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INTRODUCTION: Motor function has correlated with longevity and functionality; however, there is limited research on those with Alzheimer's disease (AD). We studied the association between motor functionality and AD pathology in primary motor and medial temporal cortices. METHODS: A total of 206 participants with a clinical diagnosis of cognitively healthy, AD, or mild cognitive impairment (MCI) underwent imaging and motor assessment. Linear regressions and analyses of variance were applied to test the prediction from AD imaging biomarkers to motor performance and the diagnosis group differences in motor performance. RESULTS: Increased neurodegeneration was associated with worsening dexterity and lower walking speed, and increased amyloid and tau were associated with worsening dexterity. AD and MCI participants had lower motor performance than the cognitively healthy participants. DISCUSSION: Increased AD pathology is associated with worsening dexterity performance. The decline in dexterity in those with AD pathology may offer an opportunity for non-pharmacological therapy intervention. HIGHLIGHTS: Noted worsening dexterity performance was associated with greater Alzheimer's disease (AD) pathology (tau, amyloid beta, and neurodegeneration) in primary motor cortices. Similarly, increased neurodegeneration and tau pathology in parahippocampal, hippocampal, and entorhinal cortices is associated with worsening dexterity performance. Motor performance declined in those with clinical and preclinical AD among an array of motor assessments.
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Postmortem studies of Parkinson's disease (PD) suggest that Lewy body pathology accumulates in a predictable topographical sequence, beginning in the olfactory bulb, followed by caudal brainstem, substantia nigra, limbic cortex, and neocortex. Diffusion-weighted imaging (DWI) is sensitive, if not specific, to early disease-related white matter (WM) change in a variety of traumatic and degenerative brain diseases. Although numerous cross-sectional studies have reported DWI differences in cerebral WM in PD, only a few longitudinal studies have investigated whether DWI change exceeds that of normal aging or coincides with regional Lewy body accumulation. This study mapped regional differences in the rate of DWI-based microstructural change between 29 PD patients and 43 age-matched controls over 18 months. Iterative within- and between-subject tensor-based registration was completed on motion- and eddy current-corrected DWI images, then baseline versus follow-up difference maps of fractional anisotropy, mean, radial, and axial diffusivity were analyzed in the Biological Parametric Mapping toolbox for MATLAB. This analysis showed that PD patients had a greater decline in WM integrity in the rostral brainstem, caudal subcortical WM, and cerebellar peduncles, compared with controls. In addition, patients with unilateral clinical signs at baseline experienced a greater rate of WM change over the 18-month study than patients with bilateral signs. These findings suggest that rate of WM microstructural change in PD exceeds that of normal aging and is maximal during early stage disease. In addition, the neuroanatomic locations (rostral brainstem and subcortical WM) of accelerated WM change fit with current theories of topographic disease progression.
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Envejecimiento/patología , Imagen de Difusión por Resonancia Magnética/métodos , Progresión de la Enfermedad , Enfermedad de Parkinson/patología , Sustancia Blanca/patología , Anciano , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/diagnóstico por imagen , Índice de Severidad de la Enfermedad , Sustancia Blanca/diagnóstico por imagenRESUMEN
Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene that result in loss of the dystrophin-glycoprotein complex, a laminin receptor that connects the myofiber to its surrounding extracellular matrix. Utrophin, a dystrophin ortholog that is normally localized to the neuromuscular junction, is naturally upregulated in DMD muscle, which partially compensates for the loss of dystrophin. Transgenic overexpression of utrophin causes broad sarcolemma localization of utrophin, restoration of laminin binding and amelioration of disease in the mdx mouse model of DMD. We previously demonstrated that overexpression of sarcospan, a dystrophin- and utrophin-binding protein, ameliorates mdx muscular dystrophy. Sarcospan boosts levels of utrophin to therapeutic levels at the sarcolemma, where attachment to laminin is restored. However, understanding the compensatory mechanism is complicated by concomitant upregulation of α7ß1 integrin, which also binds laminin. Similar to the effects of utrophin, transgenic overexpression of α7 integrin prevents DMD disease in mice and is accompanied by increased abundance of utrophin around the extra-synaptic sarcolemma. In order to investigate the mechanisms underlying sarcospan 'rescue' of muscular dystrophy, we created double-knockout mice to test the contributions of utrophin or α7 integrin. We show that sarcospan-mediated amelioration of muscular dystrophy in DMD mice is dependent on the presence of both utrophin and α7ß1 integrin, even when they are individually expressed at therapeutic levels. Furthermore, we found that association of sarcospan into laminin-binding complexes is dependent on utrophin and α7ß1 integrin.
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Antígenos CD/metabolismo , Proteínas Portadoras/metabolismo , Cadenas alfa de Integrinas/metabolismo , Laminina/metabolismo , Proteínas de la Membrana/metabolismo , Distrofia Muscular de Duchenne/metabolismo , Proteínas de Neoplasias/metabolismo , Utrofina/metabolismo , Animales , Antígenos CD/genética , Proteínas Portadoras/genética , Femenino , Humanos , Cadenas alfa de Integrinas/genética , Integrinas/genética , Integrinas/metabolismo , Laminina/genética , Masculino , Proteínas de la Membrana/genética , Ratones , Ratones Endogámicos mdx , Ratones Noqueados , Músculo Esquelético/metabolismo , Distrofia Muscular de Duchenne/genética , Proteínas de Neoplasias/genética , Unión Proteica , Utrofina/genéticaRESUMEN
INTRODUCTION: Family history (FH) of Alzheimer's disease (AD) affects mitochondrial function and may modulate effects of translocase of the outer mitochondrial membrane 40 kDa (TOMM40) rs10524523 ('523) poly-T length on memory decline. METHODS: For 912 nonapolipoprotein ε4 middle-aged adults and 365 aged adults across the AD spectrum, linear mixed models gauged FH and TOMM40 '523 interactions on memory and global cognition between baseline and up to 10 years later. A cerebrospinal fluid mitochondrial function biomarker was also assessed. RESULTS: For FH negative participants, gene-dose preservation of memory and global cognition was seen for "very long" versus "short" carriers. For FH positive, an opposite gene-dose decline was seen for very long versus short carriers. Maternal FH was a stronger predictor in aged, but not middle-aged, participants. Similar gene-dose effects were seen for the mitochondrial biomarker aspartate aminotransferase. DISCUSSION: These results may clarify conflicting findings on TOMM40 poly-T length and AD-related decline.
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Enfermedad de Alzheimer , Salud de la Familia , Predisposición Genética a la Enfermedad/genética , Proteínas de Transporte de Membrana/genética , Trastornos de la Memoria/etiología , Polimorfismo de Nucleótido Simple/genética , Adulto , Anciano , Enfermedad de Alzheimer/líquido cefalorraquídeo , Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/genética , Apolipoproteínas E/genética , Estudios de Cohortes , Femenino , Genotipo , Humanos , Masculino , Escala del Estado Mental , Persona de Mediana Edad , Proteínas del Complejo de Importación de Proteínas Precursoras Mitocondriales , Pruebas NeuropsicológicasRESUMEN
OBJECTIVES: The purpose of this study was to assess whether age-related differences in white matter microstructure are associated with altered task-related connectivity during episodic recognition. METHODS: Using functional magnetic resonance imaging and diffusion tensor imaging from 282 cognitively healthy middle-to-late aged adults enrolled in the Wisconsin Registry for Alzheimer's Prevention, we investigated whether fractional anisotropy (FA) within white matter regions known to decline with age was associated with task-related connectivity within the recognition network. RESULTS: There was a positive relationship between fornix FA and memory performance, both of which negatively correlated with age. Psychophysiological interaction analyses revealed that higher fornix FA was associated with increased task-related connectivity amongst the hippocampus, caudate, precuneus, middle occipital gyrus, and middle frontal gyrus. In addition, better task performance was associated with increased task-related connectivity between the posterior cingulate gyrus, middle frontal gyrus, cuneus, and hippocampus. CONCLUSIONS: The findings indicate that age has a negative effect on white matter microstructure, which in turn has a negative impact on memory performance. However, fornix microstructure did not significantly mediate the effect of age on performance. Of interest, dynamic functional connectivity was associated with better memory performance. The results of the psychophysiological interaction analysis further revealed that alterations in fornix microstructure explain-at least in part-connectivity among cortical regions in the recognition memory network. Our results may further elucidate the relationship between structural connectivity, neural function, and cognition.
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Mapeo Encefálico , Lóbulo Frontal/diagnóstico por imagen , Lóbulo Frontal/fisiología , Memoria Episódica , Vías Nerviosas/fisiología , Reconocimiento en Psicología/fisiología , Adulto , Factores de Edad , Anciano , Imagen de Difusión Tensora , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Vías Nerviosas/diagnóstico por imagen , Pruebas Neuropsicológicas , Estimulación Luminosa , Estadística como Asunto , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/fisiologíaRESUMEN
BACKGROUND: Postoperative urinary retention (POUR) is a relatively common complication after total joint arthroplasty (TJA). Based on the findings of a randomized, prospective study from our institution, we abandoned the routine use of indwelling urinary catheters in patients undergoing elective TJA using opioid-free spinal anesthesia. The aim of this study was to determine the incidence of and the risk factors for POUR in this patient population. PATIENTS AND METHODS: A total of 842 consecutive patients underwent TJA between January 2012 and September 2014 using opioid-free spinal anesthesia in whom indwelling urinary catheters were not used. Postoperative urinary retention was defined as the inability of a patient to void that necessitated the placement of either an indwelling urinary catheter or straight catheterization. Multivariate logistic regression analysis was used to determine risk factors for developing POUR. RESULTS: In this cohort, 79 patients (79/842; 9.3%) developed POUR. Independent risk factors for POUR were history of a benign prostatic hyperplasia (P = .02), renal disease (P = .001), longer operative time (P = .003), and age older than 67 years (P = .02). No patients in this cohort developed neurogenic bladder. CONCLUSION: This study confirms that the routine use of indwelling urinary catheters for patients undergoing TJA using an opioid-free spinal anesthesia may not be warranted. Urinary catheters may be used selectively in patients at risk for subsequent urinary retention.
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Anestesia Raquidea , Complicaciones Posoperatorias/etiología , Cateterismo Urinario/efectos adversos , Retención Urinaria/etiología , Adulto , Anciano , Anciano de 80 o más Años , Analgésicos Opioides , Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Contraindicaciones , Procedimientos Quirúrgicos Electivos/efectos adversos , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Philadelphia/epidemiología , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Estudios Prospectivos , Factores de Riesgo , Retención Urinaria/epidemiología , Retención Urinaria/prevención & controlRESUMEN
INTRODUCTION: The present study investigated the relationship between beta-amyloid (Aß) and cognition in a late middle-aged cohort at risk for Alzheimer's disease (AD). METHODS: One eighty-four participants (mean age = 60; 72% parental history of AD) completed a [C-11]Pittsburgh compound B positron emission tomography scan and serial cognitive evaluations. A global measure of Aß burden was calculated, and composite scores assessing learning, delayed memory, and executive functioning were computed. RESULTS: Higher Aß was associated with classification of psychometric mild cognitive impairment (MCI) at follow-up (P < .01). Linear mixed effects regression results indicated higher Aß was associated with greater rates of decline in delayed memory (P < .01) and executive functioning (P < .05). Apolipoprotein E (APOE) ε4 status moderated the relationship between Aß and cognitive trajectories (P values <.01). DISCUSSION: In individuals at risk for AD, greater Aß in late middle age is associated with increased likelihood of MCI at follow-up and steeper rates of cognitive decline.
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Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Disfunción Cognitiva/metabolismo , Anciano , Encéfalo/metabolismo , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas/estadística & datos numéricos , Tomografía de Emisión de Positrones/métodos , Síntomas Prodrómicos , Sistema de Registros , WisconsinRESUMEN
The aim of this study was to examine cross-sectionally whether higher cardiorespiratory fitness (CRF) might favorably modify amyloid-ß (Aß)-related decrements in cognition in a cohort of late-middle-aged adults at risk for Alzheimer's disease (AD). Sixty-nine enrollees in the Wisconsin Registry for Alzheimer's Prevention participated in this study. They completed a comprehensive neuropsychological exam, underwent 11C Pittsburgh Compound B (PiB)-PET imaging, and performed a graded treadmill exercise test to volitional exhaustion. Peak oxygen consumption (VO2peak) during the exercise test was used as the index of CRF. Forty-five participants also underwent lumbar puncture for collection of cerebrospinal fluid (CSF) samples, from which Aß42 was immunoassayed. Covariate-adjusted regression analyses were used to test whether the association between Aß and cognition was modified by CRF. There were significant VO2peak*PiB-PET interactions for Immediate Memory (p=.041) and Verbal Learning & Memory (p=.025). There were also significant VO2peak*CSF Aß42 interactions for Immediate Memory (p<.001) and Verbal Learning & Memory (p<.001). Specifically, in the context of high Aß burden, that is, increased PiB-PET binding or reduced CSF Aß42, individuals with higher CRF exhibited significantly better cognition compared with individuals with lower CRF. In a late-middle-aged, at-risk cohort, higher CRF is associated with a diminution of Aß-related effects on cognition. These findings suggest that exercise might play an important role in the prevention of AD.
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Amiloide/metabolismo , Trastornos del Conocimiento/rehabilitación , Aptitud Física/fisiología , Adulto , Anciano , Enfermedad de Alzheimer/complicaciones , Péptidos beta-Amiloides/líquido cefalorraquídeo , Compuestos de Anilina/farmacocinética , Trastornos del Conocimiento/líquido cefalorraquídeo , Trastornos del Conocimiento/diagnóstico por imagen , Trastornos del Conocimiento/etiología , Estudios de Cohortes , Estudios Transversales , Prueba de Esfuerzo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Consumo de Oxígeno , Fragmentos de Péptidos/líquido cefalorraquídeo , Tomografía de Emisión de Positrones , Escalas de Valoración Psiquiátrica , Tiazoles/farmacocinética , Aprendizaje VerbalRESUMEN
Cerebral blood flow (CBF) provides an indication of the metabolic status of the cortex and may have utility in elucidating preclinical brain changes in persons at risk for Alzheimer's disease (AD) and related diseases. In this study, we investigated CBF in 327 well-characterized adults including patients with AD (n = 28), patients with amnestic mild cognitive impairment (aMCI, n = 23), older cognitively normal (OCN, n = 24) adults, and asymptomatic middle-aged adults (n = 252) with and without a family history (FH) of AD. Compared with the asymptomatic cohort, AD patients displayed significant hypoperfusion in the precuneus, posterior cingulate, lateral parietal cortex, and the hippocampal region. Patients with aMCI exhibited a similar but less marked pattern of hypoperfusion. Perfusion deficits within the OCN adults were primarily localized to the inferior parietal lobules. Asymptomatic participants with a maternal FH of AD showed hypoperfusion in hippocampal and parietofrontal regions compared with those without a FH of AD or those with only a paternal FH of AD. These observations persisted when gray matter volume was included as a voxel-wise covariate. Our findings suggest that having a mother with AD might confer a particular risk for AD-related cerebral hypoperfusion in midlife. In addition, they provide further support for the potential utility of arterial spin labeling for the measurement of AD-related neurometabolic dysfunction, particularly in situations where [18F]fluorodeoxyglucose imaging is infeasible or clinically contraindicated.
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Enfermedad de Alzheimer/patología , Encéfalo/fisiopatología , Circulación Cerebrovascular/fisiología , Hijo de Padres Discapacitados , Relaciones Madre-Hijo , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/genética , Apolipoproteína E4/genética , Mapeo Encefálico , Disfunción Cognitiva/genética , Disfunción Cognitiva/patología , Femenino , Humanos , Imagenología Tridimensional , Imagen por Resonancia Magnética , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Insulin resistance (IR) increases Alzheimer's disease (AD) risk. IR is related to greater amyloid burden post-mortem and increased deposition within areas affected by early AD. No studies have examined if IR is associated with an in vivo index of amyloid in the human brain in late middle-aged participants at risk for AD. METHODS: Asymptomatic, late middle-aged adults (N = 186) from the Wisconsin Registry for Alzheimer's Prevention underwent [C-11]Pittsburgh compound B (PiB) positron emission tomography. The cross-sectional design tested the interaction between insulin resistance and glycemic status on PiB distribution volume ratio in three regions of interest (frontal, parietal, and temporal). RESULTS: In participants with normoglycemia but not hyperglycemia, higher insulin resistance corresponded to higher PiB uptake in frontal and temporal areas, reflecting increased amyloid deposition. CONCLUSIONS: This is the first human study to demonstrate that insulin resistance may contribute to amyloid deposition in brain regions affected by AD.
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Amiloide/metabolismo , Encéfalo/metabolismo , Resistencia a la Insulina , Anciano , Compuestos de Anilina/farmacocinética , Apolipoproteínas E/genética , Índice de Masa Corporal , Encéfalo/diagnóstico por imagen , Femenino , Humanos , Hiperglucemia/complicaciones , Imagenología Tridimensional , Imagen por Resonancia Magnética , Masculino , Escala del Estado Mental , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Valor Predictivo de las Pruebas , Tiazoles/farmacocinéticaRESUMEN
Sarcospan (SSPN) is a core component of the major adhesion complexes in skeletal muscle, the dystrophin- and utrophin (Utr)-glycoprotein complexes (DGC and UGC). We performed a rigorous analysis of SSPN-null mice and discovered that loss of SSPN decreased DGC and UGC abundance, leading to impaired laminin-binding activity and susceptibility to eccentric contraction-induced injury in skeletal muscle. We show that loss of SSPN increased levels of α7ß1 integrin. To genetically test whether integrin compensates for the loss of DGC and UGC function in SSPN-nulls, we generated mice lacking both SSPN and α7 integrin (DKO, double knockout). Muscle regeneration, sarcolemma integrity and fibrosis were exacerbated in DKO mice and were remarkably similar to muscle from Duchenne muscular dystrophy (DMD) patients, suggesting that secondary loss of integrin contributes significantly to pathogenesis. Expression of the DGC and UGC, laminin binding and Akt signaling were negatively impacted in DKO muscle, resulting in severely diminished specific force properties. We demonstrate that SSPN is a necessary component of dystrophin and Utr function and that SSPN modulation of integrin signaling is required for extracellular matrix attachment and muscle force development.
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Antígenos CD/genética , Proteínas Portadoras/genética , Distrofina/genética , Cadenas alfa de Integrinas/genética , Proteínas de la Membrana/genética , Músculo Esquelético/metabolismo , Proteínas de Neoplasias/genética , Fenotipo , Utrofina/genética , Animales , Antígenos CD/metabolismo , Proteínas Portadoras/metabolismo , Modelos Animales de Enfermedad , Femenino , Cadenas alfa de Integrinas/metabolismo , Masculino , Proteínas de la Membrana/metabolismo , Ratones , Ratones Noqueados , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/metabolismo , Proteínas de Neoplasias/metabolismo , Sarcolema/metabolismoRESUMEN
OBJECTIVES: Although age-related brain changes are becoming better understood, midlife patterns of change are still in need of characterization, and longitudinal studies are lacking. The aim of this study was to determine if baseline fractional anisotropy (FA), obtained from diffusion tensor imaging (DTI) predicts volume change over a 4-year interval. EXPERIMENTAL DESIGN: Forty-four cognitively healthy middle-age adults underwent baseline DTI and longitudinal T1-weighted magnetic resonance imaging. Tensor-based morphometry methods were used to evaluate volume change over time. FA values were extracted from regions of interest that included the cingulum, entorhinal white matter, and the genu and splenium of the corpus callosum. Baseline FA was used as a predictor variable, whereas gray and white matter atrophy rates as indexed by Tensor-based morphometry were the dependent variables. PRINCIPAL OBSERVATIONS: Over a 4-year period, participants showed significant contraction of white matter, especially in frontal, temporal, and cerebellar regions (P < 0.05, corrected for multiple comparisons). Baseline FA in entorhinal white matter, genu, and splenium was associated with longitudinal rates of atrophy in regions that included the superior longitudinal fasciculus, anterior corona radiata, temporal stem, and white matter of the inferior temporal gyrus (P < 0.001, uncorrected for multiple comparisons). CONCLUSIONS: Brain change with aging is characterized by extensive shrinkage of white matter. Baseline white matter microstructure as indexed by DTI was associated with some of the observed regional volume loss. The findings suggest that both white matter volume loss and microstructural alterations should be considered more prominently in models of aging and neurodegenerative diseases.
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Mapeo Encefálico , Encéfalo/patología , Leucoencefalopatías/diagnóstico , Adulto , Anciano , Anisotropía , Apolipoproteína E4/genética , Atrofia/patología , Imagen de Difusión por Resonancia Magnética , Imagen de Difusión Tensora , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The relative influence of amyloid burden, neuronal structure and function, and prior cognitive performance on prospective memory decline among asymptomatic late middle-aged individuals at risk for Alzheimer's disease (AD) is currently unknown. We investigated this using longitudinal cognitive data from 122 middle-aged adults (21 "Decliners" and 101 "Stables") enrolled in the Wisconsin Registry for Alzheimer's Prevention who underwent multimodality neuroimaging [11C-Pittsburgh Compound B (PiB), 18F-fluorodeoxyglucose (FDG), and structural/functional magnetic resonance imaging (fMRI)] 5.7 ± 1.4 years (range = 2.9-8.9) after their baseline cognitive assessment. Covariate-adjusted regression analyses revealed that the only imaging measure that significantly distinguished Decliners from Stables (p = .027) was a Neuronal Function composite derived from FDG and fMRI. In contrast, several cognitive measures, especially those that tap episodic memory, significantly distinguished the groups (p's<.05). Complementary receiver operating characteristic curve analyses identified the Brief Visuospatial Memory Test-Revised (BVMT-R) Total (.82 ± .05, p < .001), the BVMT-R Delayed Recall (.73 ± .06, p = .001), and the Reading subtest from the Wide-Range Achievement Test-III (.72 ± .06, p = .002) as the top three measures that best discriminated the groups. These findings suggest that early memory test performance might serve a more clinically pivotal role in forecasting future cognitive course than is currently presumed.
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Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/patología , Amiloide/metabolismo , Encéfalo/metabolismo , Encéfalo/patología , Trastornos del Conocimiento/etiología , Adulto , Anciano , Enfermedad de Alzheimer/genética , Análisis de Varianza , Apolipoproteína E4/genética , Encéfalo/irrigación sanguínea , Encéfalo/diagnóstico por imagen , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Neuroimagen , Pruebas Neuropsicológicas , Oxígeno/sangre , Curva ROC , Cintigrafía , Estudios Retrospectivos , Factores de RiesgoRESUMEN
In Parkinson's disease (PD), reduced cerebral cortical thickness may reflect network-based degeneration. This study performed cognitive assessment and brain MRI in 30 PD participants and 41 controls at baseline and 18 months later. We hypothesized that cerebral cortical thickness and volume, as well as change in these metrics, would differ between PD participants who remained cognitively stable and those who experienced cognitive decline. Dividing the participant sample into PD-stable, PD-decline, and control-stable groups, we compared mean cortical thickness and volume within segments that comprise the prefrontal cognitive-control, memory, dorsal spatial, and ventral object-based networks at baseline. We then compared the rate of change in cortical thickness and volume between the same groups using a vertex-wise approach. We found that the PD-decline group had lower cortical thickness within all 4 cognitive networks in comparison with controls, as well as lower cortical thickness within the prefrontal and medial temporal networks in comparison with the PD-stable group. The PD-decline group also experienced a greater rate of volume loss in the lateral temporal cortices in comparison with the control group. This study suggests that lower thickness and volume in prefrontal, medial, and lateral temporal regions may portend cognitive decline in PD.
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BACKGROUND: The All of Us Research Program seeks to advance precision medicine and reduce health disparities by recruiting people in demographic categories that are underrepresented in biomedical research. Asian Americans, Native Hawaiians and Pacific Islanders are the most understudied of all racial/ethnic groups in the United States. We propose a national engagement strategy for the recruitment of Asian Americans, Native Hawaiians and Pacific Islanders into biomedical research using a community-based participatory research approach. METHODS: We partnered with Asian serving community-based organizations across the United States to increase education and awareness and developed a culturally and linguistically tailored approach for the engagement of AANHPIs into All of Us Research Program. RESULTS: In the first year, our national engagement strategy reached more than 35,000 AANHPIs through promotional events and educational sessions. CONCLUSIONS: Our success is a result of our equal and mutually beneficial partnership with community-based organizations who have access to rich, local knowledge and hold a unique role within the community.
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Investigación Biomédica , Salud Poblacional , Asiático , Investigación Participativa Basada en la Comunidad , Humanos , Grupos Minoritarios , Estados UnidosRESUMEN
Neurite orientation dispersion and density imaging (NODDI) is an advanced diffusion imaging technique, which can detect more distinct microstructural features compared to conventional Diffusion Tensor Imaging (DTI). NODDI allows the signal to be divided into multiple water compartments and derive measures for orientation dispersion index (ODI), neurite density index (NDI) and volume fraction of isotropic diffusion compartment (FISO). This study aimed to investigate which diffusion metric-fractional anisotropy (FA), mean diffusivity (MD), NDI, ODI, or FISO-is most influenced by aging and reflects cognitive function in a population of healthy older adults at risk for Alzheimer's disease (AD). Age was significantly associated with all but one diffusion parameters and regions of interest. NDI and MD in the cingulate region adjacent to the cingulate cortex showed a significant association with a composite measure of Executive Function and was proven to partially mediate the relationship between aging and Executive Function decline. These results suggest that both DTI and NODDI parameters are sensitive to age-related differences in white matter regions vulnerable to aging, particularly among older adults at risk for AD.
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Introduction: This study examined the relationship between cardiorespiratory fitness (CRF) and longitudinal cognitive functioning in a cohort enriched with risk factors for Alzheimer's disease (AD). Methods: A total of 155 enrollees in the Wisconsin Registry for Alzheimer's Prevention completed repeat comprehensive neuropsychological evaluations that assessed six cognitive domains. Peak oxygen consumption (VO2peak) was the primary measure of CRF. Random effects regression was used to investigate the effect of CRF on cognitive trajectories. Results: Higher CRF was associated with slower decline in the cognitive domains of verbal learning and memory (P < .01) and visual learning and memory (P < .042). Secondary analyses indicated that these effects were stronger among men than women, and for noncarriers of the apolipoprotein E ε4 allele. Discussion: Higher CRF was associated with a slower rate of the decline in episodic memory that occurs as a natural consequence of aging in a cohort enriched with risk factors for AD.
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Insulin resistance (IR) has been related to reduced cerebral glucose metabolism in regions identified as hypometabolic in Alzheimer's clinical syndrome. Insulin secretion (IS) has been less studied than IR despite findings that decreased IS is an early indicator of future type 2 diabetes and a potential predictor of Alzheimer's clinical syndrome. We investigated whether higher IR and lower IS would be associated with greater age-related reductions in regional cerebral glucose metabolism and worse cognitive performance. Two-hour oral glucose tolerance testing and 18F-fluorodeoxyglucose positron emission tomography were performed on 1-2 occasions on a sample of healthy middle-aged and older adults from the Wisconsin Alzheimer's Disease Research Center. Neuropsychological tests were completed during Alzheimer's Disease Research Center Clinical Core visits. Pattern of findings suggested that lower (not higher) IS was related to higher regional cerebral glucose metabolism in middle aged but not older adults, and lower (not higher) IS was also related to better immediate recall. In the context of healthy insulin sensitivity, lower IS may be beneficial to brain health.
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Envejecimiento/metabolismo , Envejecimiento/psicología , Encéfalo/metabolismo , Cognición/fisiología , Glucosa/efectos adversos , Glucosa/metabolismo , Resistencia a la Insulina/fisiología , Secreción de Insulina/efectos de los fármacos , Factores de Edad , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/etiología , Enfermedad de Alzheimer/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Masculino , Memoria a Corto Plazo , Persona de Mediana Edad , Pruebas NeuropsicológicasRESUMEN
Cerebral hypoperfusion is thought to contribute to cognitive decline in Alzheimer's disease, but the natural trajectory of cerebral perfusion in cognitively healthy adults has not been well-studied. This longitudinal study is consisted of 950 participants (40-89 years), who were cognitively unimpaired at their first visit. We investigated the age-related changes in cerebral perfusion, and their associations with APOE-genotype, biological sex, and cardiometabolic measurements. During the follow-up period (range 0.13-8.24 years), increasing age was significantly associated with decreasing cerebral perfusion, in total gray-matter (ß=-1.43), hippocampus (-1.25), superior frontal gyrus (-1.70), middle frontal gyrus (-1.99), posterior cingulate (-2.46), and precuneus (-2.14), with all P-values < 0.01. Compared with male-É4 carriers, female-É4 carriers showed a faster decline in global and regional cerebral perfusion with increasing age, whereas the age-related decline in cerebral perfusion was similar between male- and female-É4 non-carriers. Worse cardiometabolic profile (i.e., increased blood pressure, body mass index, total cholesterol, and blood glucose) was associated with lower cerebral perfusion at all the visits. When time-varying cardiometabolic measurements were adjusted in the model, the synergistic effect of sex and APOE-É4 on age-related cerebral perfusion-trajectories became largely attenuated. Our findings demonstrate that APOE-genotype and sex interactively impact cerebral perfusion-trajectories in mid- to late-life. This effect may be partially explained by cardiometabolic alterations.
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Enfermedad de Alzheimer/metabolismo , Apolipoproteína E4/genética , Corteza Cerebral/diagnóstico por imagen , Circulación Cerebrovascular/genética , Disfunción Cognitiva/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/diagnóstico , Apolipoproteína E4/metabolismo , Factores de Riesgo Cardiometabólico , Corteza Cerebral/irrigación sanguínea , Corteza Cerebral/metabolismo , Circulación Cerebrovascular/fisiología , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/etiología , Femenino , Estudios de Seguimiento , Genotipo , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Factores Sexuales , Marcadores de SpinRESUMEN
BACKGROUND: Korean-American women experience a higher incidence of cervical cancer than non-Hispanic White women as well as other Asian-American women. A prominent cause of such a disproportional health risk among Korean-American women is a lack of awareness and knowledge of cervical cancer screening. Identifying factors related to cervical cancer screening awareness and literacy is critical for increasing cervical cancer screening among this population. METHODS: Researchers surveyed 230 Korean-American women in a metro area in a Southeastern state, USA. Based on Anderson's Behavioral Model of Health Services Use, predisposing, enabling, and need factors were explored to predict cervical cancer screening awareness and literacy. RESULTS: Monthly income, education, English proficiency, and annual checkups had significantly positive associations with cervical cancer screening awareness. Having an acquaintance giving support and receiving an annual checkup had significantly positive relationships with cervical cancer screening literacy. DISCUSSION: This study recommends culture specific guidelines to promote annual checkups through primary care physicians and the transfer of information about cervical cancer screening through acquaintances giving support.