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The aim of this 3-year follow-up study was to investigate whether corpus callosum (CC) atrophy may predict future motor and cognitive impairment in an elderly population. On baseline MRI from 563 subjects with age-related white matter changes (ARWMC) from the Leukoaraiosis And DISability (LADIS) study, the CC was segmented and subdivided into five anterior-posterior regions (CC1-CC5). Associations between the CC areas and decline in motor performance and cognitive functions over a 3-year period were analyzed. CC atrophy at baseline was significantly associated with impaired cognitive performance (p<0.01 for CC1, p<0.05 for CC5), motor function (p<0.05 for CC2 and CC5), and walking speed (p<0.01 for CC2 and CC5, p<0.05 for CC3 and total CC), and with development of dementia at 3 years (p<0.05 for CC1) after correction for appropriate confounders (ARWMC volume, atrophy, age, gender and handedness). In conclusion, CC atrophy, an indicator of reduced functional connectivity between cortical areas, seems to contribute, independently of ARWMC load, to future cognitive and motor decline in the elderly., (Copyright © 2011 Elsevier B.V. All rights reserved.)

We have previously shown that a high cholesterol (HC) diet results in increases in microglia load and levels of the pro-inflammatory cytokine interleukin-6 (IL-6) in the brains of wild type (WT) and apolipoprotein E knockout (ApoE-/-) mice. In the present investigation, we analyzed whether treatment with rosuvastatin, an inhibitor of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, would prevent the increases in inflammatory microglia and IL-6 levels in the brain and plasma of WT and ApoE-/- mice. We report that a HC diet resulted in an increased microglia load in the brains of WT and ApoE-/- mice, in support of our previous study. Treatment with rosuvastatin significantly decreased the microglia load in the brains of WT and ApoE-/- mice on a HC diet. Rosuvastatin treatment resulted in lowered plasma IL-6 levels in WT mice on a HC diet. However, in the present study the number of IL-6 positive cells in the brain was not significantly affected by a HC diet. A recent clinical study has shown that rosuvastatin reduces risk of ischemic stroke in patients with high plasma levels of the inflammatory marker C-reactive protein by 50%. The results from our study show that rosuvastatin reduces inflammatory cells in the brain. This finding is essential for furthering the prevention and treatment of neurodegenerative diseases such as Alzheimer's disease (AD) and stroke., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Corpus callosum (CC) is the main tract connecting the hemispheres, but the clinical significance of CC atrophy is poorly understood. The aim of this work was to investigate clinical and functional correlates of CC atrophy in subjects with age-related white matter changes (ARWMC). In 569 elderly subjects with ARWMC from the Leukoaraiosis And DISability (LADIS) study, the CC was segmented on the normalised mid-sagittal magnetic resonance imaging (MRI) slice and subdivided into five regions. Correlations between the CC areas and subjective memory complaints, mini mental state examination (MMSE) score, history of depression, geriatric depression scale (GDS) score, subjective gait difficulty, history of falls, walking speed, and total score on the short physical performance battery (SPPB) were analyzed. Significant correlations between CC atrophy and MMSE, SPPB, and walking speed were identified, and the CC areas were smaller in subjects with subjective gait difficulty. The correlations remained significant after correction for ARWMC grade. In conclusion, CC atrophy was independently associated with impaired global cognitive and motor function in subjects with ARWMC.

The diagnosis of Alzheimer's disease (AD) in patients with mild cognitive impairment (MCI) is limited because it is based on non-specific behavioral and neuroimaging findings. The lesions of Alzheimer's disease: amyloid beta (Abeta) deposits, tau pathology and cellular oxidative damage, affect the hippocampus in the earlier stages causing memory impairment. In a 2-year longitudinal study of MCI patients and normal controls, we examined the hypothesis that cerebrospinal fluid (CSF) markers for these pathological features improve the diagnostic accuracy over memory and magnetic resonance imaging (MRI)-hippocampal volume evaluations. Relative to control, MCI patients showed decreased memory and hippocampal volumes and elevated CSF levels of hyperphosphorylated tau and isoprostane. These two CSF measures consistently improved the diagnostic accuracy over the memory measures and the isoprostane measure incremented the accuracy of the hippocampal volume achieving overall diagnostic accuracies of about 90%. Among MCI patients, over 2 years, longitudinal hippocampal volume losses were closely associated with increasing hyperphosphorylated tau and decreasing amyloid beta-42 levels. These results demonstrate that CSF biomarkers for AD contribute to the characterization of MCI.

The hypothesis of a functional disconnection of neuro-cognitive networks in patients with mild cognitive impairment (MCI) and Alzheimer Dementia was investigated using baseline resting EEG data. EEG databases from New York (264 subjects) and Stockholm (155 subjects), including healthy controls and patients with varying degrees of cognitive decline or Alzheimer Dementia were analyzed using Global Field Synchronization (GFS), a novel measure of global EEG synchronization. GFS reflects the global amount of phase-locked activity at a given frequency by a single number; it is independent of the recording reference and of implicit source models. Patients showed decreased GFS values in Alpha, Beta, and Gamma frequency bands, and increased GFS values in the Delta band, confirming the hypothesized disconnection syndrome. The results are discussed within the framework of current knowledge about the functional significance of the affected frequency bands.

Jargonagraphia is known to occur after discrete brain lesions but not in primary degenerative dementia. We report a patient with frontotemporal dementia who developed jargonagraphia and nonfluent aphasia. Written output was graphically preserved but consisted of short words intermingled with abstruse neologisms. MRI showed predominant right frontotemporal cortical atrophy accompanied by white matter hyperintensities in the right anterior subcallosal periventricular region. Diagnosis and MRI were corroborated by extensive neuropathological findings obtained 8 months later. The agraphia in this case is discussed with reference to both specific macroscopic and microscopic pathoanatomical lesions. We suggest that jargonagraphia can appear in frontotemporal dementia depending on the localization of lesions., (Copyright 2001 Academic Press.)

The present study evaluated the clinical course of patients with mild cognitive impairment (MCI), the pattern of electroencephalography (EEG) changes following cognitive deterioration, as well as the potential of neurophysiological measures in predicting dementia. Twenty-seven subjects with MCI were followed for a mean follow up period of 21 months. Fourteen subjects (52%) progressed (P MCI) to clinically manifest Alzheimer's disease (AD), and 13 (48%) remained stable (S MCI). The two MCI subgroups did not differ in baseline EEG measures between each other and the healthy controls (n = 16), but had significantly lower theta relative power at left temporal, temporo-occipital, centro-parietal, and right temporo-occipital derivation when compared to the reference AD group (n = 15). The P MCI baseline alpha band temporo-parietal coherence, alpha relative power values at left temporal and temporo-occipital derivations, theta relative power values at frontal derivations, and the mean frequency at centro-parietal and temporo-occipital derivations overlapped with those for AD and control groups. After the follow-up, the P MCI patients had significantly higher theta relative power and lower beta relative power and mean frequency at the temporal and temporo-occipital derivations. A logistic regression model of baseline EEG values adjusted for baseline Mini-Mental Test Examination showed that the important predictors were alpha and theta relative power and mean frequency from left temporo-occipital derivation (T5-O1), which classified 85% of MCI subjects correctly.

Purpose: This study aimed at evaluate the effect of aging on the central nervous system in "successfully aged" elderly subjects. The brain was studied with magnetic resonance imaging and neuropsychological tests at three different occasions during a time period of 5 yr., Materials and Methods: Twenty-four successfully aged elderly were repeatedly examined with cerebral MRI and neuropsychological tests. The first examinations were performed in 1987 and then followed-up in 1989 and 1993. Two different MRI systems were used, in 1987 and 1989, a system operating at 0.02 T and in 1993 a system operating at 0.5 T. Ten subjects (42%) did not participate in the follow-up studies. MRI was used to study the degree of and increase in signal hyperintensities in the cerebrum, the basal ganglia, and in the infratentorial areas as well as changes in the volumes of the cerebro spinal fluid (CSF) spaces., Results: At the start of the study in 1987, mild signal hyperintensities were observed in 11 of the 13 subjects who completed the follow up study. A modest increase in signal hyperintensity was found in almost all of the subjects, with the increases in cerebral white matter and basal ganglia signal hyperintensity being statistically significant (p < .03 and p < .05). The increases in periventricular hyperintensity and the hyperintensity from the infratentorial areas did not reach statistical significance. Volumes of the lateral ventricles and the frontal CSF spaces increased significantly (p < .03 in both cases) during the observation period, whereas the other volumes remained unchanged. The neuropsychological tests were unchanged during the observation period with the exception of the psychomotor capacity, which deteriorated. No statistical significant correlations were seen between the degree of or increase in signal hyperintensities and results from any of the neuropsychological tests., Conclusion: During a 5-yr observation of successfully aged elderly it was found that there was a mild increase in signal hyperintensity in the cerebral white matter and basal ganglia, as well as an increase in the frontal and ventricular CSF volumes. These changes were not related to changes in psychometric test results, nor were they related to the clinical outcome during the time of observation.

Fifteen out of 25 successfully aged individuals completed a 5 year EEG follow-up study from the eighth to ninth decade of life with comprehensive neuropsychological investigation. One subject suffered from stroke and one developed symptoms of dementia during the follow-up. Of 13 subjects who completed the follow-up as being healthy, MRI showed subtle enlargement of ventricles or subarachnoid spaces and mild signal hyperintensities in a few regions in 2 subjects. General cognitive decline was not observed (WAIS-R IQ: 113.4 at entry, 114.3 five years later). There were no EEG dominant frequencies below 8 c-sec and no more background slowing than a few theta waves per 10 sec, either at entry or 5 years later. Intermittent slowing was observed in 9 subjects at entry and in 8 subjects 5 years later. The prevalence of intermittent slowing was suggested to increase with advancing age when compared to previous studies with younger elderly. However, intermittent slowing occurred only a few times in an EEG test and lasted for less than 2 sec. Moreover, the presence of intermittent slowing did not correlate with any neuropsychological decline or any MRI change. This type of intermittent slowing was regarded as non-specific and clinically silent.

The aim of the study was to investigate whether the regional distribution of white matter hyperintensities (WMH) observed by magnetic resonance imaging differed between vascular dementia and patients with late onset Alzheimer's disease. Another aim was to investigate the relations between the occurrence and degree of WMH and clinical and laboratory data as well as measures of cognitive decline. White matter hyperintensities were assessed with a low field magnetic resonance imager on 23 subjects with probable Alzheimer's disease, 25 with possible Alzheimer's disease and 31 subjects with vascular dementia. The degree and regional distribution of the WMH (expressed as relative volumes) were calculated and compared in the three groups. The relation between cognitive impairment and the degree of the WMH was also studied. The regional distribution of the WMH differed between the groups with significantly more changes in the posterior part of the brain (p < .0001) as well as in the right hemisphere (p < .0005) in the vascular demented as compared to the patients with Alzheimer's disease. No significant correlations between cognitive impairment and the degree of the WMH were found in any of the groups. The total volume of the WMH as well as the regional distribution of these changes differed significantly between vascular dementia and Alzheimer's disease. White matter hyperintensities seem not to be related to the degree of global cognitive decline in dementia and whether it plays a causative role in the development of dementia symptoms needs to be more thoroughly investigated.

A method for estimating total body fat (TBF) and the amount and distribution of adipose tissue in humans by using magnetic resonance imaging (MRI) is described. Thirty transaxial images of subjects were taken by a nuclear magnetic imager (0.02 T). Adipose tissue volume was calculated from adipose tissue area in each image and from the distances between images. The CV when estimating total volume of body adipose tissue was 1.5%. TBF of healthy Swedish women was estimated by the MRI method (n = 25), by underwater weighing (UWW) (n = 20), and by body-water dilution (BWD) (n = 23). When assessed by MRI and BWD, women contained 1.4 +/- 2.9% less and 4.7 +/- 4.0% more TBF, respectively, than when assessed by UWW. On average, 74.2% of total adipose tissue volume was situated subcutaneously. Subcutaneous fat:fat-free body weight and nonsubcutaneous fat:fat-free body weight were both significantly correlated with percent TBF but the women stored excess fat subcutaneously rather than nonsubcutaneously.

In the present study we have investigated the connection between cerebrospinal fluid spaces and cognitive function in patients with senile dementia of Alzheimer type (SDAT) and in successfully aged control subjects. The cerebrospinal fluid (CSF) volumes were measured using a low field MRI technique, and the cognitive functions were assessed with a number of psychometric tests. We found that the SDAT patients showed significantly larger relative volumes in all examined CSF spaces. The largest differences between the groups were found in the volumes of the temporal horns. We also found a significant correlation between the relative CSF volumes in the basal parts of the brain, and episodic memory tests. Significant correlations were also detected between the relative volumes of the lateral ventricles, and degree of dementia as well as between the relative volumes of the lateral ventricles and episodic memory tests.

The size of the cerebrospinal fluid spaces and the occurrence of white matter lesions were estimated from the intracranial volumes of 76 apparently healthy adult volunteers of different ages using 0.02-T/0.8-MHz magnetic resonance imaging. A relation between the occurrence of white matter lesions and the size of cerebrospinal fluid spaces independent of age could not be demonstrated. In men, white matter changes were more numerous and lateral ventricular size was larger, but sex differences were not statistically significant except for lateral ventricular size. The results confirm that age is the most significant parameter correlated with alterations in brain anatomy over time. Body mass and other clinical parameters were not influential factors in the present material.

Computer-assisted tissue classification based on MR intensity values in spin echo and inversion recovery images were used for area measurements of different brain structures in 76 apparently healthy volunteers of various ages. The classification was made from transaxial sections through the basal ganglia and discriminated between brain tissue and cerebrospinal fluid. The measurements based on this discrimination demonstrated larger intracranial areas in men than women. In the total group, sex differences were not observed when the measured structures were corrected for interindividual differences in cranial size. In subjects older than 60 years relative lateral ventricular area was larger and relative brain area smaller in men than women. The lateral ventricles, the Sylvian fissures and the brain area showed the most marked relation to age. The age-relation was more marked for left hemispheric structures.

Twenty-five elderly subjects were examined with brain magnetic resonance imaging (MRI). The subjects were divided into two groups: those with Mini-Mental State Examination (MMSE) scores above 25, and those subjects with MMSE scores between 18 and 24. The degree of white matter abnormalities (WMA) (expressed as relative volumes) as well as the presence of cerebrovascular risk factors were evaluated in the two groups. We found that a) subjects with low MMSE scores had significantly larger relative volumes of WMA than the subjects with higher scores, b) a significant correlation (rs = 0.53, p < 0.009) between MMSE scores and the relative volume of WMA was also established, and c) a weak significant correlation (rs = -0.51, p < 0.05) between arterial blood pressure and WMA was found in the subjects with high MMSE scores. Besides these findings no other correlations between the presence of cerebrovascular risk factors and WMA were found in any of the groups.

Twenty-four chronic alcoholic men were investigated with 0.02 Tesla/0.8 MHz magnetic resonance imaging on days 7-9 of acute alcohol withdrawal state. Estimates of T1 and T2 relaxation times were obtained from the white matter and basal ganglia nuclei in an axial section. This section was also used for area measurements of intracranial structures using computer-assisted tissue classification. The relation between T1 and age was more marked in the alcoholic patients than in the control group. Mean values of T1 and T2 did not differ between the two groups, but differences in the age dependence of T1 were highly significant for all regions. The number of years of drinking was influential to T1, but to a lesser extent than age. Lateral ventricular area correlated significantly with T1 of the white matter in the alcoholic patients. Using visual ratings of the entire intracranial volume the alcoholic patients demonstrated wider lateral ventricles and cortical sulci, but there was no increased frequency of white matter lesions.

The cerebral involvement of a 13-yr-old boy with Wilson's disease was serially evaluated during the first 18 mo of D-penicillamine treatment. An ultra-low-field magnetic resonance imaging (ULF MRI) system, operating at 0.02 T, with computerized image processing was used. The half-yr period prior to the clinical diagnosis was set, the patient had showed poor school performance, emotional lability, deteriorating handwriting, progressively slow, gross, and fine motor functions, and a fixed rigid smile. No overt signs of liver disease were found. With D-penicillamine treatment (1-1.5 g/d) a continuous improvement was seen. The pretreatment MRI investigation showed pronounced pathological transformation in the basal ganglia. However, changes were seen also in most other parts of the brain indicating diffuse involvement. During treatment the computerized MR images became gradually more normal. The current magnetic resonance imaging system with computerized image processing is a sensitive and simple method for evaluation of subtle parenchymal changes of the brain.

The accuracy of ultra-low field magnetic resonance imaging (MRI) compared to medium-field MRI in detecting syringomyelia and associated Chiari malformations is examined. In all cases the size of the syrinxes and the type and extent of the Chiari malformations was clearly shown at low-field MRI. The present spatial solution and high sensitivity allows for low-field imagers to localize even minor morphological changes of the spinal cord, brainstem, and cerebellum.

In order to assess possible structural changes and possible alterations in T1 relaxation times in the brains in a group of female patients (67-74 years) infected with HIV following transfusion ultra low field (ULF) magnetic resonance imaging (MRI) was performed. The width of the ventricles, the width of the subarachnoid spaces, the degree of white matter lesions and T1 relaxation times in the frontal white matter, the basal ganglia and thalamus were studied. No temporal structural changes nor alterations in T1 relaxation times were found in the brains in this group of transfusion infected patients, who were followed regularly over a period of 12 months compared both to themselves and to age matched controls.

Low grade gliomas were studied with ultra low field magnetic resonance imaging (ULF MRI). The tumors exhibited high tissue contrast in both T1 and T2-weighted images as compared to normal brain tissue. Moreover they were sharply delineated towards the surrounding brain tissue. When compared with X-ray computed tomography the tumors were more readily detected and delineated by using ultra-low field magnetic imaging. A computer-assisted classification procedure was used to define new regions of interest for relaxation time estimations. By using this procedure more accurate estimations of the T1 and T2 values were obtained.

With an ultra low field magnetic resonance imager (ULF-MRI) operating at 0.02 Tesla we describe a case of increased signal intensity from the transverse and sigmoid sinuses of the brain. A comparison with radionuclide angiography and skull computer tomography is made. The difficulties in differentiating low blood flow and venous thrombosis is also discussed.