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Steen G Hasselbalch

Publications and source records attributed to Steen G Hasselbalch.

11 recordsLinked to original sources
PubMed2006

[Diagnostic imaging in dementia evaluation].

INTRODUCTION: The aim of the study was to evaluate the changes in diagnoses and treatment by structural scanning in dementia evaluation. MATERIAL AND METHODS: 336 elderly, consecutively evaluated patients from two university memory clinics (mean age 75 y, mean MMSE 21.7), were retrospectively diagnosed without and with inclusion of scan results. These results were compared to prospective data obtained from 137 patients scanned as part of a population based study (The Odense Study, mean age 78.5, mean MMSE 23.3). CT and MRI were performed in 93% and 7% of the patients, respectively. RESULTS: Potentially reversible structural pathology was found in 3.5% of the memory clinic patients, and in 2% of the population based patients. By applying international diagnostic criteria and treatment recommendations to the retrospective memory clinic data, it was found that adding a structural scan changed diagnoses and treatment in 37% and 33% of the patients, primarily due to identification of cerebrovascular disease (CVD) in patients with no clinical signs or symptoms of CVD. In comparison, the change in diagnosis found in the prospective population data was lower (15%). It was not possible to identify a group of patients that would not benefit from scanning. CONCLUSION: Our data support recent guidelines that suggest CT scan as a routine investigation in dementia evaluation.

Aged↗
PubMed2006

Patient versus informant reported quality of life in the earliest phases of Alzheimer's disease.

OBJECTIVES: The study investigated if patient and informant reported Quality of Life (QoL) differed in early Alzheimer's disease (AD). In addition, we examined whether anosognosia had an impact on the agreement between patient and informant ratings of QoL and whether anosognosia, dementia severity, depression and behavioural symptoms were significantly correlated to QoL in early AD. METHODS: From a prospective research program including newly referred patients (age >60 years and MMSE > or = 20), 48 patients with very early AD were included. QoL was assessed using the QoL-AD and EQ-5D scales. Anosognosia was rated on a categorical scale by an examiner. MMSE, Geriatric Depression Scale, Danish Adult Reading Test and Frontal Behavioural Inventory were also administered. RESULTS: On most QoL measures patients rated their QoL higher than their informants. Anosognosia was not associated with QoL but significantly with an inverse impact on the agreement between patient and informant ratings of QoL. Self-reported QoL was significantly correlated to depression but not to age, dementia severity, behavioural symptoms or memory impairment. Informant ratings of QoL were significantly correlated to behavioural symptoms and informant ratings on the EQ-5D Visual Analogue Scale were significantly correlated to patient reported depression. CONCLUSION: Patients with early AD generally reported higher QoL than their informants. This disagreement was associated with the presence of anosognosia. Self-reported QoL did not correlate with the MMSE score. Behavioural changes and depressive symptoms may be associated with low QoL.

Aged↗
PubMed2006

Global cerebral blood flow and metabolism during acute hyperketonemia in the awake and anesthetized rat.

In the human setting, it has been shown that acute increase in the concentration of ketone bodies by infusion of beta-hydroxybutyrate increased the cerebral blood flow (CBF) without affecting the overall cerebral metabolic activity. The mechanism by which this effect of ketone bodies was mediated is not known. Alterations in several parameters may possibly explain the increase in CBF and the resetting of the relation between CBF and cerebral metabolism. To study this phenomenon further, we measured global CBF and global cerebral metabolism with the Kety-Schmidt technique in the wakeful rat before and during infusion of ketone bodies. During acute hyperketonemia (average concentration of beta-hydroxybutyrate: 6 mmol/L), global CBF increased 65% from 108 to 178 mL/100 g min and the cerebral metabolic rates for both oxygen and glucose remained constant. This resetting of the relation between CBF and cerebral metabolism could not be explained by alterations in blood pH or arterial CO2 tension. By measuring cerebral intracellular pH by 31P nuclear magnetic resonance spectroscopy, it could further be concluded that the brain pH was unchanged during acute hyperketonemia. These observations indicate that the mechanism responsible for the increase in CBF is rather a direct effect on the cerebral endothelium than via some metabolic interactions.

3-Hydroxybutyric Acid↗
PubMed2005

Patients with obsessive-compulsive disorder have increased 5-HT2A receptor binding in the caudate nuclei.

The pharmacological efficacy of serotonergic-acting drugs suggest that patients with obsessive-compulsive disorder (OCD) may have alterations in their cerebral serotonergic (5-HT) receptor system, and previous neuroimaging studies of OCD patients have shown abnormalities in several fronto-subcortical regions. In this study we investigated cerebral 5-HT(2A) receptor binding in 15 untreated OCD patients and in 15 age- and gender-matched healthy volunteers by magnetic resonance imaging and [(18)F]altanserin positron emission tomography (PET). Eleven of the patients were rescanned with PET after receiving treatment with a selective serotonin reuptake inhibitor (SSRI). The distribution volumes of specific tracer binding (DV(3)') were calculated for 12 brain regions, and comparisons were made between: (1) healthy volunteers vs. untreated OCD patients, (2) healthy volunteers vs. treated OCD patients, and (3) OCD patients before and during treatment. When comparing the distribution volume for specific fronto-subcortical brain regions, significantly higher values were recorded in the caudate nuclei in OCD patients (DV(3)': 0.24+/-0.14) compared to the healthy control group (DV(3)': 0.15+/-0.13) (p<0.05, Wilcoxon matched-pairs test). This difference between groups was not present after treatment with SSRIs. There was no correlation between the severity of OCD symptoms and 5-HT(2A )receptor binding. An increase in 5-HT(2A) receptor binding is found in the caudate nuclei of untreated patients with OCD. The up-regulation in 5-HT(2A) receptors might be compensatory for a lack of serotonin in the feedback loop between the thalamus and orbito-frontal cortex, the caudate nuclei, and the globus pallidus.

Adolescent↗
PubMed2005

Cognitive and functional neuroimaging correlate for anosognosia in mild cognitive impairment and Alzheimer's disease.

OBJECTIVES: To investigate the correlation between anosognosia and behavioural symptoms, performance on executive tests, and frontal cortex regional cerebral blood flow (rCBF) in patients with 'amnestic mild cognitive impairment' (MCI) and mild Alzheimer's disease (AD). METHODS: From a prospective Memory Clinic cohort including consecutively referred patients, age 60 years or above, and with MMSE score 20 or above, 36 patients with AD and 30 with MCI were included in this study. Anosognosia was assessed using a categorical scale and discrepancy scores between patients' and relatives' reports on a 20-item Memory Questionnaire (MQ). Behavioural symptoms were assessed with Frontal Behavioural Inventory (FBI). Executive functions were examined with a range of neuropsychological tests. Tc99m-HMPAO SPECT was obtained in an unselected sample of 55 of the 66 patients, and rCBF was analysed in six cortical frontal regions. RESULTS: Insight was equally impaired in the two patient groups. A significant correlation was found between impaired awareness and dementia severity (MMSE). Discrepancy-scores on the MQ were significantly correlated to scores on FBI and to rCBF in the right inferior frontal gyrus, but not to executive tests. The groups classified by the categorical ratings 'full', 'shallow' and 'no' awareness were not characterized by differences in behavioural symptoms, executive performance or frontal rCBF. CONCLUSIONS: Impaired awareness is associated with behavioural symptoms and may reflect functional impairment in the right inferior frontal cortex.

Aged↗
PubMed2004

MR-based automatic delineation of volumes of interest in human brain PET images using probability maps.

The purpose of this study was to develop and validate an observer-independent approach for automatic generation of volume-of-interest (VOI) brain templates to be used in emission tomography studies of the brain. The method utilizes a VOI probability map created on the basis of a database of several subjects' MR-images, where VOI sets have been defined manually. High-resolution structural MR-images and 5-HT(2A) receptor binding PET-images (in terms of (18)F-altanserin binding) from 10 healthy volunteers and 10 patients with mild cognitive impairment were included for the analysis. A template including 35 VOIs was manually delineated on the subjects' MR images. Through a warping algorithm template VOI sets defined from each individual were transferred to the other subjects MR-images and the voxel overlap was compared to the VOI set specifically drawn for that particular individual. Comparisons were also made for the VOI templates 5-HT(2A) receptor binding values. It was shown that when the generated VOI set is based on more than one template VOI set, delineation of VOIs is better reproduced and shows less variation as compared both to transfer of a single set of template VOIs as well as manual delineation of the VOI set. The approach was also shown to work equally well in individuals with pronounced cerebral atrophy. Probability-map-based automatic delineation of VOIs is a fast, objective, reproducible, and safe way to assess regional brain values from PET or SPECT scans. In addition, the method applies well in elderly subjects, even in the presence of pronounced cerebral atrophy.

Aged↗
PubMed2004

Mosaicism of the CAG repeat sequence in the Huntington disease gene in a pair of monozygotic twins.

We report on a pair of monozygotic twins belonging to a family segregating Huntington disease (HD). In routine DNA analysis of blood cells, they displayed three alleles of the CAG repeat sequence in the HD gene. Two different cell lines, carrying the normal allele together with either an expanded allele with 47 CAGs or an intermediate allele with 37 CAGs, were detected in blood and buccal epithelium from both twins. To our knowledge, this is the first case described of HD gene CAG repeat length mosaicism in blood cells. Haplotype analysis established that the 37 CAG allele most likely arose by contraction of the maternal 47 CAG allele. The contraction must have taken place postzygotically, possibly at a very early stage of development, and probably before separation of the twins. One of the twins has presented symptoms of HD for 4 years; his skin fibroblasts and hair roots carried only the cell line with the 47 CAG repeat allele. The other twin, who is without symptoms at present, displayed mosaicism in skin fibroblasts and hair roots. If the proportion of the two cell lines in the brain of each twin resembles that of their hair roots (another tissue originating from the ectoderm), the mosaicism in the unaffected twin would mean that only a part of his brain cells carried the expanded allele, which could explain why he, in contrast to his brother, has no symptoms at this time.

Adult↗
PubMed2004

A database of [(18)F]-altanserin binding to 5-HT(2A) receptors in normal volunteers: normative data and relationship to physiological and demographic variables.

This study presents the results of an analysis of 5-hydroxytryptamine (5-HT)(2A) receptors in 52 healthy subjects. Thirty men and twenty-two women aged between 21 and 79 years were investigated with magnetic resonance imaging (MRI) and [(18)F]-altanserin positron emission tomography (PET). The distribution volumes of specific tracer binding (DV(3)') was calculated for 15 brain regions using either cerebellum or pons as reference regions and correlations between DV(3)' and physiological and demographic variables were made. The regional distribution of [(18)F]-altanserin binding in the healthy human brain was in agreement with existing in vitro post-mortem human 5-HT(2A) data. Apart from nonspecific cerebellar binding (DV(2)), there was no gender difference in 5-HT(2A) binding. A positive correlation between cerebellar binding and age was observed and negative correlations between age and DV(3)' were found in all cortical regions, except occipital cortex, corresponding to a decrease in DV(3)' of 6% or 4% per decade with cerebellum or pons as reference regions, respectively. In several temporal and frontal cortical regions, positive correlations were found between body mass index (BMI) and DV(3)'. Our findings provide a resource to aid design of clinical studies of the 5-HT(2A) receptors. [(18)F]-altanserin binding appears to be unaffected by gender, but the effects of ageing must be considered for clinical studies. The correlations between different cortical regions' 5-HT(2A) binding and BMI should be explored in future studies.

Adult↗
PubMed2004

[18F]altanserin binding to human 5HT2A receptors is unaltered after citalopram and pindolol challenge.

The aim of the present study was to develop an experimental paradigm for the study of serotonergic neurotransmission in humans using positron emission tomography and the 5-HT2A selective radioligand [18F]altanserin. [18F]altanserin studies were conducted in seven subjects using the bolus/infusion approach designed for attaining steady state in blood and brain 2 hours after the initial [18F]altanserin administration. Three hours after commencement of radiotracer administration, 0.25 mg/kg of the selective serotonin reuptake inhibitor, citalopram (Lundbeck, Valby, Denmark), was administered to all subjects as a constant infusion for 20 minutes. To reduce 5-HT1A-mediated autoinhibition of cortical 5-HT release, four of the seven subjects were pretreated with the partial 5-HT1A agonist pindolol for 3 days at an increasing oral dose (25 mg on the day of scanning). In each subject, the baseline condition (120 to 180 minutes) was compared with the stimulated condition (195 to 300 minutes). Despite a pronounced increase in plasma prolactin and two subjects reporting hot flushes compatible with an 5-HT-induced adverse effect, cortical [18F]altanserin binding was insensitive to the citalopram challenge, even after pindolol pretreatment. The biochemical and cellular events possibly affecting the unsuccessful translation of the citalopram/pindolol challenge into a change in 5-HT2A receptor binding of [18F]altanserin are discussed.

Adrenergic beta-Antagonists↗
PubMed2003

Quantification of 5-HT2A receptors in the human brain using [18F]altanserin-PET and the bolus/infusion approach.

The aim of the present study is to describe and validate a method for accurate quantification of 5-hydroxytryptamine (5-HT)(2A) receptors using [18F]altanserin-positron emission tomography (PET) and the bolus/infusion approach. A bolus/infusion ratio of 1.75 h aimed at attaining rapid steady state in blood and brain was predicted from previous bolus studies performed in our laboratory. The infusion schedule was tested in normal subjects (n = 10) using dynamic PET and frequent plasma sampling for 6 h. Steady state was attained in brain and plasma within 2 h, and time-activity curves remained constant for another 3 h. To represent free and nonspecifically bound [18F]altanserin and its radiolabeled metabolites only, cerebellum must show no displacement in 5-HT(2A) displacement studies. To validate this, saturating doses of cold ketanserin were administered and it was found that specific binding of [18F]altanserin decreased uniformly to the level of the cerebellum and no change in the cerebellar time-activity curve was found after ketanserin administration. A shorter experimental setup was tested in a second group (n = 20) including patients with neuropsychiatric disorders. Dynamic PET (five frames of 8 minutes each) and venous blood sampling at midscan time started 2 h after [18F]altanserin administration. The mean percentage rate of change per hour in the outcome parameter, DV(3)', was low (mean -0.3% h-1; range -7.3-7.2% h-1) and no correlation of DV(3)' versus time was demonstrated. It is concluded that 5-HT(2A) receptor studies can be conducted within 2 h of [18F]altanserin infusion, yielding reliable results.

Adult↗