RESUMEN
Postmortem (PM) magnetic resonance imaging (MRI) can serve as a bridge between in vivo imaging and histology by connecting MRI observed macrostructural findings to histological staining and microstructural changes. Data were acquired from 20 formalin-fixed brains including T2, T1, PD, and T2*-weighted images of left hemispheres and 6-mm-thick coronal slices. Tissue slices were bisected, aligned to MR images and used to guide histological sampling. Markers of myelin and oligodendroglia alterations were semiquantitatively rated and compared within white matter hyperintensities (WMHs) and normal-appearing white matter. Tissue priors were created from 3T in vivo data and used to guide segmentation of WMH. PM WMH and hemisphere volumes were compared to volumes derived from in vivo data. PM T2 WMH and T1 hemisphere volumes were correlated with in vivo 3T FLAIR WMH and T1 hemisphere volumes. WMH showed significant myelin loss, decreased GFAP expression and increased vimentin expression. MR-visible perivascular spaces and cortical microvascular lesions were successfully captured on histopathological sections. PM MRI can quantify cerebrovascular disease burden and guide tissue sampling, allowing for more comprehensive characterization of cerebrovascular disease that may be used to study etiologies of age-related cognitive change.
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Trastornos Cerebrovasculares , Sustancia Blanca , Humanos , Encéfalo/patología , Imagen por Resonancia Magnética/métodos , Trastornos Cerebrovasculares/patología , Sustancia Blanca/patología , Vaina de MielinaRESUMEN
OBJECTIVE: Periventricular white matter hyperintensities (pvWMHs) are commonly observed on MRI in older individuals and are associated with cognitive and motor decline. The etiology of pvWMH remains unknown. Venous collagenosis has been implicated, which may also interfere with perivascular fluid flow leading to dilation of perivascular spaces (PVS). Here, we examine relationships between in vivo pvWMH volume and ex vivo morphological quantification of collagenosis and the PVS in veins and arteries. METHODS: Brain tissue from 25 Oregon Alzheimer's Disease Research Center subjects was selected to cover the full range of WMH burden. Tissue from white matter abutting the ventricle was stained with Masson's trichrome and smooth muscle actin. An automated hue based algorithm identified and segmented vessel into collagenized vessel walls, lumen, and PVS. Multiple linear regressions with pvWMH volume as the dependent variable and either collagen thickness or PVS width were performed with covariates of vessel diameter, age at death, sex, and interval between MRI and death. RESULTS: PVS width and collagen thickness were significantly correlated in both arteries (r = 0.21, p = 0.001) and veins (r = 0.23, p = 0.001). Increased venous collagen (p = 0.017) was a significant predictor of higher pvWMH burden while arterial collagen was not (p = 0.128). Neither PVS width in arteries (p = 0.937) nor veins (p = 0.133) predicted pvWMH burden. INTERPRETATION: These findings are consistent with a model in which venous collagenosis mediates the relationship between vascular risk factors and pvWMH. This study confirms the importance of changes to the venous system in contributing to MRI white matter lesions commonly observed with advanced age. ANN NEUROL 2022;92:992-1000.
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Enfermedad de Alzheimer , Sustancia Blanca , Humanos , Anciano , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Imagen por Resonancia Magnética , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Ventrículos Cerebrales/patología , Enfermedad de Alzheimer/patologíaRESUMEN
Recent interest in enlarged perivascular spaces (ePVS) in the brain, which can be visualized on MRI and appear isointense to cerebrospinal fluid on all sequence weightings, has resulted in the necessity of reliable algorithms for automated segmentation to allow for whole brain assessment of ePVS burden. However, several publicly available datasets do not contain sequences required for recently published algorithms. This prospective study presents a method for identification of enlarged perivascular spaces (ePVS) in white matter using 3T T1 and FLAIR MR imaging (MAPS-T1), making the algorithm accessible to groups with valuable sets of limited data. The approach was applied identically to two datasets: 1) a repeated measurement in a dementia-free aged human population (Nâ¯=â¯14), and 2) an aged sample of multisite ADNI datasets (Nâ¯=â¯30). ePVS segmentation was accomplished by a stepwise local homogeneity search of white matter-masked T1-weighted data, constrained by FLAIR hyperintensity, and further constrained by width, volume, and linearity measurements. Pearson's r was employed for statistical testing between visual (gold standard) assessment and repeated measures in cohort one. Visual ePVS counts were significantly correlated with MAPS-T1 (r = .72, Pâ¯<â¯.0001). Correlations between repeated measurements in cohort one were significant for both visual and automated methods in the single visually-rated slice (MAPS-T1: r = .87, Pâ¯<â¯.0001, visual: (r = .86, Pâ¯<â¯.0001) and for whole brain assessment (MAPS-T1: r = .77, Pâ¯=â¯.001). Results from each cohort were manually inspected and found to have positive predictive values of 77.5% and 87.5%, respectively. The approach described in this report is an important tool for detailed assessment of ePVS burden in white matter on routinely acquired MRI sequences.
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Envejecimiento , Algoritmos , Enfermedad de Alzheimer/diagnóstico por imagen , Trastornos Cerebrovasculares/diagnóstico por imagen , Sistema Glinfático/diagnóstico por imagen , Interpretación de Imagen Asistida por Computador/métodos , Imagen por Resonancia Magnética/métodos , Neuroimagen/métodos , Sustancia Blanca/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Conjuntos de Datos como Asunto , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Clearance of perivascular wastes in the brain may be critical to the pathogenesis of amyloidopathies. Enlarged perivascular spaces (ePVS) on MRI have also been associated with amyloidopathies, suggesting that there may be a mechanistic link between ePVS and impaired clearance. Sleep and traumatic brain injury (TBI) both modulate clearance of amyloid-beta through glymphatic function. Therefore, we sought to evaluate the relationship between sleep, TBI, and ePVS on brain MRI. A retrospective study was performed in individuals with overnight polysomnography and 3T brain MRI consented from a single site (n = 38). Thirteen of these individuals had a medically confirmed history of TBI. ePVS were visually assessed by blinded experimenters and analyzed in conjunction with sleep metrics and TBI status. Overall, individuals with shorter total sleep time had significantly higher ePVS burden. Furthermore, individuals with TBI showed a stronger relationship between sleep and ePVS compared to the non-TBI group. These results support the hypothesis that ePVS may be modulated by sleep and TBI, and may have implications for the role of the glymphatic system in ePVS.
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Lesiones Traumáticas del Encéfalo/fisiopatología , Sistema Glinfático/patología , Sueño , Encéfalo/diagnóstico por imagen , Femenino , Sistema Glinfático/fisiopatología , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Estudios RetrospectivosRESUMEN
Waste clearance from the brain parenchyma occurs along perivascular pathways. Enlargement of the perivascular space (ePVS) is associated with pathologic features of Alzheimer's disease (AD), although the mechanisms and implications of this dilation are unclear. Fluid exchange along the cerebral vasculature is dependent on the perivascular astrocytic water channel aquaporin-4 (AQP4) and loss of perivascular AQP4 localization is found in AD. We directly measured ePVS in postmortem samples of pathologically characterized tissue from participants who were cognitively intact or had AD or mixed dementia (vascular lesions with AD). We found that both AD and mixed dementia groups had significantly increased ePVS compared to cognitively intact subjects. In addition, we found increased global AQP4 expression of the AD group over both control and mixed dementia groups and a qualitative reduction in perivascular localization of AQP4 in the AD group. Among these cases, increasing ePVS burden was associated with the presence of tau and amyloid-ß pathology. These findings are consistent with the existing evidence of ePVS in AD and provide novel information regarding differences in AD and vascular dementia and the potential role of astroglial pathology in ePVS.
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Enfermedad de Alzheimer/patología , Acuaporina 4/metabolismo , Astrocitos/patología , Encéfalo/patología , Demencia Vascular/patología , Sistema Glinfático/patología , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/metabolismo , Astrocitos/metabolismo , Encéfalo/metabolismo , Demencia Vascular/metabolismo , Femenino , Sistema Glinfático/metabolismo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The deposition of misfolded proteins, including amyloid beta plaques and neurofibrillary tangles is the histopathological hallmark of Alzheimer's disease (AD). The glymphatic system, a brain-wide network of perivascular pathways that supports interstitial solute clearance, is dependent upon expression of the perivascular astroglial water channel aquaporin-4 (AQP4). Impairment of glymphatic function in the aging rodent brain is associated with reduced perivascular AQP4 localization, and in human subjects, reduced perivascular AQP4 localization is associated with AD diagnosis and pathology. Using human transcriptomic data, we demonstrate that expression of perivascular astroglial gene products dystroglycan (DAG1), dystrobrevin (DTNA) and alpha-syntrophin (SNTA1), are associated with dementia status and phosphorylated tau (P-tau) levels in temporal cortex. Gene correlation analysis reveals altered expression of a cluster of potential astrocytic endfoot components in human subjects with dementia, with increased expression associated with temporal cortical P-tau levels. The association between perivascular astroglial gene products, including DTNA and megalencephalic leukoencephalopathy with subcortical cysts 1 (MLC1) with AD status was confirmed in a second human transcriptomic dataset and in human autopsy tissue by Western blot. This suggests changes in the astroglial endfoot domain may underlie vulnerability to protein aggregation in AD.
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Astrocitos/metabolismo , Demencia/genética , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Tauopatías/genética , Transcriptoma , Anciano , Anciano de 80 o más Años , Péptidos beta-Amiloides/metabolismo , Acuaporina 4/genética , Acuaporina 4/metabolismo , Femenino , Humanos , Masculino , Modelos Biológicos , Especificidad de Órganos/genética , Lóbulo Parietal/metabolismo , Lóbulo Parietal/patologíaRESUMEN
OBJECTIVE: We aimed to describe and compare baseline cerebral blood flow (CBF) and microstructural characteristics of normal-appearing white matter (NAWM) within the vulnerable periventricular white matter hyperintensity (PVWMH) penumbra region in predicting white matter hyperintensity (WMH) growth over time. METHODS: Fifty-two patients, aged 82.8 years, underwent serial brain MRI, including pulsed arterial spin labeling and diffusion tensor imaging (DTI). New WMH and persistent NAWM voxels in relation to WMH penumbra at follow-up were identified. Mean baseline CBF and DTI variables of the new WMH and persistent NAWM voxels were computed. Univariate analyses with paired t tests were performed. Generalized estimating equation analyses were used to compare the relationships of baseline CBF, and structural penumbras with WMH growth, controlling for confounders. RESULTS: Low baseline CBF and fractional anisotropy, and high mean diffusivity (MD), were independently associated with new PVWMH voxels, with MD being the best predictor of WMH growth. A separate model demonstrated that radial diffusivity had the strongest relationship with WMH growth compared with CBF and axial diffusivity. CONCLUSION: CBF and DTI measures independently predict WMH growth over time. DTI is a more sensitive predictor of WMH growth than CBF, with WMH progression likely due to demyelinating injury secondary to low perfusion. Findings support the use of MD as a sensitive marker of NAWM vulnerability in future trials aimed at preserving WM integrity.
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Encéfalo/irrigación sanguínea , Encéfalo/patología , Circulación Cerebrovascular , Sustancia Blanca/patología , Anciano , Anciano de 80 o más Años , Ventrículos Cerebrales/patología , Imagen de Difusión Tensora , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Marcadores de Spin , Sustancia Blanca/diagnóstico por imagenRESUMEN
Purpose To describe a fully automated segmentation method that yields object-based morphologic estimates of enlarged perivascular spaces (ePVSs) in clinical-field-strength (3.0-T) magnetic resonance (MR) imaging data. Materials and Methods In this HIPAA-compliant study, MR imaging data were obtained with a 3.0-T MR imager in research participants without dementia (mean age, 85.3 years; range, 70.4-101.2 years) who had given written informed consent. This method is built on (a) relative normalized white matter, ventricular and cortical signal intensities within T1-weighted, fluid-attenuated inversion recovery, T2-weighted, and proton density data and (b) morphologic (width, volume, linearity) characterization of each resultant cluster. Visual rating was performed by three raters, including one neuroradiologist, after established single-section guidelines. Correlations between visual counts and automated counts, as well session-to-session correlation of counts within each participant, were assessed with the Pearson correlation coefficient r. Results There was a significant correlation between counts by visual raters and automated detection of ePVSs in the same section (r = 0.65, P < .001; r = 0.69, P < .001; and r = 0.54, P < .01 for raters 1, 2, and 3, respectively). With regard to visual ratings and whole-brain count consistency, average visual rating scores were highly correlated with automated detection of total burden volume (r = 0.58, P < .01) and total ePVS number (r = 0.76, P < .01). Morphology of clusters across 28 data sets was consistent with published radiographic estimates of ePVS; mean width of clusters segmented was 3.12 mm (range, 1.7-13.5 mm). Conclusion This MR imaging-based method for multimodal autoidentification of perivascular spaces yields individual whole-brain morphologic characterization of ePVS in clinical MR imaging data and is an important tool in the detailed assessment of these features. © RSNA, 2017 Online supplemental material is available for this article.
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Sustancia Blanca/irrigación sanguínea , Anciano , Anciano de 80 o más Años , Circulación Cerebrovascular/fisiología , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Imagen Multimodal/métodos , Neuroimagen/métodos , Estudios Retrospectivos , Relación Señal-Ruido , Sustancia Blanca/anatomía & histologíaRESUMEN
OBJECTIVES: Preclinical studies have shown that blueberry supplementation can improve cognitive performance and neural function in aged animals and have identified associations between anthocyanins and such benefits. Preliminary human trials also suggest cognitive improvement in older adults, although direct evidence of enhancement of brain function has not been demonstrated. In this study, we investigated the effect of blueberry supplementation on regional brain activation in older adults at risk for dementia. METHODS: In a randomized, double-blind, placebo-controlled trial we performed pre- and post-intervention functional magnetic resonance imaging during a working memory (WM) task to assess the effect of blueberry supplementation on blood oxygen level-dependent (BOLD) signal in older adults with mild cognitive impairment, a risk condition for dementia. RESULTS: Following daily supplementation for 16 weeks, blueberry-treated participants exhibited increased BOLD activation in the left pre-central gyrus, left middle frontal gyrus, and left inferior parietal lobe during WM load conditions (corrected P < 0.01). There was no clear indication of WM enhancement associated with blueberry supplementation. Diet records indicated no between-group difference in anthocyanin consumption external to the intervention. DISCUSSION: These data demonstrate, for the first time, enhanced neural response during WM challenge in blueberry-treated older adults with cognitive decline and are consistent with prior trials showing neurocognitive benefit with blueberry supplementation in this at-risk population.
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Arándanos Azules (Planta)/química , Encéfalo/diagnóstico por imagen , Disfunción Cognitiva/dietoterapia , Anciano , Anciano de 80 o más Años , Antocianinas/farmacología , Encéfalo/efectos de los fármacos , Encéfalo/fisiología , Disfunción Cognitiva/diagnóstico por imagen , Demencia , Suplementos Dietéticos , Método Doble Ciego , Femenino , Lóbulo Frontal/diagnóstico por imagen , Lóbulo Frontal/efectos de los fármacos , Frutas , Humanos , Imagen por Resonancia Magnética , Masculino , Memoria a Corto Plazo , Lóbulo Parietal/diagnóstico por imagen , Lóbulo Parietal/efectos de los fármacos , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/efectos de los fármacosRESUMEN
Amyloid-ß (Aß) plaques are a key histopathological hallmark of Alzheimer's disease (AD), and soluble Aß species are believed to play an important role in the clinical development of this disease. Emerging biomarker data demonstrate that Aß plaque deposition begins decades before the onset of clinical symptoms, suggesting that understanding the biological determinants of the earliest steps in the development of AD pathology may provide key opportunities for AD treatment and prevention. Although a clinical association between sleep disruption and AD has long been appreciated, emerging clinical studies and insights from the basic neurosciences have shed important new light on how sleep and Aß homeostasis may be connected in the setting of AD. Aß, like many interstitial solutes, is cleared in part through the exchange of brain interstitial fluid and cerebrospinal fluid along a brain-wide network of perivascular pathways recently termed the glymphatic system. Glymphatic function is primarily a feature of the sleeping brain, rather than the waking brain, and is slowed in the aging and posttraumatic brain. These changes may underlie the diurnal fluctuations in interstitial and cerebrospinal fluid Aß levels observed in both the rodent and the human. These and other emerging studies suggest that age-related sleep disruption may be one key factor that renders the aging brain vulnerable to Aß deposition and the development of AD. If this is true, sleep may represent a key modifiable risk factor or therapeutic target in the preclinical phases of AD.
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Enfermedad de Alzheimer/etiología , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Líquido Cefalorraquídeo/metabolismo , Líquido Extracelular/metabolismo , Sistema Glinfático/metabolismo , Trastornos del Sueño-Vigilia/metabolismo , Animales , HumanosRESUMEN
BACKGROUND: While diagnostic criteria for Alzheimer's disease (AD) include neuroimaging biomarkers, there remains no definitive biomarker of mild cognitive impairment (MCI). MCI is a risk factor for AD that may be amenable to early intervention. Early decline in white matter (WM) integrity identified by diffusion tensor imaging (DTI) is a predictor of future progression of neurodegeneration. OBJECTIVE: Identify regionally specific WM differences between individuals with MCI and those with age-associated memory impairment (AAMI) and relationships with specific memory decrements. METHODS: DTI and neuropsychological data were acquired from 38 participants (23 MCI and 15 AAMI). A region of interest approach was used to evaluate regional differences between groups and correlative relationships with performance on memory tasks. RESULTS: Fornix WM had higher mean (MD), radial (DR), and axial (DA) diffusivity in MCI participants relative to AAMI. Temporal stem (TS) WM had higher MD and DR in MCI than in AAMI. In MCI, TS MD and DR varied, while fornix MD and DR was uniformly high, and in AAMI, TS MD and DR were uniformly low and fornix MD and DR varied. In MCI, TS MD and DA were inversely associated with associative learning but not list learning. CONCLUSIONS: In addition to supporting prior evidence implicating the fornix in early AD pathology, these data implicate a profile of neurodegeneration associated with early MCI. Further, they suggest that associative learning tasks are more sensitive to early neurodegeneration and may be useful in identifying individuals at risk for AD.
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Aprendizaje por Asociación , Encéfalo/patología , Disfunción Cognitiva/patología , Trastornos de la Memoria/patología , Sustancia Blanca/patología , Anciano , Disfunción Cognitiva/psicología , Imagen de Difusión Tensora , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Aprendizaje , Masculino , Trastornos de la Memoria/psicología , Pruebas NeuropsicológicasRESUMEN
Diffusion tensor imaging (DTI) is used to detect tissue pathology. In Alzheimer's disease (AD) research, DTI has been used to elucidate differences in disease stages and to track progression over time and clinical severity. Many of these studies have identified the fornix as particularly vulnerable in the early stages of pathology associated with memory decline in prodromal AD. Emerging research suggests principal tensor components, axial (DA) and radial (DR) diffusivity, are more sensitive to underlying tissue pathology than are mean diffusivity (MD) and fractional anisotropy (FA). Given the established regionally specific tissue decline in MCI, we examined components of the full diffusion tensor (MD, FA, DR, and DA) for sensitivity to regional pathology associated with specific memory deficits in 18 individuals with MCI. We investigated multiple regions of interest, including fornix, temporal stem, and control regions for association with severity of impairment on multiple memory measures, including a type of neuropsychological task shown to be particularly sensitive to early memory decline in MCI. Better paired associate learning was selectively associated with lower DA (ß = -0.663, p = 0.003), but not with DR, MD, or FA of the temporal stems. Conversely, better paired associate learning was associated with lower DR (ß = -0.523, p = 0.026), higher FA (ß = 0.498, p = 0.036), and lower MD (ß = -0.513, p = 0.030), but not DA in the fornix. No association was found for control regions, or for control cognitive measures. These findings suggest disparate pathology of temporal stems and fornix white matter in association with early memory impairment in MCI. Further, they highlight the methodological importance of evaluating the full tensor, rather than only summative metrics in research using DTI.
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Enfermedad de Alzheimer/patología , Encéfalo/patología , Disfunción Cognitiva/patología , Imagen de Difusión Tensora , Fibras Nerviosas Mielínicas/patología , Anciano , Anisotropía , Mapeo Encefálico , Femenino , Lateralidad Funcional/fisiología , Humanos , Masculino , Pruebas Neuropsicológicas , Escalas de Valoración PsiquiátricaRESUMEN
Changes in diffusion tensor imaging (DTI) values co-occur with neurological and functional changes after stroke. However, quantitative DTI metrics have not been examined in response to participation in targeted rehabilitative interventions in chronic stroke. The primary purpose of this pilot study was to examine whether changes in DTI metrics co-occur with paretic arm movement changes among chronic stroke patients participating in a regimen of electrical stimulation targeting the paretic arm. Three subjects exhibiting stable arm hemiparesis were administered 30-minute (n = 1) or 120-minute (n = 2) therapy sessions emphasizing paretic arm use during valued, functional tasks and incorporating an electrical stimulation device. These sessions occurred every weekday for 8 weeks. A fourth subject served as a treatment control, participating in a 30-minute home exercise regimen without electrical stimulation every weekday for 8 weeks. DTI and behavioral outcome measures were acquired at baseline and after intervention. DTI data were analyzed using a region of interest (ROI) approach, with ROIs chosen based on tract involvement in sensorimotor function or as control regions. Behavioral outcome measures were the Fugl-Meyer Scale (FM) and the Action Research Arm Test (ARAT). The treatment control subject exhibited gains in pinch and grasp, as shown by a 5-point increase on the ARAT. The subject who participated in 30-minute therapy sessions exhibited no behavioral gains. Subjects participating in 120-minute therapy sessions displayed consistent impairment reductions and distal movement changes. DTI changes were largest in subjects two and three, with mean diffusivity (MD) decreases in the middle cerebellar peduncle and posterior limb of the internal capsule following treatment. No changes in fractional anisotropy (FA) were observed for sensorimotor tracts. Our preliminary results suggest that active rehabilitative therapies augmented by electrical stimulation may induce positive behavioral changes which are underscored by DTI changes indicative of increased white matter tract integrity in regions specific to sensory-motor function.
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Encéfalo/patología , Imagen de Difusión Tensora/métodos , Terapia por Estimulación Eléctrica/métodos , Manipulaciones Musculoesqueléticas/métodos , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular/patología , Anciano , Femenino , Estudios de Seguimiento , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Paresia/etiología , Paresia/patología , Paresia/rehabilitación , Proyectos Piloto , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular/complicaciones , Resultado del Tratamiento , Extremidad SuperiorRESUMEN
Polyphenol compounds found in berry fruits, in particular flavonoids, have been associated with health benefits including improvement in cognition and neuronal function with aging. Concord grape juice contains polyphenols, including anthocyanins and flavanols, and previous research has shown improvement in a number of human health conditions with grape juice supplementation. In the current study, older adult subjects with mild cognitive impairment consumed Concord grape juice or placebo for 16 weeks and were administered assessments of memory function and brain activation pre- and postintervention. Participants who consumed grape juice showed reduced semantic interference on memory tasks. Relatively greater activation in anterior and posterior regions of the right hemisphere was also observed with functional magnetic resonance imaging in the grape juice treated subjects. These findings provide further evidence that Concord grape juice can enhance neurocognitive function in older adults with mild memory decline.
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Envejecimiento/fisiología , Bebidas/análisis , Frutas/química , Polifenoles/administración & dosificación , Vitis/química , Anciano , Anciano de 80 o más Años , Antocianinas/administración & dosificación , Antioxidantes/administración & dosificación , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Cognición/efectos de los fármacos , Método Doble Ciego , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Memoria/efectos de los fármacos , Estudios ProspectivosRESUMEN
BACKGROUND: Although nonallergic rhinitis (NAR) patients tend to be more sensitive to chemical/olfactory stimuli, a suprathreshold olfactory response or the presence of specific olfactory receptor genes do not explain why their symptoms are triggered by such exposures. OBJECTIVE: To investigate differential neurogenic responses to azelastine in NAR patients, using functional magnetic resonance imaging (fMRI) in response to specific olfactory triggers. METHODS: A longitudinal study design on 12 subjects with a physician diagnosis of NAR previously demonstrated to be clinically responsive to intranasal azelastine (Astelin) was performed. Subjects underwent fMRI during exposure to unpleasant (hickory smoke) and pleasant (vanilla) odorants while off and then on azelastine for 2 weeks. The olfactory fMRI paradigm consisted of a visually triggered sniff every 21 seconds with synchronized delivery of a 4 second pulse of odorant. Each odorant was presented 18 times over 4-6-minute fMRI runs. Continuous fresh air was presented to wash out each odorant after presentation. RESULTS: Nonallergic rhinitis patients exhibited increased blood flow to several regions of the brain in response to both pleasant and unpleasant odorants, specifically in odor-sensitive regions, while off intranasal azelastine. Treatment with intranasal azelastine significantly attenuated blood flow to regions of the brain relevant to either olfactory sensation or sensory processing in response to these odorants compared with fresh air. CONCLUSION: The general reduction compared with increase in brain activation in NAR patients on versus off azelastine suggests that a possible effect of this medication may be reduction of brain responses to odorants.
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Encéfalo/fisiopatología , Odorantes , Ftalazinas/uso terapéutico , Rinitis/tratamiento farmacológico , Rinitis/fisiopatología , Administración Intranasal , Adulto , Encéfalo/irrigación sanguínea , Encéfalo/efectos de los fármacos , Femenino , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Percepción Olfatoria , Ftalazinas/administración & dosificación , Ftalazinas/efectos adversos , Humo , Resultado del Tratamiento , Vanilla , Adulto JovenRESUMEN
Insulin resistance is implicated in the pathophysiological changes associated with Alzheimer's disease, and pharmaceutical treatments that overcome insulin resistance improve memory function in subjects with mild cognitive impairment (MCI) and early Alzheimer's disease. Chromium (Cr) supplementation improves glucose disposal in patients with insulin resistance and diabetes. We sought to assess whether supplementation with Cr might improve memory and neural function in older adults with cognitive decline. In a placebo-controlled, double-blind trial, we randomly assigned 26 older adults to receive either chromium picolinate (CrPic) or placebo for 12 weeks. Memory and depression were assessed prior to treatment initiation and during the final week of treatment. We also performed functional magnetic resonance imaging (fMRI) scans on a subset of subjects. Although learning rate and retention were not enhanced by CrPic supplementation, we observed reduced semantic interference on learning, recall, and recognition memory tasks. In addition, fMRI indicated comparatively increased activation for the CrPic subjects in right thalamic, right temporal, right posterior parietal, and bifrontal regions. These findings suggest that supplementation with CrPic can enhance cognitive inhibitory control and cerebral function in older adults at risk for neurodegeneration.
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Cromo/uso terapéutico , Cognición , Demencia/prevención & control , Suplementos Dietéticos , Trastornos de la Memoria/prevención & control , Memoria , Fármacos Neuroprotectores/uso terapéutico , Anciano , Glucemia/análisis , Encéfalo/metabolismo , Cromo/orina , Demencia/sangre , Demencia/metabolismo , Demencia/orina , Depresión/prevención & control , Método Doble Ciego , Femenino , Humanos , Aprendizaje , Masculino , Trastornos de la Memoria/sangre , Trastornos de la Memoria/metabolismo , Trastornos de la Memoria/orina , Recuerdo Mental , Enfermedades Neurodegenerativas/prevención & control , Fármacos Neuroprotectores/orina , Ácidos Picolínicos/administración & dosificación , Reconocimiento en Psicología , Retención en PsicologíaRESUMEN
The purpose of this study was to conduct a preliminary investigation of the number of response options for self-reports of pain interference. Responses to interference items of the 11-category Brief Pain Inventory (BPI) were obtained in a sample of 434 persons from two sites and modeled using the partial credit model. In successive calibrations, response categories were collapsed and new scores were generated. Scores based on two to three categories produced poor results. Four to five categories yielded better results. However, scoring using more than five categories did not appreciably improve the reliability, person separation, or validity of scores. These results suggest that fewer response categories-as few as five or six-may function as well as the 11 response categories that are conventionally used. The results are preliminary since the number of response categories actually presented was not manipulated in the study design. Future research should compare the reliability and validity of scores based on the BPI interference items when items are presented with the conventionally 11-response format, versus presentation with fewer response options.
RESUMEN
Brain-mapping techniques have proven to be vital in understanding the molecular, cellular, and functional mechanisms of recovery after stroke. This article briefly summarizes the current molecular and functional concepts of stroke recovery and addresses how various neuroimaging techniques can be used to observe these changes. The authors provide an overview of various techniques including diffusion-tensor imaging (DTI), magnetic resonance spectroscopy (MRS), ligand-based positron emission tomography (PET), single-photon emission computed tomography (SPECT), regional cerebral blood flow (rCBF) and regional metabolic rate of glucose (rCMRglc) PET and SPECT, functional magnetic resonance imaging (fMRI), near infrared spectroscopy (NIRS), electroencephalography (EEG), magnetoencephalography (MEG), and transcranial magnetic stimulation (TMS). Discussion in the context of poststroke recovery research informs about the applications and limitations of the techniques in the area of rehabilitation research. The authors also provide suggestions on using these techniques in tandem to more thoroughly address the outstanding questions in the field.