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Biomedical subjects

Lars-Olof Wahlund

Publications and source records attributed to Lars-Olof Wahlund.

At least 37 records · Page 2Linked to original sources
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

Medial temporal lobe atrophy on MRI predicts dementia in patients with mild cognitive impairment.

BACKGROUND: Although detailed volumetric MRI assessment of medial temporal lobe atrophy (MTA) can predict dementia in patients with mild cognitive impairment (MCI), it is not easily applied to routine clinical practice. OBJECTIVE: To test the predictive accuracy of visually assessed MTA in MCI patients using a standardized visual rating scale. METHODS: Seventy-five MCI patients (mean age 63 years) underwent a coronal three-dimensional magnetization-prepared rapid gradient echo brain MRI sequence. MTA was rated visually using a 5-point rating scale. RESULTS: The mean follow-up period for the cohort was 34 months. At follow-up, 49% of the enrolled MCI patients fulfilled criteria for dementia. MTA assessed using a standardized visual rating scale was significantly associated with dementia at follow-up, with a hazard ratio of 1.5 for every point increase in atrophy score (p < 0.001) and of 3.1 for the presence of atrophy based on the dichotomized atrophy score (p = 0.003). The predictive accuracy of visually assessed MTA was independent of age, gender, education, Mini-Mental State Examination score, Clinical Dementia Rating Sum of Boxes score, Verbal Delayed Recall, and the presence of hypertension, depression, the APOE epsilon4 allele, and white matter hyperintensities. CONCLUSIONS: Visual assessment of MTA on brain MRI using a standardized rating scale is a powerful and independent predictor of conversion to dementia in relatively young MCI patients. As overlap existed in MTA scores between patients with and without dementia at follow-up, the results should be interpreted in the light of the odds for the individual patient.

Aged↗
PubMed2004

Intracranial volume in mild cognitive impairment, Alzheimer's disease and vascular dementia: evidence for brain reserve?

OBJECTIVE: The possibility of brain volume reserve effects was examined in a sample of geriatric outpatients with mild cognitive impairment (MCI), Alzheimer's disease (AD) and vascular dementia (VaD). The total intracranial volume (ICV) served as an estimate of the maximum attained brain volume in life. METHODS: Subjects (n = 181, mean age 60.7) were consecutive referrals to a geriatric outpatients clinic (n = 96) and a group of age-matched healthy control subjects (n = 85). ICV and brain volume were attained from T1-weighted magnetic resonance images using a stereological method. Hippocampal atrophy was assessed with a visual rating scale. RESULTS: ICV was significantly smaller in patients with AD and VaD than in control subjects, but effect size was small. After adjusting for age and gender, having ICV in the smallest quartile significantly increased the risk of cognitive impairment (either MCI or dementia). In patients with dementia, but not in MCI, severity of cognitive impairment and ICV were moderately correlated. The effect of ICV on cognition was not mediated by hippocampal atrophy. CONCLUSIONS: These findings are compatible with volume reserve effects that modify the clinical expression of symptoms in both AD and VaD. They may have implications for the design of neuroimaging studies that use ICV for normalization procedures.

Adult↗
PubMed2004

Structural correlates of mild cognitive impairment.

The structural correlates of mild cognitive impairment (MCI) were examined in 105 elderly subjects whose cognitive function ranged from intact to demented, including 38 subjects with MCI. Hippocampal volumes (left and right HcV), brain volume (BV), and grey matter volume (GMV) and white matter volume (WMV) were segmented from high resolution magnetic resonance data sets and normalised to intracranial volume (ICV). Hippocampal volume reductions, but not global brain, white or grey matter atrophy, were associated with MCI. White matter lesion severity did not differ over cognitive states. In multiple logistic regression models, normalised HcV and ICV (indicating premorbid brain volume) were significant predictors of MCI versus normality. Normalised BV and ICV significantly predicted dementia versus MCI. Absolute volumetric measures of HcV and BV yielded comparable classification accuracies. Hippocampal atrophy may be the crucial step for the transition from normality to MCI. Widespread brain atrophy may be the step to determine the transition from MCI to dementia. Brain volume reserve effects appear to be involved in both of these steps.

Aged↗
PubMed2004

Diagnostic use of cerebral and extracerebral oxysterols.

BACKGROUND: 24S-Hydroxycholesterol (24OHC) and 27-hydroxycholesterol (27OHC) are two structurally similar oxysterols of different origins--the former almost exclusively formed in the brain and the latter formed to a lesser extent in the brain than in most other organs. HYPOTHESIS TO BE TESTED: Neuronal damage and/or demyelination causes increased flux of 24OHC from the brain into the cerebrospinal fluid (CSF), whereas a defect blood-brain barrier causes increased flux of 27OHC from the circulation into the CSF. METHODS: Isotope dilution-mass spectrometry was used to assay the two oxysterols in CSF and plasma from more than 250 patients with different neurological and geriatric diseases. RESULTS: The CSF-levels of the two oxysterols were much more affected by the different diseases than the plasma levels. Patients with active demyelinating diseases had increased levels of 24OHC in CSF with a relatively high 24OHC/27OHC ratio. Patients with meningitis in general had high levels of both steroids with a low 24OHC/27OHC ratio. Patients with Alzheimer's disease had slightly increased levels of 24OHC in CSF with less increase in 27OHC. Patients with multiple sclerosis had a tendency to have higher levels of 24OHC during active periods with a high 24OHC/ 27OHC ratio. CONCLUSIONS: Measurements of the two oxysterols in CSF and plasma may add significantly to existing biochemical methods for evaluation of neurological diseases.

Adult↗
PubMed2003

[Functional MRI of the elderly can complete the picture of cerebral functions].

Functional Magnetic Resonance Imaging, fMRI, is a method for the study of neuronal circuits underlying cognitive, sensory, emotional and motor activities in the living human brain. An important question is whether elderly persons and patients with cognitive deficits differ from others as regards neuronal activation. Not many studies have been published but some of them have shown surprising results. This new research has shown some very interesting new facts about the vascular response and the regulation of the microvasculature in the brain. Most fMRI studies have been performed on healthy young males, but in our opinion this method could reveal new findings to complete the picture of human cognition if studies were to be performed involving elderly people and patients with dementia.

Aged↗
PubMed2003

Cerebrospinal fluid markers for prediction of Alzheimer's disease.

A major diagnostic challenge when people seek advice for cognitive dysfunction is to differentiate between mild cognitive impairment (MCI) and incipient Alzheimer's disease (AD). We show that a combination of three cerebrospinal fluid biochemical markers, total-tau, phospho-tau and beta-amyloid(1-42), can detect incipient AD among patients fulfilling the criteria for MCI with a sensitivity of 68% (95% CI 45-86%) and a specificity of 97% (95% CI 83-100%). The usefulness of these markers is further emphasized by the finding of a positive predictive value of 94% and a negative predictive value of 81%.

Aged↗
PubMed2003

Determination of isoprostanes in urine samples from Alzheimer patients using porous graphitic carbon liquid chromatography-tandem mass spectrometry.

F2-isoprostanes (F2-iPs) comprise four classes of isomers produced non-enzymatically by free radical attack on arachidonic acid, a component of the cell membrane. This paper describes a new method for the quantification of F2-isoprostanes in urine samples from thoroughly diagnosed Alzheimer's disease (AD) patients. The sample pretreatment consisted of liquid extraction of 900 microl urine with diethyl ether, its subsequent evaporation, and finally, reconstitution in 50 microl water. Of this, 20 microl was injected into a HPLC system with a 15 mm x 1 mm porous graphitic carbon column coupled to a triple quadrupole mass spectrometer running in negative electrospray ionization mode. The F2-isoprostanes were separated in 15 min using a linear solvent gradient comprising water, methanol, acetonitrile and ammonium hydroxide at a pH of 9.5. The average recovery obtained was approximately 75%. The limit of detection (3S/N) was calculated for iPF2alpha-III to be 0.7 pg injected on column, corresponding to 0.1 nM. The average level of iPF2alpha was 241 +/- 163 pg/mg creatinine in the urine samples from AD patients (average +/- standard deviation). The corresponding control values were 216 +/- 101 pg/mg creatinine, i.e. no statistically significant difference was noticed. No correlation pattern specific to Alzheimer's disease was revealed by principal component analysis of the isoprostane peaks obtained either. The results from this study support earlier findings that levels of peripheral isoprostanes are not increased in patients with Alzheimer's disease.

Aged↗
PubMed2003

The relationship between head size and intracranial volume in elderly subjects.

OBJECTIVE: To study the relationship between parenchymal head volume (PHV) and intracranial volume (ICV), and to compare the ability of these two measurements to reflect the association between maximum mature brain volume and late-life cognition. METHODS: An elderly sample of humans with a range of cognitive functions from normality, via mild cognitive impairment (MCI) to dementia (mean age 78.6, S.D. 2.8; mean MMSE 25.4, S.D. 4.2) was examined. Head-to-head measurements of ICV and parenchymal head volume (PHV) were obtained from three-dimensional T1 weighted magnetic resonance images using automated procedures. Analyses of cognitive functions were based on continuous and categorial variables. RESULTS: PHV explained 55% of the variance in ICV. The ratio between PHV and ICV remained constant with increasing age and cognitive impairment. Measurements of PHV and ICV yielded comparable correlations with global cognitive performance. Group differences over gender and cognitive states were equally present in ICV and PHV. The relative risks of cognitive impairment that were associated with either small ICV or PHV were comparable. CONCLUSIONS: Measures of PHV can be considered as useful estimates of ICV and cerebral volume reserve.

Aged↗
PubMed2003

Prognostic significance of white matter changes in a memory clinic population.

Non-specific white matter changes (WMC) can be seen on neuroimaging of the brain in healthy elderly but are more common in dementia. WMC are correlated to specific cognitive deficits and might also contribute to global cognitive decline. The value of WMC as a predictor of cognitive impairment has been incompletely elucidated. We studied the prognostic significance of extensive WMC in a group of patients with memory disturbances, to evaluate if the presence of such changes predicts a poorer outcome. We retrospectively selected a group of 24 patients with prominent WMC on magnetic resonance imaging (MRI) and with different grades of memory impairment. We matched each patient, with regard to age, education, length of follow-up, initial score on the Mini Mental State Examination (MMSE) and initial diagnosis, to a patient without white matter pathology. The matched pairs were evaluated and the decrease in MMSE score after follow-up (range 2-4 years) was used as the outcome measure. Results showed no difference in the decrease in MMSE score at follow-up between patients with or without WMC. In conclusion, the presence of WMC in cognitively impaired patients had no effect on the progression rate of dementia, as measured by MMSE decline.

Aged↗
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

A critical discussion of the role of neuroimaging in mild cognitive impairment.

OBJECTIVE: In this paper, the current neuroimaging literature is reviewed with regard to characteristic findings in mild cognitive impairment (MCI). Particular attention is drawn to the possible value of neuroimaging modalities in the prediction and early diagnosis of Alzheimer's disease (AD). METHODS: First, the potential contribution of neuroimaging to an early, preclinical diagnosis of degenerative disorders is discussed at the background of our knowledge about the pathogenesis of AD. Second, relevant neuroimaging studies focusing on MCI are explored and summarized. Neuroimaging studies were found through Medline search and by systematically checking through the bibliographies of relevant articles. RESULTS: Structural volumetric magnetic resonance imaging (MRI) and positron emission tomography (PET)/single photon emission tomography (SPECT) are currently the most commonly used neuroimaging modalities in studies focusing on MCI. There were considerable variations in demographical and clinical characteristics across studies. However, significant hippocampal and entorhinal cortex volume reductions were consistently found in subjects with MCI as compared with cognitively unimpaired controls. While hippocampal and entorhinal cortex atrophy in subjects with MCI are also well-established risk factors for the development of AD, these measures cannot be regarded as being of high predictive value in an individual case. Evidence for other typical neuroimaging changes in MCI is still scarce. In PET and SPECT studies, reduced blood flow and/or glucose metabolism in temporoparietal association areas, posterior cingulate and hippocampus were associated with a higher risk of progressive cognitive decline in MCI. In quantitative electroencephalogram (QEEG), low beta, high theta, low alpha and slowed mean frequency were associated with development of dementia. CONCLUSIONS: Existing studies suggest that neuroimaging measures have the potential to become valuable tools in the early diagnosis of AD. To establish their value in routine use, larger studies, preferably with long prospective follow-up are needed.

Alzheimer Disease↗
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

Mild cognitive impairment: experience from a memory clinic.

Mild cognitive impairment (MCI) is sometimes a transition between normal aging and dementia. We investigated the occurrence of MCI in a population referred to a memory clinic. The criteria used to diagnose the state were similar to those used by Petersen et al. in many previous publications. A clinical evaluation after approximately 3 years was also performed. In a subsample of 43 subjects, we found that, during 1 year, 37% (136/402) of all investigated subjects were patients with MCI. After a mean follow-up time of 3 years, 11% (5/43) showed cognitive improvement, while 53% (23/43) were stable and showed no cognitive decline or improvement. Fifteen out of 42 patients (35%) deteriorated and were diagnosed as demented during the same time. We conclude that MCI is a heterogeneous concept and that the outcome at follow-up is dependent on which population is studied and how MCI has been defined.

Aged↗
PubMed2002

Cingulate cortex hypoperfusion predicts Alzheimer's disease in mild cognitive impairment.

BACKGROUND: Mild cognitive impairment (MCI) was recently described as a heterogeneous group with a variety of clinical outcomes and high risk to develop Alzheimer's disease (AD). Regional cerebral blood flow (rCBF) as measured by single photon emission computed tomography (SPECT) was used to study the heterogeneity of MCI and to look for predictors of future development of AD. METHODS: rCBF was investigated in 54 MCI subjects using Tc-99m hexamethylpropyleneamine oxime (HMPAO). An automated analysis software (BRASS) was applied to analyze the relative blood flow (cerebellar ratios) of 24 cortical regions. After the baseline examination, the subjects were followed clinically for an average of two years. 17 subjects progressed to Alzheimer's disease (PMCI) and 37 subjects remained stable (SMCI). The baseline SPECT ratio values were compared between PMCI and SMCI. Receiver operating characteristic (ROC) analysis was applied for the discrimination of the two subgroups at baseline. RESULTS: The conversion rate of MCI to AD was 13.7% per year. PMCI had a significantly decreased rCBF in the left posterior cingulate cortex, as compared to SMCI. Left posterior cingulate rCBF ratios were entered into a logistic regression model for ROC curve calculation. The area under the ROC curve was 74%-76%, which indicates an acceptable discrimination between PMCI and SMCI at baseline. CONCLUSION: A reduced relative blood flow of the posterior cingulate gyrus could be found at least two years before the patients met the clinical diagnostic criteria of AD.

Alzheimer Disease↗
PubMed2002

[Progressive aphasia. New data on an old phenomenon].

Progressive aphasias are distinct but infrequently recognized clinical expressions of non-Alzheimer lobar atrophy. We review and illustrate two such syndromes--semantic dementia (SD) and progressive nonfluent aphasia (PA). SD involves loss of conceptual structure due to bilateral infratemporal atrophy. PA is a phonetic-syntactic disorder resulting from left perisylvian atrophy. Early research on Pick disease--originally defined as circumscribed cerebrocortical atrophy--highlighted left temporal lobe atrophy and aphasia. For this reason (among others), Pick disease or Pick complex is still a useful and convenient label for progressive aphasias and other clinical manifestations of non-AD lobar atrophy.

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