Latin American Initiative for Lifestyle Intervention to Prevent Cognitive Decline (LatAm-FINGERS): Study design and harmonization.

INTRODUCTION: Latin American Initiative for Lifestyle Intervention to Prevent Cognitive Decline (LatAm-FINGERS) is the first non-pharmacological multicenter randomized clinical trial (RCT) to prevent cognitive impairment in Latin America (LA). Our aim is to present the study design and discuss the strategies used for multicultural harmonization. METHODS: This 1-year RCT (working on a 1-year extension) investigates the feasibility of a multi-domain lifestyle intervention in LA and the efficacy of the intervention, primarily on cognitive function. An external harmonization process was carried out to follow the FINGER model, and an internal harmonization was performed to ensure this study was feasible and comparable across the 12 participating LA countries. RESULTS: Currently, 1549 participants have been screened, and 815 randomized. Participants are ethnically diverse (56% are Nestizo) and have high cardiovascular risk (39% have metabolic syndrome). DISCUSSION: LatAm-FINGERS overcame a significant challenge to combine the region's diversity into a multi-domain risk reduction intervention feasible across LA while preserving the original FINGER design.

Association of ictal aphasia with hypoperfusion in language areas in temporal lobe epilepsy patients.

Ictal clinical phenomenology, including aphasia, is usually associated with increased regional cerebral perfusion. We present an unusual pattern of ictal cerebral perfusion in three patients with pharmacoresistant, lesional temporal lobe epilepsy and ictal/postictal aphasia studied with prolonged video-EEG, ictal, and interictal SPECT and MRI for pre-surgical evaluation. Subtraction of ictal-interictal SPECT images co-registered with MRI (SISCOM) showed ictal hyperperfusion in the temporal epileptogenic area in all patients. In addition, hypoperfusion of Broca's area in one case, Wernicke's area in other patient, and both areas in the remaining one were observed. Ictal aphasia in these patients may be explained by functional inhibition of a primary language area, driven by the epileptogenic network. This pattern can contribute to understand the pathophysiology of some ictal signs, with an impact on the evaluation of individual surgical risks.

Biomarkers for dementia in Latin American countries: Gaps and opportunities.

Limited knowledge on dementia biomarkers in Latin American and Caribbean (LAC) countries remains a serious barrier. Here, we reported a survey to explore the ongoing work, needs, interests, potential barriers, and opportunities for future studies related to biomarkers. The results show that neuroimaging is the most used biomarker (73%), followed by genetic studies (40%), peripheral fluids biomarkers (31%), and cerebrospinal fluid biomarkers (29%). Regarding barriers in LAC, lack of funding appears to undermine the implementation of biomarkers in clinical or research settings, followed by insufficient infrastructure and training. The survey revealed that despite the above barriers, the region holds a great potential to advance dementia biomarkers research. Considering the unique contributions that LAC could make to this growing field, we highlight the urgent need to expand biomarker research. These insights allowed us to propose an action plan that addresses the recommendations for a biomarker framework recently proposed by regional experts.

18F-fallypride and 11C-methionine positron emission tomography/computed tomography for the study of prolactinomas and nonfunctioning pituitary adenomas: A case series.

Some studies have assessed the expression of dopaminergic dopamine 2 (D2)/3 receptors in prolactinomas and nonfunctioning pituitary adenomas (NFPA) by positron emission tomography/computed tomography (PET/CT) with 11C-raclopride, proving that this modality can be useful to predict the response to treatment with dopamine agonists. However, the use of 11C-labeled radiotracers is limited, as it requires a cyclotron in the PET center. 18F-fallypride is a radiotracer that has proven useful in assessing the expression of D2/3 receptors. As it is labeled with 18F, it can be produced and transported to distant PET centers. There are no studies on the usefulness of 18F-fallypride for the evaluation of patients with prolactinomas and NFPA. The aim of this study was to describe the first case series of patients with prolactinomas and NFPA studied with 18F-fallypride and 11C-methionine PET/CT to reveal D2/3 expression and amino acid (AA) metabolism. 18F-fallypride and 11C-methionine uptake were assessed in a case series of six patients, five with prolactinomas and one with a NFPA, and compared with clinical presentation and follow-up at 6-18 months. All patients presented with macroadenomas, with a wide range of AA metabolism, as revealed by 11C-methionine PET/CT. 18F-fallypride PET/CT identified low to moderate/high D2/3 expression in the tumors. The patient that presented low expression of D2/3 in the tumor and high AA metabolism showed a poor response to DA therapy. 18F-fallypride was able to reveal D2/3 receptor expression in prolactinomas and NFPA, with the advantage of been a more accessible radiotracer in comparison with previous 11C labeled analogs.

Brain SPECT as a Biomarker of Neurodegeneration in Dementia in the Era of Molecular Imaging: Still a Valid Option?

Biomarkers are playing a progressively leading role in both clinical practice and scientific research in dementia. Although amyloid and tau biomarkers have gained ground in the clinical community in recent years, neurodegeneration biomarkers continue to play a key role due to their ability to identify different patterns of brain involvement that sign the transition between asymptomatic and symptomatic stages of the disease with high sensitivity and specificity. Both 18F-FDG positron emission tomography (PET) and perfusion single photon emission computed tomography (SPECT) have proved useful to reveal the functional alterations underlying various neurodegenerative diseases. Although the focus of nuclear neuroimaging has shifted to PET, the lower cost and wider availability of SPECT make it a still valid alternative for the study of patients with dementia. This review discusses the principles of both techniques, compares their diagnostic performance for the diagnosis of neurodegenerative diseases and highlights the role of SPECT to characterize patients from low- and middle-income countries, where special care of additional costs is particularly needed to meet the new recommendations for the diagnosis and characterization of patients with dementia.

Clinical Impact of PET With 18F-FDG and 11C-PIB in Patients With Dementia in a Developing Country.

Introduction: The objective of this study was to evaluate the clinical impact PET with 18F-FDG and 11C-PIB in patients with dementia in a developing country. Methodology: Retrospective study of the patients referred for the evaluation of dementia to the only PET center in Uruguay. A total of 248 patients were identified, from which 70 patients were included based on the availability of medical history and clinical follow-up. Main outcomes included change in diagnosis, diagnostic dilemma and AD treatment. We evaluated the association of clinical outcomes with PET concordance with baseline diagnosis, diagnostic dilemma, level of education, AD pathology/Non-AD pathology (AD/Non-AD), baseline diagnosis and 11C-PIB PET result. Results: Baseline clinical diagnosis was concordant with 18F-FDG and 11C-PIB PET results in 64.7 and 77.1% of the patients, respectively. Change in diagnosis after PET was identified in 30.0% of the patients and was associated with discordant 18F-FDG (p = 0.002) and 11C-PIB (p < 0.001) PET results, previous diagnostic dilemma (p = 0.005), low education (p = 0.027), Non-AD baseline diagnosis (p = 0.027), and negative 11C-PIB PET result (p < 0.001). Only the last variable remained significant in the multivariate analysis (adjusted p = 0.038). Diagnostic dilemma decreased after PET from 15.7 to 7.1% (p = 0.11) and was associated with Non-AD diagnosis (p = 0.002) and negative 11C-PIB PET result (p = 0.003). Change in AD treatment after PET occurred in 45.7% of the patients. Conclusion: 18F-FDG and 11C-PIB PET had a significant clinical impact in terms of change in diagnosis and treatment in patients with dementia in a developing country, similar to that reported in high-income countries.

SPECT activation patterns in psychogenic non-epileptic seizures in temporal lobe epilepsy patients.

INTRODUCTION: The diagnosis of psychogenic non-epileptic seizures (PNES) can often be challenging. When video-electroencephalography (EEG) is not conclusive, single-photon emission computed tomography (SPECT) can be useful by quantifying changes in regional cerebral blood flow (rCBF). METHODS: We conducted a retrospective case-control study in adult patients with pharmacoresistant temporal lobe epilepsy (TLE). Those patients with an ictal SPECT obtained during an event finally diagnosed as PNES were included as cases (PNES+). The control group consisted of patients with TLE without PNES (PNES-). Clinical episodes were analysed and classified according to PNES subtypes. Subtraction ictal SPECT coregistered to MRI (SISCOM) analysis was performed for the detection of areas with significant changes in perfusion compared to individual interictal studies. Group comparisons in SPM12 included paired t-tests of ictal vs. interictal studies in each group of temporal lobe seizures and PNES events. RESULTS: Ten patients with TLE and PNES were included. We found no patterns of regional hyperperfusion typical of TLE seizures during the PNES events. In two of these cases, an ictal SPECT during a confirmed epileptic seizure was also obtained, showing antero-mesial temporal lobe hyperperfusion. Group comparisons between ictal and interictal SPECTs showed increased rCBF in the temporal lobe with reduced perfusion in the default mode network areas and cerebellum during temporal lobe seizures in PNES- patients and decreased perfusion restricted to the posterior parietal cortex without significant rCBF increases in PNES events. CONCLUSIONS: Ictal SPECT can be a helpful tool to characterize rCBF changes in PNES and for differential diagnosis with seizures in TLE patients.

Dementia in Latin America: Paving the way toward a regional action plan.

Across Latin American and Caribbean countries (LACs), the fight against dementia faces pressing challenges, such as heterogeneity, diversity, political instability, and socioeconomic disparities. These can be addressed more effectively in a collaborative setting that fosters open exchange of knowledge. In this work, the Latin American and Caribbean Consortium on Dementia (LAC-CD) proposes an agenda for integration to deliver a Knowledge to Action Framework (KtAF). First, we summarize evidence-based strategies (epidemiology, genetics, biomarkers, clinical trials, nonpharmacological interventions, networking, and translational research) and align them to current global strategies to translate regional knowledge into transformative actions. Then we characterize key sources of complexity (genetic isolates, admixture in populations, environmental factors, and barriers to effective interventions), map them to the above challenges, and provide the basic mosaics of knowledge toward a KtAF. Finally, we describe strategies supporting the knowledge creation stage that underpins the translational impact of KtAF.

3-(Benzyloxy)-1-(5-[18F]fluoropentyl)-5-nitro-1H-indazole: a PET radiotracer to measure acetylcholinesterase in brain.

AIM: Noninvasive studies of the acetylcholinesterase (AChE) level in Alzheimer's disease (AD) patients can contribute to a better understanding of the disease and its therapeutic. We propose 3-(benzyloxy)-1-(5-[18F]fluoropentyl)-5-nitro-1H-indazole, [18F]-IND1, structurally related to the AChE-inhibitor CP126,998, as a new positron emission tomography-radiotracer. EXPERIMENTAL: Radiosynthesis, with 18F, stability, lipophilicity and protein binding of [18F]-IND1 were studied. In vivo behavior, in normal mice and on AD mice models, were also analyzed. RESULTS: [18F]-IND1 was obtained in good radiochemical yield, was stable for at least 2 h in different conditions, and had adequate lipophilicity for blood-brain barrier penetration. Biodistribution studies, in normal mice, showed that [18F]-IND1 was retained in the brain after 1 h. In vivo tacrine-blocking experiments indicated this uptake could be specifically due to AChE interaction. Studies in transgenic AD mice showed differential, compared with normal mice, binding in many brain regions. CONCLUSION: [18F]-IND1 can be used to detect AChE changes in AD patients.

Early Detection of Bone Metastasis in Small Cell Neuroendocrine Carcinoma of the Cervix by 68Ga-DOTATATE PET/CT Imaging.

The neuroendocrine small cell carcinoma of the cervix is a rare malignancy that has a poor prognosis due to early lymphatic and hematogenous spread. We herein report a case of a 27- year-old woman who was referred for initial staging of a neuroendocrine small cell carcinoma with previous unremarkable structural imaging. Ga-DOTATATE PET/CT revealed focal uptake at the primary tumor and in a solitary pelvic bone lesion suggestive of metastases that was further confirmed by CT-guided biopsy. Somatostatin receptor PET/CT may be a useful image modality for early detection of metastases to guide treatment in these patients.

PET and the multitracer concept in the study of neurodegenerative diseases / PET e o conceito de multitraçador no estudo de doenças degenerativas

ABSTRACT The complexity of the pathological reactions of the brain to an aggression caused by an internal or external noxa represents a challenge for molecular imaging. Positron emission tomography (PET) can indicate in vivo,anatomopathological changes involved in the development of different clinical symptoms in patients with neurodegenerative disorders. PET and the multitracer concept can provide information from different systems in the brain tissue building an image of the whole disease. We present here the combination of 18F-flourodeoxyglucose (FDG) and N-[11C-methyl]-L-deuterodeprenyl (DED), FDG and N-[11C-methyl] 2-(4'-methylaminophenyl)-6-hydroxybenzothiazole (PIB), PIB and L-[11C]-3'4-Dihydrophenylalanine (DOPA) and finally PIB and [15O]H2O.

RESUMO A complexidade das reações patológicas do cérebro à agressões causadas por noxa interna ou externa representa um desafio para a imagem molecular. Tomografia por emissão de positron (PET) pode indicar, in vivo, alterações anatomopatológicas envolvidas no desenvolvimento de diferentes sintomas clínicos em pacientes com desordens neurodegenerativas. PET e o conceito de multitraçador pode fornecer informações de diferentes sistemas no tecido cerebral, construindo assim uma imagem da doença como um todo. Nós apresentamos neste artigo a combinação de 18F-flourodeoxyglucose (FDG) e N-[11C-methyl]-L-deuterodeprenyl (DED), FDG e N-[11C-methyl] 2-(4'-methylaminophenyl)-6-hydroxybenzothiazole (PIB), PIB e L-[11C]-3'4-Dihydrophenylalanine (DOPA) e finalmente, PIB e [15O]H2O .

PET and the multitracer concept in the study of neurodegenerative diseases.

The complexity of the pathological reactions of the brain to an aggression caused by an internal or external noxa represents a challenge for molecular imaging. Positron emission tomography (PET) can indicate in vivo, anatomopathological changes involved in the development of different clinical symptoms in patients with neurodegenerative disorders. PET and the multitracer concept can provide information from different systems in the brain tissue building an image of the whole disease. We present here the combination of 18F-flourodeoxyglucose (FDG) and N-[11C-methyl]-L-deuterodeprenyl (DED), FDG and N-[11C-methyl] 2-(4'-methylaminophenyl)-6-hydroxybenzothiazole (PIB), PIB and L-[11C]-3'4-Dihydrophenylalanine (DOPA) and finally PIB and [15O]H2O.

A complexidade das reações patológicas do cérebro à agressões causadas por noxa interna ou externa representa um desafio para a imagem molecular. Tomografia por emissão de positron (PET) pode indicar, in vivo, alterações anatomopatológicas envolvidas no desenvolvimento de diferentes sintomas clínicos em pacientes com desordens neurodegenerativas. PET e o conceito de multitraçador pode fornecer informações de diferentes sistemas no tecido cerebral, construindo assim uma imagem da doença como um todo. Nós apresentamos neste artigo a combinação de 18F-flourodeoxyglucose (FDG) e N-[11C-methyl]-L-deuterodeprenyl (DED), FDG e N-[11C-methyl] 2-(4'-methylaminophenyl)-6-hydroxybenzothiazole (PIB), PIB e L-[11C]-3'4-Dihydrophenylalanine (DOPA) e finalmente, PIB e [15O]H2O .

Fluorodeoxyglucose PET in Neurology and Psychiatry.

PET imaging with the most widely available PET tracer, 2-deoxy-2-[(18)F]fluoro-d-glucose (FDG), is a powerful tool in the differential diagnosis of numerous neurologic and psychiatric disorders, particularly in early disease stages. It also plays an important role in the longitudinal evaluation of treatment effects and the depiction of disease courses. A selection of established and eligible application areas of FDG PET in neurology and psychiatry, such as different types of dementia, epilepsy, schizophrenia, and bipolar disorder, are reviewed in this article. A general methodology for clinical FDG PET examinations and typical diagnostic criteria and pitfalls are addressed.

(18)F-FDG PET-CT for Staging of Conjunctival Melanoma.

The value of F-18 fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET-CT) for the evaluation of cutaneous melanoma has been demonstrated previously. However, there are few reports regarding the use PET-CT for the staging of conjunctival melanoma (CM). We report here a case, a 34-year-old male with a six-month history of a pigmented nodule at the palpebral conjunctiva of the left eye, and a firm left preauricular lymph node detected on physical examination. Biopsy of the ocular lesion confirmed CM, and fine needle aspiration cytology of the preauricular node was positive for malignancy. CT showed three pulmonary nodules. An (18)F-FDG PET-CT was performed to restage the patient. The study showed hypermetabolic lesions in the left eye, and in the left preauricular node. The scan was negative for metastasis. These findings were important in guiding management of the disease in this patient. Future prospective studies should further evaluate the role of (18)F-FDG PET-CT for the staging of CM.

Conservación del ombusillo, planta amenazada de la provincia de Buenos Aires, Argentina / Conserving ombusillo, an endangered plant from the province of Buenos Aires, Argentina

Phytolacca tetramera Hauman "ombusillo", es una especie vegetal endémica del SE de la Provincia de Buenos Aires, Argentina, que se halla en peligro crítico de extinción. Su principal factor de amenaza es la reducción del hábitat por acción antrópica. Esta especie presenta principios activos fungicidas y, posiblemente, dada su afinidad con otras especies del mismo género, presente compuestos antivirales, antitumorales, bactericidas e insecticidas. Se realizaron ensayos de macropropagación con distintas concentraciones de reguladores de crecimiento de tipo auxínicos que muestran claramente un enraizamiento óptimo correspondiente a segmentos de ejes aéreos vegetales “estacas” sometidas a 300 ppm de ácido indol butírico y a segmentos de tallos subterráneos sin aplicación de hormonas. Así mismo, se realizaron ensayos de germinación, en condiciones de luz y de oscuridad, comprobándose que las semillas presentan fotoblastismo positivo con un porcentaje de germinación del 65%, el cual disminuye enormemente luego del año de cosecha.

Phytolacca tetramera Hauman "ombusillo" is an endemic plant species which is in critical danger of becoming extinct; it comes from the south-east of the province of Buenos Aires. The main factor threatening this species is the reduction of its natural environment by antropic action.This species has antifungal properties and, due to its relationship with other species from the same genus, it could also have antiviral, antitumour, antibacterial and insecticidal compounds. Macropropagation experiments were carried out using different concentrations of auxinic growth regulators. Segements of aerial axis “stakes” treated with 300 ppm of indol-butiric acid and segments of underground stems without hormonal treatment provided optimum rooting. Germination experiments in dark and light conditions were also carried out, finding that seeds showed positive photoblastisme with a 65% germination rate which declined considerably after the crop had been harvested.