RESUMO
OBJECTIVE: To evaluate the role of immunohistochemical staining overexpression of p16 protein (p16 IHC) as a prognostic factor of persistence or recurrence of intraepithelial disease after excision procedure in young women diagnosed with HSIL (CIN2). PATIENTS AND METHODS: 62 women with a histological diagnosis of HSIL (CIN2) subjected to "cervix sparing" excisional procedure were included in this retrospective study. All had age less than or equal to 35 years, negative history of immunosuppression, available follow-up, and assessment of the resection margins state. Immunohistochemical staining for the p16 protein was evaluated on reviewed and confirmed HSIL (CIN2) histological specimens with negative resection margins. The post-treatment follow-up, including cytology, colposcopy, and histology, ranged from a minimum of 6 months to a maximum of 60 months. The persistence or recurrence of SIL during the follow-up period was based on histologic referral and defined as "the presence of SIL", "the presence of HSIL" and "progression to HSIL (CIN3)". RESULTS: 31/62 patients were positive for immunostaining (p16 IHC+), and 31/62 were negative (p16 IHC-). Persistence or recurrence after excision occurred more frequently within the p16 IHC+ than in p16 IHC- group, both as SIL (29% p16 IHC- vs. 32.3% p16 IHC+, p = 0.783) and HSIL (6.5% p16 IHC- vs. 12.9% p16 IHC+, p = 0.671). None of the patients in the p16 IHC- group showed progression to CIN3 for the entire observation period, whereas 9.7% of p16 IHC+ women progressed to CIN3 lesion (p = 0.042). The p16 IHC positivity showed a significant association with progression to CIN3 in 5 years of follow-up (p = 0.029) and with the presence of SIL after two years of follow-up (p = 0.031). The differences between the two groups increased after two years post-treatment: the p16 IHC- patients still had SIL only in 3.2% of cases and no longer had HSIL, while the p16 IHC+ women still showed SIL in 19.4% and HSIL in 6.5% of cases. The negative predictive value (NPV) of p16 IHC in predicting SIL's presence after treatment increased with the severity of the lesion (NPV for SIL 70.97%, for HSIL 93.55%, for CIN3 100%). CONCLUSIONS: The study suggests that young patients with p16 IHC- HSIL (CIN2) have a better post-excisional course of the cervical intraepithelial disease compared to p16 IHC+ women and that p16 IHC could have prognostic utility during the long-term follow-up, especially in forecasting progression to CIN3 in consideration of the high NPV (up to 100%). The efficacy of the adjuvant HPV vaccination in the management of HSIL (CIN2) p16+ young women is to be evaluated as part of the fertility-sparing treatment.
Assuntos
Inibidor p16 de Quinase Dependente de Ciclina/genética , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/genética , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/genética , Adulto , Inibidor p16 de Quinase Dependente de Ciclina/imunologia , Feminino , Humanos , Prognóstico , Estudos Retrospectivos , Neoplasias do Colo do Útero/imunologia , Adulto Jovem , Displasia do Colo do Útero/imunologiaRESUMO
OBJECTIVE: As an analogy with mild cognitive impairment (MCI), the mild behavioral impairment (MBI) construct has been proposed as a diagnostic label for those presenting late-onset behavioral symptoms. To date, however, the clinical, cognitive, and structural imaging features associated with an increased risk of conversion from MBI to dementia are poorly understood. METHODS: We retrospectively analyzed the cognitive performance and structural brain MRI of 113 subjects, with a clinical follow-up of at least 4 years available. Subjects were randomly assigned to a Group A (56 subjects; age: 65.4 ± 7.9 years, 15 females, MMSE score: 28.4 ± 2.3)) or to a Group B (57 subjects, age: 66.6 ± 6.4, 17 females, MMSE score: 28.0 ± 1.4). In the Group A, cognitive and structural variables were compared between converters (at 4 years) and nonconverters and then verified in the Group B group. RESULTS: In the Group A, 14 patients converted to behavioral-variant of frontotemporal dementia (bv-FTD) and 4 to Alzheimer's Disease (AD). Converters presented at baseline lower executive function scores and total Theory of Mind (ToM scores), as well as more severe focal frontal atrophy. In the Group B, 13 subjects converted to bv-FTD and none to AD. The combination of the variables identified in the Group A significantly (p <0.001) discriminated between converters and nonconverters in the Group B with a sensitivity of 0.615 and a specificity of 1 (total accuracy 91.22%). CONCLUSION: The combined presence of executive deficit, impaired ToM, and presence of isolated frontal atrophy was associated with risk of progression from MBI to a clinically evident neurodegenerative condition, mainly bv-FTD, over a 4-year period.
Assuntos
Doença de Alzheimer/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Função Executiva , Lobo Frontal/patologia , Demência Frontotemporal/diagnóstico por imagem , Idoso , Doença de Alzheimer/fisiopatologia , Doença de Alzheimer/psicologia , Atrofia , Sintomas Comportamentais , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/psicologia , Progressão da Doença , Feminino , Demência Frontotemporal/fisiopatologia , Demência Frontotemporal/psicologia , Humanos , Modelos Logísticos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
PURPOSE: To develop and validate a semi-quantification method (time-delayed ratio, TDr) applied to amyloid PET scans, based on tracer kinetics information. METHODS: The TDr method requires two static scans per subject: one early (~ 0-10 min after the injection) and one late (typically 50-70 min or 90-100 min after the injection, depending on the tracer). High perfusion regions are delineated on the early scan and applied onto the late scan. A SUVr-like ratio is calculated between the average intensities in the high perfusion regions and the late scan hotspot. TDr was applied to a naturalistic multicenter dataset of 143 subjects acquired with [18F]florbetapir. TDr values are compared to visual evaluation, cortical-cerebellar SUVr, and to the geometrical semi-quantification method ELBA. All three methods are gauged versus the heterogeneity of the dataset. RESULTS: TDr shows excellent agreement with respect to the binary visual assessment (AUC = 0.99) and significantly correlates with both validated semi-quantification methods, reaching a Pearson correlation coefficient of 0.86 with respect to ELBA. CONCLUSIONS: TDr is an alternative approach to previously validated ones (SUVr and ELBA). It requires minimal image processing; it is independent on predefined regions of interest and does not require MR registration. Besides, it takes advantage on the availability of early scans which are becoming common practice while imposing a negligible added patient discomfort.
Assuntos
Doença de Alzheimer , Amiloidose , Doença de Alzheimer/diagnóstico por imagem , Amiloide/metabolismo , Compostos de Anilina , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Humanos , Cinética , Tomografia por Emissão de PósitronsRESUMO
BACKGROUND AND PURPOSE: Biomarkers support the aetiological diagnosis of neurocognitive disorders in vivo. Incomplete evidence is available to drive clinical decisions; available diagnostic algorithms are generic and not very helpful in clinical practice. The aim was to develop a biomarker-based diagnostic algorithm for mild cognitive impairment patients, leveraging on knowledge from recognized national experts. METHODS: With a Delphi procedure, experienced clinicians making variable use of biomarkers in clinical practice and representing five Italian scientific societies (neurology - Società Italiana di Neurologia per le Demenze; neuroradiology - Associazione Italiana di Neuroradiologia; biochemistry - Società Italiana di Biochimica Clinica; psychogeriatrics - Associazione Italiana di Psicogeriatria; nuclear medicine - Associazione Italiana di Medicina Nucleare) defined the theoretical framework, relevant literature, the diagnostic issues to be addressed and the diagnostic algorithm. An N-1 majority defined consensus achievement. RESULTS: The panellists chose the 2011 National Institute on Aging and Alzheimer's Association diagnostic criteria as the reference theoretical framework and defined the algorithm in seven Delphi rounds. The algorithm includes baseline clinical and cognitive assessment, blood examination, and magnetic resonance imaging with exclusionary and inclusionary roles; dopamine transporter single-photon emission computed tomography (if no/unclear parkinsonism) or metaiodobenzylguanidine cardiac scintigraphy for suspected dementia with Lewy bodies with clear parkinsonism (round VII, votes (yes-no-abstained): 3-1-1); 18 F-fluorodeoxyglucose positron emission tomography for suspected frontotemporal lobar degeneration and low diagnostic confidence of Alzheimer's disease (round VII, 4-0-1); cerebrospinal fluid for suspected Alzheimer's disease (round IV, 4-1-0); and amyloid positron emission tomography if cerebrospinal fluid was not possible/accepted (round V, 4-1-0) or inconclusive (round VI, 5-0-0). CONCLUSIONS: These consensus recommendations can guide clinicians in the biomarker-based aetiological diagnosis of mild cognitive impairment, whilst guidelines cannot be defined with evidence-to-decision procedures due to incomplete evidence.
Assuntos
Doença de Alzheimer/diagnóstico , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico , Doença de Alzheimer/sangue , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico por imagem , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Disfunção Cognitiva/sangue , Disfunção Cognitiva/líquido cefalorraquidiano , Disfunção Cognitiva/diagnóstico por imagem , Consenso , Humanos , Itália , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons/métodosRESUMO
BACKGROUND: amyloid-PET reading has been classically implemented as a binary assessment, although the clinical experience has shown that the number of borderline cases is non negligible not only in epidemiological studies of asymptomatic subjects but also in naturalistic groups of symptomatic patients attending memory clinics. In this work we develop a model to compare and integrate visual reading with two independent semi-quantification methods in order to obtain a tracer-independent multi-parametric evaluation. METHODS: We retrospectively enrolled three cohorts of cognitively impaired patients submitted to 18F-florbetaben (53 subjects), 18F-flutemetamol (62 subjects), 18F-florbetapir (60 subjects) PET/CT respectively, in 6 European centres belonging to the EADC. The 175 scans were visually classified as positive/negative following approved criteria and further classified with a 5-step grading as negative, mild negative, borderline, mild positive, positive by 5 independent readers, blind to clinical data. Scan quality was also visually assessed and recorded. Semi-quantification was based on two quantifiers: the standardized uptake value (SUVr) and the ELBA method. We used a sigmoid model to relate the grading with the quantifiers. We measured the readers accord and inconsistencies in the visual assessment as well as the relationship between discrepancies on the grading and semi-quantifications. CONCLUSION: It is possible to construct a map between different tracers and different quantification methods without resorting to ad-hoc acquired cases. We used a 5-level visual scale which, together with a mathematical model, delivered cut-offs and transition regions on tracers that are (largely) independent from the population. All fluorinated tracers appeared to have the same contrast and discrimination ability with respect to the negative-to-positive grading. We validated the integration of both visual reading and different quantifiers in a more robust framework thus bridging the gap between a binary and a user-independent continuous scale.
Assuntos
Doença de Alzheimer/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Placa Amiloide/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Radioisótopos de Flúor/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Placa Amiloide/metabolismo , Tomografia por Emissão de Pósitrons/tendências , Estudos RetrospectivosRESUMO
CONTEXT: Technological advances in fetal and neonatal medicine, recent changes in the French legal framework, and encouraging results of the long-term outcomes in children with neonatal renal failure provide elements for an ethical reflection. METHODS: We led a nationwide enquiry among French pediatric nephrologists, intensivists, and neonatologists, exploring the decision-making process when contemplating starting renal replacement therapy (RRT) or delivering palliative care to neonates or infants with pre-end-stage or end-stage renal disease; and the ethical quandaries at hand in such scenarios. RESULTS: A total of 134 responses with complete national coverage were obtained. Care to be delivered to an infant in pre-end-stage or end-stage renal disease did not achieve consensus. Pediatric nephrologists were more prone to initiate a dialysis/graft program than pediatric intensivists. When chronic kidney disease was associated with comorbidities, especially neurological impairment, physicians, regardless of their subspecialty, were more reluctant to initiate conservative treatment. Many of the doctors surveyed did not give their opinion in these prenatal and/or postnatal situations, considered to be unique and warranting a multidisciplinary reflection. CONCLUSION: Such ethical dilemmas are challenging for parents and physicians. They can only be overcome by taking into account both concrete on the ground realities and general principles and values acknowledged to be a basis for respecting the individual. In this way, it ensures humaneness and humanization of a practice that must meet a variety of challenges, one by one. The answer is not simple; it is always unique to each child and can only be approached by a multidisciplinary, time-consuming, open discussion, which will never totally erase uncertainty.
Assuntos
Tomada de Decisões/ética , Falência Renal Crônica/terapia , Padrões de Prática Médica/estatística & dados numéricos , Terapia de Substituição Renal/estatística & dados numéricos , Adulto , Idoso , Feminino , França , Humanos , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Pais , Médicos , Padrões de Prática Médica/ética , Terapia de Substituição Renal/ética , Inquéritos e QuestionáriosRESUMO
BACKGROUND AND PURPOSE: Recommendations for using fluorodeoxyglucose positron emission tomography (FDG-PET) to support the diagnosis of dementing neurodegenerative disorders are sparse and poorly structured. METHODS: Twenty-one questions on diagnostic issues and on semi-automated analysis to assist visual reading were defined. Literature was reviewed to assess study design, risk of bias, inconsistency, imprecision, indirectness and effect size. Critical outcomes were sensitivity, specificity, accuracy, positive/negative predictive value, area under the receiver operating characteristic curve, and positive/negative likelihood ratio of FDG-PET in detecting the target conditions. Using the Delphi method, an expert panel voted for/against the use of FDG-PET based on published evidence and expert opinion. RESULTS: Of the 1435 papers, 58 papers provided proper quantitative assessment of test performance. The panel agreed on recommending FDG-PET for 14 questions: diagnosing mild cognitive impairment due to Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD) or dementia with Lewy bodies (DLB); diagnosing atypical AD and pseudo-dementia; differentiating between AD and DLB, FTLD or vascular dementia, between DLB and FTLD, and between Parkinson's disease and progressive supranuclear palsy; suggesting underlying pathophysiology in corticobasal degeneration and progressive primary aphasia, and cortical dysfunction in Parkinson's disease; using semi-automated assessment to assist visual reading. Panellists did not support FDG-PET use for pre-clinical stages of neurodegenerative disorders, for amyotrophic lateral sclerosis and Huntington disease diagnoses, and for amyotrophic lateral sclerosis or Huntington-disease-related cognitive decline. CONCLUSIONS: Despite limited formal evidence, panellists deemed FDG-PET useful in the early and differential diagnosis of the main neurodegenerative disorders, and semi-automated assessment helpful to assist visual reading. These decisions are proposed as interim recommendations.
Assuntos
Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Demência/diagnóstico por imagem , Fluordesoxiglucose F18 , Doenças Neurodegenerativas/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Consenso , Diagnóstico Diferencial , Humanos , Medicina Nuclear , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: We evaluated the prevalence of cervicovaginal Bacteria, group B Streptococcus (GBS), Gardnerella vaginalis (GV), Candida spp., Chlamydia trachomatis (CT), Mycoplasma hominis (MH) and Ureaplasma urealyticum (UU) in pregnant women with and without diabetes mellitus (DM). PATIENTS AND METHODS: Cervicovaginal swabs were gathered from 473 pregnant patients divided into 127 diabetic and 346 non-diabetic. The results were correlated to gestational age, parity and glycemic control. RESULTS: A higher prevalence of MH/UU (p=0.012) was found in the diabetic patients. After the 28th week of pregnancy, the prevalence for all investigated microorganisms appeared similar except for MH/UU (p=0.014). In multigravida, there were statistical differences between two groups in testing for Bacteria (p=0.015) and for MH/UU (p=0.037). The diabetic condition correlated to the state of multigravida in cases positive for Candida spp. (p=0.049) and in those testing positive for at least one microorganism (p=0.043). Pregnant with a blood glucose > 92 have twice the risk of being positive to a single microbiological test than those with better glycemic control. CONCLUSIONS: The higher prevalence of MH/UU after the 28th weeks can be explained with the physiologically reduced insulin tolerance characteristic of this gestational period. Among the diabetic testing positive to Candida spp. the statistically significant association was observed only in multigravida condition. These data suggest that diabetic multigravida women are at increased risk for Candida spp. infection in relation to the improper glycemic control.
Assuntos
Infecções por Chlamydia/microbiologia , Infecções por Mycoplasma/microbiologia , Complicações Infecciosas na Gravidez/microbiologia , Gravidez em Diabéticas/microbiologia , Infecções por Ureaplasma/microbiologia , Adulto , Infecções por Chlamydia/epidemiologia , Estudos de Coortes , Feminino , Humanos , Infecções por Mycoplasma/epidemiologia , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Gravidez em Diabéticas/epidemiologia , Prevalência , Infecções por Ureaplasma/epidemiologiaRESUMO
BACKGROUND: In the field of Alzheimer's disease (AD), the validation of biomarkers for early AD diagnosis and for use as a surrogate outcome in AD clinical trials is of considerable research interest. OBJECTIVE: To characterize the clinical profile and genetic, neuroimaging and neurophysiological biomarkers of prodromal AD in amnestic mild cognitive impairment (aMCI) patients enrolled in the IMI WP5 PharmaCog (also referred to as the European ADNI study). METHODS: A total of 147 aMCI patients were enrolled in 13 European memory clinics. Patients underwent clinical and neuropsychological evaluation, magnetic resonance imaging (MRI), electroencephalography (EEG) and lumbar puncture to assess the levels of amyloid ß peptide 1-42 (Aß42), tau and p-tau, and blood samples were collected. Genetic (APOE), neuroimaging (3T morphometry and diffusion MRI) and EEG (with resting-state and auditory oddball event-related potential (AO-ERP) paradigm) biomarkers were evaluated. RESULTS: Prodromal AD was found in 55 aMCI patients defined by low Aß42 in the cerebrospinal fluid (Aß positive). Compared to the aMCI group with high Aß42 levels (Aß negative), Aß positive patients showed poorer visual (P = 0.001), spatial recognition (P < 0.0005) and working (P = 0.024) memory, as well as a higher frequency of APOE4 (P < 0.0005), lower hippocampal volume (P = 0.04), reduced thickness of the parietal cortex (P < 0.009) and structural connectivity of the corpus callosum (P < 0.05), higher amplitude of delta rhythms at rest (P = 0.03) and lower amplitude of posterior cingulate sources of AO-ERP (P = 0.03). CONCLUSION: These results suggest that, in aMCI patients, prodromal AD is characterized by a distinctive cognitive profile and genetic, neuroimaging and neurophysiological biomarkers. Longitudinal assessment will help to identify the role of these biomarkers in AD progression.
Assuntos
Doença de Alzheimer/diagnóstico , Idoso , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Apolipoproteínas E/genética , Biomarcadores/líquido cefalorraquidiano , Encéfalo/diagnóstico por imagem , Eletroencefalografia , Feminino , Genótipo , Humanos , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Fragmentos de Peptídeos/líquido cefalorraquidiano , Punção Espinal , Proteínas tau/líquido cefalorraquidianoRESUMO
PURPOSE: The present work aims at showing how dyspareunia linked to endometriosis can affect the life of fertile age women and how surgical treatment of endometriosis can relieve painful symptoms and consequently improve sex and social life. METHODS: From a cohort of 320 women with a clinical and instrumental diagnosis of pelvic endometriosis, 67 patients were selected. These patients had deep dyspareunia that underwent laparoscopic surgical treatment. All the patients had filled out a pre- and post-surgery questionnaire. RESULTS: Six months after laparoscopic treatment, a significant reduction of dyspareunia was recorded, per VAS scores. A statistically significant improvement in sex life was observed between the pre- and post-surgical condition: in particular, an increased number of coituses and of non-difficult coituses, a higher number of patients who declared that pain did not negatively affect sexual pleasure and of patients achieving orgasm. CONCLUSIONS: The quality of the sex life in patients with endometriosis and dyspareunia showed significant improvement 6 months after laparoscopic treatment. In view of the diagnostic delay characterizing this disease and confirmed by our results, it is essential to involve a multidisciplinary team to assess all the signs and symptoms of endometriosis that may appear in a women of fertile age. This clinical approach is able to ensure a treatment that is as personalized as possible and an appropriate follow-up also with the objective of preserving reproductive performance.
Assuntos
Dispareunia/etiologia , Endometriose/cirurgia , Laparoscopia/métodos , Dor Pélvica/cirurgia , Qualidade de Vida , Disfunções Sexuais Psicogênicas/etiologia , Adulto , Coito , Diagnóstico Tardio , Dispareunia/psicologia , Endometriose/complicações , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Orgasmo , Dor Pélvica/etiologia , Comportamento Sexual , Disfunções Sexuais Psicogênicas/psicologia , Inquéritos e Questionários , Resultado do TratamentoRESUMO
The Stroop color and word test (SCWT) is widely used to evaluate attention, information processing speed, selective attention, and cognitive flexibility. Normative values for the Italian population are available only for selected age groups, or for the short version of the test. The aim of this study was to provide updated normal values for the full version, balancing groups across gender, age decades, and education. Two kinds of indexes were derived from the performance of 192 normal subjects, divided by decade (from 20 to 90) and level of education (4 levels: 3-5; 6-8; 9-13; >13 years). They were (i) the correct answers achieved for each table in the first 30 s (word items, WI; color items, CI; color word items, CWI) and (ii) the total time required for reading the three tables (word time, WT; color time, CT; color word time, CWT). For each index, the regression model was evaluated using age, education, and gender as independent variables. The normative data were then computed following the equivalent scores method. In the regression model, age and education significantly influenced the performance in each of the 6 indexes, whereas gender had no significant effect. This study confirms the effect of age and education on the main indexes of the Stroop test and provides updated normative data for an Italian healthy population, well balanced across age, education, and gender. It will be useful to Italian researchers studying attentional functions in health and disease.
Assuntos
Teste de Stroop , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Atenção , Escolaridade , Função Executiva , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Atividade Motora , Valores de Referência , Análise de Regressão , Fatores Sexuais , Teste de Stroop/estatística & dados numéricos , Percepção Visual , Adulto JovemRESUMO
According to the new research criteria for the diagnosis of Alzheimer's disease, episodic memory impairment, not significantly improved by cueing, is the core neuropsychological marker, even at a pre-dementia stage. The FCSRT assesses verbal learning and memory using semantic cues and is widely used in Europe. Standardization values for the Italian population are available for the colored picture version, but not for the 16-item printed word version. In this study, we present age- and education-adjusted normative data for FCSRT-16 obtained using linear regression techniques and generalized linear model, and critical values for classifying sub-test performance into equivalent scores. Six scores were derived from the performance of 194 normal subjects (MMSE score, range 27-30, mean 29.5 ± 0.5) divided per decade (from 20 to 90), per gender and per level of education (4 levels: 3-5, 6-8, 9-13, >13 years): immediate free recall (IFR), immediate total recall (ITR), recognition phase (RP), delayed free recall (DFR), delayed total recall (DTR), Index of Sensitivity of Cueing (ISC), number of intrusions. This study confirms the effect of age and education, but not of gender on immediate and delayed free and cued recall. The Italian version of the FCSRT-16 can be useful for both clinical and research purposes.
Assuntos
Sinais (Psicologia) , Transtornos da Memória/diagnóstico , Rememoração Mental/fisiologia , Testes Neuropsicológicos/normas , Aprendizagem Verbal/fisiologia , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico , Estudos de Casos e Controles , Escolaridade , Feminino , Humanos , Itália , Masculino , Transtornos da Memória/etiologia , Pessoa de Meia-Idade , Tempo de Reação/fisiologia , Valores de Referência , Adulto JovemRESUMO
An emerging issue in neuroimaging is to assess the diagnostic reliability of PET and its application in clinical practice. We aimed at assessing the accuracy of brain FDG-PET in discriminating patients with MCI due to Alzheimer's disease and healthy controls. Sixty-two patients with amnestic MCI and 109 healthy subjects recruited in five centers of the European AD Consortium were enrolled. Group analysis was performed by SPM8 to confirm metabolic differences. Discriminant analyses were then carried out using the mean FDG uptake values normalized to the cerebellum computed in 45 anatomical volumes of interest (VOIs) in each hemisphere (90 VOIs) as defined in the Automated Anatomical Labeling (AAL) Atlas and on 12 meta-VOIs, bilaterally, obtained merging VOIs with similar anatomo-functional characteristics. Further, asymmetry indexes were calculated for both datasets. Accuracy of discrimination by a Support Vector Machine and the AAL VOIs was tested against a validated method (PALZ). At the voxel level SMP8 showed a relative hypometabolism in the bilateral precuneus, and posterior cingulate, temporo-parietal and frontal cortices. Discriminant analysis classified subjects with an accuracy ranging between .91 and .83 as a function of data organization. The best values were obtained from a subset of 6 meta-VOIs plus 6 asymmetry values reaching an area under the ROC curve of .947, significantly larger than the one obtained by the PALZ score. High accuracy in discriminating MCI converters from healthy controls was reached by a non-linear classifier based on SVM applied on predefined anatomo-functional regions and inter-hemispheric asymmetries. Data pre-processing was automated and simplified by an in-house created Matlab-based script encouraging its routine clinical use. Further validation toward nonconverter MCI patients with adequately long follow-up is needed.
Assuntos
Doença de Alzheimer/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Compostos RadiofarmacêuticosRESUMO
Several non motor symptoms (NMS) can precede the onset of the classical motor Parkinson's disease (PD) syndrome. The existence of pre-motor and even pre-clinical PD stages has been proposed but the best target population to be screened to disclose PD patients in a pre-clinical, thus asymptomatic, stage is still matter of debate. The REM sleep behavior disorder (RBD) often affects PD patients at different stages of the disease and could precede the onset of motor symptoms by several years. However, RBD could also precede other synucleinopathies (namely, dementia with Lewy bodies and multisystem atrophy), and less frequently could be related to other neurological conditions or remain idiopathic. Moreover, not all PD patients exhibit RBD. Despite these caveats, RBD probably represents the best feature to disclose pre-motor PD patients given its high-risk of developing a full motor syndrome. Other clinical clues in the premotor stages of PD undergoing active investigation include hyposmia, depression, and autonomic dysfunction. Effective biomarkers are needed in order to improve the diagnostic accuracy in the pre-motor stage of PD, to monitor disease progression and to plan both pharmacological and non-pharmacological intervention. Functional imaging, in particular radionuclide methodologies, has been often used to investigate dopaminergic and non-dopaminergic features as well as cortical functioning in patients with RBD in its idiopathic form (iRBD) and/or associated with PD. Recently, new tracers to image α-synuclein pathologies are under development. Functional imaging in pre-motor PD, and in particular in iRBD, could improve our knowledge about the underlying mechanisms and the neurodegenerative progress of PD.
Assuntos
Doença de Parkinson/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Transtorno do Comportamento do Sono REM/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Córtex Cerebral/diagnóstico por imagem , Dopamina/metabolismo , Fluordesoxiglucose F18 , Humanos , Transtorno do Comportamento do Sono REM/complicações , Reprodutibilidade dos Testes , RiscoRESUMO
Clinical assessment and management of sleep disturbances in patients with mild cognitive impairment and dementia has important clinical and social implications. Poor sleep results in an increased risk of morbidities and mortality in demented patients and is a source of stress for caregivers. Sleep disturbances show high prevalence in mild cognitive impairment and dementia patients and they are often associated one to another in the same patient. A careful clinical evaluation of sleep disorders should be performed routinely in the clinical setting of individuals with cognitive decline. The Sleep Study Group of the Italian Dementia Research Association (SINDem) reviewed evidence from original research articles, meta-analyses and systematic reviews published up to December 2013. The evidence was classified in quality levels (I, II, III) and strength of recommendations (A, B, C, D, E). Where there was a lack of evidence, but clear consensus, good practice points were provided. These recommendations may not be appropriate for all circumstances and should therefore be adopted only after a patient's individual characteristics have been carefully evaluated.
Assuntos
Disfunção Cognitiva/complicações , Demência/complicações , Avaliação de Resultados em Cuidados de Saúde/normas , Transtornos do Sono-Vigília/etiologia , Transtornos do Sono-Vigília/terapia , Humanos , Itália , Avaliação de Resultados em Cuidados de Saúde/métodosRESUMO
Described for the first time in 1971, Schimke immuno-osseous dysplasia (SIOD) is an autosomal-recessive multisystem disorder that is caused by bi-allelic mutations of SMARCAL1, which encodes a DNA annealing helicase. To define better the dental anomalies of SIOD, we reviewed the records from SIOD patients with identified bi-allelic SMARCAL1 mutations, and we found that 66.0% had microdontia, hypodontia, or malformed deciduous and permanent molars. Immunohistochemical analyses showed expression of SMARCAL1 in all developing teeth, raising the possibility that the malformations are cell-autonomous consequences of SMARCAL1 deficiency. We also found that stimulation of cultured skin fibroblasts from SIOD patients with the tooth morphogens WNT3A, BMP4, and TGFß1 identified altered transcriptional responses, raising the hypothesis that the dental malformations arise in part from altered responses to developmental morphogens. To the best of our knowledge, this is the first systematic study of the dental anomalies associated with SIOD.
Assuntos
Arteriosclerose/complicações , Síndromes de Imunodeficiência/complicações , Síndrome Nefrótica/complicações , Osteocondrodisplasias/complicações , Embolia Pulmonar/complicações , Anormalidades Dentárias/etiologia , Alelos , Anodontia/etiologia , Arteriosclerose/genética , Dente Pré-Molar/anormalidades , Proteína Morfogenética Óssea 4/análise , Técnicas de Cultura de Células , Proliferação de Células , Sobrevivência Celular , Células Cultivadas , DNA Helicases/análise , DNA Helicases/genética , Fibroblastos/patologia , Humanos , Síndromes de Imunodeficiência/genética , Dente Molar/anormalidades , Mutação/genética , Síndrome Nefrótica/genética , Odontogênese/genética , Osteocondrodisplasias/genética , Doenças da Imunodeficiência Primária , Embolia Pulmonar/genética , Pele/citologia , Germe de Dente/patologia , Raiz Dentária/anormalidades , Dente Decíduo/anormalidades , Transcrição Gênica/genética , Fator de Crescimento Transformador beta1/análise , Proteína Wnt3A/análiseRESUMO
BACKGROUND/AIMS: Sleep disturbances are common in the elderly and in persons with cognitive decline. The aim of this study was to describe frequency and characteristics of insomnia, excessive daytime sleepiness, sleep-disordered breathing, REM behavior disorder and restless legs syndrome in a large cohort of persons with mild cognitive impairment or dementia. METHODS: 431 consecutive patients were enrolled in 10 Italian neurological centers: 204 had Alzheimer's disease, 138 mild cognitive impairment, 43 vascular dementia, 25 frontotemporal dementia and 21 Lewy body dementia or Parkinson's disease dementia. Sleep disorders were investigated with a battery of standardized questions and questionnaires. RESULTS: Over 60% of persons had one or more sleep disturbances almost invariably associated one to another without any evident and specific pattern of co-occurrence. Persons with Alzheimer's disease and those with mild cognitive impairment had the same frequency of any sleep disorder. Sleep-disordered breathing was more frequent in vascular dementia. REM behavior disorder was more represented in Lewy body or Parkinson's disease dementia. CONCLUSION: A careful clinical evaluation of sleep disorders should be performed routinely in the clinical setting of persons with cognitive decline. Instrumental supports should be used only in selected patients.