Biomedical subjects

Gunhild Waldemar

Publications and source records attributed to Gunhild Waldemar.

At least 37 records · Page 2Linked to original sources

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↗

PubMed2005

Identification and diagnostic evaluation of possible dementia in general practice. A prospective study.

OBJECTIVE: To investigate the rate of diagnostic evaluation of dementia for patients in whom a suspicion of dementia was raised, and to investigate reasons why a diagnostic evaluation was not always being performed. DESIGN: A prospective study among elderly patients aged 65+, and a follow-up study. SETTING: In all, 17 general practices in Copenhagen with 40 865 patients on their lists of whom 2934 were aged 65+. SUBJECTS: A total of 793 patients consulting their GP regardless of reason of encounter, in October and November 2002. MAIN OUTCOME MEASURES: MMSE score < or = 23, GP clinical impression of dementia, laboratory-screening tests prescribed by the GPs and referral status after 6 months, and follow-up questionnaire. RESULTS: Of 793 patients a total of 138 patients were identified with possible dementia. Among the identified patients 26 (20%) were referred for further evaluation within 6 months, and 4 (3%) were treated for depression or referred for another condition. A total of 6 patients were lost to follow-up. In the remaining 102 undiagnosed patients the main reasons for not performing a diagnostic evaluation of dementia were patient/relative hesitation (34%), the GP thought that it would not have any consequences for the patient, or the GP estimated that the patient was too fragile (21%). CONCLUSION: In 17% of elderly patients in general practice a suspicion of dementia could be raised based on the clinical impression of the GP or MMSE score. However, only 23% of this group were evaluated by their GP or referred to a memory clinic within a subsequent period of 6 months.

Aged↗

PubMed2005

Years of severe and isolated amnesia can precede the development of dementia in early-onset Alzheimer's disease.

A young patient with a severe and isolated memory disorder, meeting the criteria for MCI, was followed for a period of 8 years. His overall functional level remained stable with a CDR-score at 0.5 until the last year when it dropped to 1.0. Neuropsychological testing showed severe memory deficits but otherwise normal cognitive functions. Only minimal progression was measured; however, the last testing showed impaired abstraction and executive functioning as well as discrete problems generating names of objects and people. Neuroimaging, with MRI and SPECT, was consistent with a progressive degenerative disorder, and cerebrospinal fluid levels of beta-amyloid 1-42, tau protein, and phosphorylated tau protein were characteristic of Alzheimer's disease (AD). We argue that this is a case of prodromal AD, which illustrates an extreme version of the normal course with respect to slow progression of the disease and severity of amnesia early in the course.

Alzheimer Disease↗

PubMed2005

Evidence-based evaluation of magnetic resonance imaging as a diagnostic tool in dementia workup.

BACKGROUND: The diagnostic utility of magnetic resonance imaging in dementia workups has increased recently. The basic use is to exclude space-occupying processes in the brain. However, magnetic resonance imaging offers major opportunities for studying atrophy of specific brain areas. A great interest has been put in whether atrophy in the medial temporal lobe can serve as an early diagnostic marker for Alzheimer disease. METHODS AND RESULTS: In this evaluation, we used evidence-based techniques and reviewed more than 400 articles that address this issue. Our main finding is that a variety of methods in studying brain areas were used, and this made it difficult to extract conclusive information in a systematic way. CONCLUSION: However, we were able to conclude that atrophy of the hippocampus can distinguish patients with Alzheimer disease from healthy subjects, but there was a lack of evidence because of insufficient studies concerning the usefulness of medial temporal lobe atrophy as a diagnostic marker in a more general setting.

Alzheimer Disease↗

PubMed2005

The executive interview as a screening test for executive dysfunction in patients with mild dementia.

OBJECTIVES: To validate the Executive Interview (EXIT25) as a screening instrument for executive cognitive dysfunction in patients with mild dementia. DESIGN: Validation using group comparison and correlation studies. SETTING: The Copenhagen University Hospital Memory Clinic, a multidisciplinary outpatient clinic based in a neurological setting. PARTICIPANTS: Thirty-three patients with mild dementia (MMSE score > or =20) and 30 healthy controls. MEASUREMENTS: The EXIT25, a 25-item screening instrument for executive dysfunction, was administered to all participants. Global cognitive function was measured using the MMSE. Patients were evaluated using traditional neuropsychological tests for executive dysfunction (Wisconsin Card Sorting Test, Trail Making Part B, Stroop Test, verbal fluency, design fluency, and verbal abstraction). Changes in behavior and functional impairment in activities of daily living were assessed using the Frontal Behavioral Inventory (FBI) and the Disability Assessment for Dementia Scale. RESULTS: EXIT25 scores were significantly higher in patients than in the healthy controls; MMSE scores could not account for the differences. Thirteen of the 25 items separated the two groups. EXIT25 was found to correlate significantly with the Stroop Test, the verbal fluency tests, and the FBI. CONCLUSION: The EXIT25 is able to capture executive cognitive deficits not primarily related to the general level of intellectual reduction in patients with mild dementia. In clinical practice, the EXIT25 might be a valuable supplement to the MMSE.

Aged↗

PubMed2005

Impact of age-related cerebral white matter changes on the transition to disability -- the LADIS study: rationale, design and methodology.

Age-related white matter changes (ARWMC) on brain MRI have been associated with cognitive, motor, mood and urinary disturbances. These factors are known to contribute to disability in elderly people, but the impact of ARWMC and of their progression on the transition to disability is not determined. The LADIS (Leukoaraiosis and Disability in the Elderly) study aims at assessing the role of ARWMC as an independent predictor of the transition to disability in initially nondisabled elderly (65-84 years). Subjects who are not impaired or impaired on only 1 item of the Instrumental Activity of Daily Living (IADL) scale, presenting with different grades of ARWMC severity, were enrolled. Eleven European centers are involved. All the patients were assessed at baseline using an extensive set of clinical and functional tests including global functioning, cognitive, motor, psychiatric and quality of life measures. MRI studies were performed at baseline and will be repeated at the end of the follow-up period to evaluate changes of ARWMC and other lesions. ARWMC were categorized into mild, moderate or severe using the scale of Fazekas et al. For each ARWMC severity class, the primary study outcome is the transition to disability defined as an impairment on 2 or more IADL scale items. Secondary outcomes are the occurrence of dementia, depression, vascular events or death. Six-hundred and thirty-nine subjects (mean age 74.13 +/- 5.0 years, M/F: 288/351) were enrolled in a hospital-based setting and are being followed up for up to 3 years. The large and comprehensive set of measures in LADIS enables a comprehensive description of their functional and clinical features to be examined in relation to different morphological patterns and severity of ARWMC. The longitudinal design will give insight into the possible role of ARWMC and their progression as an independent contributor to disability in the elderly, eventually helping to develop preventive strategies to reduce the burden of disability in late life. The study results may also help to standardize, on an international basis, tools and criteria to identify early stages of disability.

Activities of Daily Living↗

PubMed2004

Semantic memory impairment in the earliest phases of Alzheimer's disease.

The presence and the nature of semantic memory dysfunction in Alzheimer's disease (AD) have been widely debated. This study aimed to determine the frequency of impaired semantic test performances in mild AD and to study whether incipient semantic impairments could be identified in predementia AD. Five short neuropsychological tests sensitive to semantic memory and easily applicable in routine practice were administered to 102 patients with mild AD (Mini-Mental State Examination score above 19), 22 predementia AD patients and 58 healthy subjects. 'Category fluency' and 'naming of famous faces' were the most frequently impaired tests in both patient groups. The study demonstrated that impairments on semantically related tests are common in mild AD and may exist prior to the clinical diagnosis. The results imply that assessment of semantic memory is relevant in the evaluation of patients with suspected AD.

Aged↗

PubMed2004

Temporal lobe hypoperfusion in isolated amnesia with slow onset: a single photon emission computer tomography study.

Single photon emission computer tomography (SPECT) applied early in the course of Alzheimer's disease (AD) may identify regions with impaired brain function. Moreover, it may be relevant to characterize SPECT perfusion patterns in patients with mild cognitive impairment (MCI), in particular the subgroup of MCI patients with isolated amnesia, as these patients have been demonstrated to convert to AD in more than half of the cases within 3 years. The primary aim of the present study was to characterize the regional cerebral blood flow (CBF) in patients with neuropsychologically verified isolated amnesia. We examined 32 patients (11 men/21 women) with isolated amnesia according to strict neuropsychological criteria and 15 healthy volunteers (11 men/4 women). All subjects had an SPECT-99mTc-d,l-HMPAO perfusion study and neuropsychological assessments. Cranial MRI or CT was performed in all subjects. Semiquantitative (cerebellar relative) flow values were calculated and statistically compared. Patients with isolated amnesia had significant hypoperfusion in several cortical regions of interest compared to control subjects, most prominently in the left temporal cortex. Additionally, there was a trend towards globally reduced CBF in the patients, although this was not significant. These findings may indicate the presence of a progressive degenerative illness affecting multiple brain regions at its early or preclinical stage.

Adult↗

PubMed2004

Awareness of deficits in mild cognitive impairment and Alzheimer's disease: do MCI patients have impaired insight?

In this study we investigated impaired awareness of cognitive deficits in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Very few studies have addressed this topic, and methodological inconsistencies make the comparison of previous studies difficult. From a prospective research program 36 consecutive patients with mild AD (MMSE above 19), 30 with amnesic MCI and 33 matched controls were examined. Using three methods for awareness assessment we found no significant differences in the level of awareness between MCI and AD. Both groups had impaired awareness and significant heterogeneity in the clinical presentation of awareness. The results demonstrate that subjective memory problems should not be a mandatory prerequisite in suspected dementia or MCI, which makes reports from informants together with thorough clinical interview and observation central when assessing suspected dementia disorders.

Aged↗

PubMed2004

Prepulse inhibition in patients with Alzheimer's disease.

Prepulse inhibition (PPI) is used as a measure for sensorimotor gating. Studies in animals have indicated that hippocampus and entorhinal cortex, structures which are affected in mild Alzheimer's disease (AD), are involved in the regulation of PPI. The objectives of this study were to determine if patients with very mild AD had altered PPI, and to study possible correlations between PPI and cognitive performance or neuropsychiatric symptoms. A passive acoustic PPI paradigm was applied in 48 patients with either mild AD or Mild Cognitive Impairment (MCI) and in 49 healthy controls. No differences were found between patients and healthy controls regarding PPI. Further, PPI was not found to correlate with cognitive performance or neuropsychiatric symptoms. PPI is significantly altered in patients with neuropsychiatric disorders associated with dopaminergic, glutamatergic and/or serotonergic dysfunctions, such as schizophrenia. Since mild AD is primarily associated with loss of cholinergic markers in the limbic regions this study suggests that acetylcholine only plays a minor role in the regulation of PPI.

Acetylcholine↗

PubMed2003

Neurofilament inclusion body disease: a new proteinopathy?

We describe four cases of a new clinicopathological entity presenting with either a frontotemporal dementia or corticobasal degeneration syndrome with a mean age of onset of 45 years (range 41-50) characterized pathologically by deposition of neurofilament proteins. All four patients had a rapidly progressive course and have become mute and non-ambulatory, and three have died after mean illness duration of only 3 years (range 2 1/2 -4). Both structural (MRI) and functional (PET and SPECT) imaging demonstrated frontal and temporal lobe and basal ganglia involvement. Gross neuropathological examination in the three deceased patients (the fourth patient, still alive, was diagnosed by brain biopsy) revealed changes affecting predominantly the frontal and temporal cortices, basal ganglia and brainstem. There was superficial linear spongiosis affecting the frontal lobes in all three autopsied patients, and severe caudate atrophy was noted in two of them and demonstrated on MRI in the living patient. On routine staining, there were numerous intracytoplasmic inclusions, which ranged from eosinophilic to basophilic. Some had a clearly defined basophilic margin, while others were granular with a hyaline core. With modified Bielschowsky silver technique, a small number of the inclusions were intensely stained. Inclusions were not labelled with other silver stains. Immuno histochemistry revealed that the inclusions were immunoreactive with antibodies to neurofilament heavy and light chain subunits and to ubiquitin, but not with antibodies to tau and alpha-synuclein. These neurofilament- and ubiquitin-positive inclusions were widespread, specific to neurons and occasionally intranuclear. The frequency and distribution of the inclusions and the silver and immunohistochemical profiles in these four cases is novel and has not been described in detail before. We propose the term neurofilament inclusion body disease for this entity.

Adult↗

PubMed2003

[Frontotemporal dementia--new understanding of Pick disease].

Frontotemporal dementia is a relatively new term, which encompasses several degenerative diseases involving the frontal and anterior temporal lobes. The article gives a short overview of new knowledge in this field. Clinical criteria are in focus, but neuropathological aspects are also mentioned.

Aphasia, Primary Progressive↗

PubMed2003

Psychiatric morbidity in a neurology-based memory clinic: the effect of systematic psychiatric evaluation.

OBJECTIVES: To estimate the prevalence of psychiatric morbidity and the effect of systematic psychiatric evaluation in patients referred to a memory clinic in a neurological setting. DESIGN: Descriptive case-series study in consecutive referrals to a memory clinic. SETTING: An outpatient multidisciplinary memory clinic in a neurological setting. PARTICIPANTS: An index group of 100 consecutive patients (aged 60-89) referred for diagnostic evaluation of cognitive symptoms during a period of 8 months and a reference group of 686 consecutive patients (aged 60-98) referred during a previous period of 54 months. In the index group, a systematic psychiatric evaluation was performed in addition to the neurological evaluation and routine investigations. In the reference group, patients had the same basic evaluation, but psychiatric evaluation was optional and was performed in 21% of the patients. MEASUREMENTS: Prevalence of primary psychiatric morbidity in the index and reference groups according to international clinical criteria and multidisciplinary consensus report and three key psychiatric symptoms: delusions, hallucinations, and affective symptoms in the index group. RESULTS: Twenty-three percent of patients in the index group had a primary psychiatric disease. A primary psychiatric disease was diagnosed in 8% of patients in the reference group (P<.001). One or more psychiatric symptoms were identified in 72% of all patients in the index group. CONCLUSION: Psychiatric conditions and symptoms are frequent in elderly patients with cognitive symptoms, including those referred to a neurological memory clinic. The data provide evidence for a multispecialty and multidisciplinary approach to the diagnosis and management of patients with possible dementia.

Aged↗

PubMed2003

Implementation of a clinical dementia guideline. A controlled study on the effect of a multifaceted strategy.

OBJECTIVE: To assess the impact of a multifaceted implementation strategy aiming to improve GP adherence to a clinical guideline on dementia. DESIGN: Controlled before and after study using data records from regional laboratories. The guideline was mailed to all GPs. The multifaceted implementation strategy was planned with local GPs, and consisted of seminars, outreach visits, reminders and continuing medical education (CME) small group training. SETTING: Primary health care. SUBJECTS: 535 GP practices with 727 physicians in Denmark. MAIN OUTCOME MEASURES: The diffusion and use of the guideline was measured by a mailed survey. Adherence to guideline recommendations was monitored by data on laboratory tests from general practice in patient's > or = 65 years: thyroid stimulating hormone requested with vitamin B12 or methylmalonate. The use of these tests as part of a diagnostic evaluation of dementia was subsequently verified by a questionnaire to the practices. RESULTS: Of the GPs who read the guideline, 88% found it applicable in primary care. No increase in the adherence to guideline recommendations was observed regarding the use of laboratory tests or cognitive tests in the diagnostic evaluation of dementia in general practice. CONCLUSION: Although GPs regarded the guideline applicable in primary care, no change in practice adherence to guideline recommendations was detected after a multifaceted implementation.

Chi-Square Distribution↗

PubMed2003

An economic evaluation of donepezil in mild to moderate Alzheimer's disease: results of a 1-year, double-blind, randomized trial.

The costs and consequences of donepezil versus placebo treatment in patients with mild to moderate Alzheimer's disease (AD) were evaluated as part of a 1-year prospective, double-blind, randomized, multinational clinical trial. Patients received either donepezil (n = 142; 5 mg/day for 28 days followed by 10 mg/day according to the clinician's judgement) or placebo (n = 144). Unit costs were assessed in 1999 Swedish kronas (SEK) and converted to US dollars (USD). Donepezil-treated patients gained functional benefits relative to placebo on the Progressive Deterioration Scale (p = 0.042) and Instrumental Activities of Daily Living scale (p = 0.025) at week 52. Caregivers of donepezil-treated patients spent an average of 400 h less annually providing care than caregivers of placebo-treated patients. Mean annual healthcare costs were SEK 137,752 (USD 16,438) per patient for the donepezil group and SEK 135,314 (USD 16,147) in the placebo group. With the average annual cost of donepezil at SEK 10,723 (USD 1,280) per patient, the SEK 2,438 (USD 291) cost difference represented a 77% cost offset. When caregiver time and healthcare costs were included, mean annual costs were SEK 209,244 (USD 24,969) per patient in the donepezil group and SEK 218,434 (USD 26,066) in the placebo group, a total saving associated with donepezil treatment of SEK 9,190 (USD 1,097) per patient [95% CI of SEK -43,959 (USD -5,246), SEK 25,581 (USD 3,053); p = 0.6]. The positive effects on the efficacy outcome measures combined with no additional costs from a societal perspective indicate that donepezil is a cost-effective treatment, representing an improved strategy for the management of patients with AD.

Aged↗

PubMed2002

Diagnostic profile of young and middle-aged memory clinic patients.

With the objective of characterizing the underlying conditions in younger patients with cognitive symptoms, 314 consecutive patients were studied, aged <60 years, referred to a multidisciplinary memory clinic over a period of 54 months. Fifteen percent of the patients fulfilled Diagnostic and Statistical Manual IV criteria for dementia, 17% had selective cognitive deficits, and 55% had no cognitive deficits. Cognitive symptoms in younger patients rarely reflect dementia but more often other medical and psychiatric conditions.

Adolescent↗

PubMed2002

[Strategies for the diagnosis of dementia. Experiences of collaboration between general practitioners and district nurses].

INTRODUCTION: The aim was to explore the context and experiences of collaboration between the general practitioner (GP) and the district nurse (DN) on diagnosing dementia, in order to identify possible procedures to improve care. MATERIAL AND METHODS: Two group interviews respectively with four DNs and five GPs working in the municipality of Copenhagen. RESULTS: The group interviews revealed that the suboptimised collaboration could be caused by 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. DISCUSSION: This study indicates a possibility of improving the collaboration between the two professional groups on diagnosing dementia. Possible approaches to improved care should focus on an inter-professional understanding of the importance of early, shared, decision-making, emphasising early identification and care of diagnosed demented patients.

Adult↗

PubMed2002

Regulation of cerebral blood flow in patients with autonomic dysfunction and severe postural hypotension.

BACKGROUND: Whether cerebral blood flow (CBF) autoregulation is maintained in autonomic dysfunction has been debated for a long time, and the rather sparse data available are equivocal. The relationship between CBF and mean arterial blood pressure (MABP) was therefore tested in eight patients with symptoms and signs of severe cardiovascular autonomic dysfunction. PATIENTS AND METHODS: Eight patients were included, three of whom had Parkinson's disease, three diabetes, one pure autonomic failure and the last one had multiple system atrophy. By the use of two techniques, the arteriovenous oxygen [(a-v)O2] method and xenon-inhalation with single photon emission tomography, 15 measurements (range 10-20) and three to four CBF measurements, respectively, were obtained in each patient. Following CBF measurements during baseline, MABP was raised gradually using intravenous noradrenaline infusion, and then lowered by application of lower body negative pressure. From the (a-v)O2 samples the CBF response to changes in MABP was evaluated using a computer program fitting one or two regression lines through the plot. RESULTS AND CONCLUSION: Preserved autoregulation was observed in three patients, while the remaining five patients showed a linear relationship between CBF and MABP. Comparison of the results of the tomographic CBF measurements to the (a-v)O2 data demonstrated that it is not possible to assess whether CBF is autoregulated or not with only three to four pairs of data.

Administration, Inhalation↗