Structural brain CT changes and cognitive deficits in elderly depressives with and without reversible dementia ('pseudodementia')

Twenty-six elderly (greater than 60 yrs) patients with DSM-III major depression were compared to 13 patients with NINCDS/ADRDA probable Alzheimer's disease (AD), and to 31 screened normal controls. Subjects were matched on age and sex. Fifteen of the 26 depressed patients were cognitively impaired on the Mini-Mental State Examination (MMSE) upon admission, but after treatment returned to the normal range. These 15 patients were defined as having the dementia syndrome of depression (DOD). The remaining 11 depressed patients were termed depressed, cognitively normal (DCN). All subjects received standardized cranial CT scans for assessment of ventricular brain ratio (VBR) and CT attenuation numbers. Subjects also received neuropsychological evaluation. CT values for the 26 depressed patients lay between those of AD patients and normal controls. CT values for the DOD subgroup clustered near those of AD patients. Patterns of cognitive deficits and correlations of CT attenuation values with cognitive measures were also similar in AD and DOD. Most patients were reassessed at a mean of two years after initial testing; of the 11 of the 15 DOD re-examined, only one had undergone cognitive decline. By contrast, all AD patients retested had declined significantly. Episodes of DOD and DCN tended to 'breed true'. This study suggests that while patients with DOD may have underlying structural brain abnormalities, obvious short-term progression to AD does not commonly occur.     

Subcortical hyperintensities on brain magnetic resonance imaging: a comparison between late age onset and early onset elderly depressed subjects

Subcortical structural changes have been reported to occur in some elderly subjects with late age onset depression. Given the association between diseases affecting subcortical structures and affective disorders, this suggests that these structural changes may be involved in the etiology of late age onset depression in some patients. With the advent of Brain Magnetic Resonance Imaging (MRI), "in vivo" analysis of these subcortical structures is now possible. The authors report a higher occurrence of caudate (60% vs. 11%) and large deep white matter hyperintensities (60% vs. 11%) in late age onset elderly depressed subjects compared with early onset elderly depressed subjects. These results suggest that late age onset depression may be mediated by caudate and white matter structural changes in some patients.     

1H MRS in stroke patients with and without cognitive impairment

The pathophysiological basis of cognitive impairment in patients with cerebrovascular disease (CVD) is not well understood, particularly in relation to the role of non-infarction ischemic change and associated Alzheimer-type pathology. We used single voxel 1H MRS to determine the differences in brain neurometabolites in non-infarcted frontal white matter and occipito-parietal gray matter of 48 stroke patients with or without cognitive impairment and 60 elderly controls. The results showed that there were no significant neurometabolite differences between the stroke cohort and healthy elderly controls, but there was a difference in NAA/H2O between the stroke patients that had cognitive impairment (vascular dementia (VaD) and vascular cognitive impairment (VCI)) compared with those patients with no impairment. This was significant in the occipito-parietal gray matter, but not in the frontal white matter, although the results were in the same direction for the latter. This suggests that cognitive impairment in stroke patients may be related to cortical neuronal dysfunction rather than purely subcortical change. Moreover, cortical regions not obviously infarcted may have dysfunctional neurons, the pathophysiological basis for which needs further study.     

MRI in schizophrenia: basal ganglia and white matter T1 times

The T1 relaxation time of the basal ganglia (putamen, globus pallidus and head of caudate) and of the frontoparietal centrum semiovale was compared between 49 schizophrenic patients and 36 healthy controls. Previous reports of increased T1 time in the basal ganglia were not confirmed, and group differences were not detected within the white matter. Within patients T1 values could not be related to tardive dyskinesia or other clinical features. Normal variation seen in basal ganglia T1 times is described for the first time: lowest values occur in the globus pallidus and highest in the caudate, and values within the putamen increase rostrally.     

Fibrosis and stenosis of the long penetrating cerebral arteries: the cause of the white matter pathology in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

In cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) the vascular smooth muscle cells are destroyed and granular osmiophilic material is deposited followed by fibrosis of the arterial wall. To verify whether true stenosis of the fibrotic white matter arteries is a key pathogenic event in CADASIL, we analyzed the thickness of walls (expressed as sclerotic index) and luminal diameters of penetrating arterioles in both grey matter and white matter of four CADASIL patients due to the C475T (R133C) mutation in the Notch3 gene and in 9 age-matched controls. We also reconstructed 9 arterioles from 1000 serial sections in two CADASIL patients. The thickness of the arteriolar walls in both grey matter and white matter was significantly increased in the CADASIL patients compared with controls. Furthermore, in CADASIL patients the arteriolar walls were significantly thicker in the white matter than in the grey matter. The distribution curve of arteriolar internal diameters in CADASIL patients shifted towards smaller sizes. In serial sections, the marked increase in the thickness of the white matter penetrating arterioles or their branches did not occur until the internal diameters had decreased to about 20 to 30 pm and external diameters to about 100 to 130 microm. In conclusion, long penetrating arterioles and their branches supplying subcortical structures in CADASIL are stenosed and their walls are thickened. This conforms to the abundance of infarcts and primary ischemic damage in CADASIL patients' white matter.     

Distinct Patterns of Brain Atrophy associated with Mild Behavioral Impairment in Cognitively Normal Elderly Adults

A cross-sectional study was conducted to evaluate patterns of gray matter changes in cognitively normal elderly adults with mild behavioral impairment (MBI). Sixteen MBI patients and 18 healthy controls were selected. All the participants underwent a neuropsychological assessment battery, including the Mini-mental State Examination (MMSE), Geriatric Depression Scale (GDS), Self-rating Anxiety Scale (SAS), and Chinese version of the mild behavioral impairment-checklist scale (MBI-C), and magnetic resonance imaging (MRI) scans. Imaging data was analyzed based on voxel-based morphometry (VBM). There was no significant difference in age, gender, MMSE score, total intracranial volume, white matter hyperdensity, gray matter volume, white matter volume between the two groups (p > 0.05). MBI group had shorter education years and higher MBI-C score, GDS and SAS scores than the normal control group (p < 0.05). For neuroimaging analysis, compared to the normal control group, the MBI group showed decreased volume in the left brainstem, right temporal transverse gyrus, left superior temporal gyrus, left inferior temporal gyrus, left middle temporal gyrus, right occipital pole, right thalamus, left precentral gyrus and left middle frontal gyrus(uncorrected p < 0.001). The grey matter regions correlated with the MBI-C score included the left postcentral gyrus, right exterior cerebellum, and left superior frontal gyrus. This suggests a link between MBI and decreased grey matter volume in cognitively normal elderly adults. Atrophy in the left frontal cortex and right thalamus in MBI patients is in line with frontal-subcortical circuit deficits, which have been linked to neuropsychiatric symptoms (NPS) in dementia. These initial results imply that MBI might be an early harbinger for subsequent cognitive decline and dementia.     

Brain volume alteration and the correlations with the clinical characteristics in drug-naïve first-episode MDD patients: A voxel-based morphometry study

Structural brain abnormalities have been widely reported in major depressive disorder (MDD). However, many previous results cannot exclude the interferences of medication or multiple recurrent episodes. In this study, we examined structural brain abnormalities by comparing 68 drug-naïve first-episode adult-onset MDD and 68 healthy controls (HCs). Structural magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) methods were used. The mean values of grey matter volume/white matter volume (GMV/WMV) were calculated, then the differences between MDD and HCs were analyzed, and the associations of the differences with clinical characteristics of depression were discussed. The whole brain GMV/WMV did not differ between MDD patients and HCs; however, the regional GMV of the right pre-supplementary motor area (pre-SMA) was smaller in MDD patients. The GMV of both hippocampi was positively correlated with symptom severity and lower in patients with long durations. These results indicate the GMV reduction of the pre-SMA at an early stage of depression, whereas the GMV of the hippocampus is associated with depressive characteristics. Moreover, the whole brain GMV/WMV was negatively related to the duration of depression, supporting that volume loss could become progressive during the development of disease. These results may suggest the importance of identifying and intervening depression at an early stage, especially the first year after onset, to prevent volume loss in the brain.     

Mapping joint grey and white matter reductions in Alzheimer's disease using joint independent component analysis

Alzheimer's disease (AD) is a neurodegenerative disease concomitant with grey and white matter damages. However, the interrelationship of volumetric changes between grey and white matter remains poorly understood in AD. Using joint independent component analysis, this study identified joint grey and white matter volume reductions based on structural magnetic resonance imaging data to construct the covariant networks in twelve AD patients and fourteen normal controls (NC). We found that three networks showed significant volume reductions in joint grey–white matter sources in AD patients, including (1) frontal/parietal/temporal-superior longitudinal fasciculus/corpus callosum, (2) temporal/parietal/occipital-frontal/occipital, and (3) temporal-precentral/postcentral. The corresponding expression scores distinguished AD patients from NC with 85.7%, 100% and 85.7% sensitivity for joint sources 1, 2 and 3, respectively; 75.0%, 66.7% and 75.0% specificity for joint sources 1, 2 and 3, respectively. Furthermore, the combined source of three significant joint sources best predicted the AD/NC group membership with 92.9% sensitivity and 83.3% specificity. Our findings revealed joint grey and white matter loss in AD patients, and these results can help elucidate the mechanism of grey and white matter reductions in the development of AD.     

首发重症抑郁症的弥散张量成像研究:基于纤维束示踪的空间统计学分析结果

目的:应用基于纤维束示踪的空间统计分析(Tract-Based Spatial Statistics,TBSS)方法,探讨重症抑郁症病患者全脑白质纤维的完整性是否受到损害。方法:对20(8男,12女)例重症抑郁症病患者组和20(8男,12女)例与抑郁症组按性别、年龄、教育程度匹配的正常人进行全脑弥散张量成像扫描。应用TBSS方法来比较两组的各向异性分数。结果:抑郁症组的左侧内囊前肢、右侧海马旁回、左侧后扣带回的各向异性分数显著低于正常组(P<0.05,t>3,校正),患者组内囊前肢的各向异性分数和抑郁症严重程度呈现负相关。结论:白质病变在抑郁症发病早期即已存在,这些病变区域主要涉及前额叶和边缘系统等与认知和情感调节关系较密切的神经环路的纤维束,这些改变可能导致皮层和皮层下连接受损,从而有利于深入了解抑郁症疾病的发病机理。     

Quantitative computed tomographic study in schizophrenia: cerebral density and ventricle measures

Twenty-seven chronic schizophrenics and nineteen controls, all male, were evaluated by computed tomography (CT) scans. Lateral, third and fourth ventricles and cerebral density numbers were measured. In the schizophrenic patients there was a significant increase in third ventricle width, Ventricular Brain Ratio (VBR) and there were significantly higher densities of white matter in the right frontal and parietal region.     

Cerebellar volume correlates with saccadic gain and ataxia in adult Niemann-Pick type C

Background and purposeCerebellar Purkinje cells are known to be highly vulnerable to neuronal pathology in Niemann-Pick type C (NPC), a disease where widespread white matter changes have also been reported. We sought to determine the relationship between white and grey matter cerebellar changes and clinical variables in NPC.Materials and methodsTen adult patients with NPC were matched to control subjects (n = 27) on age and gender. Patients were rated for symptom duration and severity, degree of ataxia, and were assessed for saccadic eye measures. Cerebellar white and grey matter volumes were automatically segmented using the Freesurfer software package.ResultsNPC patients had a significant reduction in both grey and white matter volumes. Volume did not correlate with symptom duration or severity, but did correlate with saccadic gain and ataxia measures.ConclusionsBoth cerebellar grey and white matter volume decreases in adult NPC, and these changes are associated with impairments in saccadic gain and in motor control.     

Intravoxel water diffusion heterogeneity imaging of human high‐grade gliomas

This study aimed to determine the potential value of intravoxel water diffusion heterogeneity imaging for brain tumor characterization and evaluation of high‐grade gliomas, by comparing an established heterogeneity index (α value) measured in human high‐grade gliomas to those of normal appearing white and grey matter landmarks. Twenty patients with high‐grade gliomas prospectively underwent diffusion‐weighted magnetic resonance imaging using multiple b‐values. The stretched‐exponential model was used to generate α and distributed diffusion coefficient (DDC) maps. The α values and DDCs of the tumor and contralateral anatomic landmarks were measured in each patient. Differences between α values of tumors and landmark tissues were assessed using paired t‐tests. Correlation between tumor α and tumor DDC was assessed using Pearson's correlation coefficient. Mean α of tumors was significantly lower than that of contralateral frontal white matter (p = 0.0249), basal ganglia (p < 0.0001), cortical grey matter (p < 0.0001), and centrum semiovale (p = 0.0497). Correlation between tumor α and tumor DDC was strongly negative (Pearson correlation coefficient, ?0.8493; p < 0.0001). The heterogeneity index α of human high‐grade gliomas is significantly different from those of normal brain structures, which potentially offers a new method for evaluating brain tumors. The observed negative correlation between tumor α and tumor DDC requires further investigation. Copyright © 2009 John Wiley & Sons, Ltd.     

Voxel-based morphometry in autopsy proven PSP and CBD

The aim of this study was to compare the patterns of grey and white matter atrophy on MRI in autopsy confirmed progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), and to determine whether the patterns vary depending on the clinical syndrome. Voxel-based morphometry was used to compare patterns of atrophy in 13 PSP and 11 CBD subjects and 24 controls. PSP and CBD subjects were also subdivided into those with a dominant dementia or extrapyramidal syndrome. PSP subjects showed brainstem atrophy with involvement of the cortex and underlying white matter. Frontoparietal grey and subcortical grey matter atrophy occurred in CBD. When subdivided, PSP subjects with an extrapyramidal syndrome had more brainstem atrophy and less cortical atrophy than CBD subjects with an extrapyramidal syndrome. PSP subjects with a dementia syndrome had more subcortical white matter atrophy than CBD subjects with a dementia syndrome. These results show regional differences between PSP and CBD that are useful in predicting the underlying pathology, and help to shed light on the in vivo distribution of regional atrophy in PSP and CBD.     

White matter alterations in narcolepsy patients with cataplexy: tract‐based spatial statistics

Functional imaging studies and voxel‐based morphometry analysis of brain magnetic resonance imaging showed abnormalities in the hypothalamus–thalamus–orbitofrontal pathway, demonstrating altered hypocretin pathway in narcolepsy. Those distinct morphometric changes account for problems in wake–sleep control, attention and memory. It also raised the necessity to evaluate white matter changes. To investigate brain white matter alterations in drug‐naïve narcolepsy patients with cataplexy and to explore relationships between white matter changes and patient clinical characteristics, drug‐naïve narcolepsy patients with cataplexy (n = 22) and healthy age‐ and gender‐matched controls (n = 26) were studied. Fractional anisotropy and mean diffusivity images were obtained from whole‐brain diffusion tensor imaging, and tract‐based spatial statistics were used to localize white matter abnormalities. Compared with controls, patients showed significant decreases in fractional anisotropy of white matter of the bilateral anterior cingulate, fronto‐orbital area, frontal lobe, anterior limb of the internal capsule and corpus callosum, as well as the left anterior and medial thalamus. Patients and controls showed no differences in mean diffusivity. Among patients, mean diffusivity values of white matter in the bilateral superior frontal gyri, bilateral fronto‐orbital gyri and right superior parietal gyrus were positively correlated with depressive mood. This tract‐based spatial statistics study demonstrated that drug‐naïve patients with narcolepsy had reduced fractional anisotropy of white matter in multiple brain areas and significant relationship between increased mean diffusivity of white matter in frontal/cingulate and depression. It suggests the widespread disruption of white matter integrity and prevalent brain degeneration of frontal lobes according to a depressive symptom in narcolepsy.     

The prevalence of depression in relation to cerebral atrophy and cognitive performance in 70- and 74-year-old women in Gothenburg. The Women's Health Study

BACKGROUND: Hospital-based studies report that depression in the elderly is associated with brain atrophy. This notion could not be confirmed in a population study on 85-year-olds. We aimed to assess depression in relation to brain atrophy and cognition in 70- and 74-year-old women. METHODS; A representative sample of 70- and 74-year-old women (N = 501) was examined with a psychiatric examination including the Mini-Mental State Examination (MMSE), measuring global cognitive function, and computerized tomography (CT) of the brain (N = 268). Depression was diagnosed according to DSM-III-R. Previous depression was diagnosed by history and by information from previous examinations in this 24-year longitudinal study. RESULTS: The prevalence of depression was 11.6%, including 8.4% with major depression (MDD). Among those who were currently mentally healthy, 43.0% had a history of previous depression. Women with current MDD had lower scores on the MMSE than the mentally healthy women. This association was only found in women with a lower level of education. Current depressives, previous depressives and mentally healthy women without a history of depression did not differ on CT with regard to brain atrophy or white matter lesions. The association between MDD and lower cognitive performance was independent of the association of cognitive performance with structural brain changes on CT. CONCLUSIONS: Brain atrophy on CT is not associated with depression in the general population, despite the fact that individuals with depression have a worse cognitive performance. The finding that cognitive performance was not decreased in individuals with previous depression suggests that cognitive dysfunction is a state phenomenon in depression.     

Sex-differences in grey-white matter structure in normal-reading and dyslexic adolescents

MR images were used to look for brain structure irregularities in adolescent children with dyslexia by use of combined grey and white matter volume measurements and fractal dimension (FD) of the grey-white matter border. The data were collected from 13 dyslexic adolescent (8 boys and 5 girls) that were compared with 18 control subjects (8 boys and 10 girls). The MR images were first segmented, and the volume as well as the FD of the grey/white matter border for the whole brain and for each hemisphere was computed. Changes were found in the measured volumes of both grey and white matter and were best reflected in the ratio of grey/white matter and in FD values, especially in the left hemisphere. The results showed that, although dyslexia is less frequent in women, the structural differences in the brain are more pronounced in their case, pointing to an increased vulnerability of the female brain to morphological changes associated with dyslexia.     

Antigenic differentiation of the grey and white matter of the brain in man

Summary Saline extracts of the grey and white matter of the human brain were tested by the complement fixation reaction with various anticerebral sera.Rabbit serum obtained after immunization by white matter of the human brain enabled precise differentiation of the antigen of the white matter from that of the grey matter the absorption by the tissue of the grey matter. The difference in the immunological properties of the grey and white matter of the human brain was also revealed in investigation of the horse sera of horses immunized with a cerebral emulsion of mice. There was a selective reaction of these sera with the antigens of the grey matter (as compared with the antigens of the white matter). Thus, the results which were obtained show the presence of an antigenic difference between the tissues of the grey and white matter of the human brain.Presented by Active Member of the AMN SSSR N. N. Zhukov-Verezhnikov     

Decreased platelet 3H-imipramine binding in primary major depression compared with depression secondary to medical illness in elderly outpatients

Platelet 3H-imipramine binding and monoamine oxidase (MAO) activity were investigated in elderly outpatients with primary major depression, and in a group with depression secondary to medical illness (organic mood disorder, depressed by DSM-III-R criteria) in a multidisciplinary geriatric clinic. The density of the binding of 3H-imipramine (Bmax) was decreased significantly in subjects with major depression compared to subjects with secondary depression, and to controls. There was no difference in Bmax values between subjects with secondary depression and controls. MAO activity was increased in the group with secondary depression, but not in the group with primary major depression. These results provide preliminary evidence for the relative specificity of platelet 3H-imipramine binding as a marker for primary major depressive disorder compared to secondary depression in medically ill elderly people, supports the concept of biological heterogeneity in secondary depression, and extends the findings of decreased Bmax values in two previous studies in non-medically ill depressed elderly patients.     

White matter changes in mild cognitive impairment and AD: A diffusion tensor imaging study

Diffusion tensor imaging (DTI) can detect, in vivo, the directionality of molecular diffusion and estimate the microstructural integrity of white matter (WM) tracts. In this study, we examined WM changes in patients with Alzheimer's disease (AD) and in subjects with amnestic mild cognitive impairment (MCI) who are at greater risk for developing AD. A DTI index of WM integrity, fractional anisotropy (FA), was calculated in 14 patients with probable mild AD, 14 participants with MCI and 21 elderly healthy controls (NC). Voxel-by-voxel comparisons showed significant regional reductions of FA in participants with MCI and AD compared to controls in multiple posterior white matter regions. Moreover, there was substantial overlap of locations of regional decrease in FA in the MCI and AD groups. These data demonstrate that white matter changes occur in MCI, prior to the development of dementia.     

晚发型抑郁症患者脑白质胆碱能通路的磁共振研究

目的探讨晚发型抑郁症患者脑白质胆碱能通路的改变及其与认知功能障碍的关系。方法晚发型抑郁症患者(患者组,n=20)行磁共振检查,采用胆碱能通路高信号评分(CHIPS)评估患者脑白质胆碱能通路的改变、采用蒙特利尔认知评估量表(MoCA)评定认知功能,并与正常老年人(对照组,n=20)进行对照。结果①患者组CHIPS评分显著高于对照组、MoCA评分显著低于对照组,差异均有统计学意义(t=3.119,3.025;P=0.0032,0.0044);②患者组、对照组的CHIPS评分均与MoCA评分负相关(r=-0.490,-0.482;P=0.026,0.038)。结论晚发型抑郁症患者存在脑白质胆碱能通路受损,并与患者的认知功能改变有关。