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BACKGROUND: Spinocerebellar ataxia type 2 (SCA2) exhibits mainly cerebellar and oculomotor dysfunctions but also, frequently, cognitive impairment and neuropsychological symptoms. The mechanism of the progression of SCA2 remains unclear. This study aimed to evaluate longitudinal structural changes in the brains of SCA2 patients based on atrophy rate. METHODS: The OpenNeuro Dataset ds001378 was used. It comprises the demographic data and two magnetic resonance images each of nine SCA2 patients and 16 healthy controls. All structural images were preprocessed using FreeSurfer software, and each region's bilateral volume was summed. Atrophy rates were calculated based on the concept of symmetrised percent change and compared between SCA2 patients and healthy controls using non-parametric statistics. As post hoc analysis, correlation analysis was performed between infratentorial volume ratio and the accumbens area atrophy rates in SCA2 patients. RESULTS: There were no significant differences between groups for age, gender, and the time between scans. Statistical analysis indicated a significantly larger atrophy rate of the accumbens area in SCA2 patients than in controls. Additionally, the infratentorial volume ratio and accumbens area atrophy rates showed moderate negative correlation. CONCLUSIONS: This study found that nucleus accumbens (NAc) atrophy was significantly accelerated in SCA2 patients. Anatomically, the NAc is densely connected with infratentorial brain regions, so it is reasonable to posit that degeneration propagates from the cerebellum and brainstem to the NAc and other supratentorial areas. Functionally, the NAc is essential for appropriate behaviour, so NAc degeneration might contribute to neuropsychological symptoms in SCA2 patients.
Subject(s)
Cognitive Dysfunction , Nucleus Accumbens , Spinocerebellar Ataxias , Humans , Atrophy , Brain , Nucleus Accumbens/pathology , Spinocerebellar Ataxias/pathologyABSTRACT
BACKGROUND: Subcortical atrophy and increased cerebral ß-amyloid and tau deposition are linked to cognitive decline in type 2 diabetes. However, whether and how subcortical atrophy is related to Alzheimer's pathology in diabetes remains unclear. This study therefore aimed to investigate subcortical structural alterations induced by diabetes and the relationship between subcortical alteration, Alzheimer's pathology and cognition. METHODS: Participants were 150 patients with type 2 diabetes and 598 propensity score-matched controls without diabetes from the Alzheimer's Disease Neuroimaging Initiative. All subjects underwent cognitive assessments, magnetic resonance imaging (MRI), and apolipoprotein E (ApoE) genotyping, with a subset that underwent amyloid positron emission tomography (PET) and cerebrospinal fluid (CSF) assays to determine cerebral ß-amyloid deposition (n = 337) and CSF p-tau (n = 433). Subcortical structures were clustered into five modules based on Pearson's correlation coefficients of volumes across all subjects: the ventricular system, the corpus callosum, the limbic system, the diencephalon, and the striatum. Using structural equation modeling (SEM), we investigated the relationships among type 2 diabetes, subcortical structural alterations, and AD pathology. RESULTS: Compared with the controls, the diabetic patients had significant reductions in the diencephalon and limbic system volumes; moreover, patients with longer disease duration (>6 years) had more severe volume deficit in the diencephalon. SEM suggested that type 2 diabetes, age, and the ApoE ε4 allele (ApoE-ε4) can affect cognition via reduced subcortical structure volumes (total effect: age > ApoE-ε4 > type 2 diabetes). Among them, age and ApoE-ε4 strongly contributed to AD pathology, while type 2 diabetes neither directly nor indirectly affected AD biomarkers. CONCLUSION: Our study suggested the subcortical atrophy mediated the association of type 2 diabetes and cognitive decline. Although both type 2 diabetes and AD are correlated with subcortical neurodegeneration, type 2 diabetes have no direct or indirect effect on the cerebral amyloid deposition and CSF p-tau.
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Corticobasal syndrome (CBS) is a rare neurodegenerative condition characterized by four-repeat tau aggregation in the cortical and subcortical brain regions and accompanied by severe atrophy. The aim of this study was to evaluate partial volume effect correction (PVEC) in patients with CBS compared to a control cohort imaged with the 18-kDa translocator protein (TSPO) positron emission tomography (PET) tracer [18F]GE-180. Eighteen patients with CBS and 12 age- and sex-matched healthy controls underwent [18F]GE-180 PET. The cortical and subcortical regions were delineated by deep nuclei parcellation (DNP) of a 3D-T1 MRI. Region-specific subcortical volumes and standardized uptake values and ratios (SUV and SUVr) were extracted before and after region-based voxel-wise PVEC. Regional volumes were compared between patients with CBS and controls. The % group differences and effect sizes (CBS vs. controls) of uncorrected and PVE-corrected SUVr data were compared. Single-region positivity in patients with CBS was assessed by a >2 SD threshold vs. controls and compared between uncorrected and PVE-corrected data. Smaller regional volumes were detected in patients with CBS compared to controls in the right ventral striatum (p = 0.041), the left putamen (p = 0.005), the right putamen (p = 0.038) and the left pallidum (p = 0.015). After applying PVEC, the % group differences were distinctly higher, but the effect sizes of TSPO uptake were only slightly stronger due to the higher variance after PVEC. The single-region positivity of TSPO PET increased in patients with CBS after PVEC (100 vs. 83 regions). PVEC in the cortical and subcortical regions is valuable for TSPO imaging of patients with CBS, leading to the improved detection of elevated [18F]GE-180 uptake, although the effect sizes in the comparison against the controls did not improve strongly.
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INTRODUCTION: Genetically defined spinocerebellar ataxia (SCA) type 1 and 2 patients have differential clinical profile along with probable distinctive cortical and subcortical neurodegeneration. We compared the degree of brain atrophy in the two subtypes with their phenotypic and genotypic parameters. METHODS: MRI was performed using a 3T scanner (Philips, Achieva) to obtain 3D T1-weighted scans of the whole brain and analyzed by FreeSurfer (version 5.3 and 6 dev.) software. Genetically proven SCA1 (n = 18) and SCA2 (n = 25) patients with age-matched healthy controls (n = 8) were recruited. Clinical severity was assessed by the International Cooperative Ataxia Rating Scale (ICARS). To know the differential pattern of atrophy, the groups were compared using ANOVA/Kruskal-Wallis test and followed by correlation analysis with multiple corrections. Further, machine learning-based classification of SCA subtypes was carried out. RESULT: We found (i) bilateral frontal, parietal, temporal, and occipital atrophy in SCA1 and SCA2 patients; (ii) reduced volume of cerebellum, regions of brain stem, basal ganglia along with the certain subcortical areas such as hippocampus, amygdala, thalamus, diencephalon, and corpus callosum in SCA1 and SCA2 subtypes; (iii) higher subcortical atrophy SCA2 than SCA1 (iv) correlation between brain atrophy and disease attributes; (v) differential predictive pattern of two SCA subtypes using machine learning approach. CONCLUSION: The present study suggests that SCA1 and SCA2 do not differ in cortical thinning while a characteristic pattern of subcortical atrophy SCA2 > SCA1 is observed along with correlation of brain atrophy and disease attributes. This may provide the diagnostic guidance of MRI to SCA subtypes and differential therapies.
Subject(s)
Spinocerebellar Ataxias , Atrophy/pathology , Brain/diagnostic imaging , Cerebellum/pathology , Humans , Magnetic Resonance Imaging , Spinocerebellar Ataxias/diagnostic imagingABSTRACT
BACKGROUND: Appropriate patient selection is critical for successful deep brain stimulation (DBS) for Parkinson disease (PD). Subcortical atrophy is a possible determinant of postoperative DBS outcomes in patients with idiopathic PD, but it has not been well evaluated for DBS of the globus pallidus interna (GPi). We investigated perioperative subcortical atrophy measures in patients with PD and their relationship to postoperative motor response in bilateral GPi-targeted DBS. METHODS: A retrospective cohort study examined correlations among indices of subcortical volumetry, disease duration, and age with postoperative outcomes at 6 months (Unified Parkinson's Disease Rating Scale Part III motor score quotient, levodopa equivalent daily dosing, and 39-item Parkinson's Disease Questionnaire mobility subscore). Subcortical volumetry was assessed by bicaudate ratio, Evans index, and third ventricular width on perioperative imaging. Linear regression models established correlations between preoperative variables and postoperative outcomes. RESULTS: Data from 34 patients with PD who were treated with GPi-targeted DBS were evaluated. Age was found to exhibit statistically significant positive correlations with all 3 measures of subcortical atrophy (P ≤ 0.002). None of the measures correlated with disease duration. Only Evans index and third ventricular width correlated with preoperative medication response (P < 0.05). Age and all 3 measures of atrophy exhibited statistically significant correlations with Unified Parkinson's Disease Rating Scale Part III motor score quotient (P ≤ 0.01), but not with levodopa equivalent daily dosing or 39-item Parkinson's Disease Questionnaire motor subscores (P > 0.05). CONCLUSIONS: Perioperative age and subcortical atrophy as measured in this study correlated with motor responsiveness at 6 months postoperatively among patients receiving bilateral GPi-targeted DBS stimulation for PD.
Subject(s)
Brain/diagnostic imaging , Caudate Nucleus/diagnostic imaging , Deep Brain Stimulation/methods , Globus Pallidus , Parkinson Disease/therapy , Aged , Atrophy , Brain/pathology , Caudate Nucleus/pathology , Cohort Studies , Female , Humans , Linear Models , Male , Middle Aged , Organ Size , Parkinson Disease/diagnostic imaging , Parkinson Disease/physiopathology , Prognosis , Retrospective Studies , Treatment OutcomeABSTRACT
OBJECTIVES: Cognitive impairment is common in multiple sclerosis, but the brain MRI correlates in relapsing remitting multiple sclerosis remain controversial. The current study aimed to investigate whether cognitive decline can be predicted by global and/or regional brain atrophy. METHODS: Sixty-three patients with relapsing remitting multiple sclerosis (36 men, mean age 39.9 ± 9.4 years old, mean EDSS 1.4 ± 1.2, mean disease duration 4.9 ± 4.3 years) and 46 healthy controls (21 men, mean age 37.5 ± 10.8 years old) were included. Demographic data were obtained, and a longitudinal neuropsychological and global and regional MRI brain volume assessment was performed. RESULTS: The patients performed worse than controls in most neuropsychological tests at baseline. The percentage of patients with clinically meaningful cognitive decline ranged from only 0% to 7.9%. Statistically significant volume reduction was found for all MRI measures except for the left accumbens nucleus. Whole or regional brain atrophy ranged from -0.02% to -0.25%, with subcortical structures showing the largest atrophy rates. A total of 22.2% to 93.7% patients showed atrophy across the brain structures assessed volumetrically. DISCUSSION: It was regional rather than whole-brain changes that significantly predicted cognitive decline for the patients in the tasks that tested processing speed, visuo-spatial and inhibition skills. The overall data suggest that the progression of cognitive impairment in relapsing remitting multiple sclerosis as captured by conventional neuropsychological testing is the tip of the iceberg of neurodegenerative sequelae in the disease. Also, regional volumetric changes are better than whole-brain atrophy at predicting cognitive dysfunction.
Subject(s)
Cognitive Dysfunction/etiology , Cognitive Dysfunction/pathology , Multiple Sclerosis, Relapsing-Remitting/complications , Multiple Sclerosis, Relapsing-Remitting/pathology , Adult , Atrophy/etiology , Atrophy/pathology , Brain/pathology , Female , Humans , Magnetic Resonance Imaging , Male , Middle AgedABSTRACT
BACKGROUND: Cognitive impairment and cardiovascular dysautonomia are two major non-motor features of Parkinson's disease (PD). They have been investigated separately and extensively, but their interactive outcomes have rarely been studied. OBJECTIVE: The purpose of this study was to examine the association between central atrophy and cognition and to assess the influence of cardiovascular lability on this association in PD patients. METHODS: Out of 151 early PD patients, 47 subjects were ultimately enrolled according to our selection criteria. Their cognitive status was examined by comprehensive neuropsychological tests assessing five domains of cognition. Supine and orthostatic blood pressures were recorded during head-up tilt tests, and orthostatic mean arterial pressure change was calculated. Every patient underwent brain magnetic resonance imaging, and intercaudate nucleus ratio was obtained as a central atrophy surrogate marker. The associations and interactions between central atrophy, cognition, and blood pressure variability were analyzed. RESULTS: Among 47 subjects, 20 (42.6%) had orthostatic hypotension. Attention/working memory, executive function, and delayed recall were inversely associated with central atrophy (râ=â-0.332, pâ=â0.028; râ=â-0.314, pâ=â0.038; râ=â-0.399, pâ=â0.024; respectively). In a multiple regression model, only attention/working memory was independently associated with central atrophy when modulated by orthostatic mean arterial pressure change (pâ<â0.05). CONCLUSION: This study revealed that cardiovascular dysautonomia interacted with the inverse association between cerebral atrophy and cognition, and it reinforced its relationship. Interaction between these two non-motor features should be kept in mind in clinical practice, particularly in PD patients with co-morbid vascular factors.
Subject(s)
Blood Pressure/physiology , Caudate Nucleus/pathology , Cognitive Dysfunction , Hypotension, Orthostatic , Parkinson Disease , Primary Dysautonomias , Aged , Atrophy/pathology , Caudate Nucleus/diagnostic imaging , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/etiology , Cognitive Dysfunction/pathology , Cognitive Dysfunction/physiopathology , Female , Humans , Hypotension, Orthostatic/etiology , Hypotension, Orthostatic/physiopathology , Magnetic Resonance Imaging , Male , Middle Aged , Neuropsychological Tests , Parkinson Disease/complications , Parkinson Disease/diagnostic imaging , Parkinson Disease/pathology , Parkinson Disease/physiopathology , Primary Dysautonomias/etiology , Primary Dysautonomias/physiopathology , Tilt-Table TestABSTRACT
BACKGROUND AND PURPOSE: Subcortical structures are affected by neurodegeneration in Alzheimer's disease (AD) and Lewy body disease (LBD). Although the co-occurrence of AD and LBD pathologies and their possible interaction have been reported, the effect of AD and LBD on subcortical structures remains unknown. The effects of AD and LBD on subcortical atrophy and their relationship with cognitive dysfunction were investigated. METHODS: The cross-sectional study recruited 42 patients with pure AD related cognitive impairment (ADCI), 30 patients with pure LBD related cognitive impairment (LBCI), 58 patients with mixed ADCI and LBCI, and 29 normal subjects. A general linear model was used to compare subcortical volume and shape amongst the groups, to investigate the independent and interaction effects of ADCI and LBCI on subcortical shape and volume, and to analyze the relationship between subcortical volume and cognitive dysfunction in each group. RESULTS: Alzheimer's disease related cognitive impairment and LBCI were independently associated with subcortical atrophies in the hippocampus and amygdala and in the hippocampus and putamen respectively, but their interaction effect was not significant. Compared to the control group, the pure LBCI group exhibited additional local atrophies in the amygdala, caudate and thalamus. Subcortical atrophies correlated differently with cognitive dysfunction according to the underlying causes of cognitive dysfunction. CONCLUSIONS: The patterns of subcortical atrophies and their correlation with cognitive dysfunction differ according to the underlying AD, LBD or concomitant AD and LBD.
Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Lewy Body Disease , Alzheimer Disease/complications , Atrophy , Cognitive Dysfunction/etiology , Cross-Sectional Studies , Humans , Lewy Body Disease/complicationsABSTRACT
X-linked adrenoleukodystrophy (X-ALD) is a rare inherited metabolic disease affecting the nervous system and the adrenal glands. It is caused by a mutation of the ABCD1 gene, resulting in the impaired degradation of very long-chain fatty acids and their subsequent accumulation in several organs and tissues. X-ALD is notable for its high phenotypical variability, that includes isolated adrenocortical insufficiency, slowly progressive myelopathy with paraparesis, ataxia, and peripheral neuropathy to severe childhood cerebral forms. Here, we describe the case of an X-ALD patient with a p.Gly343Val mutation in ABCD1 gene, who presented in adulthood with a spinal syndrome of mild severity, and later developed a progressive cognitive and behavioral syndrome. Our patient showed a striking correlation between clinical phenotype and neuroimaging, including a brain fluoro-2-deoxy-d-glucose positron emission tomography that displayed an atypical cerebral glucose metabolism.
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Cognitive impairment in Parkinson's disease (PD) results in significant morbidity and mortality being early diagnosis essential. Identification of patients who are at higher risk of developing cognitive impairment based only on clinical data is not sufficient. To this end, magnetic resonance imaging (MRI) with automatic segmentation, such as FreeSurfer, could be a useful tool with high accuracy because it has histological validation. OBJECTIVES: The objective of this study was to evaluate clinical, neuropsychological and FreeSurfer variables that may be related to worse cognitive outcomes over 18 months in PD patients compared with controls. METHODS: PD patients were recruited according to established inclusion and exclusion criteria as well individuals without any neurological or psychiatric diagnosis and were submitted to the same protocol: neurological, neuropsychological and neuroimaging evaluations. After 18 months, the study subjects were reassessed by neurological and neuropsychological evaluations. RESULTS: Of 171 individuals selected for first evaluation, 96 concluded the study during 18-month follow-up. The PD group presented worse performance in the neuropsychological assessment during both the initial and final evaluations. The results obtained by FreeSurfer revealed a significant reduction (unilateral or bilateral) in the volume of thalamus, caudate nucleus, putamen, hippocampus, amygdala, accumbens, corpus callosum and cerebral gray matter in the PD group. A worse cognitive outcome was more prevalent in the PD group. CONCLUSIONS: Worse cognitive performance documented by neuropsychological assessment in the PD group was correlated with reduced volume of several structures by FreeSurfer analysis and may be a biomarker of cognitive decline.
Subject(s)
Brain Mapping , Brain/pathology , Cognition Disorders/etiology , Cognition Disorders/pathology , Parkinson Disease/complications , Brain/diagnostic imaging , Cognition Disorders/diagnostic imaging , Female , Follow-Up Studies , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Middle Aged , Neuropsychological TestsABSTRACT
BACKGROUND: Plasma homocysteine levels are increasingly studied as a potential risk factor for dementia. Elevated homocysteine levels have been linked with gray and white matter volume reduction among individuals with mild cognitive impairment and Alzheimer's disease. However, the effects of homocysteine on brain changes in preclinical stages of dementia remain unexplored. OBJECTIVE: To examine the association of elevated homocysteine levels with markers of neurodegeneration, i.e., white and gray matter volume in an elderly population. METHODS: The study included 768 participants (mean age: 69.6±6.5 years, 51.3% women) from the Epidemiology of Dementia In Singapore study. Participants underwent a brain MRI scan and blood tests. Serum homocysteine was measured using competitive immunoassay. Cortical thickness and subcortical structural volume were quantified using FreeSurfer whereas white matter volume was quantified using a previous validated method. RESULTS: Higher homocysteine levels were significantly associated with decreased global white matter volume [mean difference (ß) in volume (ml) per micromole per liter (µmol/l) increase in homocysteine levels: - 0.555, 95% Confidence Interval (CI): - 0.873; - 0.237], decreased parietal cortical thickness [ß in thickness (µm) per µmol/l increase in homocysteine levels:- 1.429, 95% CI: - 2.781; - 0.077], and smaller volumes of the thalamus [ß: - 0.017, 95% CI: - 0.026; - 0.008], brainstem [ß: - 0.037, 95% CI: - 0.058; - 0.016], and accumbens [ß: - 0.004, 95% CI: - 0.006; - 0.002]. CONCLUSION: Higher homocysteine levels were associated with cerebral atrophy. Further studies are required to assess whether lowering plasma homocysteine levels may prevent neurodegenerative changes or delay progression of clinical symptoms before the development of dementia.
Subject(s)
Dementia/blood , Dementia/pathology , Homocysteine/blood , White Matter/pathology , Aged , Atrophy , Biomarkers/blood , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Organ Size , Risk Factors , SingaporeABSTRACT
BACKGROUND: Neuropsychiatric symptoms impact the patients' quality of life and caregivers' burdens in Parkinson's disease (PD). We aimed to investigate the effects of striatal dopaminergic depletion and brain atrophy on the neuropsychiatric symptoms of patients with PD. METHODS: Two hundred and seven patients with de novo drug-naïve PD underwent dopamine transporter (DAT) positron emission tomography and brain MRI scanning. In addition, the patients were assessed with caregiver-administered neuropsychiatric inventory (NPI) questionnaires. To evaluate the effects of DAT uptake, subcortical volume and cortical thinning on the patients' neuropsychiatric symptoms, we performed logistic regression and negative binomial regression analyses on the NPI data after controlling for possible confounders. RESULTS: Frontal cortical thinning was associated with the presence of nighttime behaviour and irritability, and the thinning correlated with the severity of the nighttime behaviour. Temporal cortical thinning was associated with the presence of aggression/agitation, and it correlated with the severity of the aggression/agitation. Subcortical atrophy in the accumbens was associated with the presence of disinhibition and correlated with the severity of the disinhibition. Putamen atrophy and insular thinning were independently associated with the presence of apathy, but only insular thinning correlated with the severity of the apathy. Of the predictors, only frontal cortical thinning correlated with the total NPI score. CONCLUSIONS: The results of this study suggested that accumbens atrophy and frontotemporal cortical thinning, especially frontal cortical thinning, independently contributed to neuropsychiatric symptoms in patients with PD, while DAT uptake did not affect the neuropsychiatric symptoms.
Subject(s)
Aggression/psychology , Apathy , Brain/diagnostic imaging , Depression/psychology , Inhibition, Psychological , Irritable Mood , Parkinson Disease/psychology , Aged , Anxiety/psychology , Appetite , Atrophy , Brain/metabolism , Brain/pathology , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/metabolism , Cerebral Cortex/pathology , Dopamine Plasma Membrane Transport Proteins/metabolism , Female , Fluorine Radioisotopes , Humans , Logistic Models , Magnetic Resonance Imaging , Male , Middle Aged , Nucleus Accumbens/diagnostic imaging , Nucleus Accumbens/metabolism , Nucleus Accumbens/pathology , Organ Size , Parkinson Disease/diagnostic imaging , Parkinson Disease/metabolism , Parkinson Disease/pathology , Positron-Emission Tomography , TropanesABSTRACT
Objective To investigate the predictive role of cerebral white matter lesions (WML) and subcortical atrophy on cognitive function in patients with acute ischemic stroke (AIS) after 3 months.Methods 233 cases of AIS patients admitted to hospital continuously from September 2016 to March 2018 were enrolled and all of them underwent brain MRI.The degree of WML on FLAIR was evaluated according to the Fazekas grading standard.The linear measurement of subcortical atrophy on T1WI was carried out on the subcortical brain atrophy index,including EVANS ratio (ER),inverse cella media index (iCMI),caudate head index (CHI) and basal cistern index (BCI).Demographic,clinical and imaging data of all patients were also recorded.Mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA) were conducted at 3 months after AIS.The patients were divided into normal cognitive function (NCI) group and post stroke cognitive impairment (PSCI) group according to evaluation results of MMSE and MoCA.Multivariate logistic regression analysis was used to screen the independent risk factors of cognitive impairment.Results Univariate analysis showed that age (t=-4.233,P=0.000),sex (x2 =7.501,P=0.006),education (H=21.188,P=0.000),NHISS score (H =5.791,P=0.016),history of atrial fibrillation (x2 =6.484,P=0.011),TIA (x2 =9.015,P=0.003),smoking history (x2 =6.943,P=0.008),Fazekas WML score (x2 =27.885,P=0.000),EVANS ratio (H =31.129,P =0.000),inverse cella media index (H =9.434,P =0.002),caudate head index (H=15.148,P=0.000),basal cistern index (t=-1.979,P=0.049) and baseline cognitive function (x2=136.994,P=0.000) were related to cognitive impairment in patients with AIS after 3 months (P<0.05).Multivariate logistic regression analysis showed that WML score (OR=3.416,P=0.047,95%CI:1.017-11.482),EVANS ratio (OR=1.245,P=0.038,95%CI:1.012-1.531) and caudate head index (OR =1.187,P=0.040,95 % CI:1.008-1.397) were risk factors for cognitive impairment in AIS patients after 3 monfths adjusting for age,education,disease severity and baseline cognitive function.Conclusion WML,EVANS ratio and caudate head index can predict short-term cognitive function in patients with AIS.
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BACKGROUND AND PURPOSE: Mild cognitive impairment (MCI) is associated with pronounced grey matter atrophy in various brain regions. However, the association between atrophy patterns and progression from no cognitive impairment (NCI) to Parkinson's disease (PD)-MCI is not clearly known. We investigated the pattern and progression of atrophy in subcortical structures and its impact on cognition in patients with mild PD. METHODS: Sixty-five patients with mild PD with baseline and longitudinal clinical and neuropsychological assessments, and structural magnetic resonance imaging scans were studied. Movement Disorder Society Task Force criteria were used to classify patients with PD into PD-NCI (n = 54) and PD-MCI (n = 11). Based on progression over time, those who remained without cognitive impairment were classified as PD-stable (n = 42) and those who converted to MCI over 18 months were classified as PD-converters (n = 12). FreeSurfer was used to measure cortical thickness and subcortical volumes at baseline and follow-up. RESULTS: Parkinson's disease-MCI showed baseline thalamus atrophy and progressive atrophy in the thalamus, caudate, presubiculum, cornu ammonis 1 and 2-3, and significant memory and executive dysfunction compared with PD-NCI. PD-converters had greater accumbens atrophy at baseline and progressive atrophy in the thalamus, caudate and accumbens with dysfunctions in memory and executive domains. CONCLUSIONS: Progression of cognitive impairment in non-demented PD is associated with a specific pattern of subcortical atrophy. Findings from this study will allow future studies to investigate in the role of subcortical structures as a biomarker for PD dementia.
Subject(s)
Cerebral Cortex/pathology , Cognition Disorders/pathology , Cognition Disorders/psychology , Parkinson Disease/pathology , Parkinson Disease/psychology , Aged , Atrophy , Cognition Disorders/etiology , Cognitive Dysfunction/etiology , Cognitive Dysfunction/psychology , Disease Progression , Executive Function , Female , Humans , Longitudinal Studies , Magnetic Resonance Imaging , Male , Memory , Middle Aged , Neuropsychological Tests , Parkinson Disease/complicationsABSTRACT
INTRODUCTION: About 20% to 26% of patients with multiple sclerosis (MS) show alterations in visuospatial/visuoconstructive (VS-VC) skills even though temporo-parieto-occipital impairment is a frequent finding in magnetic resonance imaging. No studies have specifically analysed the relationship between these functions and lesion volume (LV) in these specific brain areas. OBJECTIVE: To evaluate the relationship between VS-VC impairment and magnetic resonance imaging temporo-parieto-occipital LV with subcortical atrophy in patients with MS. METHODOLOGY: Of 100 MS patients undergoing a routine neuropsychological evaluation, 21 were selected because they displayed VS-VC impairments in the following tests: Incomplete picture, Block design (WAIS-III), and Rey-Osterrieth complex figure test. We also selected 13 MS patients without cognitive impairment (control group). Regional LV was measured in FLAIR and T1-weighted images using a semiautomated method; subcortical atrophy was measured by bicaudate ratio and third ventricle width. Partial correlations (controlling for age and years of school) and linear regression analysis were employed to analyse correlations between magnetic resonance imaging parameters and cognitive performance. RESULTS: All measures of LV and brain atrophy were significantly higher in patients with cognitive impairment. Regional LV, bicaudate ratio, and third ventricle width are significantly and inversely correlated with cognitive performance; the strongest correlation was between third ventricle width and VC performance (Block design: P=.001; Rey-Osterrieth complex figure: P<.000). In the multivariate analysis, third ventricle width only had a significant effect on performance of VC tasks (Block design: P=.000; Rey-Osterrieth complex figure: P=.000), and regional FLAIR VL was linked to the VS task (Incomplete picture; P=.002). CONCLUSIONS: Measures of subcortical atrophy explain the variations in performance on visuocostructive tasks, and regional FLAIR VL measures are linked to VS tasks.
Subject(s)
Motor Skills , Multiple Sclerosis/pathology , Multiple Sclerosis/psychology , Space Perception , Adult , Atrophy , Brain/diagnostic imaging , Brain/pathology , Cognition Disorders/etiology , Cognition Disorders/psychology , Cost of Illness , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Multiple Sclerosis/diagnostic imaging , Neurologic Examination , Neuropsychological Tests , Psychomotor PerformanceABSTRACT
BACKGROUND: Cortical atrophy is a key neuroimaging feature of dementia. However, the role of subcortical gray matter reduction in cognitive impairment has not been explored extensively. OBJECTIVES: We examined the risk factors of subcortical structures on neuroimaging and their association with cognitive impairment and dementia. METHODS: Data from two studies were used: a subsample from the Epidemiology of Dementia in Singapore (EDIS) study of non-demented community-dwelling subjects (nâ=â550) and a case-control study. Subjects underwent similar neuropsychological tests and brain MRI. Subcortical volumes of accumbens, amygdala, caudate, pallidum, putamen, thalamus, hippocampus, and brainstem were measured. Cognitive impairment no dementia (CIND), dementia and its subtypes, vascular cognitive impairment (VCI), were defined using accepted criteria. Cognitive function was also expressed as both composite and domain-specific Z-scores. RESULTS: In the EDIS study, age, female gender, Malay ethnicity, diabetes, lacunar-infarcts, and white matter lesions were the most important risk factors for subcortical atrophy. Moreover, smaller volumes of accumbens, amygdala, caudate, thalamus, and brainstem were significantly associated with lower cognitive composite Z-scores. With respect to clinical outcomes in the case-control study, structures such as the accumbens, caudate, putamen, and hippocampus were associated with both CIND and dementia. Smaller caudate and pallidum volumes were related to VCI whereas amygdalar atrophy was only associated with non-VCI. Furthermore, subcortical atrophy was related to both VCI and non-VCI. CONCLUSION: Subcortical gray matter atrophy is not only observed in dementia, but also in the preclinical stages of cognitive impairment. Furthermore, besides VCI, subcortical structures were also related to non-VCI.
Subject(s)
Brain/pathology , Cognition Disorders/pathology , Dementia/pathology , Gray Matter/pathology , Aged , Atrophy , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/pathology , Cardiovascular Diseases/psychology , Case-Control Studies , Cognition , Cognition Disorders/epidemiology , Cognition Disorders/psychology , Dementia/epidemiology , Dementia/psychology , Female , Humans , Magnetic Resonance Imaging , Male , Neuropsychological Tests , Organ Size , Prodromal Symptoms , Risk Factors , Singapore/epidemiologyABSTRACT
OBJECTIVES: To investigate the severity of subcortical atrophy in frontotemporal dementia (FTD) without extrapyramidal symptoms (EPS) and dementia with EPS. In addition, we aim to verify if there is correlation between demographic and clinical characteristics and subcortical atrophy in the groups. Methodology : The sample was composed of 21 patients with dementia and EPS as well as 19 patients with FTD without EPS. A linear assessment was conducted in order to identify the degree of subcortical atrophy (i.e., bifrontal index - BFI) using MRI. Moreover, the Mini-Mental State Examination (MMSE), Pfeffer Functional Activities Questionnaire (FAQ) and the Clinical Dementia Rating (CDR) were used to investigate clinical aspects. Results : It was verified that patients with dementia and EPS was older than the patients with FTD (p=0.01). The severity of cognitive deficits was associated with BFI, as well as the dementia severity in the EPS group. Conclusion : FTD group presented mean BFI scores above the cutoff for normal elderly population, indicating the presence of subcortical atrophy in this group. Mean BFI was higher (although not statistically significant) in FTD group than in dementia with EPS, which can suggest at least that subcortical pathology in FTD may be as important as in the dementia with EPS group. Subcortical atrophy is a good biological marker for cognitive deterioration in FTD and in dementia with EPS.
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BACKGROUND AND PURPOSE: Triphasic waves (TWs) are archetypal waveforms seen on electroencephalography (EEG) in some forms of encephalopathy. Their particular underlying pathological substrates are largely unexplored. This case-control study was designed to identify and quantify specific clinical and neuroradiological associations underlying TWs and to determine if TWs predicate outcome. METHODS: From 2004 to 2012, adult encephalopathic patients with TWs (cases) were matched 1:1 with encephalopathic patients without TWs (controls) by Glasgow Coma Scale (GCS) and the frequency range of EEG background activity. Clinical characteristics, neuroimaging and outcomes were assessed. RESULTS: The mean age of 190 patients (95 with and 95 without TWs) was 66.6 years (±15.6). In multivariable analyses, patients with TWs had significantly higher odds for liver insufficiency [odds ratio (OR) = 8.10, 95% confidence interval (CI) 1.98-33.08], alcohol abuse (OR = 3.65, 95% CI 1.25-10.63), subcortical brain atrophy (OR = 2.82, 95% CI 1.39-5.71) and respiratory tract infections (OR = 1.28, 95% CI 1.01-4.71). With each additional independent predictor, the odds increased for the occurrence of TWs (1 predictor, OR = 2.40, 95% CI 1.16-5.13; ≥2 predictors, OR = 9.20, 95% CI 3.27-25.62). Mortality was 15% and tended to be higher in patients with TWs (19% with vs. 11% without TWs). CONCLUSIONS: Alcohol abuse, liver insufficiency, infections and subcortical brain atrophy were independently associated with TWs in patients matched for clinical and EEG features of encephalopathy. These associations strengthen the hypothesis that TWs evolve from an interplay of pathological neurostructural, metabolic and toxic conditions. When matched for EEG background activity and GCS, TWs were not associated with death.
Subject(s)
Brain Diseases/physiopathology , Brain Waves/physiology , Brain/physiopathology , Electroencephalography , Acute Disease , Adult , Aged , Aged, 80 and over , Brain Diseases/diagnosis , Brain Diseases/mortality , Case-Control Studies , Female , Glasgow Coma Scale , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Retrospective Studies , Tomography Scanners, X-Ray ComputedABSTRACT
OBJECTIVES: The objective of this paper is to investigate conventional and nonconventional brain magnetic resonance imaging (MRI) findings in systemic lupus erythematosus (SLE) patients with diffuse neuropsychiatric involvement (dNPSLE) compared to healthy controls (HCs). METHODS: Twenty-six (26) SLE patients with one or more diffuse NP syndromes related to the central nervous system (CNS) (dNPSLE) and 36 age- and sex-matched HCs were scanned on a 3T MRI using a multimodal imaging approach. Univariate and multivariate analyses were used to determine MRI-specific measure differences between dNPSLE and HCs for lesion burden, tissue-specific atrophy, magnetization transfer ratio (MTR) and diffusion-tensor imaging (DTI) outcomes. RESULTS: In univariate analyses, dNPSLE patients showed significantly increased T1 lesion number (p = .001) and T1-lesion volume (LV, p = .008) compared to HCs. dNPSLE patients showed decreased whole brain volume (p < .0001), gray matter volume (p < .0001), cortical volume (p < .0001) and increased lateral ventricle volume (p = .004) compared to HCs. dNPSLE patients had increased axial diffusivity (AD) of NAWM (p = .008) and NA brain tissue (p = .017) compared to HCs. In the multivariate regression analysis, decreased cortical volume was associated with SLE (R (2) = 0.59, p < .0001). CONCLUSIONS: This study shows that cortical and central atrophy are associated with SLE patients with diffuse CNS syndromes. Microscopic tissue injury in the NAWM on AD DTI measures in SLE patients indicates a predominant reduction of axonal density.
Subject(s)
Brain/pathology , Lupus Vasculitis, Central Nervous System/pathology , Magnetic Resonance Imaging , Adult , Axons/metabolism , Case-Control Studies , Diffusion Tensor Imaging , Female , Humans , Lupus Vasculitis, Central Nervous System/diagnosis , Male , Middle Aged , Multivariate Analysis , Regression AnalysisABSTRACT
Cerebral subcortical atrophy occurs in both Alzheimer's disease (AD) and frontotemporal dementia (FTD) but its significance for clinical manifestations and differential diagnosis between these common types of dementia has not been extensively investigated. OBJECTIVES: To compare the severity of cerebral subcortical atrophy in FTD and AD and to analyze the correlations between cerebral subcortical atrophy and demographics and clinical characteristics. METHODS: Twenty three patients with FTD and 21 with AD formed the sample, which comprised 22 men and 22 women, aged 33 to 89, with mean age (±SD) of 68.52±12.08 years, with schooling ranging from 1 to 20 years, with a mean (±SD) of 7.35±5.54 years, and disease duration with a mean (±SD) of 3.66±3.44 years. The degree of cerebral subcortical atrophy was measured indirectly with a linear measurement of subcortical atrophy, the Bifrontal Index (BFI), using magnetic resonance imaging. We evaluated cognition, activities of daily living and dementia severity with the Mini-Mental State Examination, Functional Activities Questionnaire and the Clinical Dementia Rating, respectively. RESULTS: There was no significant difference (p>0.05) in BFI between FTD and AD. The severity of cognitive deficits (for both FTD and AD groups) and level of daily living activities (only for AD group) were correlated with BFI. CONCLUSIONS: A linear measurement of cerebral subcortical atrophy did not differentiate AD from FTD in this sample. Cognitive function (in both FTD and AD groups) and capacity for independent living (only in AD group) were inversely correlated with cerebral subcortical atrophy.
Atrofia subcortical cerebral ocorre na doença de Alzheimer e na demência frontotemporal (DFT) mas sua importância para as manifestações clínicas e para o diagnóstico diferencial não foram amplamente investigadas. OBJETIVOS: Comparar a gravidade da atrofia subcortical cerebral na DA e na DFT e analisar as correlações entre atrofia subcortical cerebral e características demográficas e clínicas. MÉTODOS: Vinte e três pacientes com diagnóstico de DFT e 21 com DA formaram a amostra que foi constituída por 22 homens e 22 mulheres, com idades entre 33 e 89 anos, idade média (±DP) de 68,52 (±12,08) anos, escolaridade variando de 1 a 20 anos, média de 7,35 (±5,54) e duração da doença com média de 3,66 (±3,44). O grau de atrofia subcortical foi avaliado indiretamente com uma medida linear de atrofia subcortical, o índice bifrontal (IBF) com o emprego de imagem por ressonância magnetica. A cognição, atividades de vida diária e gravidade da demência foram avaliadas com o Mini-Exame do Estado Mental, Questionário de Atividades Funcionais e Escore Clínico de Demência, respectivamente. RESULTADOS: O IBF não foi diferente entre os grupos com AD e DFT (p>0.05). A gravidade do transtorno cognitivo (tanto para DA como DFT) e as atividades de vida diária (apenas para DA) correlacionaram-se com o IBF. CONCLUSÕES: Uma medida linear de atrofia subcortical não foi diferente entre pacientes com DA e DFT nesta amostra. A cognição (na DA e na DFT) e a capacidade de vida independente (apenas na DA) correlacionaram-se inversamente com a atrofia subcortical cerebral.