The impact of magnetic resonance imaging-detected white matter hyperintensities on longitudinal changes in regional cerebral blood flow.

White matter hyperintensities are frequently detected on cranial magnetic resonance imaging (MRI) scans of older adults. Given the presumed ischemic contribution to the etiology of these lesions and the posited import of resting brain activity on cognitive function, we hypothesized that longitudinal changes in MRI-detected white matter disease, and its severity at a given time point, would be associated with changes in regional cerebral blood flow (rCBF) over time. We evaluated MRI scans and resting H(2)(15)O positron emission tomographic rCBF at baseline and after an average of 7.7-year follow-up in Baltimore Longitudinal Study of Aging participants without dementia. Differences in patterns of rCBF were evident at baseline and at follow-up between the group of subjects showing increased white matter disease over the 8-year interval compared with the group with stable white matter ratings. Furthermore, longitudinal changes over time in rCBF also differed between the two groups. Specifically, the group with progressive white matter abnormalities showed greater increase in the right inferior temporal gyrus/fusiform gyrus, right anterior cingulate, and the rostral aspect of the left superior temporal gyrus. Regions of greater longitudinal decrease in this group were evident in the right inferior parietal lobule and at the right occipital pole. Changes in white matter disease over time and its severity at any given time are associated significantly with both cross-sectional and longitudinal patterns of rCBF. The longitudinal increases may reflect cortical compensation mechanisms for reduced efficacy of interregional neural communications that result from white matter deterioration.     

Cognitive profiles and regional cerebral blood flow patterns in dementia of the Alzheimer type

Individual cognitive profiles and correlations between cognitive functions and regional cerebral blood flow (rCBF) were analyzed in 20 consecutive patients with a clinical diagnosis of probable Alzheimer's disease (AD). CBF was measured with high resolution single photon emission computed tomography (SPECT) and [^99mTc]d,l-HMPAO. The analysis of cognitive profiles was based on the composite scores for six cognitive domains, derived from a detailed neuropsychological test battery, as compared with corresponding test data obtained in a control group of 28 age-matched healthy volunteers. The cognitive profiles displayed a marked heterogeneity as concerned the general level of cognitive impairment, the number of significantly affected cognitive domains, the spectrum of affected and non-affected cognitive domains, and the severity of each cognitive dysfunction. Statistically significant correlations with rCBF were found for memory scores (right frontal and temporal cortex), abstraction scores (frontal/parietal ratio of rCBF), language scores (left frontal and temporal cortex), visual perception scores (rCBF throughout the right hemisphere), and for visuo-construction scores (side-to-side asymmetry of parietal rCBF). We conclude that the previously observed topographical heterogeneity of rCBF distribution patterns in probable AD was reflected by differences in cognitive profiles. The observed heterogeneities stress the relevance of analyzing individual cognitive and rCBF data, as a supplement to group comparisons of data, in the investigation of diseases with potential heterogeneous affections of the brain.     

White matter hyperintensities in dementia of Alzheimer's type and in healthy subjects without cerebrovascular risk factors. A magnetic resonance imaging study

T2-weighted (0.5 T) magnetic resonance images were used to study the prevalence of subcortical white matter hyperintensities (WMHIs) in 22 patients with dementia of Alzheimer's type (DAT), 20 age-matched older healthy control subjects, and 10 younger healthy control subjects. Exclusionary criteria for all groups included cerebrovascular risk factors. All subjects had Hachinski Ischemic Index scores of less than 2 and computed tomographic scans showing no infarct. The WMHIs were classified as periventricular WMHIs or deep WMHIs and graded 0 through 3 (0 indicated absent, and 3, severe). For the group with DAT and older control subjects, periventricular WMHIs and deep WMHIs were graded 2 or 3 in fewer than 17% and 27% of subjects, respectively, whereas in the younger control subjects, all ratings were grade 1 or less. Serum cholesterol and systolic blood pressure values, although within the normal range, were elevated significantly in older control subjects when compared with those in younger control subjects. No significant differences in WMHI ratings, blood pressure, cholesterol, or triglyceride levels were found between patients with DAT and age-matched control subjects. Systolic blood pressure levels correlated with the severity of periventricular WMHIs only in older control subjects. Age correlated with periventricular WMHIs and deep WMHIs within both the older control subjects and the patients with DAT. There was no significant correlation between WMHIs and the severity of dementia in the group with DAT. These results suggest that, in subjects screened for cerebrovascular risk factors, WMHIs are rare and occur with identical frequency in patients with DAT as in age-matched healthy control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

脑血管病性痴呆与Alzheimer病患者脑局部区域的血流量

目的 测定多灶脑梗塞痴呆及Ａｌｚｈｅｉｍｉｅｒ病患者的脑局部区域的血流量（ｒＣＢＦ）,方法 用＾１３３氙（＾１３３Ｘｅ）吸入法测定１０例多灶脑梗塞痴呆患者。１０例Ａｌｚｈｅｉｍｅｒ病及２０名正常人的ｒＣＢＦ。结果 两个病例组双半球,脑干－小脑ｒＣＢＦ均明显低于正常健康组,脑梗塞痴呆组多数病例双侧半球灰质ｒＣＢＦ降低呈斑块状,Ａｌｚｈｅｉｍｅｒ病例组均为双侧大脑半球弥散性对称性的ｒＣＢＦ降低,前乾脑     

White matter volumes and periventricular white matter hyperintensities in aging and dementia

OBJECTIVE: To determine the relationship between MRI periventricular white matter hyperintensities, cerebral white matter volumes, neuropathologic findings, and cognitive status in aged individuals. BACKGROUND: The significance of periventricular white matter hyperintensities seen on MR images in aged individuals remains controversial. The Nun Study is a longitudinal cohort aging study in which all 678 initially enrolled participants agreed to autopsy neuropathologic examination. METHODS: We used MRI to measure white matter volumes of the cerebral hemispheres in 52 formaldehyde-fixed brains for correlation with white matter and neocortical pathology, postmortem MRI observations, and cognitive measures. RESULTS: Reduced white matter volume is associated with dementia, but periventricular white matter hyperintensities were not related to white matter volume, stroke, or dementia. CONCLUSIONS: Our results do not support the hypothesis that periventricular hyperintensities seen on MR images have deleterious consequences in these aged individuals.     

White matter hyperintensities and cortical acetylcholinesterase activity in parkinsonian dementia

OBJECTIVE: To investigate the relationship between the severity of white matter hyperintensities (WMH) and cortical acetylcholinesterase (AChE) activity in parkinsonian dementia (PDem). METHODS: PDem (n = 11) and control subjects (n = 14) underwent [11C]methyl-4-piperidinyl propionate (11C-PMP) AChE brain positron emission tomography and magnetic resonance (MR) imaging. Presence of WMH on proton density and T2 MR images was scored using a modified version of the semi-quantitative rating scale by Scheltens et al. [J Neurol Sci114 (1993)]. RESULTS: Analysis demonstrated significantly lower mean cortical (11)C-PMP k3 hydrolysis rates in PDem (-19.9%) when compared with control subjects (P < 0.0001). PDem subjects had higher mean severity of WMH (+20.1%) when compared with control subjects (P < 0.05). When WMH severity was entered into the analysis of variance model, there was no significant co-variate effect on cortical AChE activity (F = 0.24, ns). CONCLUSIONS: The concomitant presence of mild to moderate WMH in patients with PDem does not have a significant effect on cortical AChE activity.     

Decreased cerebral blood flow precedes multi-infarct dementia, but follows senile dementia of Alzheimer type

A 7-year prospective study among 181 neurologically normal elderly volunteers (mean age, 70.6 years) revealed an incidence of 3.3%, or 0.47% new cases per year, for Alzheimer's disease (SDAT) and 5.5%, or 0.78% new cases per year, for multi-infarct dementia (MID). The unusually high incidence of MID is considered to reflect preselection of a large percentage of volunteers (48.6%) with risk factors for (but without symptoms of) atherothrombotic stroke. Of 88 volunteers at risk of stroke, 11.4% developed MID within 7 years. In MID patients, cerebral blood flow (CBF) values began to decline around 2 years before onset of symptoms, while in SDAT patients, CBF levels remained normal until symptoms of dementia appeared; thereafter, CBF declined rapidly.     

Low cerebral blood flow velocity and risk of white matter hyperintensities

Cerebral blood flow velocity (CBF-V) measured by transcranial doppler was assessed in 628 elderly individuals who had cerebral magnetic resonance imaging performed as part of a population-based study on vascular aging. Cerebral white matter hyperintensities (WMHs) were associated with low CBF-V, such as the adjusted odds ratios of severe WMHs from highest (referent) to lowest quartile of mean CBF-V were 1.0, 1.7, 3.7, and 4.3 (p = 0.001). Further, CBF-V was found to be a stronger risk factor for WMHs than high blood pressure. These findings suggest that the assessment of CBF-V might be a powerful tool in future studies on WMHs.     

Regional cerebral blood flow in depressed patients with white matter magnetic resonance hyperintensity.

BACKGROUND: Functional neuroimaging studies have consistently demonstrated decreased regional cerebral blood flow (rCBF) or metabolism in the frontal lobe, temporal lobe, or anterior cingulate gyrus of depressed patients. On the other hand, white matter hyperintensity as defined by magnetic resonance imaging (MRI) has been the most consistently replicated finding in structural neuroimaging studies on depression; however, these functional and structural neuroimaging findings of depression have not been well integrated. We aimed to clarify the possible associations of MRI-defined subcortical hyperintensities with rCBF changes in depressed patients. METHODS: Twelve depressed patients with subcortical hyperintensities defined by MRI, 11 depressed patients without MRI hyperintensities, and 25 healthy volunteers underwent 99mTc ECD SPECT. Group comparisons of their rCBF and correlation analysis between MRI hyperintensity and rCBF in patients were performed with a voxel-based analysis using statistical parametric mapping (SPM) software. RESULTS: Depressed patients showed decreased rCBF compared with control subjects in the frontal lobe, temporal lobe, and anterior cingulate gyrus whether subcortical hyperintensity existed or not; however, the patients with MRI hyperintensity showed decreased rCBF in the thalamus, basal ganglia, and brainstem in addition to cortical areas. Further, the score for white matter hyperintensity correlated negatively with rCBF in subcortical brain structures, including the thalamus and right basal ganglia. CONCLUSION: Our study indicates that depressed patients with MRI hyperintensities may have dysfunction in subcortical brain structures in addition to dysfunction in the fronto-temporal cortical structures.     

White matter hyperintensities on magnetic resonance imaging of the brain in children with psychiatric disorders

The current study sought to determine the prevalence, severity, and location of white matter signal hyperintensities (WMH) on brain magnetic resonance imaging assessments of children and adolescents with psychiatric disorders. Seventy-one percent (N = 934) of children admitted to the McLean Hospital Child and Adolescent inpatient treatment unit were evaluated with the Diagnostic Interview Schedule for Children (DISC) within 7 days of admission during the period 1988 to 1993 (total, 1,308 admissions). Four hundred eight of these subjects (43.7%) were referred for brain magnetic resonance imaging (MRI) scans and became our study subjects (mean age, 12.4 years [SD = 2.7]; male/female, 230/178). Study subjects were grouped according to a hierarchical diagnostic system as follows: schizophrenia (n = 42), bipolar disorder (n = 56), unipolar depression (n = 94), conduct disorder/attention deficit disorder (n = 103), and other neurotic disorders (n = 30). Subjects without any level 2 diagnosis on DISC (n = 83) constituted the comparison group. Bipolar disorder, unipolar depression, and conduct disorder/attention deficit disorder groups were significantly more likely to have severe levels of WMH than the comparison group (prevalence rates: 17.9%, 13.8%, 13.6% v 1.2%). In addition, the bipolar disorder group was significantly more likely to have severe levels of WMH than the schizophrenia group (prevalence rates: 17.9% v 2.4%). The frontal lobes were the predominant locations of WMH in the bipolar disorder and unipolar depression groups (76.9% and 60.0%, respectively) and also the most frequent location for the conduct disorder/attention deficit disorder group (35.7%). The current study reports an increased prevalence and severity of WMH in children with bipolar disorder, unipolar depression, and conduct disorder/attention deficit disorder relative to the comparison group and in children with bipolar disorder compared to those with schizophrenia. The development of brain WMH, especially in the frontal lobes, may play a role in the pathophysiology of affective disorders in children and adolescents.     

White matter lesions,quantitative magnetic resonance imaging,and dementia

The authors performed quantitative and qualitative image analysis on a sample of the elderly population of Cache County, Utah, relating neuroimaging findings to Mini-Mental Status Examination (MMSE) scores and the presence of the apolipoprotein E epsilon4 allele. Neuroimaging measures included white, gray, and hippocampal volumes; a ventricle-to-brain ratio (VBR); and qualitative ratings of white matter lesions (WMLs) in the periventricular (PV) and centrum semiovale (CS) regions. Subjects included 85 persons with possible and probable Alzheimer disease (AD), 21 with vascular dementia (VaD), 30 with cognitive symptoms classified as mild/ambiguous (M/A), a heterogenous group of 39 non-AD or VaD subjects but diagnosed with some form of neuropsychiatric disorder ("Mixed Neuropsychiatric" group), and 20 normal control subjects aged 65 years or older. Controlling for age, sex, and length of disease, the authors found that AD and VaD subjects differed significantly from control subjects on WMLs, but only the VaD subjects significantly differed from M/A subjects. The two dementia groups also displayed, as expected, significant cerebral atrophy. The WMLs generally increased with age and severity of dementia. PV WMLs were significantly but only modestly associated with white matter volume loss and greater impairment on the MMSE. Modest correlations were also present between the quantitative measures of cerebral structure and MMSE performance. However, when degree of cerebral atrophy was controlled by using the VBR measure, WML effects on MMSE performance became nonsignificant, with the only significant relationship remaining being that between hippocampal volume and MMSE performance. There were no significant qualitative or quantitative findings related to presence of the epsilon4 allele and MMSE performance. The role of WMLs in aging and dementia is discussed.     

White matter hyperintensities on brain magnetic resonance imaging: comparison of early-onset and late-onset restless legs syndrome

ObjectivePrevious studies have suggested that early-onset RLS (EOR) and late-onset RLS (LOR) might have different etiopathophysiologies. Few previous studies have examined accumulation of cerebrovascular ischemic changes as a potential cause of LOR.MethodsWe recruited 39 RLS subjects (LOR: defined as age of RLS onset ≥45, n = 18 and EOR: age of onset <45; n = 21); and 39 healthy control subjects matched on age and sex. Structural magnetic resonance imaging (MRI) of the brain was performed for each subject, and images were graded for severity of periventricular white matter hyperintensities (PVH) and deep white matter hyperintensities (DWMH) independently by trained raters according to standardized methods.ResultsInterrater reliabilities were 0.861 (p <0.001) for PVH and 0.900 (p <0.001) for DWMH. LOR subjects had a significantly higher grade of DWMH than the EOR subjects (p = 0.043) and age- and sex-matched controls (p = 0.015). In contrast, there was no difference in DWMH severity rating between the EOR group and the EC group or in PVH severity between the LOR or EOR groups and their age-matched controls.ConclusionOur findings suggest that the presence and severity of DWMH is associated with LOR, but not with EOR. Further examination of the contribution of cerebrovascular disease to the etiopathogenesis of LOR is warranted.     

Clinical and radiological correlates of reduced cerebral blood flow measured using magnetic resonance imaging

BACKGROUND: Methods for determining cerebral blood flow (CBF) using bolus-tracking magnetic resonance imaging (MRI) have recently become available. Reduced apparent diffusion coefficient (ADC) values of brain tissue are associated with reductions in regional CBF in animal stroke models. OBJECTIVES: To determine the clinical and radiological features of patients with severe reductions in CBF on MRI and to analyze the relationship between reduced CBF and ADCs in acute ischemic stroke. DESIGN: Case series. SETTING: Referral center. METHODS: We studied 17 patients with nonlacunar acute ischemic stroke in whom perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) were performed within 7 hours of symptom onset. A PWI-DWI mismatch of more than 20% was required. We compared patients with ischemic lesions that had CBF of less than 50% relative to the contralateral hemisphere with patients with lesions that had relative CBF greater than 50%. Characteristics analyzed included age, time to MRI, baseline National Institutes of Health Stroke Scale score, mean ADC, DWI and PWI lesion volumes, and 1-month Barthel Index score. RESULTS: Patients with low CBF (n = 5) had lower ADC values (median, 430 x 10 (-6) mm(2)/s vs. 506 x 10 (-6) mm(2)/s; P =.04), larger DWI volumes (median, 41.8 cm(3) vs. 14.5 cm(3); P =.001) and larger PWI lesions as defined by the mean transit time volume (median, 194.6 cm(3) vs. 69.3 cm(3); P =.01), and more severe baseline National Institutes of Health Stroke Scale scores (median, 15 vs. 9; P =.02). CONCLUSION: Ischemic lesions with severe CBF reductions, measured using bolus-tracking MRI, are associated with lower mean ADCs, larger DWI and PWI volumes, and higher National Institutes of Health Stroke Scale scores.     

Cycloid psychosis: regional cerebral blood flow correlates of a psychotic episode.

Eight patients meeting Leonhard's criteria for cycloid psychosis were investigated on repeated occasions during a psychotic episode, with regional cerebral blood flow measurements and clinical ratings. The results showed that, at admission to the hospital, when the patients were clinically exacerbated, the mean hemispheric blood flow was significantly elevated compared with values from a normal control group. The hemispheric blood flow level covaried significantly with the degree of clinical symptoms, such that the more elevated the cortical blood flow was, the more behaviorally disturbed was the patient. At discharge from the hospital, the patients had no residual symptoms and the cortical blood flow was normal. These findings differ distinctly from those commonly made in other psychoses, such as schizophrenia.     

Cerebral white matter perfusion in dementia of Alzheimer type.

Local cerebral blood flow was measured in 19 patients with probable dementia of Alzheimer type (DAT) by using xenon-enhanced computerized tomography (CT) and CT densitometry to accurately differentiate white from gray matter. Patients met standard diagnostic criteria for probable DAT and results were compared with similar measures in 26 age-matched, neurologically and cognitively normal volunteers. Perfusions of frontal and occipital white matter as well as frontal, parietal, temporal, and occipital cortex were reduced in DAT compared with age-matched normals. White matter perfusion differences were not observed among DAT patients with and without risk factors for stroke. Reduced perfusion of frontal white matter correlated significantly with reduced perfusion of thalamus and putamen in patients with DAT. Results confirm the frequent association of white matter abnormalities in patients with DAT that are possibly caused by amyloid angiopathy and may contribute to cognitive impairments.