Biomedical subjects

Ove Almkvist

Publications and source records attributed to Ove Almkvist.

18 recordsLinked to original sources

PubMed2006

Differential CSF biomarker levels in APOE-epsilon4-positive and -negative patients with memory impairment.

OBJECTIVES: To investigate the relationships between episodic memory, APOE genotype, CSF markers (total tau, T-tau; phospho-tau, P-tau; beta-amyloid, Abeta42) and longitudinal cognitive decline. METHODS: 124 memory clinic patients were retrospectively divided into 6 groups based on (i) episodic memory function (Rey Auditory Verbal Learning Test, RAVLT): severe, moderate or no impairment (SIM, MIM or NIM), and (ii) APOE genotype (epsilon4+ or epsilon4-). CSF marker levels and cognitive decline were compared across groups. RESULTS: Episodic memory function, according to RAVLT scores, was significantly correlated with CSF marker levels only among epsilon4+ subjects and not among epsilon4- subjects. When comparing the 6 subgroups, SIM epsilon4+ and MIM epsilon4+ groups showed significantly lower Abeta42 levels than the other groups. T-tau and P-tau levels were significantly increased in SIM epsilon4+ when compared to all the other groups, including the SIM epsilon4- group. However, both SIM epsilon4+ and SIM epsilon4- declined cognitively during the follow-up. CONCLUSION: It remains to be determined whether APOE genotype affects the expression of biomarkers in CSF, or whether the different biomarker patterns reflect different types of disease processes in patients with progressive cognitive dysfunction.

Amyloid beta-Protein Precursor↗

PubMed2006

Two-year follow-up of amyloid deposition in patients with Alzheimer's disease.

Beta amyloid is one of the major histopathological hallmarks of Alzheimer's disease. We recently reported in vivo imaging of amyloid in 16 Alzheimer patients, using the PET ligand N-methyl[11C]2-(4'-methylaminophenyl)-6-hydroxy-benzothiazole (PIB). In the present study we rescanned these 16 Alzheimer patients after 2.0 +/- 0.5 years and have described the interval change in amyloid deposition and regional cerebral metabolic rate for glucose (rCMRGlc) at follow-up. Sixteen patients with Alzheimer's disease were re-examined by means of PET, using PIB and 2-[18F]fluoro-2-deoxy-d-glucose (FDG) after 2.0 +/- 0.5 years. The patients were all on cholinesterase inhibitor treatment and five also on treatment with the N-methyl-d-aspartate (NMDA) antagonist memantine. In order to estimate the accuracy of the PET PIB measurements, four additional Alzheimer patients underwent repeated examinations with PIB within 20 days (test-retest). Relative PIB retention in cortical regions differed by 3-7% in the test-retest study. No significant difference in PIB retention was observed between baseline and follow-up while a significant (P < 0.01) 20% decrease in rCMRGlc was observed in cortical brain regions. A significant negative correlation between rCMRGlc and PIB retention was observed in the parietal cortex in the Alzheimer patients at follow-up (r = 0.67, P = 0.009). A non-significant decline in Mini-Mental State Examination (MMSE) score from 24.3 +/- 3.7 (mean +/- standard deviation) to 22.7 +/- 6.1 was measured at follow-up. Five of the Alzheimer patients showed a significant decline in MMSE score of >3 (21.4 +/- 3.5 to 15.6 +/- 3.9, P < 0.01) (AD-progressive) while the rest of the patients were cognitively more stable (MMSE score = 25.6 +/- 3.1 to 25.9 +/- 3.7) (AD-stable) compared with baseline. A positive correlation (P = 0.001) was observed in the parietal cortex between Rey Auditory Verbal Learning (RAVL) test score and rCMRGlc at follow-up while a negative correlation (P = 0.018) was observed between RAVL test and PIB retention in the parietal at follow-up. Relatively stable PIB retention after 2 years of follow-up in patients with mild Alzheimer's disease suggests that amyloid deposition in the brain reaches a plateau by the early clinical stages of Alzheimer's disease and therefore may precede a decline in rCMRGlc and cognition. It appears that anti-amyloid therapies will need to induce a significant decrease in amyloid load in order for PIB PET images to detect a drug effect in Alzheimer patients. FDG imaging may be able to detect a stabilization of cerebral metabolism caused by therapy administered to patients with a clinical diagnosis of Alzheimer's disease.

Aged↗

PubMed2006

PET imaging of cortical 11C-nicotine binding correlates with the cognitive function of attention in Alzheimer's disease.

RATIONALE: Patients suffering from Alzheimer's disease (AD) experience a marked reduction in cortical nicotinic acetylcholine receptors (nAChRs). In particular, selective loss of the alpha4beta2 nAChR subtype was observed in postmortem AD brain tissue. The alpha4 and alpha7 nAChR subunits were suggested to play an important role in cognitive function. Positron emission tomography (PET) has so far been used to visualize neuronal nAChRs in vivo by 11C-nicotine binding. OBJECTIVES: To investigate the relationship between measures of cognitive function and in vivo 11C-nicotine binding in mild AD brain as assessed by PET. MATERIALS AND METHODS: Twenty-seven patients with mild AD were recruited in this study. A dual tracer model with administration of 15O-water for regional cerebral blood flow and (S)(-)11C-nicotine was used to assess nicotine binding sites in the brain by PET. Cognitive function was assessed using neuropsychological tests of global cognition, episodic memory, attention, and visuospatial ability. RESULTS: Mean cortical 11C-nicotine binding significantly correlated with the results of attention tests [Digit Symbol test (r = -0.44 and p = 0.02) and Trail Making Test A (TMT-A) (r = 0.42 and p = 0.03)]. No significant correlation was observed between 11C-nicotine binding and the results of tests of episodic memory or visuospatial ability. Regional analysis showed that 11C-nicotine binding in the frontal and parietal cortex, which are the main areas for attention, correlated significantly with the Digit Symbol test and TMT-A results. CONCLUSION: Cortical nicotinic receptors in vivo in mild AD patients are robustly associated with the cognitive function of attention.

Aged↗

PubMed2006

Increased sensitivity in mapping task demand in visuospatial processing using reaction-time-dependent hemodynamic response predictors in rapid event-related fMRI.

Searching for the neural correlates of visuospatial processing using functional magnetic resonance imaging (fMRI) is usually done in an event-related framework of cognitive subtraction, applying a paradigm comprising visuospatial cognitive components and a corresponding control task. Besides methodological caveats of the cognitive subtraction approach, the standard general linear model with fixed hemodynamic response predictors bears the risk of being underspecified. It does not take into account the variability of the blood oxygen level-dependent signal response due to variable task demand and performance on the level of each single trial. This underspecification may result in reduced sensitivity regarding the identification of task-related brain regions. In a rapid event-related fMRI study, we used an extended general linear model including single-trial reaction-time-dependent hemodynamic response predictors for the analysis of an angle discrimination task. In addition to the already known regions in superior and inferior parietal lobule, mapping the reaction-time-dependent hemodynamic response predictor revealed a more specific network including task demand-dependent regions not being detectable using the cognitive subtraction method, such as bilateral caudate nucleus and insula, right inferior frontal gyrus and left precentral gyrus.

Adult↗

PubMed2006

Identifying patients at high and low risk of cognitive decline using Rey Auditory Verbal Learning Test among middle-aged memory clinic outpatients.

OBJECTIVES: To investigate whether application of cutoff levels in an episodic memory test (Rey Auditory Verbal Learning Test, RAVLT) is a useful method for identifying patients at high and low risk of cognitive decline and subsequent dementia. METHODS: 224 patients with memory complaints (mean age = 60.7 years, mean MMSE = 28.2) followed-up at a memory clinic over approximately 3 years were assigned retrospectively to one of three memory groups from their baseline results in RAVLT [severe (SIM), moderate (MIM) or no impairment (NIM)]. These groups were investigated regarding cognitive decline. RESULTS: Patients assigned to SIM showed significant cognitive decline and progressed to dementia at a high rate, while a normal performance in RAVLT at baseline (NIM) predicted normal cognition after 3 years. Patients with MIM constituted a heterogeneous group; some patients deteriorated cognitively, while the majority remained stable or improved. CONCLUSIONS: The application of cutoff levels in RAVLT at baseline showed that patients with severely impaired RAVLT performance were at a high risk of cognitive decline and progression to dementia, while patients with normal RAVLT results did not show cognitive decline during 3 years. Furthermore, the initial degree of memory impairment was decisive in the cognitive prognosis 3 years later.

Acoustic Stimulation↗

PubMed2006

Reading words with irregular decoding rules: a test of premorbid cognitive function?

The present study investigated the relation between level of general cognitive function and the oral reading of irregular words in Swedish. Swedish is an orthographically regular language, so many irregular words are loan words from other languages. A test comprising such words (irregularly spelled words (ISW)) was designed, and tested on a sample of 48 healthy Swedish adults, stratified according to age, gender, and level of education. The results confirmed that the ability to read words that do not follow the regular rules for decoding in Swedish was positively related to general cognitive level. ISW in combination with demographic variables gave a good estimate of general cognitive function and a better estimate than demographic variables alone. Exposure to written and spoken vocabulary during the lifespan may be indexed by ISW performance, for factor analysis suggested that this may constitute a discrete factor contributing to cognitive function.

Adult↗

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↗

PubMed2004

Insidious cognitive decline in CADASIL.

BACKGROUND AND PURPOSE: Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) causes repeated ischemic attacks leading to subcortical vascular dementia. The aim of this study was to characterize cognitive function in subjects with a C475T (R133C) mutation in the Notch3 gene, leading to CADASIL. METHODS: Prestroke (n=13) and poststroke (n=13) mutation carriers and mutation carriers with dementia (n=8) were compared with healthy noncarriers from the same families using a comprehensive set of neuropsychological tests. RESULTS: Changes in working memory and executive function were observed in the very early phase of the disease before transient ischemic attack (TIA) or stroke. Later, in the poststroke phase, the cognitive impairment concerned also mental speed and visuospatial ability. Finally, the subjects with dementia had multiple cognitive deficits, which engaged even verbal functions, verbal episodic memory, and motor speed. The 2 mutation carrier groups without dementia and the controls could be reliably distinguished using 3 tests that assessed working memory/attention, executive function, and mental speed. Episodic memory was relatively well-preserved late in the disease. CONCLUSIONS: A deterioration of working memory and executive function was already observed in the prestroke phase, which means that cognitive decline may start insidiously before the first onset of symptomatic ischemic episodes.

Adult↗

PubMed2004

Task demand modulations of visuospatial processing measured with functional magnetic resonance imaging.

Brain imaging based on functional magnetic resonance imaging (fMRI) provides a useful tool to examine neural networks and cerebral structures subserving visuospatial function. It allows not only the qualitative determination of which areas are active during task processing, but also estimates the quantitative contribution of involved brain regions to different aspects of spatial processing. In this study, we investigated in 10 healthy subjects how the amount of task (computational) demand in an angle discrimination task was related to neural activity as measured with event-related fMRI. Task demand, indicated by behavioral performance, was modulated by presenting clocks with different angular disparity and length of hands. Significant activations were found in the cortical network subserving the visual and visuospatial processing, including the right and left superior parietal lobules (SPL), striate visual areas, and sensorimotor areas. Both blood oxygenation level-dependent (BOLD) signal strength and spatial extent of activation in right as well as left SPL increased with task demand. By contrast, no significant correlation or a very weak correlation was found between the task demand and the BOLD signal as well as between task demand and spatial extent of activations in the striate visual areas and in the sensorimotor areas. These results support the hypothesis that increased computational demand requires more brain resources. The brain regions that are most specialized for the execution of the visuospatial task can be assessed by relating the imposed task demand to the functional activation measured.

Adult↗

PubMed2003

Voxel- and VOI-based analysis of SPECT CBF in relation to clinical and psychological heterogeneity of mild cognitive impairment.

This study aimed to explore the heterogeneity of mild cognitive impairment (MCI) and detect differences in regional cerebral blood flow (rCBF) and cognitive function between progressive mild cognitive impairment (PMCI) and stable mild cognitive impairment (SMCI) in order to identify specific changes useful for early diagnosis of dementia. SPECT was performed in 82 MCI subjects and 20 controls using Tc-99m hexamethylpropyleneamine oxime. Cognitive functions were tested in five domains which included episodic memory, semantic memory, visuospatial function, attention, and general cognitive function. After the initial examination, MCI subjects were clinically followed for an average of 2 years. Twenty-eight subjects progressed to dementia and were defined as PMCI at baseline and 54 subjects remained stable and were defined as SMCI at baseline. The baseline rCBF and cognitive function of PMCI, SMCI, and controls were compared. PMCI had decreased relative rCBF in the parietal lobes and increased relative rCBF in prefrontal cortex compared to SMCI and controls at baseline. The cognitive function of PMCI was more severely impaired compared to SMCI with respect to episodic memory and visuospatial and general cognitive function. Both SPECT and neuropsychological tests had moderate discriminant function between PMCI and SMCI at baseline with the area under the receiver operating characteristic (ROC) curve at 75-77%. The combination of these two methods improved the diagnostic accuracy with the area under the ROC curve at 82-84%. Semantic memory and attention were negatively correlated with left prefrontal relative rCBF among the study population. The results show that the clinical heterogeneity of MCI is reflected in different patterns of psychological and CBF changes. Combined SPECT investigation and neuropsychological testing might predict the future development of dementia in patients with MCI.

Aged↗

PubMed2003

Cognitive syndrome(s) in preclinical and clinical vascular dementia.

It is still a challenge to identify typical features of cognitive function in vascular dementia (VaD) in clinical as well as in preclinical stages. Selective empirical findings are described to illuminate degrees of cognitive decline. In predementia stages, speeded performance (motor and mental) and executive functions may be affected as demonstrated by CADASIL subjects and stroke survivors. In dementia stages, motor and mental speed as well as executive functions is commonly affected in addition to typical cognitive dysfunction in dementia (memory, verbal, and visuospatial). To summarize characteristics during preclinical and clinical stages, VaD appears to be associated with impairment in motor and mental speed as well as in executive function.

Aged↗

PubMed2003

Clinical findings in nondemented mutation carriers predisposed to Alzheimer's disease: a model of mild cognitive impairment.

Individuals carrying a mutation associated with Alzheimer's disease (AD) may serve as a model of mild cognitive impairment (MCI). Nondemented individuals from these families can be subdivided into asymptomatic and symptomatic groups. Four families were studied. Two families are associated with APP mutations (KN670/671ML, E693G) and two with PS1 mutation (M146V, H163Y). Clinical symptoms, level of global cognitive functioning as evaluated by Mini-Mental State Examination, neuropsychological test results, neuroradiological examinations (magnetic resonance imaging (MRI) and single-photon emission tomography (SPECT)), as well as cerebrospinal fluid (CSF) measurements of tau and beta-amyloid are reported. Nondemented mutation carriers did not report any symptoms indicating cognitive decline. In addition, no clinical signs of dementia or marked cognitive impairment in neuropsychological tests were found. A reduction of temporal blood flow with SPECT was indicated in 5/13 nondemented mutation carriers. Two of these 13 individuals had moderate hyperintensities in deep white matter as observed on MRI. CSF measurements of A beta 42/43 were inconclusive because of large biological variation. A nonsignificant elevation of tau was detected in mutation carriers. In conclusion, clinical examinations of relatively young individuals carrying an AD mutation did not reveal any marked abnormalities before the clinical onset of dementia.

Adolescent↗

PubMed2003

The assessment of fitness to drive after a stroke: the Nordic Stroke Driver Screening Assessment.

The British Stroke Driver Screening Assessment (SDSA) is a set of four simple cognitive tests to evaluate driving fitness in stroke patients. To evaluate its usefulness in a Scandinavian context, we adapted the tests and assessed a group of 97 stroke patients from Sweden and Norway, using a driving test as the criterion. When results were calculated according to the original method, based on a discriminant function, less than 70% of the participants were correctly classified. To improve the predictive potential, a new discriminant analysis was performed, using the scores of a subsample of 49 patients, and validated on the remaining 48 participants. In total, 78% of the patients were correctly classified, but specificity was superior to sensitivity. We conclude that the Nordic version of the SDSA is a useful instrument, provided that test scores are interpreted in a balanced manner, taking into account the possibility of compensatory traffic behavior.

Adult↗

PubMed2003

Life situation, coping and quality of life in people with high and low risk of developing Alzheimer's disease.

The psychosocial consequences of being at different risk for inheriting Alzheimer's disease (AD) were investigated in a high-risk group (n = 106) and a low-risk group (n = 37). Non-affected individuals from families with AD in two or more generations answered questions about their life situation, quality of life and coping. Their answers were compared with a population sample (n = 408). The high-risk group assessed the quality of their personal relationships and everyday life higher than did the population sample. They also used less emotive and supportive coping strategies compared with the population sample. Nearly 90% in the high-risk group felt anxiety concerning their own risk or the risk of their children and grandchildren of developing AD. About 50% of the respondents complained about a lack of information. The pieces of information they asked for were early signs of the disease, treatment, and practical information on how to handle everyday life with an affected relative.

Adaptation, Psychological↗

PubMed2003

Neuropsychological features of mild cognitive impairment and preclinical Alzheimer's disease.

Recent research has identified a transitional state between the cognitive changes of normal aging and Alzheimer's disease (AD), known as mild cognitive impairment (MCI). MCI patients experience memory loss to a greater extent than one would expect for age, yet they do not meet currently accepted criteria for clinically probable AD. An issue currently under investigation is whether MCI represents the preclinical stages of AD or a distinct and static cognitive aetiology. In an attempt to address this issue, the present investigations are adopting a convergent approach to the detection of preclinical AD, where multiple risk factors are considered when making a diagnosis. Currently, one of the most important tools when assessing early cognitive changes is neuropsychological evaluation. MCI subjects typically record neuropsychological performance between that of healthy older individuals and demented patients. Tests assessing new learning, delayed recall and attention/executive function seem to provide valuable information for screening and diagnosis of MCI and early AD if interpreted properly. Recommendations concerning methodological issues and the early management of neuropsychological MCI studies were made.

Alzheimer Disease↗

PubMed2002

Semantic range and relevance of emotive utterances in patients with frontotemporal degeneration.

Patterns of aberrant language due to lateralized frontal brain lesions have been described. The present study investigated the consequences of lateralized lesion for aspects of semantic range and relevance in speech of patients with frontotemporal degeneration. Demented patients with predominantly left (n=10) and right (n=4) brain degeneration as well as 5 healthy controls participated. Significant differences were found concerning semantic range and relevance in descriptions of emotionally loaded pictures within the demented group and between the demented group and the controls. The demented individuals' speech was less varied and relevant in contrast to the healthy individuals. The speech of the left hemispheric group was more relevant but also more stereotypic and unspecified than that of the right hemispheric group. The results are discussed in terms of impaired semantic retrieval and in relation to lateralization of lesion.

Affect↗

PubMed2002

Cognitive functioning in Alzheimer's disease and vascular dementia: further evidence for similar patterns of deficits.

The purpose of the present study was to examine possible differences in patterns of cognitive performance between population-based samples of Alzheimer's disease (AD; n = 51) and vascular dementia (AD; n = 14) patients between 75 and 96 years of age. The two demented groups were comparable in age, years of education, gender distribution, and severity of dementia. The selection of cognitive tasks (letter and category fluency, Block design, Clock reading and setting, and episodic face recognition) was thought to address some of the inconsistencies in previous research. The main finding was that AD and AD patients were comparable on most tasks, although robust dementia-related deficiencies were found when comparing the results of the demented participants with those of the control participants. These findings suggest that AD and AD may affect several basic cognitive functions in an equal manner.

Aged↗

PubMedDate not supplied

Impaired motor speed, visuospatial episodic memory and verbal fluency characterize cognition in long-term stroke survivors: the Tromsø Study.

The cognitive function after stroke is examined in acute and subacute phase, but poorly characterized in long-term stroke survivors. This paper discusses cognitive function among long-term stroke survivors, with matched stroke-free subjects, based on a population survey. General cognition, verbal, executive and visuospatial function, memory, attention, and motor speed were tested as well as motor function in upper extremities. Stroke survivors and controls were most effectively discriminated by means of motor speed, followed by visuospatial episodic memory and verbal fluency. This pattern of cognitive disturbances may be a consequence of cerebral lesions in frontal subcortical areas, and is different from Alzheimer's disease.

Aged↗