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1.
Front Psychiatry ; 14: 1050236, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36816403

RESUMO

Background: Newborns' deaths and life-threatening conditions represent extremely stressful events for parents and professionals working in NICUs, facilitating the onset of secondary traumatic stress symptoms. The STRONG study aims to better understand the psychological impact on Italian NICUs staff of bereavement care. Methods: The STRONG (STress afteR lOss in NeonatoloGy) study is a cross-sectional study based on a web survey consisted of four sections: sociodemographic, CommuniCARE-Newborn questionnaire, the Maslach Burnout Inventory and the Impact of Event Scale-Revised. Results: 227 NICU workers (42.7% nurses, 23.3% midwives, 22.2% physicians, 11.8% other HCPs) answered the survey. The hardest tasks were "communicating baby's death" and "informing on autopsy results"; 44.7% of HCPs did not receive formal training in communicating bad news, 44.2% 'learned from the field' by watching other colleagues; 41.2% declared that they do not have any communication strategy. More than 90% of professionals thought that training on bereavement care is necessary. The majority of HCPs showed some degree of post-traumatic stress symptoms: 34% medium and 35.3% severe. Professionals with training in bereavement care and/or in communication had less probability to develop stress symptoms. A multivariate analysis showed that higher levels of burnout were associated with 4 or more monthly losses and medium or severe stress symptoms. Having a well-defined communication strategy for breaking bad news was independently associated with a better personal accomplishment. Conclusion: Dealing with newborns' deaths is a highly stressful task; professionals should receive proper support such as debriefing, psychological support and training in order to prevent post-traumatic stress symptoms and reduce professional burnout.

2.
J Prev Alzheimers Dis ; 9(4): 731-742, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36281678

RESUMO

BACKGROUND: The Comparative Effectiveness Dementia and Alzheimer's Registry (CEDAR) trial demonstrated that individualized, multi-domain interventions improved cognition and reduced the risk of Alzheimer's disease (AD). As biological sex is a significant risk factor for AD, it is essential to explore the differential effectiveness of targeted clinical interventions in women vs. men. METHODS: Patients were recruited from an Alzheimer's Prevention Clinic. Subjects with normal cognition, subjective cognitive decline, or asymptomatic preclinical AD were classified as "Prevention". Subjects with mild cognitive impairment due to AD or mild AD were classified as "Early Treatment." The primary outcome was the change from baseline to 18-months on the modified-Alzheimer's Prevention Cognitive Composite. Secondary outcomes included a cognitive aging composite, AD and cardiovascular (CV) risk scales, and serum biomarkers. Subjects who adhered to > 60% of recommendations in the CEDAR trial were included in this a priori sub-group analysis to examine whether individualized intervention effects were modified by sex (n=80). RESULTS: In the Prevention group, both women (p=0.0205) and men (p=0.0044) demonstrated improvements in cognition with no sex differences (p=0.5244). In the Early Treatment group, there were also no significant sex differences in cognition (p=0.3299). In the Prevention group, women demonstrated greater improvements in the Multi-Ethnic Study of Atherosclerosis risk score (MESA-RS) than men (difference=1.5, p=0.0013). Women in the Early Treatment group demonstrated greater improvements in CV Risk Factors, Aging and Incidence of Dementia (CAIDE) risk score (difference=2.3, p=0.0067), and the MESA-RS (difference=4.1, p<0.001). CONCLUSIONS: Individualized multi-domain interventions are equally effective at improving cognition in women and men. However, personally-tailored interventions led to greater improvements in calculated AD and CV risk, and CV blood biomarkers, in women compared to men. Future study in larger cohorts is necessary to further define sex differences in AD risk reduction in clinical practice.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Feminino , Humanos , Masculino , Doença de Alzheimer/tratamento farmacológico , Biomarcadores , Cognição , Disfunção Cognitiva/psicologia , Fatores de Risco , Ensaios Clínicos como Assunto
3.
Eur J Orthop Surg Traumatol ; 31(7): 1515-1521, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33660047

RESUMO

PURPOSE: Total hip arthroplasties (THAs) are rising worldwide, as the functional request of patients who undergo this procedure. The trabeculae oriented pattern (TOP) is a modern cup, which follows the philosophy of the tissue sparing surgery (TSS). Focusing on clinical and radiological results and complications, the authors aim to highlight the outcomes of the TOP at a long-term follow-up (FU). METHODS: A retrospective analysis was completed on THA performed with the TOP cup between 1997 and 2015. Five hundred and eighty-eight patients sustained surgery, for a total of 662 cup implanted. Four hundred and sixty patients (524 hips) were examined. Mean FU was 12 ± 4.9 years (range 5-22). Clinical (HHS, OHS and VAS) and radiological data were obtained. Every complication, reoperation or revision was recorded and analyzed. RESULTS: Clinical evaluation revealed a HHS of 87.1 ± 13.8 an OHS of 41.3 ± 5.4, and a VAS of 1.2 ± 1.1. Acetabular osteolysis was observed in 53 hips. Overall survival rate of the cup was 90.5% (50 revisions), the main causes of cup substitution being aseptic loosening (AL) of the cup combined with the stem (26), of the cup only (13 cases) and periprosthetic joint infection (7 cases). CONCLUSION: TOP cup has demonstrated a good overall survivorship at a long-term FU, even compared with other coated cups, providing excellent clinical result with low rate of complications. Its association with a neck sparing stem permits a physiologic load transmission, reducing the stress shielding effect that could cause early implant mobilization.


Assuntos
Artroplastia de Quadril , Prótese de Quadril , Acetábulo/diagnóstico por imagem , Acetábulo/cirurgia , Artroplastia de Quadril/efeitos adversos , Seguimentos , Humanos , Desenho de Prótese , Falha de Prótese , Reoperação , Estudos Retrospectivos
4.
Eur Spine J ; 30(1): 50-62, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32930843

RESUMO

PURPOSE: We aim at analysing the impact of anterior lumbar interbody fusion (ALIF) in restoring the main spinopelvic parameters, along with its potentials and limitations in correcting sagittal imbalance. MATERIALS AND METHODS: The 2009 PRISMA flow chart was used to systematically review the literature; 27 papers were eventually selected. The following spinopelvic parameters were observed: pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), segmental lumbar lordosis (LLseg) and sagittal vertical axis (SVA). Papers reporting on hyperlordotic cages (HLC) were analysed separately. The indirect decompression potential of ALIF was also assessed. The clinical outcome was obtained by collecting visual analogue scale (VAS) for back and leg pain and Oswestry Disability Index (ODI) scores. Global fusion rate and main complications were collected. RESULTS: PT, SS, LL, LLseg and SVA spinopelvic parameters all improved postoperatively by - 4.3 ± 5.2°, 3.9 ± 4.5°, 10.6 ± 12.5°, 6.7 ± 3.5° and 51.1 ± 44.8 mm, respectively. HLC were statistically more effective in restoring LL and LLseg (p < 0.05). Postoperative disc height, anterior disc height, posterior disc height and foraminal height, respectively, increased by 58.5%, 87.2%, 80.9% and 18.1%. Postoperative improvements were observed in VAS back and leg and ODI scores (p < 0.05). The global fusion rate was 94.5 ± 5.5%; the overall complication rate was 13%. CONCLUSION: When managing sagittal imbalance, ALIF can be considered as a valid technique to achieve the correct spinopelvic parameters based on preoperative planning. This technique permits to obtain an optimal LL distribution and a solid anterior column support, with lower complications and higher fusion rates when compared to posterior osteotomies.


Assuntos
Fusão Vertebral , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Região Lombossacral , Complicações Pós-Operatórias , Estudos Retrospectivos
5.
Musculoskelet Surg ; 104(1): 1-15, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31894472

RESUMO

The aim of this meta-analysis and systematic review is to summarize and critically analyze the influence of surgery-related factors in lumbar interbody fusion for degenerative spine diseases. A systematic review of the literature was carried out with a primary search being performed on Medline through PubMed. The 2009 PRISMA flowchart and checklist were taken into account. Sixty-seven articles were included in the analysis: 48 studies were level IV of evidence, whereas 19 were level III. All interbody fusion techniques analyzed have proved to reach a good fusion rate. An overall mean fusion rate of 93% (95% CI 92-95%, p < 0.001) was estimated pooling the selected studies. The influence of sagittal parameters and cages features in fusion rate was not clear. Autograft is considered the gold standard material. The use of synthetic bone substitutes and biological factors alone or combined with bone graft have shown conflicting results. Low level of evidence studies and high heterogeneity (χ2 = 271.4, df = 72, p < 0.001; I2 = 73.5%, τ2 = 0.05) in data analysis could result in the risk of bias. Further high-quality studies would better clarify these results in the future.


Assuntos
Vértebras Lombares/cirurgia , Doenças da Coluna Vertebral/cirurgia , Fusão Vertebral , Humanos , Fusão Vertebral/métodos , Resultado do Tratamento
6.
J Prev Alzheimers Dis ; 5(4): 225-230, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30298180

RESUMO

Along with advanced age and apolipoprotein E (APOE)-4 genotype, female sex is a major risk factor for developing late-onset Alzheimer's disease (AD). Considering that AD pathology begins decades prior to clinical symptoms, the higher risk in women cannot simply be accounted for by their greater longevity as compared to men. Recent investigation into sex-specific pathophysiological mechanisms behind AD risk has implicated the menopause transition (MT), a midlife neuroendocrine transition state unique to females. Commonly characterized as ending in reproductive senescence, many symptoms of MT are neurological, including disruption of estrogen-regulated systems such as thermoregulation, sleep, and circadian rhythms, as well as depression and impairment in multiple cognitive domains. Preclinical studies have shown that, during MT, the estrogen network uncouples from the brain bioenergetic system. The resulting hypometabolic state could serve as the substrate for neurological dysfunction. Indeed, translational brain imaging studies demonstrate that 40-60 year-old perimenopausal and postmenopausal women exhibit an AD-endophenotype characterized by decreased metabolic activity and increased brain amyloid-beta deposition as compared to premenopausal women and to age-matched men. This review discusses the MT as a window of opportunity for therapeutic interventions to compensate for brain bioenergetic crisis and combat the subsequent increased risk for AD in women.


Assuntos
Doença de Alzheimer/fisiopatologia , Encéfalo/fisiopatologia , Menopausa , Doença de Alzheimer/etiologia , Doença de Alzheimer/prevenção & controle , Feminino , Terapia de Reposição Hormonal , Humanos , Fatores de Risco
7.
J Prev Alzheimers Dis ; 5(4): 245-252, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30298183

RESUMO

Population-attributable risk models estimate that up to one-third of Alzheimer's disease (AD) cases may be preventable through risk factor modification. The field of AD prevention has largely focused on addressing these factors through universal risk reduction strategies for the general population. However, targeting these strategies in a clinical precision medicine fashion, including the use of genetic risk factors, allows for potentially greater impact on AD risk reduction. Apolipoprotein E (APOE), and specifically the APOE ε4 variant, is one of the most well-established genetic influencers on late-onset AD risk. In this review, we evaluate the impact of APOE ε4 carrier status on AD prevention interventions, including lifestyle, nutrigenomic, pharmacogenomic, AD comorbidities, and other biological and behavioral considerations. Using a clinical precision medicine strategy that incorporates APOE ε4 carrier status may provide a highly targeted and distinct approach to AD prevention with greater potential for success.


Assuntos
Doença de Alzheimer/genética , Doença de Alzheimer/prevenção & controle , Apolipoproteínas E/genética , Predisposição Genética para Doença , Apolipoproteína E4/genética , Genótipo , Humanos , Estilo de Vida , Medicina de Precisão , Fatores de Risco
8.
J Nutr Health Aging ; 19(4): 413-23, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25809805

RESUMO

OBJECTIVES: Epidemiological evidence linking diet, one of the most important modifiable lifestyle factors, and risk of Alzheimer's disease (AD) is rapidly increasing. However, there is little or no evidence for a direct association between dietary nutrients and brain biomarkers of AD. This study identifies nutrient patterns associated with major brain AD biomarkers in a cohort of clinically and cognitively normal (NL) individuals at risk for AD. DESIGN: Cross-sectional study. SETTING: Manhattan (broader area). PARTICIPANTS: Fifty-two NL individuals (age 54+12 y, 70% women, Clinical Dementia Rating=0, MMSE>27, neuropsychological test performance within norms by age and education) with complete dietary information and cross-sectional, 3D T1-weighted Magnetic Resonance Imaging (MRI; gray matter volumes, GMV, a marker of brain atrophy), 11C-Pittsburgh compound-B (PiB; a marker of fibrillar amyloid-ß, Aß) and 18F-fluorodeoxyglucose (FDG; a marker of glucose metabolism, METglc) Positron Emission Tomography (PET) scans were examined. MEASUREMENTS: Dietary intake of 35 nutrients associated with cognitive function and AD was assessed using the Harvard/Willet Food Frequency Questionnaire. Principal component analysis was used to generate nutrient patterns (NP) from the full nutrient panel. Statistical parametric mapping and voxel based morphometry were used to assess the associations of the identified NPs with AD biomarkers. RESULTS: None of the participants were diabetics, smokers, or met criteria for obesity. Five NPs were identified: NP1 was characterized by most B-vitamins and several minerals [VitB and Minerals]; NP2 by monounsaturated and polyunsaturated fats, including ω-3 and ω-6 PUFA, and vitamin E [VitE and PUFA]; NP3 by vitamin A, vitamin C, carotenoids and dietary fibers [Anti-oxidants and Fibers]; NP4 by vitamin B12, vitamin D and zinc [VitB12 and D]; NP5 by saturated, trans-saturated fats, cholesterol and sodium [Fats]. Voxel-based analysis showed that NP4 scores [VitB12 and D] were positively associated with METglc and GMV, and negatively associated with PiB retention in AD-vulnerable regions (p<0.001). In addition, both METglc and GMV were positively associated with NP2 scores [VitE and PUFA], and negatively associated with NP5 scores [Fats] (p<0.001), and METglc was positively associated with higher NP3 scores [Anti-oxidants and Fibers] (p<0.001). Adjusting for age, gender, ethnicity, education, caloric intake, BMI, alcohol consumption, family history and Apolipoprotein E (APOE) status did not attenuate these relationships. The identified 'AD-protective' nutrient combination was associated with higher intake of fresh fruit and vegetables, whole grains, fish and low-fat dairies, and lower intake of sweets, fried potatoes, high-fat dairies, processed meat and butter. CONCLUSION: Specific dietary NPs are associated with brain biomarkers of AD in NL individuals, suggesting that dietary interventions may play a role in the prevention of AD by modulating AD-risk through its effects on Aß and associated neuronal impairment.


Assuntos
Doença de Alzheimer/diagnóstico , Doença de Alzheimer/metabolismo , Biomarcadores/análise , Encéfalo/metabolismo , Cognição/fisiologia , Dieta/estatística & dados numéricos , Adulto , Idoso , Doença de Alzheimer/patologia , Doença de Alzheimer/psicologia , Amiloide/análise , Encéfalo/patologia , Estudos de Coortes , Estudos Transversais , Feminino , Glucose/metabolismo , Substância Cinzenta , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Cidade de Nova Iorque , Tomografia por Emissão de Pósitrons , Análise de Componente Principal , Inquéritos e Questionários
9.
J Prev Alzheimers Dis ; 1(1): 23-32, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25237654

RESUMO

OBJECTIVES: Epidemiological evidence linking diet, one of the most important modifiable environmental factors, and risk of Alzheimer's disease (AD) is rapidly increasing. Several studies have shown that higher adherence to a Mediterranean diet (MeDi) is associated with reduced risk of AD. This study examines the associations between high vs. lower adherence to a MeDi and structural MRI-based brain atrophy in key regions for AD in cognitively normal (NL) individuals with and without risk factors for AD. DESIGN: Cross-sectional study. SETTING: Manhattan (broader area). PARTICIPANTS: Fifty-two NL individuals (age 54+12 y, 70% women) with complete dietary information and cross-sectional, 3D T1-weighted MRI scans were examined. MEASUREMENTS: Subjects were dichotomized into those showing higher vs. lower adherences to the MeDi using published protocols. Estimates of cortical thickness for entorhinal cortex (EC), inferior parietal lobe, middle temporal gyrus, orbitofrontal cortex (OFC) and posterior cingulate cortex (PCC) were obtained by use of automated segmentation tools (FreeSurfer). Multivariate general linear models and linear regressions assessed the associations of MeDi with MRI measures. RESULTS: Of the 52 participants, 20 (39%) showed higher MeDi adherence (MeDi+) and 32 (61%) showed lower adherence (MeDi-). Groups were comparable for clinical, neuropsychological measures, presence of a family history of AD (FH), and frequency of Apolipoprotein E (APOE) ε4 genotype. With and without controlling for age and total intracranial volume, MeDi+ subjects showed greater thickness of AD-vulnerable ROIs as compared to MeDi- subjects (Wilk's Lambda p=0.026). Group differences were most pronounced in OFC (p=0.001), EC (p=0.03) and PCC (p=0.04) of the left hemisphere. Adjusting for gender, education, FH, APOE status, BMI, insulin resistance scores and presence of hypertension did not attenuate the relationship. CONCLUSION: NL individuals showing lower adherence to the MeDi had cortical thinning in the same brain regions as clinical AD patients compared to those showing higher adherence. These data indicate that the MeDi may have a protective effect against tissue loss, and suggest that dietary interventions may play a role in the prevention of AD.

10.
Neuroimage ; 100: 684-691, 2014 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-24999038

RESUMO

Interstitial concentration of amyloid beta (Aß) is positively related to synaptic activity in animal experiments. In humans, Aß deposition in Alzheimer's disease overlaps with cortical regions highly active earlier in life. White matter lesions (WML) disrupt connections between gray matter (GM) regions which in turn changes their activation patterns. Here, we tested if WML are related to Aß accumulation (measured with PiB-PET) and glucose uptake (measured with FDG-PET) in connected GM. WML masks from 72 cognitively normal (age 61.7 ± 9.6 years, 71% women) individuals were obtained from T2-FLAIR. MRI and PET images were normalized into common space, segmented and parcellated into gray matter (GM) regions. The effects of WML on connected GM regions were assessed using the Change in Connectivity (ChaCo) score. Defined for each GM region, ChaCo is the percentage of WM tracts connecting to that region that pass through the WML mask. The regional relationship between ChaCo, glucose uptake and Aß was explored via linear regression. Subcortical regions of the bilateral caudate, putamen, calcarine, insula, thalamus and anterior cingulum had WM connections with the most lesions, followed by frontal, occipital, temporal, parietal and cerebellar regions. Regional analysis revealed that GM with more lesions in connecting WM and thus impaired connectivity had lower FDG-PET (r = 0.20, p<0.05 corrected) and lower PiB uptake (r = 0.28, p<0.05 corrected). Regional regression also revealed that both ChaCo (ß = 0.045) and FDG-PET (ß = 0.089) were significant predictors of PiB. In conclusion, brain regions with more lesions in connecting WM had lower glucose metabolism and lower Aß deposition.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Glicemia/metabolismo , Encéfalo/metabolismo , Substância Branca/metabolismo , Idoso , Compostos de Anilina , Encéfalo/patologia , Feminino , Fluordesoxiglucose F18 , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Tiazóis , Substância Branca/patologia
11.
Neurodegener Dis ; 13(2-3): 163-5, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24107601

RESUMO

BACKGROUND: The pathophysiological process of Alzheimer's disease (AD) begins many years before the emergence of clinical symptoms (preclinical AD). A hypothetical biomarker progression in the pathogenesis of AD has been suggested, beginning with the deposition of amyloid-ß (Aß) and followed by increases in neurofibrillary tangles, synaptic loss, hippocampal atrophy, and lastly, cognitive impairment. OBJECTIVE: We explored the effect of several risk factors for AD on the pattern of AD biomarker expression in normal subjects. METHODS: AD biomarker evidence was examined at baseline in 96 cognitively normal elderly subjects with none or at least one of the following: ApoE4+ allele, a maternal history of AD (mFHx), sleep-disordered breathing (SDB), and longitudinal evidence of decline to mild cognitive impairment or AD (decliners) at follow-up. RESULTS: Decliners and ApoE4+ subjects presented with expected reduced cerebrospinal fluid Aß42, elevated P-tau and T-tau. In addition, decliners had fluorodeoxyglucose positron emission tomography hypometabolism in the medial temporal lobe. Individuals with mFHx demonstrated no Aß42 effect, but had elevations in P-tau and T-tau. SDB was found to be associated with elevated Aß42, P-tau and T-tau, as well as with reduced medial temporal lobe glucose metabolic rates. CONCLUSION: Our results indicate a heterogeneous biomarker expression, suggesting diversity of AD pathways in at-risk presymptomatic subjects.


Assuntos
Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico por imagem , Biomarcadores/líquido cefalorraquidiano , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/genética , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Apolipoproteína E4/genética , Disfunção Cognitiva/líquido cefalorraquidiano , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/líquido cefalorraquidiano , Tomografia por Emissão de Pósitrons , Proteínas tau/líquido cefalorraquidiano
12.
Q J Nucl Med Mol Imaging ; 56(3): 299-308, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22695340

RESUMO

AIM: Previous positron emission tomography (PET) [18F]fluorodeoxyglucose ([18F]FDG) studies in Parkinson's disease (PD) demonstrated that moderate to late stage patients display widespread cortical hypometabolism, whereas early stage PD patients exhibit little or no cortical changes. However, recent studies suggested that conventional data normalization procedures may not always be valid, and demonstrated that alternative normalization strategies better allow detection of low magnitude changes. We hypothesized that these alternative normalization procedures would disclose more widespread metabolic alterations in de novo PD. METHODS: [18F]FDG PET scans of 26 untreated de novo PD patients (Hoehn & Yahr stage I-II) and 21 age-matched controls were compared using voxel-based analysis. Normalization was performed using gray matter (GM), white matter (WM) reference regions and Yakushev normalization. RESULTS: Compared to GM normalization, WM and Yakushev normalization procedures disclosed much larger cortical regions of relative hypometabolism in the PD group with extensive involvement of frontal and parieto-temporal-occipital cortices, and several subcortical structures. Furthermore, in the WM and Yakushev normalized analyses, stage II patients displayed more prominent cortical hypometabolism than did stage I patients. CONCLUSION: The use of alternative normalization procedures, other than GM, suggests that much more extensive cortical hypometabolism is present in untreated de novo PD patients than hitherto reported. The finding may have implications for our understanding of the basic pathophysiology of early-stage PD.


Assuntos
Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/metabolismo , Processamento de Imagem Assistida por Computador/métodos , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Idoso , Estudos de Casos e Controles , Feminino , Fluordesoxiglucose F18 , Glucose/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade
13.
Neurol Sci ; 32(4): 559-69, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21630036

RESUMO

Often viewed as a potential tool for preclinical diagnosis in early asymptomatic stages of Alzheimer's disease (AD), the term "endophenotype" has acquired a recent popularity in the field. In this review, we analyze the construct of endophenotype-originally designed to discover genes, and examine the literature on potential endophenotypes for the late-onset form of AD (LOAD). We focus on the [18F]-fluoro-2-deoxyglucose (FDG) PET technique, which shows a characteristic pattern of hypometabolism in AD-related regions in asymptomatic carriers of the ApoE E4 allele and in children of AD mothers. We discuss the pathophysiological significance and the positive predictive accuracy of an FDG-endophenotype for LOAD in asymptomatic subjects, and discuss several applications of this endophenotype in the identification of both promoting and protective factors. Finally, we suggest that the term "endophenotype" should be reserved to the study of risk factors, and not to the preclinical diagnosis of LOAD.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Fluordesoxiglucose F18 , Compostos Radiofarmacêuticos , Doença de Alzheimer/genética , Doença de Alzheimer/fisiopatologia , Causalidade , Endofenótipos , Marcadores Genéticos , Humanos , Fármacos Neuroprotetores/farmacologia , Tomografia por Emissão de Pósitrons
15.
Q J Nucl Med Mol Imaging ; 55(3): 250-64, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21532539

RESUMO

The development of prevention therapies for Alzheimer's disease (AD) would greatly benefit from biomarkers that are sensitive to subtle brain changes occurring prior to the onset of clinical symptoms, when the potential for preservation of function is at the greatest. In vivo brain imaging is a promising tool for the early detection of AD through visualization of abnormalities in brain structure, function and histopathology. Currently, positron emission tomography (PET) imaging with amyloid-beta (Aß) tracers and 2-[(18)F]fluoro-2-Deoxy-D-glucose (FDG) is largely utilized in the diagnosis of AD. This paper reviews brain Aß- and FDG-PET studies in AD patients as well as in non-demented individuals at risk for AD. We then discuss the potential of combining symptoms-sensitive FDG-PET measures with pathology-specific Aß-PET to improve the early detection of AD.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Idoso , Envelhecimento/metabolismo , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Apolipoproteínas E/genética , Encéfalo/metabolismo , Demência/diagnóstico , Demência/diagnóstico por imagem , Demência/metabolismo , Diagnóstico Diferencial , Radioisótopos de Flúor , Fluordesoxiglucose F18 , Humanos , Tomografia por Emissão de Pósitrons , Valor Preditivo dos Testes , Compostos Radiofarmacêuticos
16.
Neurodegener Dis ; 7(1-3): 131-5, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20197691

RESUMO

Preclinical diagnosis of Alzheimer's disease (AD) is one of the major challenges for the prevention of AD. AD biomarkers are needed not only to reveal preclinical pathologic changes, but also to monitor progression and therapeutics. PET neuroimaging can reliably assess aspects of the molecular biology and neuropathology of AD. The aim of this article is to review the use of FDG-PET and amyloid PET imaging in the early detection of AD.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Fluordesoxiglucose F18 , Humanos
17.
PET Clin ; 5(1): 15-31, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27157481

RESUMO

Early diagnosis of Alzheimer disease (AD) is one of the major challenges for the prevention of this dementia. The pathologic lesions associated with AD develop many years before the clinical manifestations of the disease become evident, during a likely transitional period between normal aging and the appearance of first cognitive symptoms. AD biomarkers are needed not only to reveal these early pathologic changes but also to monitor progression in cognitive and behavioral decline and brain lesions. PET neuroimaging can reliably assess indirect and direct aspects of the molecular biology and neuropathology of AD. This article reviews the use of [18F] 2-fluoro-2-deoxy-D-glucose-PET and amyloid PET imaging in the early detection of AD.

18.
Q J Nucl Med Mol Imaging ; 53(6): 646-57, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20016455

RESUMO

AIM: The aim of this study was to assess whether 18F-fluorodeoxyglucose positron emission tomography differentiates amnestic (aMCI) from single-non-amnestic mild cognitive impairment (snaMCI) with executive dysfunction. METHODS: Sixteen aMCI subjects (62% females, age 75+/-8 years) and 14 snaMCI subjects (71% females, age 74+/-6 years) underwent [18F]FDG-PET and clinical follow-up. Comparisons between MCI subgroups and with seven cognitively normal elderly subjects were performed using SPM2. RESULTS: At baseline aMCI and snaMCI exhibited a similar pattern of hypometabolism, mostly in the posterior cingulate gyrus, as compared with controls. In the comparison between the MCI subtypes, the aMCI subjects showed reduced metabolism in the medial temporal lobes (MTL) (hippocampus, fusiform gyrus and amygdala). At follow-up 12 aMCI developed Alzheimer's disease (AD), while snaMCI had a heterogeneous course, including five subjects who developed Lewy body dementia. CONCLUSIONS: The patterns of altered brain metabolism in aMCI and snaMCI subjects compared to controls are similar and do not provide evidence for making clinical distinctions between them. Comparison between the two MCI subtypes showed MTL hypometabolism in aMCI subjects, possibly reflecting the fact that most had prodromal AD.


Assuntos
Amnésia/patologia , Transtornos Cognitivos/patologia , Fluordesoxiglucose F18/farmacologia , Hipocampo/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Idoso , Amnésia/diagnóstico , Automação , Transtornos Cognitivos/diagnóstico , Feminino , Glucose/metabolismo , Hipocampo/patologia , Humanos , Doença por Corpos de Lewy/patologia , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Lobo Temporal/patologia
19.
Neurology ; 72(6): 513-20, 2009 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-19005175

RESUMO

BACKGROUND: At cross-section, cognitively normal individuals (NL) with a maternal history of late-onset Alzheimer disease (AD) have reduced glucose metabolism (CMRglc) on FDG-PET in the same brain regions as patients with clinical AD as compared to those with a paternal and a negative family history (FH) of AD. This longitudinal FDG-PET study examines whether CMRglc reductions in NL subjects with a maternal history of AD are progressive. METHODS: Seventy-five 50- to 82-year-old NL received 2-year follow-up clinical, neuropsychological, and FDG-PET examinations. These included 37 subjects with negative family history of AD (FH-), 9 with paternal (FHp), and 20 with maternal AD (FHm). Two subjects had parents with postmortem confirmed AD. Statistical parametric mapping was used to compare CMRglc across FH groups at baseline, follow-up, and longitudinally. RESULTS: At both time points, the FH groups were comparable for demographic and neuropsychological characteristics. At baseline and at follow-up, FHm subjects showed CMRglc reductions in the parieto-temporal, posterior cingulate, and medial temporal cortices as compared to FH- and FHp (p < 0.001). Longitudinally, FHm had significant CMRglc declines in these regions, which were significantly greater than those in FH- and FHp (p < 0.05). CONCLUSIONS: A maternal history of Alzheimer disease (AD) predisposes normal individuals to progressive CMRglc reductions in AD-vulnerable brain regions, which may be related to a higher risk for developing AD.


Assuntos
Envelhecimento/metabolismo , Doença de Alzheimer/congênito , Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Glucose/metabolismo , Idoso , Idoso de 80 Anos ou mais , Feminino , Predisposição Genética para Doença/genética , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Mães
20.
Indoor Air ; 18(5): 365-74, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18636973

RESUMO

UNLABELLED: A study was performed to characterize the concentration of dozens of volatile organic compounds (VOCs) at 10 locations within a single large building and track these concentrations over a 2-year period. The study was performed at a shopping center (strip mall) in New Jersey. A total of 130 indoor air samples were collected from 10 retail stores within the shopping center and analyzed for 60 VOCs by US EPA Method TO-15. Indoor concentrations of up to 55,100 microg/m(3) were measured for individual VOCs. The indoor/outdoor ratio (I/O) was as high as 1500 for acetone and exceeded 100 at times for various compounds, indicating that significant indoor air sources were present. A large degree of spatial variability was observed between stores within the building, with concentrations varying by three to four orders of magnitude for some compounds. The spatial variability was dependent on the proximity of the sampling locations to the indoor sources. A large degree of temporal variability also was observed for compounds emitted from indoor sources, but the temporal variability generally did not exceed two standard deviations (sigma). For compounds not emitted from indoor sources at significant rates, both the spatial and temporal variability tended to range within an order of magnitude at each location. PRACTICAL IMPLICATIONS: Many cross-sectional studies have been published where the levels of volatile organic compounds (VOCs) were measured in indoor air at one or two locations for houses or offices. This study provides longitudinal data for a commercial retail building and also addresses spatial variability within the building. The data suggest that spatial and temporal variability are important considerations for compounds emitted from indoor sources. Elevated concentrations were found in retail spaces with no apparent emission sources due to their proximity to other retail spaces with emission sources.


Assuntos
Poluentes Ocupacionais do Ar/análise , Poluição do Ar em Ambientes Fechados/análise , Materiais de Construção/análise , Monitoramento Ambiental , Compostos Orgânicos Voláteis/análise , Materiais de Construção/efeitos adversos , Humanos , Logradouros Públicos , Medição de Risco , Ventilação , Volatilização , Local de Trabalho
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