoms. The most common interventions suggested by the team were further diagnostic evaluations, adjustment of pharmaceutical treatment, using the life history of the resident as a reference for behaviour management, and psychological behavior management. There is a need for increased focus on systematic diagnosis and treatment of behavioural disorders, observed in nursing homes, which often have multifactorial etiology.

Aged↗
PubMed1999

Shunting effects in patients with idiopathic normal pressure hydrocephalus; correlation with cerebral and leptomeningeal biopsy findings.

Normal Pressure Hydrocephalus (NPH) is a potentially treatable syndrome with abnormal cerebrospinal fluid dynamics. Meningeal fibrosis and/or obliteration of the subarachnoid space have been suggested as one of the patho-anatomical substrates. However, other types of adult onset dementia, predominantly Alzheimer's disease and Vascular Dementia, may mimic the clinical NPH characteristics. The purpose of the present study was to correlate cerebral parenchymal and leptomeningeal biopsy findings to the clinical outcome after CSF shunting in a prospective group of idiopathic NPH (INPH) patients. The study comprises 27 patients with INPH, diagnosed and shunted according to generally accepted clinical, imaging and hydrodynamic criteria. In all patients a frontal leptomeningeal and brain biopsy was obtained prior to the shunt insertion. Degenerative cerebral changes, most often Alzheimer (6 cases) or vascular changes (7 cases) were described in 14 out of 27 biopsies. Arachnoid fibrosis was found in 9 of the 18 biopsies containing arachnoid tissue. Overall, nine patients (33%) improved, of whom 6 presented Alzheimer or vascular changes in their biopsies. No correlation was found between clinical outcome and the presence or absence of degenerative cerebral changes and/or arachnoid fibrosis. However, a tendency towards higher improvement rates was noted in the subgroups presenting degenerative cerebral changes or arachnoid fibrosis. The results suggest that no constant morphological element exists in the syndrome of INPH. Various aetiologies may be involved in the pathogenesis and possibly in some cases co-existing: Patients may also improve by shunting despite the presence of degenerative cerebral parenchymal changes.

Aged↗
PubMed1999

A multidisciplinary memory clinic in a neurological setting: diagnostic evaluation of 400 consecutive patients.

This report describes the operation of a multidisciplinary university hospital memory clinic in a neurological setting, and the diagnostic evaluations in 400 consecutive patients referred for cognitive symptoms and possible dementia during a period of 27 months (1 September 1995-31 December 1997). The mean age of the patients was 63.6 years (range 19-97). On clinical and neuropsychological examination, 46% of the patients fulfilled DSM IV criteria for dementia, 5% had selective amnesia, and 14% had other selective cognitive deficits. The remaining patients had either no significant cognitive deficits (31%) or were not evaluable (4%). A wide range of disorders from the fields of neurology, psychiatry, neurosurgery and internal medicine were identified as the underlying etiologies for the cognitive symptoms. Potentially reversible conditions were observed in 26% of the patients, not including the 11% in whom no specific underlying disease was identified. Concomitant conditions or risk factors with a potential influence on cognitive functions were identified in 61% of the patients. Diagnostic evaluation of patients with mild to moderate cognitive symptoms and possible dementia is an integrated multidisciplinary task, which should focus on the identification of non-progressive and potentially reversible etiologies, co-morbidity, selective cognitive deficits, and rare or atypical neurological conditions, as well as on the early identification of common progressive dementia disorders.

Adult↗
PubMed1997

[Dementia].

Explore the source record for details and available documents.

Alzheimer Disease↗
PubMed1997

Functional brain imaging with single-photon emission computed tomography in the diagnosis of Alzheimer's disease.

High-resolution single-photon emission computed tomography (SPECT) with brain-retained technetium-99m (99mTc)-labeled tracers may be used for 3-dimensional measurements of regional cerebral blood flow (rCBF). This article summarizes important findings in SPECT studies of Alzheimer's disease (AD). There are three distinct potential applications of SPECT in diagnosing AD: (a) as a diagnostic adjunct in patients with mild cognitive or behavioral symptoms, suggesting a possible dementia disorder; (b) as a diagnostic adjunct for demented patients in whom the history, physical examination, and laboratory studies are in agreement with a diagnosis of probable AD; and (c) for determining the relative contributions of degenerative and vascular pathology to the clinical picture in demented patients with mixed disease. A clinical diagnosis of probable AD is associated with focal perfusion deficits as measured by SPECT. Characteristically, hypoperfusion is observed in the frontal and temporoparietal association areas, whereas other brain regions are relatively spared. The changes are present in the early phases of AD. The topography of rCBF deficits displays a marked heterogeneity among patients and correlates with cognitive profiles. In patients with mild cognitive complaints, the presence of focal hypoperfusion on SPECT may increase the accuracy of the diagnosis by confirming the presence of brain disease. In patients with probable AD, the presence of temporoparietal rCBF deficits on SPECT increases the accuracy of the clinical diagnosis, in particular when associated with medial temporal lobe atrophy on cranial X-ray computed tomography (CT). The role of SPECT in diagnosing patients with mixed disease remains to be clarified.

Alzheimer Disease↗
PubMed1997

Frontal brain and leptomeningeal biopsy specimens correlated with cerebrospinal fluid outflow resistance and B-wave activity in patients suspected of normal-pressure hydrocephalus.

OBJECTIVE: Normal-pressure hydrocephalus (NPH) is a potentially treatable syndrome with abnormal cerebrospinal fluid dynamics. Meningeal fibrosis and/or obliteration of the subarachnoid space has been suggested as the pathoanatomic basis. The purpose of the present study was to investigate whether meningeal fibrosis causes increased resistance to cerebrospinal fluid outflow (R(out)) and/or increased B-wave activity and whether pathological changes in the brain parenchyma after brain compliance, causing increased B-wave activity. METHODS: The study involved a group of 38 consecutively studied patients with clinical and radiological evidence of idiopathic NPH, for whom a frontal brain biopsy was obtained. For 29 patients, hydrodynamic criteria of NPH were fulfilled and a ventriculoperitoneal shunt was performed. RESULTS: Meningeal fibrosis was found in 12 of 25 biopsies containing arachnoid tissue, but no correlation with R(out) or B-waves was found. Pathological parenchymal changes, most often Alzheimer's disease (10 cases) or vascular changes (10 cases), were found in 21 biopsies, but no correlation with B-waves or R(out) was found. CONCLUSION: The results suggest that leptomeningeal fibrosis is not the only pathoanatomic basis of increased R(out) and/or B-wave activity in patients with NPH and that various degenerative changes in the parenchyma may be responsible for the altered cerebrospinal fluid dynamics characteristic of NPH.

Adult↗
PubMed1997

Differential effects of increasing doses of alpha-trinositol on cerebral blood flow autoregulation.

The effect of neuropeptide Y inhibition with alpha-trinositol on the cerebral blood flow autoregulation was studied in Wistar Kyoto rats. alpha-Trinositol was tested in two doses: one dose (5 mg kg-1 hr-1) selectively affecting neuropeptide Y and one higher dose (50 mg kg-1 hr-1) affecting both neuropeptide Y and the adrenergic response. The cerebral blood flow was measured with the intracarotid 133xenon injection method in halothane nitrous oxide-anaesthetized animals. Blood pressure was raised by norepinephrine infusion and lowered by controlled haemorrhage in separate groups of rats. In addition we examined the effect of alpha-trinositol on neuropeptide Y-induced contraction of cerebral vessels in vitro. The in vitro study demonstrated inhibition of neuropeptide Y-induced contraction with a alpha-trinositol dose selective of neuropeptide Y. The in vivo study demonstrated that cerebral blood flow autoregulation was preserved after both doses of alpha-trinositol. alpha-Trinositol in the low neuropeptide Y-selective dose (5 mg kg-1 hr-1) did not affect the blood pressure limits of cerebral blood flow autoregulation, but the higher dose (50 mg kg-1 hr-1) of alpha-trinositol shifted the upper blood pressure limit of cerebral blood flow autoregulation towards lower blood pressures, an effect probably due to inhibition of both the adrenergic and neuropeptide Y systems.

Animals↗
PubMed1995

Alterations in perivascular dilatory neuropeptides (CGRP, SP, VIP) in the external jugular vein and in the cerebrospinal fluid following subarachnoid haemorrhage in man.

A possible involvement of perivascular vasodilatory neuropeptides in subarachnoid haemorrhage (SAH) has been evaluated in man by measuring the levels of calcitonin gene related peptide (CGRP)-, substance P (SP)- and vasoactive intestinal peptide (VIP)-like immunoreactivity (LI) in the cranial venous outflow and in CSF in 34 patients admitted to the hospital after an acute SAH. After operation with aneurysm clipping and nimodipine treatment, blood samples were taken from the external jugular vein (EJV) or cerebrospinal fluid (CSF) and analysed for neuropeptide levels with specific radioimmuno assays (RIA) during the postoperative course. The degree of vasoconstriction in the patients was monitored with Doppler ultrasound recordings bilaterally from the middle cerebral (MCA) and internal carotid arteries (ICA) following the EJV blood sampling every second day. The mean value of all CGRP-LI measurements in EJV during the entire course of SAH (n = 20) revealed a significantly higher level as compared to controls. The highest CGRP-LI levels were found in patients with the highest velocity index values (vasospasm). The relationship Vmean MCA/Vmean ICA was used as an index of vasoconstriction. In patients with MCA aneurysms (n = 10), a significant correlation (r = 0.65, p < 0.05) was found between the vasospasm index and CGRP-LI levels. There were no changes observed in the SP- and VIP-LI levels. Alterations in cerebrovascular tone induced by changing arterial CO2 tension or lowering of blood pressure (ketanserin infusion test) did not alter the levels of the perivascular peptides in the EJV. In addition, CGRP-, SP-, VIP- and neuropeptide Y (NPY)-LI were analysed in CSF in the post-operative course after subarachnoid haemorrhage (SAH) in 14 patients. The CSF VIP-LI was lower in SAH than in control (p < 0.05). The CGRP-LI level was measurable in SAH CSF but not in CSF of controls. In individual patients with marked vasoconstriction increased levels of CGRP-LI (up to 14 pmol/L) and NPY-LI (up to 232 pmol/L) were observed. The results of this study are in support of our hypothesis that there is an involvement of the sensory peptide CGRP in a dynamic reflex aimed at counterbalancing vasoconstriction in SAH.

Adult↗
PubMed1995

Heterogeneous cerebral glucose metabolism in normal pressure hydrocephalus.

The regional cerebral metabolic rate for glucose (rCMRglu) has never been investigated in large consecutive groups of patients with normal pressure hydrocephalus (NPH), a potentially treatable form of dementia with an unpredictable outcome after shunt surgery. Using PET and 18F-2-fluorodeoxyglucose, rCMRglu was studied in 18 patients who fulfilled hydrodynamic criteria for NPH and in whom a biopsy of the frontal cortex was obtained. When compared with an age matched group of 11 healthy subjects, the patients with NPH showed a significant rCMRglu reduction in all cortical and subcortical regions of interest. Individual metabolic patterns, however, disclosed a large topographical heterogeneity. Furthermore, histopathological examination identified Alzheimer's disease or cerebrovascular disease in six cases, and no parenchymal disease or non-specific degenerative processes in the remaining 12. After separating the patients according to the histological diagnosis, the rCMRglu patterns were still heterogeneous, the abnormalities ranging from focal to diffuse in both subgroups. After shunt operation, 11 patients did not improve or worsened clinically. Six patients improved; of those, two had Alzheimer changes and two cerebrovascular changes in their biopsy. The metabolic pattern of these six patients did not differ from the rest of the NPH group. The results indicate that the NPH syndrome may be non-specifically associated with different degenerative disorders. The metabolic heterogeneity, together with the heterogeneous histopathological findings, indicate the necessity of reevaluating the pathogenesis of the NPH syndrome, and may account for the high variability in the success rate of shunt surgery series.

Aged↗
PubMed1995

Regional cerebral blood flow and neuropsychological performance in a Danish family with X-linked bulbo-spinal neuronopathy.

Regional Cerebral Blood Flow (rCBF) measurements and neuropsychological evaluation were performed in 6 patients from a Danish family affected with X-linked Bulbo-Spinal Neuronopathy (XBSN). This inherited form of motor neuron disease (MND) has been shown to affect various functions within the nervous and the endocrine systems. We investigated the possibility that focal or diffuse cortical deficits, already demonstrated in MND, were present in XBSN. The global CBF values of the patients, when compared to age- and sex-matched healthy controls, were found reduced, but no focal rCBF alterations, nor increased regional side-to-side asymmetry were observed. The neuropsychological evaluation showed no cognitive impairments. We conclude that cortical perfusion and cognitive functions are not significantly altered in XBSN.

Adult↗
PubMed1995

Angiotensin II receptor antagonist CV-11974 and cerebral blood flow autoregulation.

OBJECTIVE: To investigate whether the angiotensin II (Ang II) subtype 1 receptor (AT1) antagonist CV-11974 had a similar effect to angiotensin converting enzyme inhibitors on cerebral blood flow autoregulation in normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). METHODS: Sixteen WKY rats and 16 SHR were given CV-11974 0.1 mg/kg intravenously and compared with two control groups (n = 16). Their cerebral blood flow was measured with the intracarotid xenon-133 injection method and blood pressure was raised by noradrenaline infusion and lowered by controlled haemorrhage in separate groups of rats. The limits of autoregulation were determined by computed least-sum-of-squares analysis. RESULTS: The dose of CV-11974 given lowered blood pressure but did not influence baseline cerebral blood flow. In WKY rats the lower limit of autoregulation in control rats was 60 +/- 3 mmHg, whereas after CV-11974 administration it was 48 +/- 2 mmHg (P < 0.01). In SHR the corresponding values were 85 +/- 2 and 78 +/- 2 mmHg, respectively (P < 0.05). In WKY rats the upper limit of autoregulation in control rats was 144 +/- 5 mmHg, whereas after CV-11974 administration it was 126 +/- 7 mmHg (P < 0.05). In SHR the corresponding figures were 174 +/- 8 and 144 +/- 6 mmHg, respectively (P < 0.01). CONCLUSION: Thus, the AT1 receptor antagonist, although it did not influence baseline cerebral blood flow, shifted the autoregulation curve towards lower blood pressure. This effect is similar to that of angiotensin converting enzyme inhibitors, and might be due to release of Ang II-dependent tone in the larger cerebral resistance vessels.

Angiotensin II↗
PubMed1995

Functional brain imaging with SPECT in normal aging and dementia. Methodological, pathophysiological, and diagnostic aspects.

New developments in instrumentation, radiochemistry, and data analysis, particularly the introduction of 99M TC-labeled brain-retained tracers for perfusion studies, have opened up a new era of single photon emission computed tomography (SPECT). In this review critical methodological issues relating to the SPECT instrument, the radioactive tracers, the scanning procedure, the data analysis and interpretation of data, and subject selection are discussed together with the changes in regional cerebral blood flow (rCBF) observed in normal aging. An overview is given of the topography and the pathophysiological and diagnostic significance of focal rCBF deficits in Alzheimer's disease and in other dementia disorders, in which SPECT is capable of early or preclinical disease detection. In Alzheimer's disease, the diagnostic sensitivity and specificity of focal rCBF deficits measured with SPECT and brain-retained tracers are very high, in particular when combined with medial temporal lobe atrophy on CT. Together with neuropsychological testing, SPECT serves to map the topography of brain dysfunction. Thus, in the clinical setting, SPECT provides information that is supplemental to that obtained in other studies. Future applications include neuroreceptor studies and treatment studies, in which SPECT may serve as a diagnostic aid in the selection of patients and as a potential mean for monitoring treatment effects. Although positron emission tomography is the best characterized tool for addressing some of these clinical and research issues in dementia, only the less expensive and technically simpler SPECT technique will have the potential of being available as a screening diagnostic instrument in the clinical setting. It is concluded that, properly approached, functional brain imaging with SPECT represents an important tool in the diagnosis, management, and research of dementia disorders.

Aging↗