RESUMEN
BACKGROUND: Cases with the limbic-predominant age-related TAR DNA-binding protein 43 (TDP-43) encephalopathy neuropathologic change (LATE-NC), Alzheimer's disease (AD), and mixed AD+TDP-43 pathology (AD+LATE-NC) share similar symptoms, which makes it a challenge for accurate diagnosis. Exploring the patterns of gray matter structural covariance networks (SCNs) in these three types may help to clarify the underlying mechanism and provide a basis for clinical interventions. METHODS: We included ante-mortem MRI data of 10 LATE-NC, 39 AD, and 25 AD+LATE-NC from the ADNI autopsy sample. We used four regions of interest (left posterior cingulate cortex, right entorhinal cortex, frontoinsular and dorsolateral prefrontal cortex) to anchor the default mode network (DMN), salience network (SN), and executive control network (ECN). Finally, we assessed the SCN alternations using a multi-regression model-based linear-interaction analysis. RESULTS: Cases with autopsy-confirmed LATE-NC and AD showed increased structural associations involving DMN, ECN, and SN. Cases with AD+LATE-NC showed increased structural association within DMN while decreased structural association between DMN and ECN. The volume of peak clusters showed significant associations with cognition and AD pathology. CONCLUSIONS: This study showed different SCN patterns in the cases with LATE-NC, AD, and AD+LATE-NC, and indicated the network disconnection mechanism underlying these three neuropathological progressions. Further, SCN may serve as an effective biomarker to distinguish between different types of dementia.
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Enfermedad de Alzheimer , Sustancia Gris , Humanos , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/patología , Imagen por Resonancia Magnética , Autopsia , Proteínas de Unión al ADNRESUMEN
During the progression of Alzheimer's disease (AD), neuropathology may propagate transneuronally, cause disruption in memory circuit, and lead to memory impairment. However, there is a lack of in vivo evidence regarding this process. Thus, we aim to simulate and observe the progression of neuropathology in AD continuum. We included cognitively normal (CN), mild cognitive impairments (MCI), and AD subjects, and further classified them using the A/T/N scheme (Group 0: CN, A - T-; Group 1: CN, A + T-; Group 2: CN, A + T+; Group 3: MCI, A + T+; Group 4: AD, A + T+). We investigated alterations of three core memory circuit structures: hippocampus (HP) subfields volume, cingulum-angular bundles (CAB) fiber integrity, and precuneus cortex volume. HP subfields volume showed the trend of initially increased and then decreased (starting from Group 2), while precuneus volume decreased in Groups 3 and 4. The CAB integrity degenerated in Groups 3 and 4 and aggravated with higher disease stages. Further, memory circuit impairments were correlated with neuropathology biomarkers and memory performance. Conclusively, our results demonstrated a pattern of memory circuit impairments along with AD progression: starting from the HP, then propagating to the downstream projection fiber tract and cortex. These findings support the tau propagation theory to some extent.
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Enfermedad de Alzheimer/patología , Encéfalo/patología , Trastornos de la Memoria/patología , Vías Nerviosas/patología , Neuroimagen/métodos , Anciano , Enfermedad de Alzheimer/complicaciones , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Trastornos de la Memoria/etiología , Persona de Mediana EdadRESUMEN
Stroke recovery with changes in volume and perfusion of grey matter (GM) tissues remains largely unknown. We hypothesized that GM atrophy co-existed with GM plasticity presenting with increased volume and perfusion in specific regions in the period of post-stroke recovery. Twelve well-recovered stroke patients with pure subcortical lesions in the middle cerebral artery-perfused zone were included. All of them underwent structural and perfusion magnetic resonance imaging (MRI) examinations at admission and a mean of 6 months after stroke onset. Differences in GM volume (GMV) on structural images and cerebral blood flow (CBF) derived from perfusion images between two examinations were compared using voxel-based morphometry. The associations between changes in GMV and CBF with clinical scores were analysed. Decreased GMV was found in post-central gyrus, pre-central gyrus, precuneus, angular gyrus, insula, thalamus and cerebellum, and increased GMV was found in hippocampus, orbital gyrus and lingual gyrus (all corrected P < 0.05) at the follow-up examination. Increased CBF was found in subcallosal cingulate gyrus, hippocampus and lingual gyrus (all corrected P < 0.05) at the follow-up examination. Only decreased GMV in the anterior lobe of cerebellum was negatively associated with improvement of Barthel index (ß = -0.683, P = 0.014). Our study provides the imaging evidence of GM atrophy co-existing with GM plasticity involving in increased volume and perfusion in specific regions (including cognition, vision and emotion) in well-recovered stroke patients, which advances our understanding of neurobiology of stroke recovery.
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Isquemia Encefálica/diagnóstico por imagen , Sustancia Gris/diagnóstico por imagen , Accidente Cerebrovascular/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Encéfalo/diagnóstico por imagen , Isquemia Encefálica/rehabilitación , Circulación Cerebrovascular , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Rehabilitación de Accidente CerebrovascularRESUMEN
Early-onset Alzheimer's disease (EOAD) involves multiple cognitive domains and shows more rapid progression than late-onset Alzheimer's disease (LOAD). However, the difference in pathogenesis between EOAD and LOAD is still unclear. Accordingly, we applied intrinsic network analysis to explore the potential neuropathological mechanism underlying distinct clinical phenotypes. According to the cut-off age of 65, we included 20 EOAD patients, 20 LOAD patients, and 36 age-matched controls (19 young and 17 old controls). We employed resting-state functional MRI and network centrality analysis to explore the local (degree centrality (DC)) and global (eigenvector centrality (EC)) functional integrity. Two-sample t-test analysis was performed, with gray matter volume, age, gender, and education as covariates. Furthermore, we performed a correlation analysis between network metrics and cognition. Compared to young controls, EOAD patients exhibited lower DC in the middle temporal gyrus (MTG), parahippocampal gyrus (PHG), superior temporal gyrus (STG), and lower EC in the MTG, PHG, and postcentral gyrus. In contrast, LOAD patients exhibited lower DC in the STG and anterior cingulum gyrus and higher DC in the middle frontal gyrus compared to old controls. No significant difference in EC was observed in LOAD patients. Furthermore, both DC and EC correlated with cognitive performance. Our study demonstrated divergent functional network impairments in EOAD and LOAD patients. EOAD patients showed more complex network damage involving both local and global centrality properties, while LOAD patients mainly featured local functional connectivity changes. Such centrality impairments are related to poor cognition, especially regarding memory performance.
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Enfermedad de Alzheimer , Sustancia Blanca , Enfermedad de Alzheimer/diagnóstico por imagen , Corteza Cerebral , Humanos , Imagen por Resonancia Magnética , Red Nerviosa/diagnóstico por imagenRESUMEN
Though sleep disturbance constitutes the risk factor for Alzheimer's disease (AD), the underlying mechanism is still unclear. This study aims to explore the interaction between sleep disturbances and AD on brain function. We included 192 normal controls, 111 mild cognitive impairment (MCI), and 30 AD patients, with either poor or normal sleep (PS, NS, respectively). To explore the strength and stability of brain activity, we used static amplitude of low-frequency fluctuation (sALFF) and dynamic ALFF (dALFF) variance. Further, we examined white matter hyperintensities (WMH) and amyloid PET deposition, representing the vascular risk factor and AD-related hallmark, respectively. We observed that sleep disturbance significantly interacted with disease severity, exposing distinct effects on sALFF and dALFF variance. Interestingly, PS groups showed the dALFF variance trajectory of initially increased, then decreased and finally increased along the AD spectrum, while showing the opposite trajectory of sALFF. Further correlation analysis showed that the WMH burden correlates with dALFF variance in PS groups. Conclusively, our study suggested that sleep disturbance interacts with AD severity, expressing as effects of compensatory in MCI and de-compensatory in AD, respectively. Further, vascular impairment might act as important pathogenesis underlying the interaction effect between sleep and AD.
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Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/fisiopatología , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Imagen por Resonancia Magnética , Trastornos del Sueño-Vigilia/diagnóstico por imagen , Trastornos del Sueño-Vigilia/fisiopatología , Anciano , Algoritmos , Cognición , Femenino , Humanos , Masculino , Sustancia Blanca/patología , Sustancia Blanca/fisiopatologíaRESUMEN
BACKGROUND: There is a growing literature documenting a variety of brain abnormalities associated with obesity. However, little is known about the effects of obesity on inter-hemispheric connectivity in aging people. METHODS: Participants included 61 cognitively intact elderly (including people with obesity, overweight, and lean controls) who underwent structural MRI, resting-state functional magnetic resonance imaging (rsfMRI) and standard neuropsychological batteries. Techniques including FreeSurfer and Voxel-mirrored Homotopic Connectivity (VMHC) were employed to evaluate inter-hemispheric structural and functional connectivity respectively. RESULTS: There were no differences of cognitive abilities and vascular risks among groups. When compared to lean controls, obese group had greater VMHC in fusiform gyrus (FG); while overweight group had greater VMHC in FG, calcarine gyrus, inferior temporal gyrus (ITG), and postcentral gyrus (PCG). Moreover, the obesity group had lower VMHC in calcarine gyrus and PCG than overweight group (p<0.05, corrected). CONCLUSIONS: The present study suggested, increased inter-hemispheric information transmission in networks supporting visual and sensorimotor function may lead to gain in weight, by possibly mediating diet behaviours of individuals.
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Encéfalo/diagnóstico por imagen , Red Nerviosa/diagnóstico por imagen , Obesidad/diagnóstico por imagen , Sobrepeso/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Mapeo Encefálico , Cognición/fisiología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Pruebas Neuropsicológicas , Obesidad/psicología , Sobrepeso/psicologíaRESUMEN
Amnestic mild cognitive impairment can be further classified as single-domain aMCI (SD-aMCI) with isolated memory deficit, or multi-domain aMCI (MD-aMCI) if memory deficit is combined with impairment in other cognitive domains. Prior studies reported these clinical subtypes presumably differ in etiology. Thus, we aimed to explore the possible mechanisms between different aMCI subtypes by assessing alteration in brain activity and brain vasculature, and their relations with CSF AD biomarkers. 49 healthy controls, 32 SD-aMCI, and 32 MD-aMCI, who had undergone structural scans, resting-state functional MRI (rsfMRI) scans and neuropsychological evaluations, were identified. Regional homogeneity (ReHo) was employed to analyze regional synchronization. Periventricular white matter hyperintensities (PWMH) and deep WMH (DWMH) volume of each participant was quantitatively assessed. AD biomarkers from CSF were also measured. SD-aMCI showed decreased ReHo in medial temporal gyrus (MTG), and increased ReHo in lingual gyrus (LG) and superior temporal gyrus (STG) relative to controls. MD-aMCI showed decreased ReHo, mostly located in precuneus (PCu), LG and postcentral gyrus (PCG), relative to SD-aMCI and controls. As for microvascular disease, MD-aMCI patients had more PWMH burden than SD-aMCI and controls. Correlation analyses indicated mean ReHo in differenced regions were related with memory, language, and executive function in aMCI patients. However, no significant associations between PWMH and behavioral data were found. The Aß level was related with the ReHo value of STG in SD-aMCI. MD-aMCI displayed different patterns of abnormal regional synchronization and more severe PWMH burden compared with SD-aMCI. Therefore aMCI is not a uniform disease entity, and MD-aMCI group may show more complicated pathologies than SD-aMCI group.
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Amnesia/líquido cefalorraquídeo , Amnesia/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Disfunción Cognitiva/líquido cefalorraquídeo , Disfunción Cognitiva/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen , Anciano , Péptidos beta-Amiloides/líquido cefalorraquídeo , Biomarcadores/líquido cefalorraquídeo , Encéfalo/fisiopatología , Disfunción Cognitiva/psicología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiopatología , Pruebas Neuropsicológicas , Fragmentos de Péptidos/líquido cefalorraquídeo , Fosforilación , Descanso , Sustancia Blanca/fisiopatología , Proteínas tau/líquido cefalorraquídeoRESUMEN
APOE is one of the strongest genetic factors associated with information processing speed (IPS). Herein, we explored the neural substrates underlying APOE-related IPS alteration by measuring lobar distribution of white matter hyperintensities (WMH), cortical grey matter volume (GMV) and thickness. Using the ADNI database, we evaluated 178 cognitively normal elderly individuals including 34 APOE ε2 carriers, 54 APOE ε4 carriers and 90 ε3 homozygotes. IPS was determined using Trail Making Tests (TMT). We quantified lobar distribution of WMH, cortical GM lobar volume, cortical thickness among three groups. Finally, we used Pearson's correlation and general linear models to examine structural MRI markers in relation to IPS. There were significant differences of IPS among groups, with ε4 carriers displaying the worst performance. Across groups, significant differences in frontal and parietal WMH load were observed (the highest in ε4 carriers); however, no significant differences in cortical GMV and thickness were found. Pearson's correlation analysis showed parietal WMH volume was significantly related with IPS, especially in ε4 carriers. Subsequently a general linear model demonstrated that parietal WMH volume, age and the interaction between parietal WMH volume and age, was significantly associated with IPS, even after adjusting total intracranial volume (TIV), gender and vascular risk factors. Disruption of WM structure, rather than atrophy of GM, plays a more critical role in APOE ε4 allele-specific IPS. Moreover, specific WMH loci are closely associated with IPS; increased parietal WMH volume, especially in ε4 carriers, was independently contributed to slower IPS.
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Apolipoproteína E2/genética , Apolipoproteína E4/genética , Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética , Procesos Mentales , Anciano , Envejecimiento/genética , Envejecimiento/patología , Envejecimiento/psicología , Encéfalo/patología , Estudios Transversales , Femenino , Técnicas de Genotipaje , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Heterocigoto , Humanos , Procesamiento de Imagen Asistido por Computador , Modelos Lineales , Masculino , Pruebas Neuropsicológicas , Tamaño de los Órganos , Datos Preliminares , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patologíaRESUMEN
Leukoaraiosis is associated with increased risk of cognitive impairment, but its pathophysiological pathway is unclear. The aim of the present study was to determine whether brain structural damage or cerebral blood supply better correlated with the global cognitive outcome in subjects with leukoaraiosis. Seventy-five subjects with leukoaraiosis were included in present study, with age ranged from 43 to 85 years, with mean white matter hyperintensities (WMH) volume 30.69 ± 24.35 mL. Among them, 19(25.33%) subjects presented with cerebral microbleeds (CMB) and 40 (53.33%) subjects presented with lacunes. These participants received arterial spin labeling perfusion MRI, diffusion-tensor imaging (DTI) and diffusion Kurtosis imaging. We analyzed the cerebral blood flow (CBF) by dividing the brain tissue into three regions: WMH, normal appearing white matter (NAWM) and cortex. After adjusting for age and gender, the CBF of NAWM was significantly correlated with fractional anisotropy (FA) (r = 0.336, p = 0.004) and mean diffusion (MD) (r = -0.271, p = 0.020) of NAWM, while there lacked of association between CBF of cortex and mean kurtosis (MK) of cortex (r = -0.015, p = 0.912). Meanwhile, both NAWM-FA (r = -0.443, p < 0.001) and NAWM-MD (r = 0.293, p = 0.012), as well as cortex-MK (r = -0.341, p = 0.012) was significantly correlated with WMH volume. Univariate regression analysis demonstrated that global cognitive function was significantly associated with mean FA or MD of both WMH and NAWM, and cortex-CBF, but neither with the cortex-MK, nor the presences of CMB or lacunes. Finally, multiple linear regression analysis revealed that global cognitive function was independently associated with NAWM-FA (standardized ß = 0.403, p < 0.001) and WMH-FA (Standardized ß = 0.211, p = 0.017), but not with the cortex-CBF. A model that contained NAWM-FA, WMH-FA and years of education explained 49% of the variance of global cognitive function. Cerebral perfusion status might have a significant impact on the maintenance of white matter integrity in subjects with leukoaraiosis. Global cognitive function was more strongly associated with white matter integrity than with blood supply. DTI parameters, especially FA could serve as a potent imaging indicator for detecting the invisible alteration of white matter integrity and implying its potential cognitive relevance.
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The importance of white matter injury induced by diabetes in stroke severity and prognosis is largely unknown. We aimed to investigate the relationship between diabetes-related white matter injury beyond stroke lesions with acute neurological deficits and clinical outcome after stroke. In total, 36 stroke patients within 3-7 days after onset were enrolled. Neurological deficits on admission were assessed by National Institute of Health Stroke Score, and poor outcome at 3 months was defined as modified Rankin score >2. White matter tracts were compared between patients with diabetic and non-diabetic stroke using fractional anisotropy from diffusion tensor imaging. Regional white matter abnormality with decreased fractional anisotropy was observed in diabetic patients (n = 18) when compared to non-diabetic patients (n = 18). Decreased fractional anisotropy in ipsilesional distal corticospinal tract was independently associated with higher National Institute of Health Stroke Score motor component score (ß = -0.444, p = 0.005), and decreased fractional anisotropy in contralesional superior longitudinal fasciculus I was independently related to poor outcome (odds ratio, 0.900; p = 0.033). Our findings suggested that only white matter injury induced by diabetes in specific tracts like corticospinal tract and superior longitudinal fasciculus beyond stroke lesions has clinically relevant, providing insight into the mechanism of stroke recovery under the diabetic condition.
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Complicaciones de la Diabetes/etiología , Leucoencefalopatías/etiología , Accidente Cerebrovascular/etiología , Adulto , Anciano , Anciano de 80 o más Años , Distribución de Chi-Cuadrado , Complicaciones de la Diabetes/diagnóstico por imagen , Complicaciones de la Diabetes/fisiopatología , Imagen de Difusión Tensora , Evaluación de la Discapacidad , Femenino , Humanos , Leucoencefalopatías/diagnóstico por imagen , Leucoencefalopatías/fisiopatología , Modelos Logísticos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Actividad Motora , Análisis Multivariante , Examen Neurológico , Oportunidad Relativa , Pronóstico , Recuperación de la Función , Factores de Riesgo , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/fisiopatología , Factores de TiempoRESUMEN
Apolipoprotein E (APOE) ε4 allele is the best established genetic risk factor for sporadic Alzheimer's disease (AD). However, there is a need to understand the effects of this genotype on the brain by simultaneously assessing intrinsic brain network and cerebral spinal fluid (CSF) biomarkers changes in healthy older ε4 carriers. Thirteen cognitively intact, elderly APOE ε4 carriers and 22 ε3 homozygotes were included in the present study. Eigenvector centrality mapping (ECM) was used to identify brain network hub organization based on resting-state functional MRI (rsfMRI). We evaluated comprehensive cognitive ability and tested levels of Aß1-42, total-tau (t-tau) and phosphorylated-tau (p-tau181) in CSF. Comparisons of ECM between two groups were conducted, followed by correlations analyses between EC values with significant group differences and cognitive ability/CSF biomarkers. APOE ε4 carriers showed significantly decreased EC values in left medial temporal lobe (MTL), left lingual gyrus (LG) and increased EC values in left middle frontal gyrus (MFG) as compared to non-carriers. Correlation analysis demonstrated that left LG EC value correlated with Rey Auditory Verbal Learning Test total learning (RAVLT, r = 0.57, p < 0.05) and t-tau level (r = -0.57, p < 0.05), while left MFG EC values correlated with log-transformed Trail-Making Test B (TMT-B, r = -0.67, p < 0.05) in APOE ε4 carriers. This study suggests the APOE ε4 allele contributes to disruption of brain connectedness in certain functional nodes, which may result from neuronal death caused by toxicity of neurofibrillary tangles.
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Péptidos beta-Amiloides/líquido cefalorraquídeo , Apolipoproteína E4/genética , Encéfalo/fisiología , Cognición , Proteínas tau/líquido cefalorraquídeo , Anciano , Biomarcadores/líquido cefalorraquídeo , Encéfalo/diagnóstico por imagen , Mapeo Encefálico/métodos , Cognición/fisiología , Estudios Transversales , Femenino , Técnicas de Genotipaje , Heterocigoto , Humanos , Masculino , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiología , Pruebas Neuropsicológicas , DescansoRESUMEN
White matter hyperintensities (WMHs) are associated with cognitive decline, but less is known about pathophysiology of cognitive decline in patients with WMHs. We investigated microvasculature and microstructure in WMHs using intravoxel incoherent motion (IVIM) and their associations with cognitive function. Thirty-two subjects with WMHs were enrolled in our study. Fast diffusion coefficient (D*), perfusion fraction (f) and slow diffusion coefficient (D) from IVIM model were compared between regions of WMHs (periventricular WMHs, PWMHs and deep WMHs, DWMHs) and surrounding normal white matter. Multivariate linear model was used to determine the independent factors associated with cognitive function assessed by the Mini Mental State Examination (MMSE) and the standardized coefficient (ß) of factors was estimated. D* was significantly lower (4.95 × 10-3 mm2/s versus 8.36 × 10-3 mm2/s in PWMHs and 5.04 × 10-3 mm2/s versus 8.67 × 10-3 mm2/s in DWMHs, both P < 0.001), and f (14.64 % versus 12.01 % in PWMHs and 14.26 % versus 11.31 % in DWMHs, both P < 0.001) and D (1.02 × 10-3 mm2/s versus 0.73 × 10-3 mm2/s in PWMHs and 0.86 × 10-3 mm2/s versus 0.70 × 10-3 mm2/s in DWMHs, both P < 0.001) were significantly higher in WMHs. Only f in PWMHs was independently associated with MMSE (ß = 0.443, P = 0.016). The decreased D* and increased D in WMHs were similar to previous findings. The increased f in PWMHs relating with better cognition provides the pathophysiological basis in understanding cognitive decline in patients with WMHs.
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Envejecimiento/patología , Encéfalo/irrigación sanguínea , Reserva Cognitiva/fisiología , Microvasos/anatomía & histología , Análisis y Desempeño de Tareas , Sustancia Blanca/anatomía & histología , Adulto , Anciano , Anciano de 80 o más Años , Imagen de Difusión Tensora/métodos , Femenino , Humanos , Angiografía por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Estadística como AsuntoRESUMEN
Cerebral venous collagenosis played a role in the pathogenesis of white matter hyperintensities (WMHs) through venous ischemia. Since pathological changes of veins from intramural stenosis to luminal occlusion is a dynamic process, we aimed to create a deep medullary veins (DMVs) visual grade on susceptibility-weighted images (SWI) and explore the relationship of DMVs and WMHs based on venous drainage regions. We reviewed clinical, laboratory and imaging data from 268 consecutive WMHs patients and 20 controls. SWI images were used to observe characteristics of DMVs and a brain region-based DMVs visual score was given by two experienced neuroradiologists. Fluid attenuated inversion recovery (FLAIR) images were used to calculate WMHs volume. Logistic-regression analysis and partial Pearson's correlation analysis were used to examine the association between the DMVs score and WMHs volume. We found that the DMVs score was significantly higher in WMHs patients than in controls (p < 0.001). Increased DMVs score was independently associated with higher WMHs volume after adjusting for total cholesterol level and number of lacunes (p < 0.001). Particularly, DMVs scores were correlated with regional PVHs volumes in the same brain region most. The newly proposed DMVs grading method allows the clinician to monitor the course of DMVs disruption. Our findings of cerebral venous insufficiency in WMHs patients may help to elucidate the pathogenic mechanisms and progression of WMHs.
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BACKGROUND: Iron deposition may contribute to the clinical symptoms in Parkinson's disease (PD). With partial different clinical manifestations, the iron deposition patterns between patients with early-onset Parkinson's disease (EOPD) and middle-late-onset Parkinson's disease (M-LOPD) are still unclear. This study was designed to investigate the patterns of iron deposition and their clinical relevance in EOPD and M-LOPD patients, using quantitative susceptibility mapping technique. MATERIALS AND METHODS: Thirty-five EOPD patients and 24 matched young controls, 33 M-LOPD patients and 22 matched older controls were recruited in the study. The iron content in the deep grey matter nuclei in the basal ganglia and midbrain were measured, and compared between patients and their corresponding controls. The correlations of regional iron content and clinical features were explored in patient groups. RESULTS: Both M-LOPD and EOPD patients showed increased iron content in the substantia nigra (SN) pars compacta and SN pars reticulata. Increased iron content in the putamen was only observed in M-LOPD patients. The relationship between the increased iron content and disease severity (H&Y stages, UPDRS II scores and UPDRS III scores) was observed in M-LOPD patients, but not in EOPD patients. CONCLUSION: Our study suggested that the iron deposition pattern was greatly influenced by the age of PD onset, which increases our understanding of the different pathological underpinnings of EOPD and M-LOPD patients.
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Encéfalo/patología , Hierro/metabolismo , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/patología , Adulto , Edad de Inicio , Anciano , Encéfalo/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: It remains unclear if and how the interactions between APOE genotypes and cerebral small-vessel diseases (CSVD) lead to cognitive decline in the long term. Based on ADNI cohort, this longitudinal study aimed to clarify the potential relationship among APOE genotype, CSVD and cognition by integrating multi-level data. METHOD: There were 135 healthy elderly (including ε2, ε4 allele carriers and ε3 homozygotes) who had completed two years' follow-up. MRI markers of CSVD, including white matter hyperintensities (WMH), dilated perivascular space (dPVS), microbleeds and lacune, were assessed. Besides, neuropathological factors including Alzheimer's disease-related pathology measured by CSF and PiB-PET were assessed. Repeated measurements ANOVAs were performed to test impact of different APOE genotypes on CSVD. RESULTS: We found that APOE ε4 carriers had significantly more frontal WMH burden and basal ganglia dPVS at baseline and faster progression of frontal WMH burden during follow-up. Furthermore, our results showed that APOE ε4 carriers had significantly decreased Aß1-42 level, and its level was negatively related with baseline and progressive total WMH burden. Then, general linear modals indicated interaction between basal frontal WMH burden and ε4 allele was related with declining trend of cognition. CONCLUSION: Our findings suggested APOE ε4 allele was associated with increased Aß deposition, which may lead to the formation and progression of WMH, especially in frontal lobe. Besides, interaction between the increased frontal WMH burden and ε4 allele can exert long-term detrimental effects on individual's trajectory of cognition.
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Apolipoproteínas E/genética , Trastornos Cerebrovasculares/diagnóstico , Trastornos Cerebrovasculares/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Anciano , Anciano de 80 o más Años , Alelos , Péptidos beta-Amiloides/metabolismo , Biomarcadores , Trastornos Cerebrovasculares/etiología , Trastornos Cerebrovasculares/metabolismo , Disfunción Cognitiva , Comorbilidad , Progresión de la Enfermedad , Femenino , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neuroimagen , Pruebas Neuropsicológicas , Tomografía de Emisión de Positrones , Factores de Riesgo , Proteínas tau/metabolismoRESUMEN
BACKGROUND: Asymmetric medullary veins (AMV) are frequently observed in stroke patients and single-echo susceptibility weighted imaging (SWIs) is the main technique in detecting AMV. Our study aimed to investigate which echo time (TE) on single-echo susceptibility is the optimal echo for visualizing AMV and to compare the ability in detecting AMV in stroke patients between SWIs and multi-echo susceptibility weighted imaging (SWIc). MATERIALS AND METHODS: Twenty patients with middle cerebral artery stroke were included. SWI was acquired by using a multi-echo gradient-echo sequence with six echoes ranging from 5 ms to 35.240 ms. Three different echoes of SWIs including SWIs1 (TE = 23.144 ms), SWIs2 (TE = 29.192 ms) and SWIs3 (TE = 35.240 ms) were reconstructed. SWIc was averaged using the three echoes of SWIs. Image quality and venous contrast of medullary veins were compared between SWIs and SWIc using peak signal-to-noise ratio (PSNR), mean opinion score (MOS), contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR). The presence of AMV was evaluated in each SWIs (1-3) and SWIc. RESULTS: SWIs2 had the highest PSNR, MOS and CNR and SWIs1 had the highest SNR among three different echoes of SWIs. No significant difference was found in SNR between SWIs1 and SWIs2. PSNR, MOS and CNR in SWIc were significantly increased by 27.9%, 28.2% and 17.2% compared with SWIs2 and SNR in SWIc was significantly increased by 32.4% compared with SWIs1. 55% of patients with AMV were detected in SWIs2, SWIs3 and SWIc, while 50% AMV were found in SWIs1. CONCLUSIONS: SWIs using TE around 29ms was optimal in visualizing AMV. SWIc could improve image quality and venous contrast, but was equal to SWIs using a relative long TE in evaluating AMV. These results provide the technique basis for further research of AMV in stroke.