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2.
J Urol ; 211(5): 658-666, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38382042

RESUMO

PURPOSE: To assess the safety and efficacy of gabapentin in reducing postoperative pain among patients undergoing scrotal surgery for male infertility by conducting a randomized, double-blind, placebo-controlled trial. MATERIALS AND METHODS: In this randomized, double-blind, placebo-controlled trial, healthy men undergoing scrotal surgery with a single surgeon were randomized to receive either (1) gabapentin 600 mg given 2 hours preoperatively and 300 mg taken 3 times a day postoperatively for 3 days, or (2) inactive placebo. The primary outcome measure was difference in postoperative pain scores. Secondary outcomes included differences in opioid usage, patient satisfaction, and adverse events. RESULTS: Of 97 patients screened, 74 enrolled and underwent randomization. Of these, 4 men were lost to follow-up, and 70 were included in the final analysis (35 gabapentin, 35 placebo). Both differences in initial postoperative mean pain score (-1.14, 95% CI -2.21 to -0.08, P = .035) and final mean pain score differences (-1.27, 95% CI -2.23 to -0.32, P = .0097) indicated lower gabapentin pain compared to placebo. There were no statistically significant differences in opioid usage, patient satisfaction, or adverse events. CONCLUSIONS: These data suggest that perioperative gabapentin results in a statistically and clinically significant decrease in pain following scrotal surgery. While there was no evidence of an impact on opioid usage or patient satisfaction, given the low risk of adverse events, it may be considered as part of a multimodal pain management strategy.


Assuntos
Analgésicos , Gabapentina , Dor Pós-Operatória , Humanos , Masculino , Analgésicos/efeitos adversos , Analgésicos/uso terapêutico , Analgésicos Opioides/uso terapêutico , Método Duplo-Cego , Gabapentina/efeitos adversos , Gabapentina/uso terapêutico , Manejo da Dor/métodos , Dor Pós-Operatória/prevenção & controle
3.
medRxiv ; 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37645725

RESUMO

Background: Systemic hemodynamics and specific ventilator settings have been shown to predict survival during venoarterial extracorporeal membrane oxygenation (VA ECMO). While these factors are intertwined with right ventricular (RV) function, the independent relationship between RV function and survival during VA ECMO is unknown. Objectives: To identify the relationship between RV function with mortality and duration of ECMO support. Methods: Cardiac ECMO runs in adults from the Extracorporeal Life Support Organization (ELSO) Registry between 2010 and 2022 were queried. RV function was quantified via pulmonary artery pulse pressure (PAPP) for pre-ECMO and on-ECMO periods. A multivariable model was adjusted for Society for Cardiovascular Angiography and Interventions (SCAI) stage, age, gender, and concurrent clinical data (i.e., pulmonary vasodilators and systemic pulse pressure). The primary outcome was in-hospital mortality. Results: A total of 4,442 ECMO runs met inclusion criteria and had documentation of hemodynamic and illness severity variables. The mortality rate was 55%; non-survivors were more likely to be older, have a worse SCAI stage, and have longer pre-ECMO endotracheal intubation times (P < 0.05 for all) than survivors. Improving PAPP from pre-ECMO to on-ECMO time (Δ PAPP) was associated with reduced mortality per 10 mm Hg increase (OR: 0.91 [95% CI: 0.86-0.96]; P=0.002). Increasing on-ECMO PAPP was associated with longer time on ECMO per 10 mm Hg (Beta: 15 [95% CI: 7.7-21]; P<0.001). Conclusions: Early improvements in RV function from pre-ECMO values were associated with mortality reduction during cardiac ECMO. Incorporation of Δ PAPP into risk prediction models should be considered.

4.
Perfusion ; : 2676591231195694, 2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37559410

RESUMO

INTRODUCTION: Heater-cooler units (HCUs) are frequently incorporated into extracorporeal membrane oxygenation (ECMO) circuits to help maintain patient normothermia. However, these devices may be associated with increased cost and infection risk. This study describes our institution's experience managing adult ECMO patients without the routine use of in-circuit HCUs. METHODS: We performed a retrospective analysis of adult patients treated with veno-venous (VV) or veno-arterial (VA) ECMO at our institution. The primary outcomes were rates of HCU use and the relative duration of the ECMO treatment course in which patients maintained normothermia (36-37.5°C), with and without HCUs. Secondary outcomes of mortality and ECMO-related complications were planned across HCU and non-HCU groups; exploratory analyses were performed across a 75% "ECMO time in normothermia" threshold. RESULTS: Among a cohort of 71 patients, zero (0%) were managed with in-circuit HCUs. A majority of ECMO patient-hours were spent in the normothermic range. Median and mean percentages of ECMO normothermia time were 75% (IQR 49%-81%) and 62% (SD ± 27%). Twenty-nine patients (40%) met the threshold of 75% ECMO normothermia time, as used to evaluate secondary outcomes. At this threshold, mortality risk was significantly higher among the non-normothermic cohort; other ECMO-related complications did not vary significantly. CONCLUSIONS: In the absence of HCU use, the majority of ECMO patient-hours were spent in normothermia. However, only a minority of patients achieved normothermia for at least 75% of their ECMO course. In-circuit HCUs may be required to maintain high percentages of normothermic time in adult EMCO patients.

5.
Injury ; 54(8): 110845, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37296012

RESUMO

INTRODUCTION: Elder abuse is common, but many characteristics have not been well-described, including injury mechanisms and weapons in physical abuse. Better understanding of these may improve identification of elder abuse among purportedly unintentional injuries. Our goal was to describe mechanisms of injury and weapons used and their relation to injury patterns. METHODS: We partnered with District Attorney's offices in 3 counties and systematically examined medical, police, and legal records from 164 successfully prosecuted physical abuse cases of victims aged ≥60 from 2001 to 2014. RESULTS: Victims sustained 680 injuries (mean 4.1, median 2.0, range 1-35). Most common mechanisms were: blunt assault with hand/fist (44.5%), push/shove, fall during altercation (27.4%), and blunt assault with object (15.2%). Perpetrators more commonly used body parts as weapons (72.6%) than objects (23.8%). Most commonly used body parts were: open hands (55.5% of victims sustaining injuries from body parts), closed fists (53.8%), and feet (16.0%). Most commonly used objects were: knives (35.9% of victims sustaining injuries from objects) and telephones (10.3%). The most frequent mechanism/injury location pair was maxillofacial/dental/neck injury by blunt assault with hand/fist (20.0% of all injuries). The most frequent mechanism/injury type pair was bruising by blunt assault with hand/fist (15.1% of all injuries). Blunt assault with hand/fist injury was positively associated with victim female sex (OR: 2.27, CI: [1.08 - 4.95]; p = 0.031), while blunt assault with object mechanisms was inversely associated with victim female sex (OR: 0.32, CI: [0.12 - 0.81]; p = 0.017). CONCLUSION: Physical elder abuse victims are more commonly assaulted with an abuser's body part than an object, and the mechanisms and weapons used impact patterns of injury.


Assuntos
Contusões , Vítimas de Crime , Abuso de Idosos , Idoso , Humanos , Feminino , Criança , Abuso Físico , Contusões/epidemiologia , Pescoço
6.
PLoS One ; 18(2): e0281993, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36800368

RESUMO

Vaccine development against COVID-19 has mitigated severe disease. However, reports of rare but serious adverse events following immunization (sAEFI) in the young populations are fuelling parental anxiety and vaccine hesitancy. With a very early season of viral illnesses including COVID-19, respiratory syncytial virus (RSV), influenza, metapneumovirus and several others, children are facing a winter with significant respiratory illness burdens. Yet, COVID-19 vaccine and booster uptake remain sluggish due to the mistaken beliefs that children have low rates of severe COVID-19 illness as well as rare but severe complications from COVID-19 vaccine are common. In this study we examined composite sAEFI reported in association with COVID-19 vaccines in the United States (US) amongst 5-17-year-old children, to ascertain the composite reported risk associated with vaccination. Between December 13, 2020, and April 13, 2022, a total of 467,890,599 COVID-19 vaccine doses were administered to individuals aged 5-65 years in the US, of which 180 million people received at least 2 doses. In association with these, a total of 177,679 AEFI were reported to the Vaccine Adverse Event reporting System (VAERS) of which 31,797 (17.9%) were serious. The rates of ED visits per 100,000 recipients were 2.56 (95% CI: 2.70-3.47) amongst 5-11-year-olds, 18.25 (17.57-18.95) amongst 12-17-year-olds and 33.74 (33.36-34.13) amongst 18-65-year olds; hospitalizations were 1.07 (95% CI 0.87-1.32) per 100,000 in 5-11-year-olds, 6.83 (6.42-7.26) in 12-17-year olds and 8.15 (7.96-8.35) in 18-65 years; life-threatening events were 0.14 (95% CI: 0.08-0.25) per 100,000 in 5-11-year olds, 1.22 (1.05-1.41) in 12-17-year-olds and 2.96 (2.85-3.08) in 18-65 year olds; and death 0.03 (95% CI 0.01-0.10) per 100,000 in 5-11 year olds, 0.08 (0.05-0.14) amongst 12-17-year olds and 0.76 (0.71-0.82) in 18-65 years age group. The results of our study from national population surveillance data demonstrate rates of reported serious AEFIs amongst 5-17-year-olds which appear to be significantly lower than in 18-65-year-olds. These low risks must be taken into account in overall recommendation of COVID-19 vaccination amongst children.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Sistemas de Notificação de Reações Adversas a Medicamentos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Imunização/efeitos adversos , Estados Unidos/epidemiologia , Vacinação/efeitos adversos
7.
J Alzheimers Dis ; 87(3): 1229-1238, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35466933

RESUMO

BACKGROUND: Determining amyloid positivity is possible with cerebrospinal fluid and brain imaging of amyloid, but these methods are invasive and expensive. OBJECTIVE: To relate plasma amyloid-ß (Aß), measured using Single-molecule array (Simoatrademark) assays, to in vivo brain Aß, measured using positron emission tomography (PET), examine the accuracy of plasma Aß to predict brain Aß positivity, and the relation of APOE ɛ4 with plasma Aß. METHODS: We performed a cross-sectional analysis in a cohort of 345 late middle-aged Hispanic men and women (age 64 years, 72% women). Our primary plasma variable was Aß42/Aß40 ratio measured with Simoa. Brain Aß burden was measured as global SUVR with 18F-Florbetaben PET examined continuously and categorically. RESULTS: Plasma Aß42/Aß40 ratio was inversely associated with global Aß SUVR (ß= -0.13, 95% Confidence Interval (CI): -0.23, -0.03; p = 0.013) and Aß positivity (Odds Ratio: 0.59, 95% CI: 0.38, 0.91; p = 0.016), independent of demographics and APOE ɛ4. ROC curves (AUC = 0.73, 95% CI: 0.64, 0.82; p < 0.0001) showed that the optimal threshold for plasma Aß42/Aß40 ratio in relation to brain Aß positivity was 0.060 with a sensitivity of 82.4% and specificity of 62.8%. APOE ɛ4 carriers had lower Aß42/Aß40 ratio and a higher Aß positivity determined with the Aß42/Aß40 ratio threshold of 0.060. CONCLUSION: Plasma Aß42/Aß40 ratio assayed using Simoa is weakly correlated with in vivo brain amyloid and has limited accuracy in screening for amyloid positivity and for studying risk factors of brain amyloid burden when in vivo imaging is not feasible.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Amiloide , Fatores Etários , Doença de Alzheimer/sangue , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/metabolismo , Amiloide/sangue , Amiloide/metabolismo , Peptídeos beta-Amiloides/sangue , Peptídeos beta-Amiloides/metabolismo , Apolipoproteínas E/sangue , Apolipoproteínas E/metabolismo , Biomarcadores/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Estudos Transversais , Feminino , Hispânico ou Latino , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Fragmentos de Peptídeos/metabolismo , Tomografia por Emissão de Pósitrons
8.
Otol Neurotol ; 43(3): e382-e390, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35147609

RESUMO

OBJECTIVE: Worse hearing was linked to higher brain ß-amyloid, a pathologic hallmark of Alzheimer's disease, in a recent study. We analyze the associations between ß-amyloid and early age-related hearing loss in the right versus left ear to explore the laterality of this relationship. STUDY DESIGN: Cross-sectional analysis of a prospective cohort study. SETTING: Tertiary referral center. PARTICIPANTS: Ninety-eight late middle-age adults. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The primary outcome was whole brain and regional ß-amyloid standardized uptake value ratio (SUVR) on positron emission tomography. The exposure was hearing in the right and left ear, measured by pure tone average (PTA) and word recognition score (WRS). Linear regression analyzed the association between ß-amyloid and hearing in each ear, adjusting for potential confounders, including age, gender, education, cardiovascular disease, and hearing aid use. RESULTS: Mean age ±â€Šstandard deviation was 64.3 ±â€Š3.5 years. Mean PTA was 20.4 ±â€Š8.8 dB. Multivariable regression adjusting for covariates demonstrated that a 10 dB worsening in PTA in the left ear was associated with significantly higher ß-amyloid (SUVR) in the bilateral cingulate gyri (right coefficient: 0.029 [95% confidence interval: 0.003-0.054]; left: 0.029 [0.003-0.055]), bilateral frontal lobes (right: 0.024 [0.002-0.047]; left: 0.028 [0.006-0.049]), and the right temporal lobe (0.019 [0.002-0.037]). Consistent results were observed when WRS served as the exposure. No associations were observed between ß-amyloid and PTA or WRS in the right ear. CONCLUSIONS: Worse hearing in the left ear, but not the right ear, was associated with higher ß-amyloid. This might relate to asymmetric central auditory processing.


Assuntos
Peptídeos beta-Amiloides , Presbiacusia , Adulto , Audiometria de Tons Puros/métodos , Encéfalo/diagnóstico por imagem , Estudos Transversais , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos
9.
J Alzheimers Dis ; 82(1): 317-325, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34024821

RESUMO

BACKGROUND: The National Institute on Aging (NIA)/Alzheimer's Association (AA) 2018 framework conceptualizes Alzheimer's disease (AD) biologically. Evidence of brain amyloid by biomarkers defines AD pathologic change and the Alzheimer's continuum. The presence of tau or neurodegeneration in the absence of amyloid defines non-AD pathologic change. OBJECTIVE: To examine the relation of in vivo amyloid and neurodegeneration with verbal learning, one of the cognitive abilities affected early in AD, in late middle age. METHODS: This was a cross-sectional study of amyloid and neurodegeneration biomarkers in a community-based cohort of 350 late-middle aged Hispanics without dementia (mean age: 64.15±3.34; 72.0%women). Amyloid (A) was measured as global standardized uptake value ratio (SUVR) with 18F-Florbetaben positron emission tomography (PET). Neurodegeneration (N) was ascertained as cortical thickness (CT) in AD signature areas using brain magnetic resonance imaging. We examined A/N continuously, categorically, by A/N profiles, and profile categories. The amyloid threshold for positivity was defined using the K means method. The CT threshold was defined as 2 standard deviations below the mean CT. Verbal learning was ascertained using total recall and delayed recall in the Buschke Selective Reminding test (SRT). RESULTS: Higher cortical thickness was associated with higher performance in SRT delayed recall. Amyloid SUVR was not related to SRT performance. The low CT category was associated with lower performance in SRT delayed recall, while Amyloid categories were not related to any SRT score. The non-AD pathologic change group (A-N+) performed worse in SRT delayed recall compared to the Normal A/N profile group (A-N-). CONCLUSION: In late middle-aged Hispanics without dementia, non-AD pathologic change, but not the Alzheimer's continuum, was related to verbal learning.


Assuntos
Amiloide/metabolismo , Disfunção Cognitiva/fisiopatologia , Hispânico ou Latino/estatística & dados numéricos , Aprendizagem Verbal , Biomarcadores , Encéfalo/patologia , Estudos Transversais , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons
10.
Neurobiol Aging ; 103: 109-116, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33894641

RESUMO

It is unclear whether women have higher brain tau pathology. The objective of this study was to examine whether women have higher tau burden than men, and whether tau differences are independent of amyloid ß (Aß) burden. We conducted a cross-sectional analysis of a multiethnic sample of 252 nondemented late middle-aged (mean age: 64.1 years) adults with tau and amyloid Positron Emission Tomography (PET) data. Tau burden was measured as global standardized uptake value ratio (SUVR) in the middle/inferior temporal gyri and medial temporal cortex with 18F-MK-6240 PET. Aß was measured as global SUVR with 18F-Florbetaben PET. Women had higher middle/inferior temporal gyri tau SUVR compared to men. However, no sex differences in the medial temporal cortex were observed. Women had higher brain Aß SUVR compared to men. Continuous Aß SUVR was positively correlated with medial temporal cortex and middle/inferior temporal gyri tau SUVR. However, there was no evidence of effect modification by Aß SUVR on sex and tau. Compared with men, women in late middle age show higher tau burden, independent of Aß.


Assuntos
Caracteres Sexuais , Tauopatias/diagnóstico , Lobo Temporal/metabolismo , Proteínas tau/metabolismo , Idoso , Peptídeos beta-Amiloides/metabolismo , Biomarcadores/metabolismo , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuroimagem , Tomografia por Emissão de Pósitrons , Fatores Sexuais , Tauopatias/epidemiologia , Lobo Temporal/diagnóstico por imagem
11.
Neurobiol Aging ; 97: 89-96, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33166929

RESUMO

Metabolic syndrome (MetS) is associated with dementia, but it is unclear whether MetS is related to Alzheimer's disease (AD). We investigated the association of MetS with brain amyloid, a key AD feature, and neurodegeneration. A community-based sample of 350 middle-aged Hispanics in New York City had cerebral amyloid ß (Aß) burden ascertained with 18F-Florbetaben positron emission tomography. Neurodegeneration was ascertained as cortical thickness in AD signature regions from 3T brain MRI. MetS and its components (glucose, blood pressure, triglycerides, high-density lipoprotein, adiposity) were defined using the National Institutes of Health criteria. Neither the presence of MetS nor the MetS score was associated with Aß or neurodegeneration. Among the MetS components, elevated glucose was associated with lower Aß burden, and this association was not explained by diabetes treatment. Glucose and triglycerides were related to smaller cortical thickness. Our findings suggest that MetS as an arbitrary measure of aggregate metabolic and vascular risk does not capture the risk of AD neuropathology in late middle age and that other approaches to measure the aggregate risk should be examined.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Síndrome Metabólica/metabolismo , Síndrome Metabólica/patologia , Degeneração Neural , Fatores Etários , Doença de Alzheimer/etiologia , Compostos de Anilina , Glicemia/metabolismo , Encéfalo/diagnóstico por imagem , Imagem de Tensor de Difusão , Feminino , Hispânico ou Latino , Humanos , Masculino , Pessoa de Meia-Idade , New York , Risco , Estilbenos , Triglicerídeos/metabolismo
12.
Laryngoscope ; 131(3): 633-638, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32644260

RESUMO

OBJECTIVES/HYPOTHESIS: To analyze the association between early audiometric age-related hearing loss and brain ß-amyloid, the pathologic hallmark of Alzheimer's disease (AD). STUDY DESIGN: Cross-sectional analysis of a prospective cohort study. METHODS: A cross-sectional analysis was performed on 98 participants in a cohort study of hearing and brain biomarkers of AD. The primary outcome was whole brain ß-amyloid standardized uptake value ratio (SUVR) on positron emission tomography (PET). The exposure was hearing, as measured by either pure-tone average or word recognition score in the better ear. Covariates included age, gender, education, cardiovascular disease, and hearing aid use. Linear regression was performed to analyze the association between ß-amyloid and hearing, adjusting for potentially confounding covariates. RESULTS: The mean age ± standard deviation was 64.6 ± 3.5 years. In multivariable regression, adjusting for demographics, education, cardiovascular disease, and hearing aid use, whole brain ß-amyloid SUVR increased by 0.029 (95% confidence interval [CI]: 0.003-0.056) for every 10 dB increase in pure-tone average (P = .030). Similarly, whole brain ß-amyloid SUVR increased by 0.061 (95% CI: 0.009-0.112) for every 10% increase in word recognition score (P = .012). CONCLUSIONS: Worsening hearing was associated with higher ß-amyloid burden, a pathologic hallmark of AD, measured in vivo with PET scans. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:633-638, 2021.


Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Tomografia por Emissão de Pósitrons , Presbiacusia/metabolismo , Idoso , Doença de Alzheimer/complicações , Audiometria de Tons Puros , Biomarcadores/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Estudos Transversais , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Presbiacusia/psicologia , Estudos Prospectivos , Análise de Regressão
13.
Front Neurol ; 11: 529930, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33123070

RESUMO

Non-linear relations of brain amyloid beta (Aß) with task- based functional connectivity (tbFC) measured with functional magnetic resonance imaging (fMRI) have been reported in late middle age. Our objective was to examine the association between brain Aß and resting-state functional connectivity (rsFC) in late middle-aged adults. Global brain Aß burden was ascertained with 18F-Florbetaben Positron Emission Tomography (PET); rsFC was ascertained on 3T Magnetic Resonance Imaging (MRI) among 333 late middle-aged Hispanics adults without dementia in four major brain functional connectivity networks: default mode network (DMN), fronto-parietal control network (FPC), salience network (SAL) and dorsal attention network (DAN). We examined the relationship of global brain Aß with rsFC using multivariable linear regression adjusted for age, sex, education, and APOE-ε4 genotype. We quantified the non-linear associations both with quadratic terms and by categorizing Aß into three groups: low Aß, intermediate Aß, and positive Aß. We found no significant linear or non-linear associations between Aß, measured either continuously or categorically, with rsFC in the examined networks. Our null findings may be explained by the younger age of our participants in whom amyloid burden is relatively low. It is also possible that the recently reported non-linear relationship is exclusive to task fMRI and not rsfMRI.

14.
Neurology ; 95(15): e2086-e2094, 2020 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-32847955

RESUMO

OBJECTIVE: To examine in vivo amyloid burden in relation to APOEε4 genotype in middle-aged Hispanics. We hypothesize higher amyloid levels among APOE ε4 carriers vs APOE ε4 noncarriers. METHODS: This is a cross-sectional study in a community-based sample of 249 middle-aged Hispanics in New York City who underwent a 3T brain MRI and PET with the amyloid radioligand 18F-florbetaben. APOE genotype was the primary exposure. The primary outcome was amyloid positivity. The secondary outcome was subthreshold amyloid levels examined as a continuous variable. RESULTS: APOE ε4 carriers (n = 85) had a higher frequency (15.3%) of amyloid positivity compared to APOE ε4 noncarriers (n = 164, 1.8%). In the subthreshold group of amyloid-negative participants (n = 233), APOE ε4 carriers (n = 72) had a 0.02 (95% confidence interval [CI] 0.01-0.04) higher global brain amyloid standardized uptake value ratio (SUVR) compared to APOE ε4 noncarriers (n = 161). Compared to participants with the ε3/ε3 genotype, participants with ε4/ε4 had the highest frequency of amyloid positivity (28.6%), followed by those with ε3/ε4 (11%). Among amyloid-negative participants (n = 233), compared to participants with ε3/ε3 (n = 134), those with ε4/ε4 (n = 5) had a 0.12 (95% CI 0.07-0.17) higher global brain amyloid SUVR, and those with ε3/ε4 had a 0.02 higher SUVR (95% CI 0.003-0.04). Results were similar when a median split was used for elevated amyloid, when continuous amyloid SUVR was analyzed in all participants, and in nonparametric Mann-Whitney comparisons. CONCLUSION: Middle-aged Hispanic APOE ε4 carriers have higher in vivo brain amyloid burden compared with noncarriers, as reported in non-Hispanics.


Assuntos
Amiloide/metabolismo , Apolipoproteína E4/genética , Encéfalo/metabolismo , Hispânico ou Latino/estatística & dados numéricos , Fatores Etários , Idoso , Compostos de Anilina/metabolismo , Estudos Transversais , Feminino , Genótipo , Heterozigoto , Hispânico ou Latino/genética , Humanos , Masculino , Pessoa de Meia-Idade , Estilbenos/metabolismo
15.
J Alzheimers Dis ; 75(4): 1241-1252, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32390636

RESUMO

BACKGROUND: Type 2 diabetes is a dementia risk factor, but its relation to Alzheimer's disease (AD), the most common cause of dementia, is unclear. OBJECTIVE: Our primary objective was to examine the association of pre-diabetes and type 2 diabetes with brain amyloid-ß (Aß), the putative main culprit of AD. Our secondary objective was to examine the association of pre-diabetes and type 2 diabetes with neurodegeneration, cerebrovascular disease (CVD), and memory performance. METHODS: We conducted a cross-sectional study of 350 late middle-aged Hispanics without dementia in New York City. We classified diabetes status as normal glucose tolerance (NGT), pre-diabetes, and type 2 diabetes following American Diabetes Association criteria. Brain Aß was ascertained as global Aß standardized value uptake ratio using PET with 18F-Florbetaben. Neurodegeneration was operationalized as cortical thickness in regions affected by AD using MRI. CVD was operationalized as white matter hyperintensity volume (WMH) on MRI, and memory as performance with the selective reminding test (SRT). RESULTS: Mean age was 64.15±3.34 years, 72.00% were women, and 35.43% were APOEɛ4 carriers. Pre-diabetes, but not type 2 diabetes, was associated with higher Aß compared with NGT. Type 2 diabetes treatment was related to lower Aß. Type 2 diabetes was related to lower cortical thickness, higher WMH, and lower SRT score. CONCLUSION: Pre-diabetes, but not type 2 diabetes, is associated with higher brain Aß in late middle age, and this observation could be explained by the relation of diabetes treatment with lower brain Aß. Whether type 2 diabetes treatment lowers brain Aß requires further study.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Estado Pré-Diabético/metabolismo , Estado Pré-Diabético/patologia , Idoso , Encéfalo/diagnóstico por imagem , Estudos Transversais , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Feminino , Teste de Tolerância a Glucose , Hispânico ou Latino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Estado Pré-Diabético/diagnóstico por imagem
16.
J Alzheimers Dis ; 74(4): 1243-1252, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32250303

RESUMO

BACKGROUND: Females may have a higher risk of dementia than males. It is not clear if sex differences in Alzheimer's disease (AD) neuropathology explain the higher risk of dementia in females. Sex differences in AD neuropathology might begin in middle age, decades before the sex differences in dementia are apparent. OBJECTIVE: To examine sex differences in in vivo AD neuropathology in late middle age. METHODS: We conducted a cross-sectional comparison of AD biomarkers among 266 Hispanic males and females (mean age: 64.0; 71.8% females) without dementia. Amyloid burden was measured as global standardized uptake value ratio (SUVR) with18F-Florbetaben positron emission tomography (PET). Neurodegeneration was ascertained as cortical thickness in AD signature areas using brain magnetic resonance imaging. Tau burden was measured as tau SUVR in the middle/inferior temporal gyri and medial temporal cortex with 18F-MK-6240 in 75 of the 266 participants. RESULTS: Females had higher amyloid SUVR and tau SUVR in the middle/inferior temporal gyri than males. However, females had higher cortical thickness than males and performed better in a test of verbal memory despite having higher AD neuropathology burden. CONCLUSION: Higher amyloid and tau in females compared to males in late middle-age may explain the reported higher dementia risk in elderly females compared to males. Longitudinal follow-up is necessary to examine whether higher amyloid and tau burden in late middle age is followed by increased neurodegeneration and cognitive decline in females as compared with males.


Assuntos
Doença de Alzheimer/patologia , Hispânico ou Latino/estatística & dados numéricos , Proteínas Amiloidogênicas/metabolismo , Biomarcadores/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Encéfalo/patologia , Estudos Transversais , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Tomografia por Emissão de Pósitrons , Fatores Sexuais , Proteínas tau/metabolismo
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