Total Brain Tissue Volume Research Articles

MRI study of minor physical anomaly in childhood autism implicates aberrant neurodevelopment in infancy.

BackgroundMPAs (minor physical anomalies) frequently occur in neurodevelopmental disorders because both face and brain are derived from neuroectoderm in the first trimester. Conventionally, MPAs are measured by evaluation of external appearance. Using MRI can help overcome inherent observer bias, facilitate multi-centre data acquisition, and explore how MPAs relate to brain dysmorphology in the same individual. Optical MPAs exhibit a tightly synchronized trajectory through fetal, postnatal and adult life. As head size enlarges with age, inter-orbital distance increases, and is mostly completed before age 3 years. We hypothesized that optical MPAs might afford a retrospective ‘window’ to early neurodevelopment; specifically, inter-orbital distance increase may represent a biomarker for early brain dysmaturation in autism.MethodsWe recruited 91 children aged 7–16; 36 with an autism spectrum disorder and 55 age- and gender-matched typically developing controls. All children had normal IQ. Inter-orbital distance was measured on T1-weighted MRI scans. This value was entered into a voxel-by-voxel linear regression analysis with grey matter segmented from a bimodal MRI data-set. Age and total brain tissue volume were entered as covariates.ResultsIntra-class coefficient for measurement of the inter-orbital distance was 0.95. Inter-orbital distance was significantly increased in the autism group (p = 0.03, 2-tailed). The autism group showed a significant relationship between inter-orbital distance grey matter volume of bilateral amygdalae extending to the unci and inferior temporal poles.ConclusionsGreater inter-orbital distance in the autism group compared with healthy controls is consistent with infant head size expansion in autism. Inter-orbital distance positively correlated with volume of medial temporal lobe structures, suggesting a link to “social brain” dysmorphology in the autism group. We suggest these data support the role of optical MPAs as a “fossil record” of early aberrant neurodevelopment, and potential biomarker for brain dysmaturation in autism.

Decreased Prefrontal Cortical Volume Associated with Increased Bedtime Cortisol in Traumatized Youth

The purpose of this study was to investigate prefrontal cortex (PFC) volumes in youth with posttraumatic stress symptoms (PTSS) and explore the relationship between cortisol secretion and PFC volumes. Total brain tissue volumes, segmented areas of the PFC, and diurnal cortisol secretion were examined in a sample of 33 youth aged 10 to 16 years. Cerebral volumes were available for 45 subjects (30 PTSS and 15 control subjects). Youth with PTSS had significantly decreased total brain tissue and total cerebral gray volumes in comparison with healthy control subjects. While controlling for total cerebral gray volume, the PTSS group demonstrated decreased left ventral and left inferior prefrontal gray volumes. A significant negative association was found between prebedtime cortisol levels and left ventral PFC gray volumes for the full sample. Findings suggest associations between posttraumatic stress and PFC neurodevelopment. Findings also suggest a link between PFC development and cortisol secretion.

Relations between brain volumes, neuropsychological assessment and parental questionnaire in prematurely born children

The objective of this study is to assess the relationship between brain volumes at term equivalent age and neuropsychological functions at 5 years of age in very low birth weight (VLBW) children, and to compare the results from a neuropsychological assessment and a parental questionnaire at 5 years of age. The study group included a regional cohort of 97 VLBW children and a control group of 161 children born at term. At term equivalent age, brain magnetic resonance imaging (MRI) was performed on the VLBW children, and analysed for total and regional brain volumes. At 5 years of age, a psychologist assessed the neuropsychological performance with NEPSY II, and parents completed the Five to fifteen (FTF) questionnaire on development and behaviour. The results of the control group were used to give the age-specific reference values. No significant associations were found between the brain volumes and the NEPSY II domains. As for the FTF, significant associations were found between a smaller total brain tissue volume and poorer executive functions, between a smaller cerebellar volume and both poorer executive functions and motor skills, and, surprisingly, between a larger volume of brainstem and poorer language functions. Even after adjustment for total brain tissue volume, the two associations between the cerebellar volume and the FTF domains remained borderline significant (P = 0.05). The NEPSY II domains Executive Functioning, Language and Motor Skills were significantly associated with the corresponding FTF domains. In conclusion, altered brain volumes at term equivalent age appear to affect development still at 5 years of age. The FTF seems to be a good instrument when used in combination with other neuropsychological assessment.

Brain and Ventricles in Very Low Birth Weight Infants at Term: A Comparison Among Head Circumference, Ultrasound, and Magnetic Resonance Imaging

The aim of this study was to assess the relationship among the size of the lateral ventricles, head-circumference measure, and brain volumes. In addition, the association between ventricular dilatation and various brain lesions was defined. A total of 257 preterm very low birth weight (< or =1500 g) infants who met the inclusion criteria were born in Turku University Central Hospital between 2001 and 2006. A total of 209 (84.8%) of 218 survivors participated in the study. The measurements at term included the ventricular brain ratio, the widths of the frontal and occipital horns of the lateral ventricles by ultrasound, total and regional brain volumes by MRI, and head circumference. Brain lesions were defined by ultrasound at 3 to 5, 7 to 10, and 30 days of age monthly until discharge and by MRI and ultrasound at term. An abnormal ventricular brain ratio (>0.35), an increasing number of dilated ventricular horns, and smaller head circumference were significantly associated with smaller total brain tissue volume. The abnormal ventricular brain ratio and the increasing number of dilated ventricular horns in ultrasound associated with larger ventricular volumes in MRI, and a smaller head circumference was associated significantly with reduced regional brain tissue volumes. Brain lesions were more common in infants with ventriculomegaly. The ventricular brain ratio, widths of the lateral ventricular horns, and head circumference are appropriate measures for the estimation of both total and regional brain tissue volumes. Ventriculomegaly is strongly associated with brain lesions.

Volumetric and anatomical MRI for hypoxic–ischemic encephalopathy: relationship to hypothermia therapy and neurosensory impairments

ObjectiveTo relate volumetric MRI findings to hypothermia therapy and neurosensory impairments.Study DesignNewborns ≥ 36 weeks’ gestation with hypoxic-ischemic encephalopathy who participated in the NICHD hypothermia randomized trial at our center were eligible. We determined the relationship between hypothermia treatment and usual care (control) to absolute and relative cerebral tissue volumes. Further, we correlated brain volumes with death or neurosensory impairments at 18 to 22 months.ResultsBoth treatment groups were comparable before randomization. Total brain tissue volumes did not differ in relation to treatment assignment. However, relative volumes of subcortical white matter were significantly larger in hypothermia-treated than control infants. Furthermore, relative total brain volumes correlated significantly with death or neurosensory impairments. Relative volumes of the cortical gray and subcortical white matter also correlated significantly with Bayley Scales psychomotor development index.ConclusionSelected volumetric MRI findings correlated with hypothermia therapy and neurosensory impairments. Larger studies utilizing MRI brain volumes as a secondary outcome measure are needed.

A novel quantitative simple brain metric using MR imaging for preterm infants.

The application of volumetric techniques to preterm infants has revealed brain volume reductions. Such quantitative data are not available in routine neonatal radiologic care. The objective of this study was to develop simple brain metrics to compare brain size in preterm and term infants and to correlate these metrics with brain volumes from volumetric MR imaging techniques. MR images from 189 preterm infants <30 weeks' gestational age or <1250 g birthweight scanned at term-equivalent age and 36 term infants were studied. Fifteen tissue and fluid measures were systematically evaluated on 4 selected sections. The results were correlated with total brain, gray matter, white matter, and CSF volumes. The mean bifrontal, biparietal, and transverse cerebellar diameters were reduced (-11.6%, 95% confidence interval [CI], -13.8% to -9.3%; -12%, 95% CI, -14% to -9.8%; and -8.7%, 95% CI, -10.5% to -7% respectively) and the mean left ventricle diameter was increased (+22.3%, 95% CI, 2.9%-41.6%) in preterm infants (P < .01). Strong correlations were found between the bifrontal and biparietal measures with total brain tissue volume, whereas the size of the ventricles and the interhemispheric measure correlated with CSF volume. Intraobserver reliability was high (intraclass correlation coefficients [ICC], >0.7), where interobserver agreement was acceptable for tissue measures (ICC, >0.6) but lower for fluid measures (ICC, <0.4). Simple brain metrics at term-equivalent age showed smaller brain diameters and increased ventricle size in preterm infants compared with full-term infants. These measures represent a reliable and easily applicable method to quantify brain growth and assess brain atrophy in this at-risk population.

Head Growth in Preterm Infants: Correlation With Magnetic Resonance Imaging and Neurodevelopmental Outcome

Extremely preterm birth is associated with adverse neurodevelopmental sequelae. Head circumference has been used as a measure of brain growth. There are limited data relating head circumference to MRI. The purpose of this work was to establish the relationship between head circumference with brain MRI at term-equivalent age and to relate head circumference with neurodevelopmental outcome at 2 years. Two hundred and twenty-seven preterm infants (birth weight of <1250 g or <30 weeks' gestation) were recruited. Head circumference was measured at birth, term, and 2 years' corrected age, and z scores were computed. Microcephaly was defined as a head circumference z score of less than -2 SDs for age and gender. MRI scans at term (n = 214) were graded for white and gray matter abnormalities, and segmented volumes were calculated for different tissue types. Outcome at 2 years' corrected age (n = 202) included scores on the Bayley Scales of Infant Development II. Microcephaly increased from 7.5% at term to 29.7% at 2 years. There was no significant relationship between head circumference and white or gray matter abnormalities on MRI. There was a strong correlation between head circumference and brain volume at term. At term, microcephalic infants had significantly decreased volumes for total brain tissue and most segmented volumes compared with infants with normal head circumference, but only deep nuclear gray matter volume remained significantly lower when adjusted for total intracranial volume. At 2 years, microcephaly was associated with poorer cognitive and motor development and an increased rate of cerebral palsy. Brain volume is a determinant of head size at term. Microcephaly is associated with a reduction of brain tissue volumes, especially deep nuclear gray matter, which suggests a selective vulnerability. Poor postnatal head growth in preterm infants becomes more evident by 2 years and is strongly associated with poor neurodevelopmental outcome and cerebral palsy.

Neonate hippocampal volumes: Prematurity, perinatal predictors, and 2‐year outcome

To compare preterm (PT) and full-term (FT) infant hippocampal volumes and to investigate the relations among PT hippocampal volume, perinatal risk factors, and neurodevelopmental outcome. A total of 184 PT and 32 full-term infants underwent magnetic resonance imaging at term equivalent age with manual segmentation of the hippocampi on coronal slices. Perinatal data were collected and 2-year neurodevelopment was evaluated with the Mental Development Index and Psychomotor Development Index on the Bayley Scales of Infant Development. PT and FT infant hippocampi did not significantly differ after controlling for head size, and percentage reductions in PT hippocampi (3.4%) were less than for cortical (7%) and deep nuclear gray matter (13%), and total brain tissue volume (4.7%). PT hippocampal volumes were significantly lower in infants with moderate-to-severe white matter injury (p < 0.001), exposure to postnatal steroids (right, p = 0.001; left, p = 0.008), and indomethacin treatment (right, p = 0.01; left, p = 0.03). PT infant hippocampal volumes correlated with the Mental (p < 0.001) and Psychomotor Development Indices (right, p = 0.001; left, p = 0.002) after correcting for head size and sex, but remained significant only for the Mental Development Index and left hippocampi (p = 0.04) after additionally adjusting for white matter injury and steroids. Hippocampal volumes were reduced in PT infants exposed to several perinatal events but were preserved in PT infants without these exposures. Smaller PT hippocampal volumes were indirectly associated with delayed development at 2 years.

MRI brain volume abnormalities in young, nonpsychotic relatives of schizophrenia probands are associated with subsequent prodromal symptoms

Schizophrenia is characterized by subtle but well-replicated total and regional (frontal and temporal) brain tissue volume deficits. Studies of individuals at-risk for developing schizophrenia suggest that the onset of brain volume decrement may closely pre-date overt manifestations of schizophrenia, making brain volume abnormalities potential predictors for early identification. In an ongoing longitudinal morphometric MRI study of young, nonpsychotic first- or second-degree relatives of schizophrenia probands, we compared brain volumes in 46 relatives who are still within age range for developing schizophrenia against comparison groups of 46 schizophrenia patients and 46 healthy volunteers without family history of schizophrenia. Relatives had similar brain volume abnormalities as schizophrenia patients albeit less severe. Relatives had significantly larger whole brain, frontal, temporal and parietal gray matter (GM) volumes than patients. Relatives also had significantly smaller frontal GM volumes than healthy volunteers. Both relatives and patients had significantly larger whole brain WM (specifically parietal WM) volumes compared to healthy volunteers. Abnormally greater WM volumes in relatives and patients are suggestive of genetically-mediated dysmaturation of the age-expected myelination during adolescence through mid adulthood. On prodromal symptoms assessed in relatives one year after MRI brain scans, initial GM deficits as well as larger WM volumes correlated significantly with greater severity of subsequent prodromal symptoms. Together with previous genetic high-risk studies of adolescent or young adult relatives, these findings indicate that premorbid MRI brain abnormalities may be of predictive value for the early identification of schizophrenia.

Structural correlates of intellectual impairment and autistic features in adolescents

Intellectual disability, a common but under-researched condition, is strongly associated with autism spectrum disorders (ASD). Although studies have investigated the neural correlates of intelligence quotient (IQ) and ASD in intellectually unimpaired subjects, these issues have not been addressed in intellectually impaired subjects. We studied 63 intellectually disabled adolescents receiving additional learning support and 72 controls using whole brain tissue volumes extracted from native space and voxel-based morphometry (VBM) in normalised space. We applied a qualitative and quantitative review of VBM preprocessing and modified the optimised method to establish optimum co-registration of the brains in normalised space. We report tissue density differences at cluster level with adjustment for underlying smoothness. Individuals with intellectual disability had smaller total white matter and total brain tissue volumes than controls, as well as reduced grey matter density in the right cerebellar hemisphere and left temporo-parietal cortex, and reduced white matter density in the posterior corpus callosum. Intellectually disabled subjects were additionally subgrouped according to their degree of reported autistic features. Reduced grey matter density was detected in the thalamus of subjects with autistic features scoring within the pervasive developmental disorder range as compared to subjects below the threshold for ASD, and increased white matter density was detected in the left superior temporal gyrus of subjects scoring above the threshold for autism as compared to subjects below the threshold for ASD.

Higher blood pressure predicts lower regional grey matter volume: Consequences on short-term information processing

Hypertension is a risk factor for diffuse brain atrophy. Yet, there is little evidence that higher blood pressure predicts focal brain atrophy, as indicated by a lower volume of regional brain tissue. This voxel-based morphometry study tested (a) whether higher blood pressure predicts lower regional grey or white matter volume and (b) whether a blood-pressure-related reduction in regional brain tissue volume predicts poorer neuropsychological test performance. Participants were 76 men ( M age = 61.33, SD = 4.95 years) and 58 women ( M age = 59.86, SD = 5.10 years) without a cardiovascular, cerebrovascular, or neuropsychiatric disease. Results showed that among men, higher resting systolic blood pressure predicted lower grey matter volume in the supplementary motor area and adjacent superior frontal gyrus, the anterior cingulate cortex, and middle temporal gyrus. Among men, lower grey matter volume in the supplementary motor area also predicted a slower time to complete the Trail Making Part B Test of executive control and a poorer recall of items from the Four-word Short-term Memory Test of working memory. These relationships were independent of age, total brain tissue volume, educational history, severity of carotid atherosclerosis, and the extent of periventricular and subcortical white matter lesions. Among women, no statistically significant relationships were found between blood pressure, regional brain tissue volume, and cognitive function. These findings suggest a functional relationship among men between higher blood pressure, lower regional grey matter volume, and poorer cognitive function that is independent of other risk factors and confounding medical conditions.

43 Total Cerebral Volume Measurements Following Preterm Birth

Background. Preterm infants have reduced cerebral tissue volumes in adolescence, and relative loss of some brain regions in early childhood, but it is unclear if this is due to perinatal or more prolonged growth failure. We therefore compared total cerebral tissue volume in preterm infants at term equivalent age and term born controls. Methods. Subjects: We studied 89 preterm infants born at median 29.7 weeks GA without parenchymal lesions at median 40.57 weeks, and 20 term born controls (median 40.43 weeks GA). Image acquisition: A 1.5 Tesla MR system was used to acquire T1-weighted volume datasets with a voxel size 1x1x1.6mm, in addition to conventional and diffusion weighted imaging. Image processing: A non-rigid image registration algorithm transformed all images to a reference subject, and transformations were used to propagate region of interest (ROI) labels segmented in the reference anatomy to the corresponding structure in all subjects. The volume change for each ROI relative to the reference was computed, enabling cerebral tissue volume measurements (excluding CSF) to be calculated for each subject. Results. Mean cerebral tissue volume in preterm infants at term was 404.9cm3; and in term controls, 401.1cm3 (p=0.765). Diffuse white matter injury, oxygen requirement at 28 days, and intrauterine growth restriction were not associated with significant reductions in cerebral tissue volume. Conclusions. Despite evidence of regional and later growth failure, total brain tissue volume in preterm infants at term is similar to term born controls.

The neurodevelopmental impact of childhood onset temporal lobe epilepsy on brain structure and function and the risk of progressive cognitive effects

The purpose of this study is to explore the possibility of progressive neuropsychological decline in chronic temporal lobe epilepsy (TLE) and determine how this vulnerability may be associated with the neurodevelopmental impact of the disorder. 53 patients with TLE and 62 healthy controls underwent quantitative MRI volumetric imaging of total brain tissue and hippocampal volumes as well as assessment of intelligence and memory function. In addition to reduced hippocampal volume, childhood onset (< 14 years) but not adult onset TLE was associated with significantly reduced total brain tissue that was generalized in nature and extended into extratemporal regions. In addition to this adverse impact on brain structure, there was significantly reduced intellectual status as well as memory function in childhood onset TLE patients, consistent with the generalized nature of the MRI volumetric abnormalities. Finally, cross-sectional correlational analyses indicated that increasing duration of epilepsy in childhood onset patients was associated with declining performance across both intellectual and memory measures, suggestive of progressive cognitive effects. We propose that childhood onset TLE is associated with an adverse neurodevelopmental impact on brain structure and function which represents an early acquired vulnerability, effectively reducing cerebral reserve, placing patients at risk for progressive cognitive decline in the context of chronic and unremitting epilepsy.

Magnetic resonance imaging of the thalamus in male patients with schizophrenia

Thalamic abnormalities have been hypothesized to explain much of the psychopathology in schizophrenia, however, quantitative magnetic resonance imaging (MRI) studies have yielded discrepant results as to whether there are thalamic volume alterations. The current study utilized high resolution MRI and an axial voluming protocol to determine if there was a significant reduction in the volume of the thalamus in patients with schizophrenia. Quantitative analysis was performed on magnetic resonance images of the brain in 41 male medicated schizophrenic patients and 39 male normal control subjects similar in age, education and handedness. There were no group differences in thalamic volumes between controls and patients with schizophrenia, even after adjusting for intracranial volume, total brain tissue volume, and gray matter volume. There were also no significant correlations between thalamic volume and either current neuroleptic dose or illness duration. However, there was a significant right greater than left thalamic volume asymmetry in schizophrenics and controls, and the degree of thalamic volume asymmetry was similar in both groups. The failure to detect any significant difference in thalamic volumes may be due to the heterogeneity of the schizophrenic population and as yet undetermined chronic effects of neuroleptic medication on the thalamus. However, another reasonable explanation for the study findings is that quantitative MRI voluming of the entire thalamus may not be sensitive enough to detect more subtle regional neuropathology within the thalamus.

Medication treatment in subjects with autistic spectrum disorders.

Autism is a pervasive developmental disorder that is aetiologically and clinically heterogeneous. Twin and family genetic studies provide evidence for strong genetic components. An international consortium using an affected sib pair strategy has found a promising linkage to a region on chromosome 7. In 10-15 % of the cases autism is due to associated medical conditions that affect normal brain functioning. Post-mortem studies on small case series report cellular abnormalities in the limbic system and cerebellum. Between 10 and 20 % of subjects with autism have macrocephalia, which is in accordance with MRI findings of an increased total brain tissue volume and enlargement most prominent in the occipital and parietal lobes. The most robust and well-replicated neurobiological abnormality in autism is an elevation of whole blood serotonin found in over 30% of the patients. Pharmacological interventions with serotonin reuptake blockers or with atypical neuroleptics that block both dopamine (D2) and serotonin (5-HT2) receptors seem to offer clinical benefit and merit further study.

Autism: current theories regarding its pathogenesis and implications for rational pharmacotherapy.

Autism is a pervasive developmental disorder that is aetiologically and clinically heterogeneous. Twin and family-genetic studies provide evidence for strong genetic components. An international consortium using an affected sib pair strategy has found a promising linkage to a region on chromosome 7. In 10 to 15% of cases autism is due to associated medical conditions that affect normal brain functioning. Postmortem studies on small case series report cellular abnormalities in the limbic system and cerebellum. Between 10 and 20% of individuals with autism have macrocephalia, which is in accordance with magnetic resonance imaging (MRI) findings of an increased total brain tissue volume and enlargement most prominent in the occipital and parietal lobes. The most robust and well replicated neurobiological abnormality in autism is an elevation of whole blood serotonin (5-hydroxytryptamine; 5-HT) found in over 30% of patients. Pharmacological interventions with serotonin reuptake inhibitors or with atypical neuroleptics that block both dopamine (D2) and serotonin (5-HT2) receptors seem to offer clinical benefit and merit further study.

Magnetic resonance imaging of brain anomalies in fetal alcohol syndrome.

Postmortem studies of fetuses, infants, and young children with fetal alcohol syndrome (FAS) have demonstrated a variety of severe central nervous system (CNS) anomalies. We undertook this magnetic resonance study (1) to assess the spectrum of CNS anomalies that occur in a clinical sample of typical patients with FAS who are medically stable; and (2) to examine the relationship between CNS and facial anomalies. Magnetic resonance imaging was performed on a series of 10 patients (4 children, 3 adolescents, and 3 adults) who met criteria for FAS. We systematically evaluated each scan for brain anomalies and compared total brain tissue volume with that of healthy child, adolescent, and adult control subjects. Six patients had some type of midline anomaly, ranging from partial to complete callosal agenesis (three patients) to hypoplastic corpus callosum (one patient), cavum septi pellucidi (three patients), and cavum vergae (two patients). These midline anomalies were associated with a greater number of facial anomalies. Other brain anomalies identified included micrencephaly, ventriculomegaly, and hypoplasia of the inferior olivary eminences. Patients with classic FAS have a high incidence of midline brain anomalies. This finding is consistent with the concept that the midline CNS is a developmental field that is particularly susceptible to the teratogenic effects of alcohol. Furthermore, patients with more severe facial dysmorphologic characteristics are more likely to have midline brain anomalies. In addition, we observed a high incidence of micrencephaly with a wide range of severity.

Rapid automatic brain volumetry on the basis of multispectral 3D MR imaging data on personal computers

Fast magnetic resonance imaging sequences are an excellent basis for the volumetry of the human brain. We present a concept for an automatic three-dimensional (3D) segmentation and volumetry which provides rapid image processing along with minimal requirements of manual interaction on low-end hardware platforms. The concept is based on standard image segmentation techniques and provides for the determination of the total brain tissue and cerebrospinal fluid volumes from the input data base, a T1- and a T2-weighted 3D image data cube. We used a 3D MPRAGE sequence for the T1- and a 3D PSIF sequence for the T2-weighted images; both 3D image data cubes consisted of 128 sagittal image slices with a voxel size of 1.0 × 1.0 × 1.2 mm 3. The segmentation and volumetry tool was applied to clinical image data of volunteers and Alzheimer patients in order to prove its stability.

Correlations of leuko-araiosis with cerebral atrophy and perfusion in elderly normal subjects and demented patients.

CT images of leuko-araiosis in brain slices were quantified according to volumes of reduced Hounsfield units in frontal periventricular white matter in groups of elderly patients with multi-infarct dementia (MID, n = 23) and dementia of the Alzheimer type (DAT, n = 16). Volumes of leuko-araiosis, estimates of atrophic cerebral tissue, and local cerebral perfusion utilising inhalation of xenon gas as the indicator were correlated on the same CT slices. Ratios of frontal leuko-araiosis to total brain tissue volume were similar for patients with MID and DAT (mean 5.7 (SD 2.1)% v 6.5 (3.2%)), and both were significantly greater than ratios in elderly normal volunteers (3.1(1.3)%, 0 < 0.001). Cerebral atrophy (measured as the ratio of volumes of cerebrospinal fluid to total brain area) for DAT patients was 17.0 (6.7)%, which was greater than for MID patients (12.5 (5.4)%; p < 0.05) and both types of patients showed more cerebral atrophy than did age matched, elderly normal subjects. Cerebral perfusion was decreased in all regions measured in patients with MID and DAT compared with elderly normal subjects. Multi variate regression analyses correlated frontal leuko-araiosis with reductions of local cerebral blood flow in subcortical grey matter (p < 0.025) in patients with vascular dementia but not in those with DAT. These quantitative measures implicate decreased perfusion due to atherosclerosis in territories supplied by the deep penetrating cerebral arteries in the pathogenesis of leuko-araiosis in patients with vascular dementia, but suggest a different pathogenesis for leuko-araiosis in Alzheimer's disease.

Leuko-araiosis and cerebral hypoperfusion compared in elderly normals and Alzheimer's dementia.

To elucidate the pathogenesis of leuko-araiosis in patients with Alzheimer's disease by utilizing CT densitometry of the brain and measurements of local perfusion in order to quantify the extent of leuko-araiosis and local hypoperfusion compared with similar measurements made among age-matched normal volunteers. Cross-sectional case-control study. Out-patient visits to a specialized laboratory located in a large hospital facility. Eighteen elderly patients with probable dementia of Alzheimer type (DAT, aged 71.8 +/- 5.1 years) and 17 neurologically and cognitively normal, age-matched volunteers (aged 68.2 +/- 9.6 years) were admitted to the study according to established criteria. None Cerebral blood flow (mL/100 g brain/min) estimated by the xenon inhalation CT-CBF method correlated with volume percentage ratio (%) measured by CT densitometry for leuko-araiosis, compared to normal white and gray matter. Perfusion values for frontal and occipital white matter as well as frontal, parietal, temporal, and occipital cortex were all decreased in DAT patients. Ratios for leuko-araiosis to total brain tissue volumes were greater among patients with DAT compared with age-matched normal volunteers. White matter perfusion in zones of leuko-araiosis was decreased to a similar degree in both DAT and elderly normal volunteers. Perfusion is reduced to the same degree in regions of leuko-araiosis in elderly normals as in DAT patients, but the extent of leuko-araiosis is greater among DAT patients and presumably contributes to cognitive impairments.