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PubMed2002

Neuropathology of white matter lesions in vascular cognitive impairment.

The white matter is an important locus for tissue damage in vascular cognitive impairment and white matter lesions often dominate over gray matter changes. The spectrum of ischemic white matter lesions histopathologically represents focal and diffuse lesions, the most common form being the combination of both, in varying proportions. In the combined pathology, the diffuse lesion represents a gradient zone of damage towards surrounding normal tissue and may hold over 200 times the volume of an identified focal lesion, the lacunar infarct. Pathogenetically, the focal lesion results from the acute reaction to regional ischemia, while the diffuse white matter lesion represents the adjustment to altered perfusional and physiological conditions within the tissue.

Aged↗
PubMed2004

Reduced white matter volume of the caudate nucleus in patients with schizophrenia.

To examine volumetric abnormality, the caudate nucleus was measured in patients with schizophrenia and healthy subjects using magnetic resonance imaging. The absolute and relative volumes of white matter in the caudate nucleus were found to be significantly smaller in patients with schizophrenia compared to those in healthy subjects. There were significant correlations between dosages of neuroleptics during the previous year and absolute gray matter volumes of the caudate nucleus as well as relative white matter volumes in patients with schizophrenia. These findings suggest that reduced white matter volume of the caudate nucleus may be a factor affecting the abnormal connectivity of the corticostriatal loop, and that neuroleptic medication would be related to white matter alteration in patients with schizophrenia. Our result replicates a previous study reporting that there is a lack of negative correlation between age and caudate nucleus volume. We also suggest that the disease process of schizophrenia might interfere with normal aging.

Adult↗
PubMed2005

Cognitive correlates of cerebral white matter lesions and water diffusion tensor parameters in community-dwelling older people.

BACKGROUND: The biological basis of cognitive ageing is unknown. One underlying process might be disruption of white matter tracts connecting cortical regions. White matter lesions (WML) seen on structural MRI may disrupt cortical connections, but diffusion tensor MRI (DT-MRI) parameters - mean diffusivity ( ) and fractional anisotropy (FA) - may reflect more subtle changes in white matter integrity. Here the relationships between WML load, DT-MRI parameters and cognition in a large cohort of elderly subjects with a very narrow age range were investigated. METHODS: 105 community-dwelling volunteers underwent MRI and neuropsychological assessment. Seventy-two (68.6%) were female, and their mean age was 78.4 (SD 1.5) years. Scans were rated for WML load. and FA were measured from regions of interest in normal-appearing frontal and occipital white matter, and centrum semiovale. RESULTS: and FA differed significantly among the three brain regions studied (p << 0.01). increased with age (r = 0.22 to 0.35, p < 0.03), and was negatively correlated with FA (r = -0.20 to -0.51, p < 0.05) in all three regions. There was a trend towards increased WML load correlating with poorer cognitive function, and this was statistically significant for the Mini-Mental State Examination (rho = -0.23, p = 0.02). was generally negatively correlated with cognitive test score, and FA was positively correlated. This pattern was more consistent for than for FA, and particularly for verbal fluency ( : r = -0.22 to -0.27, p < 0.03), which measures executive function. CONCLUSIONS: DT-MRI parameters, in particular , are sensitive to early ultrastructural changes underlying cognitive ageing. Executive function may be the cognitive domain most sensitive to age-related decline in white matter tract integrity.

Aged↗
PubMed2005

Blood pressure, white matter lesions and medial temporal lobe atrophy: closing the gap between vascular pathology and Alzheimer's disease?

BACKGROUND: Vascular factors are recognized as important risk factors for Alzheimer's disease, although it is unknown whether these factors directly lead to the typical degenerative pathology such as medial temporal lobe atrophy. We set out to investigate the relation between blood pressure and medial temporal lobe atrophy in patients with senile and presenile Alzheimer's disease with or without white matter lesions. METHODS: We determined the relation between blood pressure and pulse pressure and medial temporal lobe atrophy on MRI in 159 patients with Alzheimer's disease, stratified on white matter lesions and age at onset of dementia. RESULTS: There was a linear relation between systolic blood pressure and pulse pressure (both in tertiles) and the severity of medial temporal lobe atrophy (p(trend) = 0.05 and p(trend) 0.03, respectively). A significant relation was found between pulse pressure [beta = 0.08 (95% CI: 0.00-0.15; p = 0.05) per 10 mm Hg] and (borderline significant) systolic blood pressure [beta = 0.05 (95% CI: -0.01 to 0.11; p = 0.1) per 10 mm Hg] and medial temporal lobe atrophy. White matter lesions and age-stratified analysis revealed a significant association between systolic blood pressure and pulse pressure and medial temporal lobe atrophy, only in the subsample with white matter lesions and in the subsample with a senile onset of dementia. The relations were independent of severity of dementia and diabetes mellitus. CONCLUSIONS: Systolic blood pressure and pulse pressure are associated with medial temporal lobe atrophy in Alzheimer's disease, especially in the presence of white matter lesions and in patients with a late onset of dementia. Our finding may be another step in providing a rationale on how vascular factors could ultimately result in Alzheimer's disease.

Age of Onset↗
PubMed1997

Increased water diffusion in cerebral white matter in Alzheimer's disease.

We investigated the changes in water diffusion in the cerebral white matter in 19 patients with Alzheimer's disease (AD), including 11 without and 8 with periventricular hyperintensity (PVH) lesions, using diffusion-weighted magnetic resonance imaging (MRI). The apparent diffusion coefficients in the anterior and posterior white matter were significantly higher in the 19 AD patients than in the 10 age-matched controls. The apparent diffusion coefficients were higher in patients with PVH than in those without. The anisotropic ratios, defined as diffusion restricted perpendicular to the direction of the nerve fibers, were significantly higher in AD patients, even in those without PVH, than in the controls. Our results suggest that mild myelin loss occurs in AD patients even in the apparently normal white matter. A definite loss of myelin and axons, including incomplete infarction, occurs in the white matter, as seen on T2-weighted images as PVH. Studies with diffusion-weighted MRI may allow the characterization of different pathological processes and enable the demonstration of underlying white matter lesions in AD that cannot be visualized by conventional MRI.

Aged↗
PubMed1995

Role of periaqueductal gray matter in hypertension in spontaneously hypertensive rats.

We performed experiments to study the effects of electrolytic lesions of periaqueductal gray matter on mean blood pressure, heart rate, and cardiac baroreflex in adult male spontaneously hypertensive rats. Cardiac baroreflex was assessed by the administration of randomly assigned doses of phenylephrine (0.3 to 5.0 micrograms/kg i.v.) or sodium nitroprusside (1.5 to 5.0 micrograms/kg i.v.) to unanesthetized rats. Bilateral lesions of the periaqueductal gray matter (0.5 mA/5 s) were then performed with rats under sodium pentobarbital anesthesia (35 mg/kg i.p.). Twenty hours after lesion, cardiac baroreflex was retested. Baroreflex data were analyzed by sigmoidal curve fitting. Lesion rats (n = 12) showed a significant decrease in both the gain (delta = -0.89 +/- 0.38 beats per minute [bpm]/mm Hg, P < .05) and curve midpoint (delta = -15 +/- 6 mm Hg, P < .05) of the cardiac baroreflex. Moreover, despite a moderate increase in heart rate (delta = 34 +/- 10 bpm, P < .01), resting mean blood pressure was significantly decreased 24 hours after the lesions (delta = -19 +/- 5 mm Hg, P < 01). No significant changes in cardiac baroreflex were observed in sham-lesion rats (n = 12). Histological examination showed circumscribed bilateral damage of dorsolateral periaqueductal gray matter. Dorsolateral periaqueductal gray matter is an area of the brain putatively related to fear and anxiety. It also projects onto premotor sympathetic neurons in the medulla. Although electrolytic lesions damage neurons as well as fibers of passage, these data suggest that dorsolateral periaqueductal gray matter has a far greater influence on resting cardiovascular control in spontaneously hypertensive rats than was previously suspected.

Animals↗
PubMed2006

White matter alterations in cerebral amyloid angiopathy measured by diffusion tensor imaging.

BACKGROUND AND PURPOSE: Cerebral amyloid angiopathy (CAA) represents beta-amyloid deposition in the small- and medium-sized vessels of the brain and meninges. CAA contributes to altered vessel function and is associated with white matter damage, cognitive impairment, and most salient, hemorrhagic stroke. We used diffusion tensor imaging to evaluate the anatomic distribution of white matter degeneration in participants diagnosed with advanced CAA. METHODS: Diffusion tensor imaging was obtained from 11 participants diagnosed with CAA-related intracerebral hemorrhage and 13 matched healthy control participants. Fractional anisotropy (FA) and diffusivity maps were compared using voxel based t test and region-of-interest analyses. RESULTS: FA was reduced in CAA in temporal white matter and in the splenium of the corpus callosum (P<0.001 with approximately 17% reduction in temporal white matter and 15% reduction in the splenium). FA was marginally increased in CAA in the posterior limb of the internal capsule and subthalamic gray matter regions (approximately 7% increase in subthalamic gray). FA changes were bilateral, remained significant in cluster analysis controlling for multiple comparisons, and did not depend on the hemisphere of the cerebral hemorrhage. Diffusivity was not substantially altered. CONCLUSIONS: These findings suggest that a pattern of regional brain tissue degeneration is a characteristic feature of advanced CAA.

Aged↗
PubMed1999

Characterization of white matter damage in ischemic leukoaraiosis with diffusion tensor MRI.

BACKGROUND AND PURPOSE: Information on the neuropathological changes underlying ischemic leukoaraiosis is only available postmortem, and there are limited data on histological appearances early in the disease. Diffusion tensor imaging allows determination of the directionality of diffusion, which is greater in the direction of white matter bundles. Therefore, the technique might be expected to show loss of anisotropy (directional diffusion) in leukoaraiosis. METHODS: Nine patients with ischemic leukoaraiosis (radiological leukoaraiosis and clinical lacunar stroke) and 10 age-matched controls were studied. Diffusion tensor imaging was performed, and maps of diffusion trace and fractional anisotropy were constructed. Mean values of trace and fractional anisotropy were determined in standard regions of the anterior and posterior white matter in both hemispheres. RESULTS: In all patients with ischemic leukoaraiosis, a characteristic abnormal pattern was found, with loss of anisotropy and increased trace in the white matter. For example, in the right anterior white matter mean (SD) trace/3 was 1.12 (0.33) x10(-3) mm2 s-1 in patients and 0.75 (0.11) in controls (P=0.001). In the same region, fractional anisotropy was 0.53 (0.11) in patients and 0.78 (0.09) in controls (P<0.001). Within the white matter regions, there was a strong negative correlation between mean diffusivity and anisotropy (r=-0.92, P<0.0001). CONCLUSIONS: The characteristic pattern found on diffusion tensor imaging in this patient group is consistent with axonal loss and gliosis leading to impairment to and loss of directional diffusion. The "in vivo histological" information obtained may be useful in monitoring disease progression and in investigating the pathogenesis of the cognitive impairment that may be present.

Adult↗
PubMed2001

Diffusion tensor imaging study of subcortical gray matter in cadasil.

BACKGROUND AND PURPOSE: In cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), water diffusion changes suggestive of microstructural tissue alterations have been recently reported in abnormal- and normal-appearing white matter as seen on T2-weighted images. In the subcortical gray matter, typical lacunar infarcts are repeatedly observed. Whether microstructural tissue changes are also present outside these lesions within the putamen or thalamus remains unknown. METHODS: We used diffusion tensor imaging, an MRI method highly sensitive to cerebral microstructure, in 20 CADASIL patients and 12 controls. Both the trace of the diffusion tensor [Tr(D)] and an anisotropic diffusion index (volume ratio) of diffusion were measured within the putamen and thalamus outside typical lacunar infarcts as detected on both T1- and T2-weighted images. RESULTS: A significant increase in Tr(D) and a decrease in anisotropy were observed in the putamen and thalamus in patients. The right/left indices of Tr(D) in the thalamus, but not in the putamen, were strongly correlated with the corresponding indices calculated in the white matter of the centrum semiovale. In addition, the diffusion increase in the thalamus was positively correlated with Tr(D) and with the load of small deep infarcts within the white matter and negatively correlated with the Mini-Mental State Examination score. CONCLUSIONS: Our results suggest that microstructural tissue alterations are present in the putamen and thalamus, outside the typical lacunar infarcts in CADASIL. In the thalamus, these microstructural changes appear constant and are even observed in asymptomatic subjects. Some of these thalamic changes appear to result from degeneration of thalamocortical pathways secondary to ischemic white matter damage. The importance of this degenerative phenomenon in the pathophysiology of CADASIL requires further investigation.

Analysis of Variance↗
PubMed2006

White matter changes compromise prefrontal cortex function in healthy elderly individuals.

Changes in memory function in elderly individuals are often attributed to dysfunction of the prefrontal cortex (PFC). One mechanism for this dysfunction may be disruption of white matter tracts that connect the PFC with its anatomical targets. Here, we tested the hypothesis that white matter degeneration is associated with reduced prefrontal activation. We used white matter hyperintensities (WMH), a magnetic resonance imaging (MRI) finding associated with cerebrovascular disease in elderly individuals, as a marker for white matter degeneration. Specifically, we used structural MRI to quantify the extent of WMH in a group of cognitively normal elderly individuals and tested whether these measures were predictive of the magnitude of prefrontal activity (fMRI) observed during performance of an episodic retrieval task and a verbal working memory task. We also examined the effects of WMH located in the dorsolateral frontal regions with the hypothesis that dorsal PFC WMH would be strongly associated with not only PFC function, but also with areas that are anatomically and functionally linked to the PFC in a task-dependent manner. Results showed that increases in both global and regional dorsal PFC WMH volume were associated with decreases in PFC activity. In addition, dorsal PFC WMH volume was associated with decreased activity in medial temporal and anterior cingulate regions during episodic retrieval and decreased activity in the posterior parietal and anterior cingulate cortex during working memory performance. These results suggest that disruption of white matter tracts, especially within the PFC, may be a mechanism for age-related changes in memory functioning.

Aged↗
PubMed2002

Cortical and subcortical gray matter abnormalities in schizophrenia determined through structural magnetic resonance imaging with optimized volumetric voxel-based morphometry.

OBJECTIVE: Structural neuroimaging studies have suggested an association between schizophrenia and abnormalities in brain morphology such as ventricular enlargement and differences in gray matter distribution. Less consistently reported are findings of regional abnormalities such as selective differences in thalamic volume. The authors applied an unbiased technique to test for differences in cerebral morphometry between patients with schizophrenia and matched comparison subjects. METHOD: T(1)-weighted images from 20 schizophrenic patients and matched comparison subjects were processed by using optimized automated voxel-based morphometry within multiple linear regression analyses. RESULTS: Global differences in gray matter volume were seen between the schizophrenic and comparison subjects, with selective regional gray matter differences noted in the mediodorsal thalamus and across cortical regions, including the ventral and medial prefrontal cortices. Within the schizophrenic subjects, a relationship was observed between gray matter volume loss in the medial prefrontal cortex and a positive family history of schizophrenia. There was no significant difference between patients and comparison subjects in rates of proportional gray matter reduction with age. CONCLUSIONS: These observations confirm an association between thalamocortical morphometric abnormalities and schizophrenia, consistent with theoretical models of primary pathoetiological dysfunction in filtering, integration, and information transfer processes in patients with schizophrenia.

Adult↗
PubMed2003

Progressive decrease of left superior temporal gyrus gray matter volume in patients with first-episode schizophrenia.

OBJECTIVE: Smaller temporal lobe cortical gray matter volumes, including the left superior temporal gyrus, have been reported in magnetic resonance imaging (MRI) studies of patients with chronic schizophrenia and, more recently, in patients with first-episode schizophrenia. However, it remains unknown whether there are progressive decreases in temporal lobe cortical gray matter volumes in patients with first-episode schizophrenia and whether similarly progressive volume decreases are present in patients with affective psychosis. METHOD: High-spatial-resolution MRI scans at initial hospitalization and 1.5 years later were obtained from 13 patients with first-episode schizophrenia, 15 patients with first-episode affective psychosis (mainly manic), and 14 healthy comparison subjects. MRI volumes were calculated for gray matter of superior temporal gyrus and for the amygdala-hippocampal complex. RESULTS: Patients with first-episode schizophrenia showed significant decreases in gray matter volume over time in the left superior temporal gyrus compared with patients with first-episode affective psychosis or healthy comparison subjects. This progressive decrease was more pronounced in the posterior portion of the left superior temporal gyrus (mean=9.6%) than in the anterior portions (mean=8.4%). No group differences in the rate of change over time were present in other regions. CONCLUSIONS: These findings demonstrate a progressive volume reduction of the left posterior superior temporal gyrus gray matter in patients with first-episode schizophrenia but not in patients with first-episode affective psychosis.

Adolescent↗
PubMed2003

Association of depression duration with reduction of global cerebral gray matter volume in female patients with recurrent major depressive disorder.

OBJECTIVE: The authors investigated the relationship between depression duration and cerebral gray matter volume in female patients with recurrent major depressive disorder. METHOD: Magnetic resonance imaging was used to measure intracranial and total brain volumes as well as gray matter and white matter volumes of the cerebrum; frontal, temporal, parietal, and occipital lobes; cerebellum; and the lateral and third ventricles in 23 female patients with DSM-IV major depression. RESULTS: Correlation and regression analyses showed a significant relationship between total illness duration and cerebral gray matter (including cortical lobe) volume after correction for intracranial volume and age. CONCLUSIONS: Depressive states may lead to changes in global cerebral gray matter volume.

Adult↗
PubMed2003

Increases in regional subarachnoid CSF without apparent cortical gray matter deficits in schizophrenia: modulating effects of sex and age.

OBJECTIVE: The authors investigated the modulating effects of biological sex and age on regional decreases in cortical gray matter and increases in subarachnoid CSF in 25 patients with chronic schizophrenia and 28 group-matched healthy comparison subjects. METHOD: Computational cortical pattern-matching methods were employed to measure the local proportions of gray matter and subarachnoid CSF at thousands of homologous cortical surface locations in each subject using high-resolution magnetic resonance images. Principal-component analysis reduced tissue proportion values obtained at each cortical surface point into component scores for each subject. Principal-component analysis scores were used as dependent variables in statistical analyses that included diagnosis, age, and sex as predictor variables. To reveal more regional changes in tissue proportions, statistical differences in gray matter and CSF were compared at each cortical surface location and mapped in three dimensions. RESULTS: Principal-component analyses revealed main effects of diagnosis, sex, and age for the CSF increases seen in the schizophrenia patients, in male subjects, and in association with age. Significant diagnosis-by-age, diagnosis-by-sex, and diagnosis-by-sex-by-age interactions were also observed, revealing CSF increases in male patients at younger ages. Statistical maps showed regional increases in subarachnoid CSF in association with the above effects. For cortical gray matter measurements, only main effects of age were observed. CONCLUSIONS: Regionally specific increases in sulcal and subarachnoid CSF occur during adulthood and appear prematurely in male schizophrenia patients. Cortical gray matter reductions show aging effects but are below the threshold of significance in schizophrenia.

Adult↗
PubMed2006

Evidence of white matter pathology in bipolar disorder adolescents experiencing their first episode of mania: a diffusion tensor imaging study.

OBJECTIVE: Previous diffusion tensor imaging findings have supported suggestions that bipolar disorder is characterized by subtle white matter changes. The chronic nature of the study population, however, has limited interpretation of these findings. In this study the authors utilized diffusion tensor imaging to study white matter tracts of adolescents in their first episode of mania to address whether abnormalities are present in early bipolar disorder. METHOD: Eleven medication-naive adolescents in their first episode of mania and 17 healthy subjects underwent diffusion tensor imaging scans. Fractional anisotropy and trace apparent diffusion coefficients of prefrontal and posterior regions of interest were compared between groups. RESULTS: Bipolar adolescents showed significantly decreased fractional anisotropy only in superior-frontal white matter tracts. Trace apparent diffusion coefficients did not significantly differ in any regions examined. CONCLUSIONS: These findings suggest that prefrontal white matter abnormalities are present early in bipolar disorder and may consist largely of axonal disorganization. The presence of changes in young first-episode patients also suggests that white matter pathology may represent an early marker of bipolar disorder.

Adolescent↗
PubMed2002

White-matter alterations and callosal abnormalities in syndromic patients with mental retardation.

The aim of this study was to evaluate the frequency of callosal abnormalities and white matter alterations in syndromic patients. The authors report on the cerebral magnetic resonance imaging (MRI) morphologic analysis of the corpus callosum and white matter in 73 normal subjects and 61 syndromic patients. The study of the corpus callosum was carried out by MRI using different morphometric methods: measurement of the dimensions of length and thickness of genu, body, and splenium; measurement of angles obtained using the sagittal plane; and application of the proportional grid of Talairach. The evaluation of the white matter was carried out by applying a subjective grading scale. Abnormalities of the corpus callosum were found in about 50% of the syndromic subjects; in half of these cases, the abnormalities were associated with white matter alterations. In five syndromic patients (8.2%), the white matter alterations were not associated with corpus callosum abnormalities. This study shows that corpus callosum abnormalities are frequent in syndromology regardless of the syndrome type.

Adolescent↗
PubMed2005

Maturational effects of lipopolysaccharide on white-matter injury in fetal sheep.

White-matter damage has been associated with the development of cerebral palsy in children born both prematurely and at term, and it has been suggested that intrauterine infection can contribute to the brain injury. However, the relative importance of age on white-matter injury following infectious exposure in utero remains unclear. In this study, fetal sheep were exposed to systemic endotoxemia by administration of Escherichia coli lipopolysaccharide (88.7 +/- 7.7 ng/kg) at 65% or 85% of gestation. These gestational ages approximately correspond to human brain development in preterm and near-term infants respectively. White-matter injury was evaluated 3 days after lipopolysaccharide exposure with regard to microglia activation and loss of neurofilament and myelin basic protein. The expression of oligodendrocytes at different maturational stages was demonstrated in preterm and near-term fetuses with the oligodendroglial markers O4 and 2 ,3 -cyclic nucleotide 3 -phospodiesterase. Forty percent of the fetuses in the preterm group and 22% in the near-term group died within 8 hours of the endotoxin exposure. Three of six preterm and two of seven near-term surviving fetuses demonstrated pathologic changes in the brain with regard to increased microglia activation and loss of neurofilament staining. The number of activated microglia was enhanced in the subcortical white matter in both the preterm lipopolysaccharide-exposed fetuses (lipopolysaccharide: 235 +/- 64 cells/mm2; control: 72 +/- 28 cells/mm2; P = .0374) and the near-term fetuses (lipopolysaccharide: 180 +/- 40 cells/mm2; control 23 +/- 16 cells/mm2; P = .0152). There was a loss of neurofilament staining in both preterm fetuses (lipopolysaccharide: 2.20 +/- 0.77 pixel units; control: 0.20 +/- 0.10 pixel units; P = .0306) and near-term fetuses (lipopolysaccharide: 1.15 +/- 0.48 pixel units; control: 0.06 +/- 0.06 pixel units; P = .0285). O4-positive cells were detected at both gestational ages, whereas 2,3-cyclic nucleotide 3-phospodiesterase-positive cells and myelin basic protein staining were mainly detected in the near-term fetuses. In summary, we found white-matter injury in a proportion of both preterm and near-term fetuses after administration of lipopolysaccharide. These results are in agreement with clinical evidence suggesting that both preterm and term infants are at risk of periventricular leukomalacia in association with intrauterine infection.

Animals↗
PubMedDate not supplied

The prevalence of white-matter lesions on computed tomography of the brain in demented and nondemented 85-year-olds.

The prevalence of white-matter lesions on computed tomography was studied in a representative sample of 85-year-olds living in Gothenburg, Sweden. The study included a psychiatric examination, interview of a close informant, neuropsychological examination, physical examination, comprehensive laboratory tests, electrocardiogram, chest x-ray, computed tomography scan of the head, and cerebrospinal fluid analysis. The diagnoses of dementia and other mental disorders were made according to DSM-III-R criteria. The prevalence of white-matter lesions in demented subjects was 68.9%, and in nondemented, 33.8%. Their prevalence was not increased in any mental disorder other than dementia. All severities of dementia and the subtypes, Alzheimer's disease, vascular dementia, and other types of dementia, had a significantly higher prevalence of white-matter lesions than did nondemented subjects. The risk for dementia, but not its severity, increased with the severity of these lesions. A stepwise logistic regression analysis showed that both white-matter lesions and infarcts on computed tomography contributed independently to dementia. White-matter changes may be a contributing cause of dementia in the oldest old, or may represent a disease entity of its own. They are important to recognize since they may be potentially preventable, or even treatable.

Aged↗