RESUMEN
Alzheimer's disease is a neurodegenerative disorder marked by cognitive decline and brain pathology involving amyloid plaques and neurofibrillary tangles. Current drug development focuses on disease-modifying therapies, primarily antibodies targeting amyloid or tau. However, the blood-brain barrier (BBB) poses a challenge for drug delivery to the brain. Pre- and early clinical data suggests that Focused Ultrasound (FUS) technology safely enhances BBB permeability without damaging brain tissue, enabling drug delivery. This systematic review discusses the application of FUS to open the BBB for the treatment of Alzheimer's disease (AD). We review the safety, efficacy, and potential biological effects of FUS-mediated BBB opening in AD patients.
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Enfermedad de Alzheimer , Barrera Hematoencefálica , Sistemas de Liberación de Medicamentos , Enfermedad de Alzheimer/tratamiento farmacológico , Humanos , Terapia por Ultrasonido/métodos , AnimalesRESUMEN
BACKGROUND: Disparities in Alzheimer's disease (AD) are well-documented among different racial/ethnic groups and between sex/genders. Neuropsychological assessment provides important information about cognitive changes and can offer valuable insights into disparities. However, neuropsychological measures must be comparable across racial/ethnic and sex/gender groups to accurately interpret disparities. OBJECTIVES: To evaluate measurement invariance (equivalence) of the Preclinical Alzheimer Cognitive Composite (PACC) and the Cognitive Function Index across racial/ethnic, sex/gender, and ß-amyloid (Aß) status groups. DESIGN, SETTING, PARTICIPANTS: Cross-sectional analysis of screening data from the Anti-Amyloid in Asymptomatic AD (A4) Study. The study enrolled participants aged 65-85 from sites across the United States, Canada, Australia, and Japan. MEASUREMENTS: Participants completed the PACC and the Cognitive Function Index. Participants classified as cognitively normal also underwent a Positron Emission Tomography (PET) scan to determine Aß status. RESULTS: Participants self-identified as non-Hispanic White (n=5241), non-Hispanic Black (n=267), Asian (n=228), or Hispanic White (n=225) as well as male (n=2885) or female (n=3076). Among those who underwent a PET scan, 3115 were classified as Aß- and 1309 were classified as Aß+. We found support for a one-factor model for both the PACC and Cognitive Function Index across the full sample and in samples stratified by race/ethnicity, sex/gender, and Aß status. The one-factor model of the PACC and Cognitive Function Index demonstrated scalar measurement invariance across racial/ethnic, sex/gender, and Aß status groups. CONCLUSIONS: Our findings suggest that performance on the PACC and Cognitive Function Index can be compared across the racial/ethnic, sex/gender, and Aß status groups examined in this study.
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Enfermedad de Alzheimer , Cognición , Femenino , Humanos , Masculino , Péptidos beta-Amiloides , Estudios Transversales , Pruebas Neuropsicológicas , Estados Unidos , Grupos Raciales , EtnicidadRESUMEN
BACKGROUND AND PURPOSE: White matter hyperintensities on T2-weighted MR imaging are typical in older adults and have been linked to several poor health outcomes, including cognitive impairment and Alzheimer disease. The presence and severity of white matter hyperintensities have traditionally been attributed to occlusive arteriopathy, but recent evidence also implicates deep medullary venule collagenosis and associated vasogenic edema. Historically, postmortem analyses have been the sole way to analyze cerebral veins, but SWI can be now used to examine cortical veins in vivo. The aim of the current study was to determine whether there is an association between the diameters of the large draining cerebral veins/sinuses and white matter hyperintensity volume. MATERIALS AND METHODS: T2-weighted FLAIR and SWI were performed in 682 older adults without dementia (mean age, 73.9 ± 5.9 years; 59.1% women). Total and regional white matter hyperintensity volume was derived. We measured the diameters of 5 regions of the cerebral venous draining system: internal cerebral veins, basal veins of Rosenthal, superior sagittal sinus, vein of Galen, and straight sinus terminus. RESULTS: Increased diameter of the internal cerebral veins was associated with greater total white matter hyperintensity volume (ß = 0.09, P = .02) and regionally in the parietal (ß = 0.10, P = .006), frontal (ß = 0.09, P = .02), and temporal (ß = 0.09, P = .02) lobes. Increased diameter of the basal veins of Rosenthal was associated with greater total (ß = 0.10, P = .01), frontal (ß = 0.11, P = .003), and temporal (ß = 0.09, P = .02) white matter hyperintensity volume. CONCLUSIONS: Our results suggest that the caliber of the internal cerebral veins and of the basal veins of Rosenthal relates to regional white matter disease.
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Venas Cerebrales/patología , Leucoaraiosis/patología , Anciano , Venas Cerebrales/diagnóstico por imagen , Femenino , Humanos , Leucoaraiosis/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patologíaRESUMEN
BACKGROUND AND PURPOSE: The relationship between extracranial large-artery characteristics and arterial spin-labeling MR imaging may influence the quality of arterial spin-labeling-CBF images for older adults with and without vascular pathology. We hypothesized that extracranial arterial blood velocity can explain between-person differences in arterial spin-labeling data systematically across clinical populations. MATERIALS AND METHODS: We performed consecutive pseudocontinuous arterial spin-labeling and phase-contrast MR imaging on 82 individuals (20-88 years of age, 50% women), including healthy young adults, healthy older adults, and older adults with cerebral small vessel disease or chronic stroke infarcts. We examined associations between extracranial phase-contrast hemodynamics and intracranial arterial spin-labeling characteristics, which were defined by labeling efficiency, temporal signal-to-noise ratio, and spatial coefficient of variation. RESULTS: Large-artery blood velocity was inversely associated with labeling efficiency (P = .007), temporal SNR (P < .001), and spatial coefficient of variation (P = .05) of arterial spin-labeling, after accounting for age, sex, and group. Correction for labeling efficiency on an individual basis led to additional group differences in GM-CBF compared to correction using a constant labeling efficiency. CONCLUSIONS: Between-subject arterial spin-labeling variance was partially explained by extracranial velocity but not cross-sectional area. Choosing arterial spin-labeling timing parameters with on-line knowledge of blood velocity may improve CBF quantification.
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Velocidad del Flujo Sanguíneo/fisiología , Arterias Cerebrales/diagnóstico por imagen , Arterias Cerebrales/fisiología , Circulación Cerebrovascular/fisiología , Marcadores de Spin , Adulto , Anciano , Anciano de 80 o más Años , Envejecimiento/fisiología , Anatomía Transversal , Femenino , Voluntarios Sanos , Hemodinámica , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Relación Señal-Ruido , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/fisiopatología , Sustancia Blanca/diagnóstico por imagen , Adulto JovenRESUMEN
ALS is a multisystem disorder affecting motor and cognitive functions. Bulbar-onset ALS (bALS) may be preferentially associated with cognitive and language impairments, compared with spinal-onset ALS (sALS), stemming from a potentially unique neuropathology. The objective of this systematic review was to compare neuropathology findings reported for bALS and sALS subtypes in studies of cadaveric brains. Using Cochrane guidelines, we reviewed articles in MEDLINE, Embase, and PsycINFO databases using standardized search terms for ALS and neuropathology, from inception until July 16th 2016. 17 studies were accepted for analysis. The analysis revealed that both subtypes presented with involvement in motor and frontotemporal cortices, deep cortical structures, and cerebellum and were characterized by neuronal loss, spongiosis, myelin pallor, and ubiquitin+ and TDP43+ inclusion bodies. Changes in Broca and Wernicke areas - regions associated with speech and language processing - were noted exclusively in bALS. Further, some bALS cases presented with atypical pathology such as neurofibrillary tangles and basophilic inclusions, which were not found in sALS cases. Given the limited number of studies, all with methodological biases, further work is required to better understand neuropathology of ALS subtypes.
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Encéfalo , Esclerosis Amiotrófica Lateral , Proteínas de Unión al ADN , Humanos , Cuerpos de Inclusión , Trastornos del LenguajeRESUMEN
OBJECTIVE: It is generally acknowledged that at least 50% of individuals with amyotrophic lateral sclerosis (ALS) will exhibit cognitive deficits outside of the characteristic motor neuron involvement. However, a specific cognitive profile has been difficult to ascertain due to disease-related testing barriers and limitations in the sensitivity and specificity of available assessment methods. This study assessed the level of functioning of extramotor frontal cognitive processes in ALS, and the amount of change in the functioning in these processes over time as disease progresses. METHODS: Empirical tests validated for a model of frontal lobe functioning were modified into an assessment battery appropriate for individuals with ALS in a clinical setting (the ALS-CFB, Computerised Frontal Battery). Twenty ALS participants and 36 age- and education-matched neurologically healthy controls were tested, and a sub-sample of each group (11 ALS and 20 controls) re-tested after approximately nine months. RESULTS AND CONCLUSIONS: Compared to standard neuropsychological screening tests that did not show a difference between ALS participants and healthy controls, the ALS-CFB illustrated a profile of extramotor frontal dysfunction involving energisation (preparing the neural system to respond) and executive functions, a profile that may be indicative of the nature of neurodegeneration in ALS.
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Esclerosis Amiotrófica Lateral/fisiopatología , Esclerosis Amiotrófica Lateral/psicología , Cognición , Lóbulo Frontal/fisiopatología , Edad de Inicio , Anciano , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/psicología , Progresión de la Enfermedad , Función Ejecutiva , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Tiempo de Reacción , Movimientos Sacádicos , Percepción Social , Teoría de la MenteRESUMEN
BACKGROUND AND PURPOSE: The pathogenesis of leukoaraiosis has long been debated. This work addresses a less well-studied mechanism, cerebrovascular reactivity, which could play a leading role in the pathogenesis of this disease. Our aim was to evaluate blood flow dysregulation and its relation to leukoaraiosis. MATERIALS AND METHODS: Cerebrovascular reactivity, the change in the blood oxygen level-dependent 3T MR imaging signal in response to a consistently applied step change in the arterial partial pressure of carbon dioxide, was measured in white matter hyperintensities and their contralateral spatially homologous normal-appearing white matter in 75 older subjects (age range, 50-91 years; 40 men) with leukoaraiosis. Additional quantitative evaluation of regions of leukoaraiosis was performed by using diffusion (n = 75), quantitative T2 (n = 54), and DSC perfusion MRI metrics (n = 25). RESULTS: When we compared white matter hyperintensities with contralateral normal-appearing white matter, cerebrovascular reactivity was lower by a mean of 61.2% ± 22.6%, fractional anisotropy was lower by 44.9 % ± 6.9%, and CBF was lower by 10.9% ± 11.9%. T2 was higher by 61.7% ± 13.5%, mean diffusivity was higher by 59.0% ± 11.7%, time-to-maximum was higher by 44.4% ± 30.4%, and TTP was higher by 6.8% ± 5.8% (all P < .01). Cerebral blood volume was lower in white matter hyperintensities compared with contralateral normal-appearing white matter by 10.2% ± 15.0% (P = .03). CONCLUSIONS: Not only were resting blood flow metrics abnormal in leukoaraiosis but there is also evidence of reduced cerebrovascular reactivity in these areas. Studies have shown that reduced cerebrovascular reactivity is more sensitive than resting blood flow parameters for assessing vascular insufficiency. Future work is needed to examine the sensitivity of resting-versus-dynamic blood flow measures for investigating the pathogenesis of leukoaraiosis.
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Encéfalo/irrigación sanguínea , Leucoaraiosis/fisiopatología , Sustancia Blanca/irrigación sanguínea , Adulto , Anciano , Anciano de 80 o más Años , Anisotropía , Encéfalo/fisiopatología , Circulación Cerebrovascular/fisiología , Femenino , Hemodinámica/fisiología , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Sustancia Blanca/fisiopatologíaRESUMEN
X-ray backscatter imaging can be used for a wide range of imaging applications, in particular for industrial inspection and portal security. Currently, the application of this imaging technique to the detection of landmines is limited due to the surrounding sand or soil strongly attenuating the 10s to 100s of keV X-rays required for backscatter imaging. Here, we introduce a new approach involving a 140 MeV short-pulse (< 100 fs) electron beam generated by laser wakefield acceleration to probe the sample, which produces Bremsstrahlung X-rays within the sample enabling greater depths to be imaged. A variety of detector and scintillator configurations are examined, with the best time response seen from an absorptive coated BaF2 scintillator with a bandpass filter to remove the slow scintillation emission components. An X-ray backscatter image of an array of different density and atomic number items is demonstrated. The use of a compact laser wakefield accelerator to generate the electron source, combined with the rapid development of more compact, efficient and higher repetition rate high power laser systems will make this system feasible for applications in the field. Content includes material subject to Dstl (c) Crown copyright (2014). Licensed under the terms of the Open Government Licence except where otherwise stated. To view this licence, visit http://www.nationalarchives.gov.uk/doc/open-government-licence/version/3 or write to the Information Policy Team, The National Archives, Kew, London TW9 4DU, or email: psi@ nationalarchives.gsi.gov.uk.
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Bombas (Dispositivos Explosivos)/clasificación , Rayos Láser , Intensificación de Imagen Radiográfica/instrumentación , Dispersión de Radiación , Tomografía Computarizada por Rayos X/instrumentación , Guerra , Diseño de Equipo , Análisis de Falla de Equipo , Fantasmas de Imagen , Rayos XRESUMEN
Stroke variably activates interleukin- (IL-) 17 expression, reduces regulatory T cells, and induces oxidative stress, which may support neurodegeneration. Ischemic stroke patients were screened for depressive symptoms (Center for Epidemiological Studies Depression (CES-D)) and cognitive status (Mini Mental State Examination). Proinflammatory cytokines (IL-17, IL-23, and interferon- [IFN-] γ), anti-inflammatory cytokine IL-10, and lipid hydroperoxide (LPH), a measure of oxidative stress, were assayed from fasting serum. Of 47 subjects (age 71.8 ± 14.4 years, 36% female), 19 had depressive symptoms (CES-D ≥ 16), which was associated with poorer cognitive status (F 1,46 = 8.44, P = 0.006). IL-17 concentrations did not differ between subjects with and without depressive symptoms (F 1,46 = 8.44, P = 0.572); however, IL-17 was associated with poorer cognitive status in subjects with depressive symptoms (F 1,46 = 9.29, P = 0.004). In those subjects with depressive symptoms, IL-17 was associated with higher LPH (ρ = 0.518, P = 0.023) and lower IL-10 (ρ = -0.484, P = 0.036), but not in those without. In conclusion, poststroke depressive symptoms may be associated with cognitive vulnerability to IL-17 related pathways, involving an imbalance between proinflammatory and anti-inflammatory activity and increased oxidative stress.
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Interleucina-17/sangre , Trastornos Mentales/complicaciones , Enfermedades del Sistema Nervioso/complicaciones , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/fisiopatología , Anciano , Anciano de 80 o más Años , Trastornos del Conocimiento/complicaciones , Estudios Transversales , Citocinas/sangre , Depresión/complicaciones , Femenino , Humanos , Inflamación , Peróxidos Lipídicos/sangre , Masculino , Persona de Mediana Edad , Estrés OxidativoRESUMEN
BACKGROUND: White matter hyperintensities (WMH) are associated with aging and are prevalent in various brain pathologies. The purpose of the current study was to characterize WMH perfusion in age-matched elderly controls (ECs) and patients with Alzheimer's disease (ADs). METHODS: Fifty ECs (23 men) and 61 ADs (33 men) underwent magnetic resonance imaging (MRI), 99mTc-ECD single-photon emission computed tomography (SPECT) and cognitive testing. Brain tissue type was classified on T1 weighted images, and WMH were identified on interleaved proton density/T2 weighted images. Co-registered MR images were used to characterize SPECT perfusion patterns. RESULTS: WMH perfusion was lower than normal appearing white matter (NAWM) perfusion (P < 0.001) in both EC and AD groups. There was no WMH perfusion difference between groups when considering the mean perfusion from all WMH voxels (P > 0.43). However, locations that were likely to be considered WMH tended to have lower perfusion in ADs compared with ECs. Perfusion gradients along watershed white matter regions were significantly different between EC and AD groups (P < 0.05). A relationship was found between the volume of a WMH lesion and its mean perfusion (P < 0.001) in both ECs and ADs. CONCLUSION: Global WMH were hypoperfused compared with NAWM to the same degree in EC and AD participants, which suggests a common WMH etiology between groups. However, white matter locations that were likely to contain WMH tended to be hypoperfused in ADs compared with healthy aging. This finding is suggestive of AD-specific pathology that reduces the perfusion at anatomic locations susceptible to the formation of WMH through either the neurodegenerative process or AD-related vasculopathy or both.
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Envejecimiento/fisiología , Enfermedad de Alzheimer/complicaciones , Encéfalo/irrigación sanguínea , Enfermedades de los Pequeños Vasos Cerebrales/complicaciones , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico , Anciano , Envejecimiento/patología , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/patología , Encéfalo/patología , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Enfermedades de los Pequeños Vasos Cerebrales/patología , Cisteína/análogos & derivados , Femenino , Humanos , Leucoaraiosis/complicaciones , Leucoaraiosis/diagnóstico por imagen , Leucoaraiosis/patología , Imagen por Resonancia Magnética , Masculino , Fibras Nerviosas Mielínicas/patología , Neuroimagen , Compuestos de Organotecnecio , Radiofármacos , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
Visual acuity of the commercially important sparid Pagrus auratus was tested using the optomotor response. Juvenile fish were categorized by size as group 1 (50 g), group 2 (100 g), group 3 (150 g), group 4 (300 g), group 5 (500 g) and group 6 (800 g). Group 3 fish demonstrated excellent visual acuity (minimum separable angle, M(SA), 1°), which was improved compared with the smaller fish groups (groups 1 and 2, M(SA), 2°). In the larger fish groups, however, a reduction in visual acuity was observed (groups 4, 5 and 6 M(SA), 4°). Group 2 (100 g) fish displayed positive optomotor responses in long wavelength light (red) but reduced responses in short wavelengths (blue). Red light sensitivity is beneficial for the estuarine lifestyle of these fish, where light is predominantly at long wavelengths. In contrast, group 6 (800 g) fish displayed improved acuity in blue and green light and reduced acuity in red light. Fish of this size move away from the estuary to open oceans, where light is predominantly in the shorter wavelengths (blue-green). These results support the sensitivity hypothesis for the relationship between fish visual systems and the light environment they inhabit.
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Tamaño Corporal/fisiología , Luz , Perciformes/fisiología , Agudeza Visual/fisiología , Animales , Cristalino/anatomía & histología , Perciformes/anatomía & histologíaRESUMEN
OBJECTIVE: To describe clinical characteristics and evaluate processes of care and outcomes at discharge in patients with ischemic stroke with and without preexisting dementia. METHODS: Retrospective cohort study using the Registry of the Canadian Stroke Network including patients presenting with an acute ischemic stroke between 2003 and 2008. Preexisting dementia was defined as any type of dementia that was present prior to the index stroke case. Palliative patients were excluded. Demographic information, clinical presentation, selected process measures (e.g., thrombolysis, admission to stroke unit, carotid imaging, stroke prevention), pneumonia, death, disability, and disposition at discharge were analyzed. RESULTS: Among 9,304 eligible patients with an acute ischemic stroke, 702 (9.1%) had a history of dementia. Patients with dementia were older (mean age 81 vs 70 years; p < 0.001), had more severe strokes (Canadian Neurological Scale score <4, 20.7% vs 10.5%; p < 0.001), and were more likely to have atrial fibrillation (22.8% vs 15.3%; p < 0.001) than those without dementia. Patients with dementia were slightly less likely to be admitted to a stroke unit (63% vs 67.6%; odds ratio [OR] 0.82, 95% confidence interval [CI] 0.70-0.96) or to receive thrombolysis (10.5% vs 15.7%; OR 0.63, 95% CI 0.49-0.81). There were no differences in other performance measures. Patients with preexisting dementia had higher disability at discharge (OR 3.20, 95% CI 2.64-3.87) and were less likely to be discharged to their prestroke place of residence (24% vs 45%; p < 0.001). CONCLUSIONS: In patients with stroke, preexisting dementia is associated with high rates of disability and institutionalization, representing an increasing challenge for the health care system.
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Demencia/etiología , Demencia/fisiopatología , Atención al Paciente , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/fisiopatología , Terapia Trombolítica , Anciano , Anciano de 80 o más Años , Canadá , Estudios de Cohortes , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Sistema de Registros , Estudios Retrospectivos , Accidente Cerebrovascular/patología , Resultado del TratamientoRESUMEN
BACKGROUND/AIMS: Automated, volumetrically defined atrophy in the left anterior cingulate (LAC) and anterior temporal regions (LAT) on MRI can be used to distinguish most patients with frontotemporal dementia (FTD) from controls. FTD and Alzheimer's disease (AD) can differ in the degree of anterior temporal atrophy. We explored whether clinicians can visually detect this atrophy pattern and whether they can use it to classify the 2 groups of dementia patients with the same accuracy. METHODS: Four neurologists rated atrophy in the LAC and LAT regions on MRI slices from 21 FTD, 21 controls, and 14 AD participants. Inter-rater reliability and diagnostic accuracy were assessed. RESULTS: All 4 raters agreed on the presence of clinically significant atrophy, and their atrophy scoring correlated with the volumes, but without translation into high inter-rater diagnostic agreement. CONCLUSIONS: Volumetric analyses are difficult to translate into routine clinical practice.
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Demencia Frontotemporal/diagnóstico , Demencia Frontotemporal/patología , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/patología , Atrofia , Autopsia , Diagnóstico Diferencial , Femenino , Giro del Cíngulo/patología , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Reproducibilidad de los Resultados , Factores Socioeconómicos , Lóbulo Temporal/patologíaRESUMEN
Dementia occurs after stroke in 25% of patients but also can arise from covert cerebrovascular disease (CVD). 'Silent' lacunes occur in 25% of the elderly, often associated with focal or confluent hyperintensities on T2-weighted magnetic resonance imaging, which are detected in 95% of seniors. These covert infarcts predict future stroke and faster cognitive decline. Best practice guidelines advocate screening for cognitive impairment in all phases of overt stroke, when covert CVD is uncovered, when vascular risk factors are present and if patients present with cognitive complaints. Standardised testing is recommended, emphasising executive function and speed of processing. Cholinesterase inhibitors have cognitive enhancing effects in vascular dementia, but the major thrust is still aggressive management of vascular risk factors and healthy lifestyle choices. Given that mixed Alzheimer's dementia and CVD is likely the most common substrate for dementia and that they share common vascular risk factors, a major goal for vascular medicine is cerebrovascular protection, not just to prevent heart attack and stroke, but also to maintain brain health and delay dementia.
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Infarto Encefálico/patología , Trastornos del Conocimiento , Demencia por Múltiples Infartos/patología , Demencia Vascular , Accidente Cerebrovascular/patología , Anciano , Infarto Encefálico/epidemiología , Inhibidores de la Colinesterasa/uso terapéutico , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/epidemiología , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/terapia , Demencia por Múltiples Infartos/epidemiología , Demencia Vascular/complicaciones , Demencia Vascular/diagnóstico , Demencia Vascular/patología , Demencia Vascular/terapia , HumanosRESUMEN
Subcortical hyperintensities (SH) are a commonly observed phenomenon on MRI of the aging brain (Kertesz et al., 1988). Conflicting behavioral, cognitive and pathological associations reported in the literature underline the need to develop an intracranial volumetric analysis technique to elucidate pathophysiological origins of SH in Alzheimer's disease (AD), vascular cognitive impairment (VCI) and normal aging (De Leeuw et al., 2001; Mayer and Kier, 1991; Pantoni and Garcia, 1997; Sachdev et al., 2008). The challenge is to develop processing tools that effectively and reliably quantify subcortical small vessel disease in the context of brain tissue compartments. Segmentation and brain region parcellation should account for SH subtypes which are often classified as: periventricular (pvSH) and deep white (dwSH), incidental white matter disease or lacunar infarcts and Virchow-Robin spaces. Lesion Explorer (LE) was developed as the final component of a comprehensive volumetric segmentation and parcellation image processing stream built upon previously published methods (Dade et al., 2004; Kovacevic et al., 2002). Inter-rater and inter-method reliability was accomplished both globally and regionally. Volumetric analysis showed high inter-rater reliability both globally (ICC=.99) and regionally (ICC=.98). Pixel-wise spatial congruence was also high (SI=.97). Whole brain pvSH volumes yielded high inter-rater reliability (ICC=.99). Volumetric analysis against an alternative kNN segmentation revealed high inter-method reliability (ICC=.97). Comparison with visual rating scales showed high significant correlations (ARWMC: r=.86; CHIPS: r=.87). The pipeline yields a comprehensive and reliable individualized volumetric profile for subcortical vasculopathy that includes regionalized (26 brain regions) measures for: GM, WM, sCSF, vCSF, lacunar and non-lacunar pvSH and dwSH.
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Enfermedad de Alzheimer/patología , Encéfalo/patología , Interpretación de Imagen Asistida por Computador/métodos , Imagen por Resonancia Magnética , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The effects of progressive hypoxia and re-oxygenation on cardiac function, white muscle perfusion and haemoglobin saturation were investigated in anaesthetised snapper (Pagrus auratus). White muscle perfusion and haemoglobin saturation were recorded in real time using fibre optic methodology. A marked fall in heart rate (HR) was evoked when the water bath dissolved oxygen (DO) concentration decreased below 1.5 mg L(-1). This bradycardia deepened over the subsequent 20 min of progressive hypoxia and noticeable arrhythmias occurred, suggesting that hypoxia had direct and severe effects on the cardiac myocytes. Perfusion to the white muscle decreased below a DO concentration of 3 mg L(-1), and oxyhaemoglobin concentration decreased once the DO fell below ca. 2 mg L(-1). During re-oxygenation, heart rate and white muscle perfusion increased as the DO concentration exceeded 1.9 +/- 0.1 mg L(-1), whereas haemoglobin saturation increased once the external DO concentration reached 2.9 mg L(-1). These changes occurred in anaesthetised fish, in which sensory function must be impaired, if not abolished. As white muscle perfusion both fell and increased prior to changes in white muscle oxyhaemoglobin saturation, a local hypoxia is more likely to be the consequence than the cause of the reduced blood delivery, and changes upstream from the tail vasculature must be responsible. HR and tissue haemoglobin concentrations did increase simultaneously on re-oxygenation suggesting an increased cardiac output as the cause.
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Frecuencia Cardíaca/fisiología , Hemoglobinas/metabolismo , Hipoxia/fisiopatología , Fibras Musculares de Contracción Rápida/fisiología , Oxígeno/metabolismo , Perciformes/fisiología , Análisis de Varianza , Animales , Electrocardiografía , Tecnología de Fibra Óptica/métodos , ReperfusiónAsunto(s)
Esclerosis Amiotrófica Lateral/fisiopatología , Trastornos del Conocimiento/fisiopatología , Lóbulo Frontal/fisiopatología , Trastornos Mentales/fisiopatología , Esclerosis Amiotrófica Lateral/epidemiología , Esclerosis Amiotrófica Lateral/patología , Biomarcadores/análisis , Trastornos del Conocimiento/epidemiología , Trastornos del Conocimiento/patología , Comorbilidad , Progresión de la Enfermedad , Lóbulo Frontal/patología , Predisposición Genética a la Enfermedad/genética , Humanos , Trastornos Mentales/epidemiología , Trastornos Mentales/patología , Trastornos del Humor/epidemiología , Trastornos del Humor/patología , Trastornos del Humor/fisiopatología , Red Nerviosa/metabolismo , Red Nerviosa/patología , Red Nerviosa/fisiopatologíaRESUMEN
To better understand the contributions of effort on cortical activation associated with motor tasks, healthy participants with varying capacities for isolating the control of individual finger movements performed tasks consisting of a single concurrent abduction of all digits (Easy) and paired finger abduction with digits 2 and 3 abducted together concurrently with digits 4 and 5 (Hard). Brain activity was inferred from measurement using functional magnetic resonance imaging. Effort was measured physiologically using electrodermal responses (EDR) and subjectively using the Borg scale. On average, the Borg score for the Hard task was significantly higher (p=0.007) than for the Easy task (2.9+/-1.1 vs. 1.4+/-0.7, respectively). Similarly, the average normalized peak-to-peak amplitude of the EDR was significantly higher (p=0.002) for the Hard task than for the Easy task (20.4+/-6.5% vs. 12.1+/-4.9%, respectively). The Hard task produced increases in sensorimotor network activation, including supplementary motor area, premotor, sensorimotor and parietal cortices, cerebellum and thalamus. When the imaging data were subdivided based on Borg score, there was an increase in activation and involvement of additional areas, including extrastriate and prefrontal cortices. Subdividing the data based on EDR amplitude produced greater effects including activation of the premotor and parietal cortices. These results show that the effort required for task performance influences the interpretation of fMRI data. This work establishes understanding and methodology for advancing future studies of the link between effort and motor control, and may be clinically relevant to sensorimotor recovery from neurologic injury.
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Corteza Cerebral/fisiología , Esfuerzo Físico/fisiología , Desempeño Psicomotor/fisiología , Adulto , Mapeo Encefálico , Señales (Psicología) , Electromiografía , Femenino , Dedos/fisiología , Respuesta Galvánica de la Piel/fisiología , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Movimiento/fisiología , Músculo Esquelético/fisiología , Estimulación Luminosa , Procesamiento de Señales Asistido por Computador , Estadísticas no ParamétricasRESUMEN
BACKGROUND/AIMS: This study aimed to investigate the possible association of regional cerebral perfusion and sleep loss in Alzheimer's disease (AD). METHODS: 55 AD patients were characterized as having (SL) or not having (NSL) nocturnal sleep loss based on standard AD scales assessing sleep over the previous 4 weeks. (99m)Tc-ethylcysteinate dimer SPECT scans were performed in a relaxed, wakeful state. Whole-brain analysis using Statistical Parametrical Mapping (SPM5) was performed to compare perfusion across groups. In addition, the AD groups were compared to normal control (NC) subjects of comparable age and gender to provide a context for interpretation of findings. RESULTS: SPM analysis showed increased perfusion in the right middle frontal gyrus (R-MFG, Brodman area 9, p = 0.016, familywise-error-corrected) in SL versus NSL patients. Comparison with NC subjects confirmed that perfusion in the R-MFG among SL patients did not exceed that found in NCs (relative rather than absolute hyperperfusion). CONCLUSIONS: In this sample of mild-to-moderate AD patients, relative hyperperfusion in the R-MFG is associated with reports of SL. This region may play a role in regulating sleep.
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Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/diagnóstico por imagen , Trastornos del Sueño-Vigilia/complicaciones , Trastornos del Sueño-Vigilia/diagnóstico por imagen , Anciano , Encéfalo/anatomía & histología , Mapeo Encefálico , Circulación Cerebrovascular , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Recuerdo Mental/fisiología , Pruebas Neuropsicológicas , Polisomnografía , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
BACKGROUND AND PURPOSE: Multimodal CT imaging with contrast-enhanced CT angiography (CTA) and CT perfusion (CTP) is increasingly being used to guide emergency management of acute stroke. However, little has been reported about the safety of intravenous contrast administration associated with these studies in the acute stroke population, including cases in which baseline creatinine values are unknown. We investigated the incidence of contrast-induced nephropathy (CIN), defined as a 25% or more increase in baseline creatinine levels within 72 hours of contrast administration and chronic kidney disease in patients receiving CTA+/-CTP at our regional stroke center. MATERIALS AND METHODS: We analyzed 198 patients who underwent contrast CT studies for evaluation of acute ischemic or hemorrhagic stroke at our center (2003-2007). Through retrospective chart abstraction, we analyzed serial creatinine levels (baseline to day 3) and later values (>/=day 4) where available. The incidences of CIN and/or chronic kidney disease were documented. After power analysis, CIN and non-CIN groups were compared by using the unpaired t test, Wilcoxon rank sum test, or Fisher exact test. RESULTS: None of the 198 patients developed chronic kidney disease or required dialysis. Of 175 patients with serial creatinine measurements between baseline and day 3, 5 (2.9%) developed CIN. The incidence of CIN was 2% in patients who were scanned before a baseline creatinine level was available. CONCLUSION: The incidence of renal sequelae is relatively low in acute stroke patients undergoing emergent multimodal CT scanning. Prompt CTA/CTP imaging of acute stroke, if indicated, need not be delayed in those with no history of renal impairment.