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1.
J Am Geriatr Soc ; 2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32086949

RESUMO

OBJECTIVE: To examine the association between being a medical doctor (MD) and the risk of incident dementia. DESIGN: Cohort study. SETTING: Olmsted County, Minnesota. PARTICIPANTS: A total of 3460 participants (including 104 MDs), aged 70 years or older, of the population-based Mayo Clinic Study of Aging. MEASUREMENTS: Participants were randomly selected from the community and had comprehensive cognitive evaluations at baseline and approximately every 15 months to assess for diagnosis of dementia. For participants who withdrew from the follow-up, dementia diagnosis was also assessed using information available in their medical record. The associations were examined using Cox proportional hazards models, adjusting for sex, education, and apolipoprotein E ε4, using age as the time scale. RESULTS: MDs were older (vs "general population"), and most were males (93.3%). MDs without dementia at baseline did not have a significantly different risk for incident dementia (hazard ratio = 1.12; 95% confidence interval = 0.69-1.82; P = .64) compared to the general population. CONCLUSIONS: Although the study includes a small number of older, mainly male, MDs, it provides a preliminary insight on cognitive health later in life in MDs, while most previous studies examine the health of younger MDs. Larger longitudinal studies are needed to examine these associations and investigate if associations are modified by sex.

2.
Neurobiol Aging ; 88: 42-50, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31918955

RESUMO

Loss-of-function mutations in the progranulin gene (GRN) are one of the major causes of familial frontotemporal lobar degeneration. Our objective was to determine the rates and trajectories of lobar cortical atrophy from longitudinal structural magnetic resonance imaging in both asymptomatic and symptomatic GRN mutation carriers. Individuals in this study were from the ADRC and LEFFTDS studies at the Mayo Clinic. We identified 13 GRN mutation carriers (8 asymptomatic, 5 symptomatic) and noncarriers (n = 10) who had at least 2 serial T1-weighted structural magnetic resonance images and were followed annually with a median of 3 years (range 1.0-9.8 years). Longitudinal changes in lobar cortical volume were analyzed using the tensor-based morphometry with symmetric normalization (TBM-SyN) algorithm. Linear mixed-effect models were used to model cortical volume change over time among 3 groups. The annual rates of frontal (p < 0.05) and parietal (p < 0.01) lobe cortical atrophy were higher in asymptomatic GRN mutation carriers than noncarriers. The symptomatic GRN mutation carriers also had increased rates of atrophy in the frontal (p < 0.01) and parietal lobe (p < 0.01) cortices than noncarriers. In addition, greater rates of cortical atrophy were observed in the temporal lobe cortices of symptomatic GRN mutation carriers than noncarriers (p < 0.001). We found that a decline in frontal and parietal lobar cortical volume occurs in asymptomatic GRN mutation carriers and continues in the symptomatic GRN mutation carriers, whereas an increased rate of temporal lobe cortical atrophy is observed only in symptomatic GRN mutation carriers. This sequential pattern of cortical involvement in GRN mutation carriers has important implications for using imaging biomarkers of neurodegeneration as an outcome measure in potential treatment trials involving GRN mutation carriers.

3.
J Am Soc Nephrol ; 31(2): 415-423, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31974271

RESUMO

BACKGROUND: Nephrosclerosis, nephron size, and nephron number vary among kidneys transplanted from living donors. However, whether these structural features predict kidney transplant recipient outcomes is unclear. METHODS: Our study used computed tomography (CT) and implantation biopsy to investigate donated kidney features as predictors of death-censored graft failure at three transplant centers participating in the Aging Kidney Anatomy study. We used global glomerulosclerosis, interstitial fibrosis/tubular atrophy, artery luminal stenosis, and arteriolar hyalinosis to measure nephrosclerosis; mean glomerular volume, cortex volume per glomerulus, and mean cross-sectional tubular area to measure nephron size; and calculations from CT cortical volume and glomerular density on biopsy to assess nephron number. We also determined the death-censored risk of graft failure with each structural feature after adjusting for the predictive clinical characteristics of donor and recipient. RESULTS: The analysis involved 2293 donor-recipient pairs. Mean recipient follow-up was 6.3 years, during which 287 death-censored graft failures and 424 deaths occurred. Factors that predicted death-censored graft failure independent of both donor and recipient clinical characteristics included interstitial fibrosis/tubular atrophy, larger cortical nephron size (but not nephron number), and smaller medullary volume. In a subset with 12 biopsy section slides, arteriolar hyalinosis also predicted death-censored graft failure. CONCLUSIONS: Subclinical nephrosclerosis, larger cortical nephron size, and smaller medullary volume in healthy donors modestly predict death-censored graft failure in the recipient, independent of donor or recipient clinical characteristics. These findings provide insights into a graft's "intrinsic quality" at the time of donation, and further support the use of intraoperative biopsies to identify kidney grafts that are at higher risk for failure.

4.
Alzheimers Dement ; 16(1): 37-48, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31272932

RESUMO

INTRODUCTION: Some models of therapy for neurodegenerative diseases envision starting treatment before symptoms develop. Demonstrating that such treatments are effective requires accurate knowledge of when symptoms would have started without treatment. Familial frontotemporal lobar degeneration offers a unique opportunity to develop predictors of symptom onset. METHODS: We created dementia risk scores in 268 familial frontotemporal lobar degeneration family members by entering covariate-adjusted standardized estimates of brain atrophy into a logistic regression to classify asymptomatic versus demented participants. The score's predictive value was tested in a separate group who were followed up longitudinally (stable vs. converted to dementia) using Cox proportional regressions with dementia risk score as the predictor. RESULTS: Cross-validated logistic regression achieved good separation of asymptomatic versus demented (accuracy = 90%, SE = 0.06). Atrophy scores predicted conversion from asymptomatic or mildly/questionably symptomatic to dementia (HR = 1.51, 95% CI: [1.16,1.98]). DISCUSSION: Individualized quantification of baseline brain atrophy is a promising predictor of progression in asymptomatic familial frontotemporal lobar degeneration mutation carriers.

5.
Eur J Ageing ; 16(4): 491-502, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31798373

RESUMO

In this study derived from the population-based Mayo Clinic Study of Aging, we investigated whether non-exercise physical activity (PA) was associated with global and domain-specific cognitive trajectories (memory, language, visuospatial skills, attention) and whether the association differed by apolipoprotein E (APOE) ε4 genotype status. We included 2061 community-dwelling individuals aged ≥ 70 years (50.5% males, 26.7% APOE ε4 carriers) who were cognitively unimpaired at baseline and on whom serial cognitive data and self-reported information on non-exercise PA were available. We specifically inquired about non-exercise PA carried out at two time points, i.e., midlife (between 50 and 65 years of age) and late-life (within 1 year prior to assessment) and three intensity levels, i.e., light (e.g., laundry), moderate (e.g., scrubbing floors) and heavy (e.g., hard manual labor). Linear mixed-effect models revealed that engaging in midlife PA of moderate or heavy intensity was associated with significantly less-pronounced decline of z-scores in all cognitive domains. Similarly, participants that engaged in late-life moderate or heavy PA had less decline in visuospatial, attention and global z-scores than non-active peers. These associations varied depending on APOE ε4 carrier status, i.e., APOE ε4 non-carriers but not APOE ε4 carriers that engaged in late-life PA had less decline in cognitive z-scores. In contrast, engaging in midlife PA, irrespective of intensity, was significantly associated with less decline in memory function only among APOE ε4 carriers.

6.
JAMA Netw Open ; 2(12): e1916439, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31790563

RESUMO

Importance: In patients with probable dementia with Lewy bodies (DLB), overlapping Alzheimer disease pathology is frequent and is associated with faster decline and shorter survival. More than half of patients with DLB have elevated ß-amyloid levels on carbon-11 labeled Pittsburgh compound B (PiB) positron emission tomography, but the trajectory of longitudinal ß-amyloid accumulation and its associations with clinical and cognitive decline in DLB are not known. Objectives: To determine the trajectory of ß-amyloid accumulation in patients with probable DLB and to investigate the associations of ß-amyloid accumulation with measures of clinical and cognitive decline over time in DLB. Design, Setting, and Participants: This cohort study included 35 consecutive patients with probable DLB from the Mayo Clinic Alzheimer Disease Research Center and matched them by age, sex, and apolipoprotein e4 status with 140 cognitively unimpaired participants from the population-based Mayo Clinic Study of Aging. Participants were observed from April 2010 to September 2017. Data analysis was conducted from January 2018 to January 2019. Exposure: Baseline and follow-up PiB positron emission tomography and comprehensive clinical evaluations. Main Outcomes and Measures: Rate of change in PiB standardized uptake value ratios (SUVRs) by PiB SUVR and time in years; the associations between baseline PiB SUVR, change in PiB SUVR, and change in several measures of clinical and cognitive decline. Results: A total of 175 participants were evaluated (35 [20.0%] with probable DLB; mean [SD] age, 69.6 [7.3] years; 16 [45.7%] apolipoprotein e4 carriers; 31 [88.6%] men; and 140 [80.0%] cognitively unimpaired adults; mean [SD] age, 69.7 [7.2] years; 64 [45.7%] apolipoprotein e4 carriers; 124 [88.6%] men). In both groups, the rates of change in PiB SUVR showed an initial acceleration at lower baseline PiB SUVR followed by a deceleration at higher baseline PiB SUVR, thus forming an inverted-U shape. The trajectories of the rates of change in PiB SUVR did not differ between participants with probable DLB and cognitively unimpaired participants in terms of shape (P = .59) or vertical shift (coefficient [SE] 0.007 [0.006]; P = .22). The integral association of cumulative PiB SUVR with time in years showed a sigmoid-shaped functional form in both groups. In participants with probable DLB, higher baseline PiB SUVR and change in PiB SUVR were associated with more rapid clinical decline, as measured by the Clinical Dementia Rating, sum of boxes (baseline PiB SUVR: regression coefficient [SE], 1.90 [0.63]; P = .005; R2 = 0.215; change in PiB SUVR, regression coefficient [SE], 16.17 [7.47]; P = .04; R2 = 0.124) and the Auditory Verbal Learning Test, delayed recall (baseline PiB SUVR, regression coefficient [SE], -2.09 [0.95]; P = .04; R2 = 0.182; change in PiB SUVR, regression coefficient [SE], -25.05 [10.04]; P = .02; R2 = 0.221). Conclusions and Relevance: In this study, the rate of change in PiB SUVR among participants with probable DLB increased, peaked, and then decreased, which was similar to the trajectory in cognitively unimpaired participants and the Alzheimer disease dementia continuum. Higher baseline PiB SUVR and change in PiB SUVR were associated with more rapid clinical and cognitive decline over time. Measuring the change in PiB SUVR has implications for designing anti-ß-amyloid randomized clinical trials for individuals with probable DLB.

7.
J Bone Joint Surg Am ; 101(21): 1931-1938, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31567670

RESUMO

BACKGROUND: Manual chart review is labor-intensive and requires specialized knowledge possessed by highly trained medical professionals. Natural language processing (NLP) tools are distinctive in their ability to extract critical information from raw text in electronic health records (EHRs). As a proof of concept for the potential application of this technology, we examined the ability of NLP to correctly identify common elements described by surgeons in operative notes for total hip arthroplasty (THA). METHODS: We evaluated primary THAs that had been performed at a single academic institution from 2000 to 2015. A training sample of operative reports was randomly selected to develop prototype NLP algorithms, and additional operative reports were randomly selected as the test sample. Three separate algorithms were created with rules aimed at capturing (1) the operative approach, (2) the fixation method, and (3) the bearing surface category. The algorithms were applied to operative notes to evaluate the language used by 29 different surgeons at our center and were applied to EHR data from outside facilities to determine external validity. Accuracy statistics were calculated with use of manual chart review as the gold standard. RESULTS: The operative approach algorithm demonstrated an accuracy of 99.2% (95% confidence interval [CI], 97.1% to 99.9%). The fixation technique algorithm demonstrated an accuracy of 90.7% (95% CI, 86.8% to 93.8%). The bearing surface algorithm demonstrated an accuracy of 95.8% (95% CI, 92.7% to 97.8%). Additionally, the NLP algorithms applied to operative reports from other institutions yielded comparable performance, demonstrating external validity. CONCLUSIONS: NLP-enabled algorithms are a promising alternative to the current gold standard of manual chart review for identifying common data elements from orthopaedic operative notes. The present study provides a proof of concept for use of NLP techniques in clinical research studies and registry-development endeavors to reliably extract data of interest in an expeditious and cost-effective manner.

9.
Ultrasound Med Biol ; 45(11): 2887-2897, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31488311

RESUMO

Nerve movement is decreased in patients with carpal tunnel syndrome and can be assessed with ultrasound. In addition to morphologic features, this study describes a novel approach in which nerve movement and the association with short-term patient-reported outcome are assessed. Ultrasound images at the carpal tunnel inlet were acquired during finger and wrist flexion. Linear regression models were used with the Boston Carpal Tunnel Questionnaire as main outcome. Eighty-five patients were included; 93% completed the 3-mo follow-up. Pre-surgical mean nerve area was 14.5 ± 4.2 mm2 and decreased to 13.3 ± 3.8 mm2 (p < 0.001). Displacement in dorsal direction with wrist flexion increased from 1.9 ± 1.3 to 2.4 ± 1.3 mm (p < 0.01). A pre-surgical larger nerve area was associated with more functional improvement (ß = -0.024, p = 0.02), but baseline mobility was not. Change in excursion with finger flexion was associated with symptomatic improvement, but with a small effect (ß = -0.05, p = 0.01). This indicates that there is limited prognostic potential for dynamic transverse ultrasound in carpal tunnel syndrome.

10.
Alzheimers Dement (N Y) ; 5: 338-346, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31388560

RESUMO

Introduction: The aim of this study was to investigate the rates of lobar atrophy in the asymptomatic microtubule-associated protein tau (MAPT) mutation carriers. Methods: MAPT mutation carriers (n = 14; 10 asymptomatic, 4 converters from asymptomatic to symptomatic) and noncarriers (n = 13) underwent structural magnetic resonance imaging and were followed annually with a median of 9.2 years. Longitudinal changes in lobar atrophy were analyzed using the tensor-based morphometry with symmetric normalization algorithm. Results: The rate of temporal lobe atrophy in asymptomatic MAPT mutation carriers was faster than that in noncarriers. Although the greatest rate of atrophy was observed in the temporal lobe in converters, they also had increased atrophy rates in the frontal and parietal lobes compared to noncarriers. Discussion: Accelerated decline in temporal lobe volume occurs in asymptomatic MAPT mutation carriers followed by the frontal and parietal lobe in those who have become symptomatic. The findings have implications for monitoring the progression of neurodegeneration during clinical trials in asymptomatic MAPT mutation carriers.

11.
Age Ageing ; 48(6): 888-894, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31437275

RESUMO

BACKGROUND: hearing loss has been associated with mild cognitive impairment (MCI) and dementia. Studies have not assessed whether hearing difficulties (HD) that interfere with daily activities as reported by partners can be a marker for increased risk for cognitive decline and impairment. OBJECTIVE: to assess the cross-sectional and longitudinal associations between informant-based HD, which interfere with daily activities and the risk for MCI and dementia. METHODS: the study included 4812 participants without dementia, enrolled in the Mayo Clinic Study of Aging (mean age (SD) 73.7 (9.6) years) with cognitive evaluation and informant-based report on participant's HD that interfere significantly with daily activities at baseline and for every 15 months. Cox proportional hazards models (utilising time-dependent HD status and age as the time scale) were used to examine HD and the risk for MCI or dementia, and mixed-effects models (allowing for random subject-specific intercepts and slopes) were used to examine the relationship between HD and cognitive decline. RESULTS: about, 981 participants had HD and 612 (12.7%) had prevalent MCI at baseline; 759 participants developed incident MCI and 273 developed incident dementia. In cognitively unimpaired participants at baseline, those with HD had higher risk for MCI (hazard ratio [HR] = 1.29, 95% confidence interval [CI] (1.10, 1.51), P = 0.002; adjusting for sex, years of education). In participants without dementia, those with HD had higher risk for dementia (HR: 1.39, 95% CI, (1.08-1.79), P = 0.011; adjusting sex and education). In individuals with MCI, HD was associated with modestly greater cognitive decline. CONCLUSIONS: informant-based HD was associated with increased risk for MCI and dementia.

12.
Neurology ; 93(6): e548-e558, 2019 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-31292224

RESUMO

OBJECTIVE: To investigate whether timing, number, and frequency of mentally stimulating activities in midlife and late life are associated with the risk of incident mild cognitive impairment (MCI). METHODS: We conducted a prospective cohort study in the setting of the population-based Mayo Clinic Study of Aging in Olmsted County, Minnesota, including 2,000 individuals aged ≥70 years who were cognitively unimpaired at baseline and were followed for a median of 5.0 years. Participants completed a self-reported survey on timing, number, and frequency of engagement in 5 mentally stimulating activities (reading books, computer use, social activities, playing games, craft activities) at baseline. RESULTS: The risk of incident MCI was significantly reduced for participants who engaged in social activities (hazard ratio [95% confidence interval] 0.80 [0.64-0.99]) and playing games (0.80 [0.66-0.98]) in both late life and midlife combined. Using a computer was associated with a decreased risk regardless of timing (not late life but midlife: 0.52 [0.31-0.88]; late life but not midlife: 0.70 [0.56-0.88]; late life and midlife: 0.63 [0.51-0.79]). Craft activities were associated with a reduced risk of incident MCI only when carried out in late life but not midlife (0.58 [0.34-0.97]). Furthermore, engaging in a higher number of activities in late life was associated with a significantly reduced risk of incident MCI (any 2 activities: 0.72 [0.53-0.99], any 3: 0.55 [0.40-0.77], any 4: 0.44 [0.30-0.65], all 5: 0.57 [0.34-0.96]). CONCLUSION: Engaging in a higher number of mentally stimulating activities, particularly in late life, is associated with a decreased risk of MCI among community-dwelling older persons.


Assuntos
Disfunção Cognitiva/psicologia , Processos Mentais , Idoso , Idoso de 80 Anos ou mais , Envelhecimento Cognitivo , Estudos de Coortes , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Fatores de Risco , Comportamento Social
13.
Mayo Clin Proc ; 94(8): 1516-1523, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31280871

RESUMO

OBJECTIVE: To compare the Short Test of Mental Status (STMS) with the Montreal Cognitive Assessment (MoCA) for predicting and detecting mild cognitive impairment (MCI). PARTICIPANTS AND METHODS: Participants from the community-based Mayo Clinic Study of Aging (MCSA) (November 24, 2010, through May 19, 2012) and an academic referral Alzheimer's Disease Research Center (ADRC) (March 16, 2015, through September 5, 2018) were analyzed. All participants were evaluated using a standardized neuropsychological battery, and a multidisciplinary consensus diagnosis was assigned. The MCSA and ADRC samples included 313 and 106 stable cognitively normal (CN) participants, 72 and 8 CN participants at baseline who developed incident MCI or dementia, 114 and 96 participants with prevalent MCI, and 25 and 132 participants with dementia, respectively. RESULTS: There were no statistically significant differences between the 2 tests in 6 of 7 diagnostic comparisons across academic referral and community populations. The STMS had a better area under the curve (0.90; 95% CI, 0.87-0.93) for differentiating prevalent MCI from CN participants in the MCSA cohort compared with the MoCA cohort (0.85; 95% CI, 0.81-0.89; P=.01). In addition, 53% of the stable CN participants (222 of 419) scored less than 26 on the MoCA, with specificity of 47% for diagnosing prevalent MCI. CONCLUSION: We provide evidence that the STMS performs similarly to the MoCA in a variety of settings and neurodegenerative syndromes. These results suggest that the current recommended MoCA cutoff score may be overly sensitive, consistent with previous studies. We also provide a conversion table for comparing the 2 cognitive tests.


Assuntos
Envelhecimento/fisiologia , Doença de Alzheimer/diagnóstico , Transtornos Cognitivos/diagnóstico , Testes de Estado Mental e Demência , Centros Médicos Acadêmicos , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/epidemiologia , Área Sob a Curva , Transtornos Cognitivos/epidemiologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Estudos de Coortes , Diagnóstico Diferencial , Progressão da Doença , Feminino , Avaliação Geriátrica/métodos , Humanos , Vida Independente , Masculino , Pessoa de Meia-Idade , Minnesota , Testes Neuropsicológicos , Valor Preditivo dos Testes , Prevalência , Curva ROC , Estudos Retrospectivos , Medição de Risco
14.
J Am Soc Nephrol ; 30(8): 1471-1480, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31278193

RESUMO

BACKGROUND: Age, CKD risk factors, and kidney function are associated with larger glomerular volume and a higher percentage of globally sclerotic glomeruli. Knowledge of how these associations may differ by cortical depth is limited. METHODS: To investigate glomerular volume and glomerulosclerosis across different depths of cortex, we studied wedge sections of the renal parenchyma from 812 patients who underwent a radical nephrectomy (for a tumor), separately characterizing glomeruli in the superficial (subcapsular), middle, and deep (juxtamedullary) regions. We compared the association of mean nonsclerotic glomerular volume and of glomerulosclerosis (measured as the percentage of globally sclerotic glomeruli) with age, obesity, diabetes, smoking, kidney function, and structural pathology in the superficial, middle, and deep regions. RESULTS: The superficial, middle, and deep regions showed significant differences in glomerular volume (0.0025, 0.0031, and 0.0028 µm3, respectively) and in glomerulosclerosis (18%, 7%, and 11%, respectively). There was a marked increase in glomerulosclerosis with age in the superficial region, but larger glomerular volume was not associated with age at any cortical depth. Glomerulosclerosis associated more strongly with arteriosclerosis and ischemic-appearing glomeruli in the superficial region. Hypertension, lower eGFR, and interstitial fibrosis associated with glomerulosclerosis and glomerular volume to a similar extent at any depth. Diabetes and proteinuria more strongly associated with glomerulosclerosis in the deep and middle regions, respectively, but neither associated with glomerular volume differently by depth. Obesity associated more strongly with glomerular volume in the superficial cortex. CONCLUSIONS: Most clinical characteristic show similar associations with glomerulosclerosis and glomerulomegaly at different cortical depths. Exceptions include age-related glomerulosclerosis, which appears to be an ischemic process and is more predominant in the superficial region.

15.
Neurology ; 93(3): e252-e260, 2019 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-31182505

RESUMO

OBJECTIVE: We aimed to (1) assess and compare baseline plasma and CSF neurofilament light (NfL) for cross-sectional and longitudinal associations with neuroimaging or cognition and (2) determine whether change in plasma NfL corresponded with change in these outcomes. METHODS: Seventy-nine participants without dementia, median age 76 years, had plasma and CSF NfL, neuropsychological testing, and neuroimaging (MRI, amyloid PET, FDG-PET) at the same study visit, and a repeat visit (15 or 30 months later) with both plasma NfL and neuroimaging. Plasma NfL was measured on the Simoa-HD1 Platform and CSF NfL with an in-house ELISA. Linear mixed effects models were used to examine the associations between baseline plasma or CSF NfL and cognitive and neuroimaging outcomes adjusting for age, sex, and education. The relationship between change in plasma NfL and change in the outcomes was assessed using linear regression. RESULTS: There were no cross-sectional associations between CSF or plasma NfL and any neuroimaging or cognitive measure. Longitudinally, higher baseline plasma NfL was associated with worsening in all neuroimaging measures, except amyloid PET, and global cognition. Higher baseline CSF NfL was associated with worsening in cortical thickness and diffusion MRI. The beta estimates for CSF NfL were similar to those for plasma NfL. Change in plasma NfL was associated with change in global cognition, attention, and amyloid PET. CONCLUSION: Elevated baseline plasma NfL is a prognostic marker of cognitive decline and neuroimaging measures of neurodegeneration, and has similar effect sizes to baseline CSF NfL. Change in plasma NfL also tracked with short-term cognitive change.


Assuntos
Encéfalo/diagnóstico por imagem , Cognição , Disfunção Cognitiva/metabolismo , Proteínas de Neurofilamentos/metabolismo , Idoso , Compostos de Anilina , Atenção , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/fisiopatologia , Feminino , Fluordesoxiglucose F18 , Humanos , Modelos Lineares , Estudos Longitudinais , Imagem por Ressonância Magnética , Masculino , Proteínas de Neurofilamentos/sangue , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Tiazóis
16.
Mayo Clin Proc Innov Qual Outcomes ; 3(2): 149-159, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31193902

RESUMO

Objective: To describe first episodes of bacterial cholangitis complicating autosomal dominant polycystic kidney disease (ADPKD) and autosomal dominant polycystic liver disease (ADPLD) and to identify risk factors for cholangitis episodes among patients with ADPKD-associated polycystic liver disease (PLD). Patients and Methods: We searched the electronic medical records at our tertiary referral center for episodes of cholangitis in patients with ADPKD or ADPLD from January 1, 1996, through June 30, 2017. Cases were categorized as suspected or definite cholangitis by expert review. Clinical, laboratory, and radiologic data were manually abstracted. A nested case-control study was conducted to investigate risk factors for cholangitis in patients with ADPKD. Results: We identified 29 cases of definite or suspected cholangitis complicating PLD (24 with ADPKD-associated PLD and 5 with ADPLD). Among patients with definite cholangitis in ADPKD-associated PLD (n=19) vs ADPLD (n=4), the mean ± SD age was 62.4±12.2 vs 55.1±8.6 years, and 9 (47.4%) vs 0 (0%), respectively, were male. The odds of gallstones (odds ratio [OR], 21.6; 95% CI, 3.17-927; P<.001), prior cholecystectomy (OR, 12.2; 95% CI, 1.59-552; P=.008), duodenal diverticulum (OR, 13.5; 95% CI, 2.44 to not estimable; P=.004), type 2 diabetes mellitus (OR, 6.41; 95% CI, 1.01 to not estimable; P=.05), prior endoscopic retrograde cholangiopancreatography (OR, 14.0; 95% CI, 1.80-631; P=.005), and prior kidney transplant (OR, 8.06; 95% CI, 1.72-76.0; P=.004) were higher in patients with ADPKD-associated PLD with definite cholangitis compared to controls. Conclusion: Gallstones, prior cholecystectomy, duodenal diverticulosis, type 2 diabetes mellitus, prior endoscopic retrograde cholangiopancreatography, and prior kidney transplant constituted risk factors for cholangitis among patients with ADPKD-associated PLD.

17.
Brain ; 142(8): 2483-2491, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31199475

RESUMO

Although white matter hyperintensities have traditionally been viewed as a marker of vascular disease, recent pathology studies have found an association between white matter hyperintensities and Alzheimer's disease pathologies. The objectives of this study were to investigate the topographic patterns of white matter hyperintensities associated with Alzheimer's disease biomarkers measured using PET. From the population-based Mayo Clinic Study of Aging, 434 participants without dementia (55% male) with FLAIR and gradient recall echo MRI, tau-PET (AV-1451) and amyloid-PET scans were identified. A subset had cerebral microbleeds detected on T2* gradient recall echo scans. White matter hyperintensities were semi-automatically segmented using FLAIR MRI in participant space and normalized to a custom template. We used statistical parametric mapping 12-based, voxel-wise, multiple-regression analyses to detect white matter hyperintense regions associated with Alzheimer's biomarkers (global amyloid from amyloid-PET and meta-regions of interest tau uptake from tau-PET) after adjusting for age, sex and hypertension. For amyloid associations, we additionally adjusted for tau and vice versa. Topographic patterns of amyloid-associated white matter hyperintensities included periventricular white matter hyperintensities (frontal and parietal lobes). White matter hyperintense volumes in the detected topographic pattern correlated strongly with lobar cerebral microbleeds (P < 0.001, age and sex adjusted Cohen's d = 0.703). In contrast, there were no white matter hyperintense regions significantly associated with increased tau burden using voxel-based analysis or region-specific analysis. Among non-demented elderly, amyloid load correlated with a topographic pattern of white matter hyperintensities. Further, the amyloid-associated, white matter hyperintense regions strongly correlated with lobar cerebral microbleeds suggesting that cerebral amyloid angiopathy contributes to the relationship between amyloid and white matter hyperintensities. The study did not support an association between increased tau burden and white matter hyperintense burden.

18.
J Am Coll Cardiol ; 73(21): 2676-2688, 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31146812

RESUMO

BACKGROUND: Malignancy is a major cause of late post-heart transplantation (HT) mortality. Sirolimus (SRL) exerts antiproliferative properties and its long-term use in HT as primary immunosuppression (IS) is associated with decreased mortality risk that is not fully explained by attenuation of cardiac allograft vasculopathy progression. OBJECTIVES: This study sought to examine whether conversion from calcineurin inhibitor (CNI)-based to SRL-based IS was associated with decreased risk of malignancy post-HT. METHODS: Overall, 523 patients underwent HT between 1994 and 2016 at a single institution. The main outcomes included incidence of overall de novo malignancies (excluding non-melanoma skin cancers [NMSCs]), post-transplantation lymphoproliferative disorders (PTLD), and first and subsequent primary occurrences of NMSC post-HT. RESULTS: The study identified 307 patients on SRL-based and 216 on CNI-based maintenance IS. Over a median follow-up of 10 years after HT, overall de novo malignancies (non-NMSC) occurred in 31% of CNI patients and in 13% of SRL patients (adjusted hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.18 to 0.62; p < 0.001). The incidence of the first NMSC was similar in the SRL and CNI groups (HR: 0.92; 95% CI: 0.66 to 1.28; p = 0.62). However, conversion to SRL was significantly associated with a decreased risk of subsequent primary occurrences of NMSC compared with that of CNI (adjusted HR: 0.44; 95% CI: 0.28 to 0.69; p < 0.001). The adjusted PTLD risk was significantly decreased in the SRL group (HR: 0.13; 95% CI: 0.03 to 0.59; p = 0.009). Late survival post-HT was markedly decreased in patients who developed non-NMSC, PTLD, or non-PTLD compared with patients who did not develop these malignancies, whereas NMSC had no significant effect on survival. CONCLUSIONS: Conversion to SRL was associated with a decreased risk of all de novo malignancies, PTLD, and subsequent primary occurrences of NMSC after HT. These findings provided further explanation of the late survival benefit with long-term SRL use.

19.
Alzheimers Dement ; 15(7): 878-887, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31128864

RESUMO

INTRODUCTION: We evaluated whether incident mild cognitive impairment (MCI) subtypes could be empirically derived in the Mayo Clinic Study of Aging. METHODS: We performed cluster analysis on neuropsychological data from 506 participants with incident MCI. RESULTS: The 3-cluster solution resulted in (1) amnestic, (2) dysexecutive, (3) dysnomic subtypes. The 4-cluster solution produced these same three groups and a fourth group with subtle cognitive impairment (SCI). The SCI cluster was a subset of the amnestic cluster and distinct from well-matched cognitively unimpaired participants based on memory and global z-score area under the receiver operating characteristic curve analyses and probability of progression to MCI/dementia. DISCUSSION: We empirically identified three neuropsychological subtypes of MCI that share some features with MCI subtypes identified in the Alzheimer's Disease Neuroimaging Initiative. The fourth subtype with SCI in the Mayo Clinic Study of Aging differed from the fourth cluster-derived normal group in Alzheimer's Disease Neuroimaging Initiative and could represent a group to target with early interventions.

20.
Pancreas ; 48(5): 698-705, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31091218

RESUMO

OBJECTIVES: Pancreatic lesions in autosomal dominant polycystic kidney disease (ADPKD) are primarily cysts. They are increasingly recognized, with isolated reports of intraductal papillary mucinous neoplasia (IPMN). METHODS: Retrospective study to determine prevalence, number, size, and location of pancreatic abnormalities using abdominal magnetic resonance imaging (MRI) of genotyped ADPKD patients (seen February 1998 to October 2013) and compared with age- and sex-matched non-ADPKD controls. We evaluated presentation, investigation, and management of all IPMNs among individuals with ADPKD (January 1997 to December 2016). RESULTS: Abdominal MRIs were examined for 271 genotyped ADPKD patients. A pancreatic cyst lesion (PCL) was detected in 52 patients (19%; 95% confidence interval, 15%-23%). Thirty-seven (71%) had a solitary PCL; 15 (28%) had multiple. Pancreatic cyst lesion prevalence did not differ by genotype. Intraductal papillary mucinous neoplasia was detected in 1% of ADPKD cases. Among 12 IPMN patients (7 branch duct; 5 main duct or mixed type) monitored for about 140 months, 2 with main duct IPMNs required Whipple resection, and 1 patient died of complications from small-bowel obstruction after declining surgical intervention. CONCLUSIONS: With MRI, PCLs were detected in 19% and IPMNs in 1% of 271 ADPKD patients with proven mutations, without difference across genotypes. Pancreatic cyst lesions were asymptomatic and remained stable in size.


Assuntos
Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Papilar/diagnóstico , Carcinoma Ductal Pancreático/diagnóstico , Cisto Pancreático/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Rim Policístico Autossômico Dominante/diagnóstico , Adenocarcinoma Mucinoso/diagnóstico por imagem , Adenocarcinoma Papilar/diagnóstico por imagem , Adulto , Carcinoma Ductal Pancreático/diagnóstico por imagem , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Mutação , /estatística & dados numéricos , Cisto Pancreático/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Rim Policístico Autossômico Dominante/diagnóstico por imagem , Rim Policístico Autossômico Dominante/genética , Estudos Retrospectivos
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