Search

Background To facilitate population screening and clinical trials of disease-modifying therapies for Alzheimer's disease, supportive biomarker information is necessary. This study was aimed to investigate the association of plasma amyloid-beta (A beta) levels with the presence of pathological accumulation of A beta in the brain measured by amyloid-PET. Both plasma A beta 42/40 ratio alone or combined with an FDG-PET-based biomarker of neurodegeneration were assessed as potential AD biomarkers. Methods We included 39 cognitively normal subjects and 20 patients with mild cognitive impairment from the AB255 Study who had undergone PiB-PET scans. Total A beta 40 and A beta 42 levels in plasma (TP42/40) were quantified using ABtest kits. Subjects were dichotomized as A beta-PET positive or negative, and the ability of TP42/40 to detect A beta-PET positivity was assessed by logistic regression and receiver operating characteristic analyses. Combination of plasma A beta biomarkers and FDG-PET was further assessed as an improvement for brain amyloidosis detection and diagnosis classification. Results Eighteen (30.5%) subjects were A beta-PET positive. TP42/40 ratio alone identified A beta-PET status with an area under the curve (AUC) of 0.881 (95% confidence interval [CI] = 0.779-0.982). Discriminating performance of TP42/40 to detect A beta-PET-positive subjects yielded sensitivity and specificity values at Youden's cutoff of 77.8% and 87.5%, respectively, with a positive predictive value of 0.732 and negative predictive value of 0.900. All these parameters improved after adjusting the model for significant covariates. Applying TP42/40 as the first screening tool in a sequential diagnostic work-up would reduce the number of A beta-PET scans by 64%. Combination of both FDG-PET scores and plasma A beta biomarkers was found to be the most accurate A beta-PET predictor, with an AUC of 0.965 (95% CI = 0.913-0.100). Conclusions Plasma TP42/40 ratio showed a relevant and significant potential as a screening tool to identify brain A beta positivity in preclinical and prodromal stages of Alzheimer's disease.

BACKGROUND: To facilitate population screening and clinical trials of disease-modifying therapies for Alzheimer's disease, supportive biomarker information is necessary. This study was aimed to investigate the association of plasma amyloid-beta (Aß) levels with the presence of pathological accumulation of Aß in the brain measured by amyloid-PET. Both plasma Aß42/40 ratio alone or combined with an FDG-PET-based biomarker of neurodegeneration were assessed as potential AD biomarkers. METHODS: We included 39 cognitively normal subjects and 20 patients with mild cognitive impairment from the AB255 Study who had undergone PiB-PET scans. Total Aß40 and Aß42 levels in plasma (TP42/40) were quantified using ABtest kits. Subjects were dichotomized as Aß-PET positive or negative, and the ability of TP42/40 to detect Aß-PET positivity was assessed by logistic regression and receiver operating characteristic analyses. Combination of plasma Aß biomarkers and FDG-PET was further assessed as an improvement for brain amyloidosis detection and diagnosis classification. RESULTS: Eighteen (30.5%) subjects were Aß-PET positive. TP42/40 ratio alone identified Aß-PET status with an area under the curve (AUC) of 0.881 (95% confidence interval [CI] = 0.779-0.982). Discriminating performance of TP42/40 to detect Aß-PET-positive subjects yielded sensitivity and specificity values at Youden's cutoff of 77.8% and 87.5%, respectively, with a positive predictive value of 0.732 and negative predictive value of 0.900. All these parameters improved after adjusting the model for significant covariates. Applying TP42/40 as the first screening tool in a sequential diagnostic work-up would reduce the number of Aß-PET scans by 64%. Combination of both FDG-PET scores and plasma Aß biomarkers was found to be the most accurate Aß-PET predictor, with an AUC of 0.965 (95% CI = 0.913-0.100). CONCLUSIONS: Plasma TP42/40 ratio showed a relevant and significant potential as a screening tool to identify brain Aß positivity in preclinical and prodromal stages of Alzheimer's disease.

Background: Hypofractionated radiation therapy is a feasible and safe treatment option in elderly and frail patients with glioblastoma. The aim of this study was to evaluate the effectiveness of hypofractionated radiation therapy with concurrent temozolomide in terms of feasibility and disease control in primary glioblastoma patients with poor prognostic factors other than advanced age, such as post-surgical neurological complications, high tumor burden, unresectable or multifocal lesions, and potential low treatment compliance due to social factors or rapidly progressive disease. Material and methods: GTV included the surgical cavity plus disease visible in T1WI-MRI, FLAIR-MRI and in the MET-uptake. The CTV was defined as the GTV plus 1.5-2 cm margin; the PTV was the CTV+0.3 cm margin. Forty, fourty-five, and fifty grays in 15 fractions were prescribed to 95% of PTV, CTV, and GTV, respectively. Treatment was delivered using IMRT or the VMAT technique. Simultaneously, 75 mg/m2/day of temozolomide were administered. Results: Between January 2010 and November 2017, we treated a total of 17 patients. The median age at diagnosis was 68-years; median KPS was 50-70%. MGMT-methylation status was negative in 5 patients, and 8 patients were IDH-wildtype. Eight of 18 patients were younger than 65-years. Median tumor volume was 26.95cc; median PTV volume was 322cc. Four lesions were unresectable; 6 patients underwent complete surgical resection. Median residual volume was 1.14cc. Progression-free survival was 60% at 6 months, 33% at 1-year and 13% at 2-years (median OS = 7 months). No acute grade 3-5 toxicities were documented. Symptomatic grade 3 radiation necrosis was observed in one patient. Conclusions: Patients with poor clinical factors other than advanced age can be selected for hypofractionated radiotherapy. The OS and PFS rates obtained in our series are similar to those in patients treated with standard fractionation, assuring good treatment adherence, low rates of toxicity and probable improved cost-effectiveness.

BACKGROUND: Easily accessible biomarkers are needed for the early identification of individuals at risk of developing Alzheimer's disease (AD) in large population screening strategies. OBJECTIVES: This study evaluated the potential of plasma ß-amyloid (Aß) biomarkers in identifying early stages of AD and predicting cognitive decline over the following two years. DESIGN: Total plasma Aß42/40 ratio (TP42/40) was determined in 83 cognitively normal individuals (CN) and 145 subjects with amnestic mild cognitive impairment (a-MCI) stratified by an FDG-PET AD-risk pattern. RESULTS: Significant lower TP42/40 ratio was found in a-MCI patients compared to CN. Moreover, a-MCIs with a high-risk FDG-PET pattern for AD showed even lower plasma ratio levels. Low TP42/40 at baseline increased the risk of progression to dementia by 70%. Furthermore, TP42/40 was inversely associated with neocortical amyloid deposition (measured with PiB-PET) and was concordant with the AD biomarker profile in cerebrospinal fluid (CSF). CONCLUSIONS: TP42/40 demonstrated value in the identification of individuals suffering a-MCI, in the prediction of progression to dementia, and in the detection of underlying AD pathology revealed by FDG-PET, Amyloid-PET and CSF biomarkers, being, thus, consistently associated with all the well-established indicators of AD.

BACKGROUND: Easily accessible biomarkers are needed for the early identification of individuals at risk of developing Alzheimer's disease (AD) in large population screening strategies. OBJECTIVES: This study evaluated the potential of plasma ß-amyloid (Aß) biomarkers in identifying early stages of AD and predicting cognitive decline over the following two years. DESIGN: Total plasma Aß42/40 ratio (TP42/40) was determined in 83 cognitively normal individuals (CN) and 145 subjects with amnestic mild cognitive impairment (a-MCI) stratified by an FDG-PET AD-risk pattern. RESULTS: Significant lower TP42/40 ratio was found in a-MCI patients compared to CN. Moreover, a-MCIs with a high-risk FDG-PET pattern for AD showed even lower plasma ratio levels. Low TP42/40 at baseline increased the risk of progression to dementia by 70%. Furthermore, TP42/40 was inversely associated with neocortical amyloid deposition (measured with PiB-PET) and was concordant with the AD biomarker profile in cerebrospinal fluid (CSF). CONCLUSIONS: TP42/40 demonstrated value in the identification of individuals suffering a-MCI, in the prediction of progression to dementia, and in the detection of underlying AD pathology revealed by FDG-PET, Amyloid-PET and CSF biomarkers, being, thus, consistently associated with all the well-established indicators of AD.

Alzheimer's disease (AD) is a neurodegenerative condition characterized by progressive cognitive decline and memory loss, and is the most common form of dementia. Amyloid plaques with neurofibrillary tangles are a neuropathological hallmark of AD that produces synaptic dysfunction and culminates later in neuronal loss. Amyloid PET is a useful, available and non-invasive technique that provides in vivo information about the cortical amyloid burden. In the latest revised criteria for the diagnosis of AD biomarkers were defined and integrated: pathological and diagnostic biomarkers (increased retention on fibrillar amyloid PET or decreased A beta(1-42) and increased T-Tau or P-Tau in CSF) and neurodegeneration or topographical biomarkers (temporoparietal hypometabolism on F-18-FDG PET and temporal atrophy on MRI). Recently specific recommendations have been created as a consensus statement on the appropriate use of the imaging biomarkers, including amyloid PET: early-onset cognitive impairment/dementia, atypical forms of AD, mild cognitive impairment with early age of onset, and to differentiate between AD and other neurodegenerative diseases that occur with dementia. Amyloid PET is also contributing to the development of new therapies for AD, as well as in research studies for the study of other neurodegenerative diseases that occur with dementia where the deposition of A beta amyloid is involved in its pathogenesis. In this paper, we review some general concepts and study the use of amyloid PET in depth and its relationship with neurodegenerative diseases and other diagnostic techniques. (C) 2018 Sociedad Espanola de Medicina Nuclear e Imagen Molecular. Published by Elsevier Espana, S.L.U. All rights reserved.

Objetivo. Este trabajo evalúa la idoneidad del radiotrazador 11C-(+)-α -dihidrotetrabenazina (11C-(+)DTBZ) para cuantificar mediante tomografía de emisión de positrones (PET) la inervación dopaminérgica en rata y mono, especies utilizadas como modelos animales en el estudio de la enfermedad de Parkinson. Material y métodos. En ratas se estudió una población control sana (n = 10) y el efecto del neurotóxico 6-hidroxidopamina (6-OHDA), además de realizarse estudios PET con 6-[(18)F]-fluoro-L-DOPA (18F-DOPA) y de autorradiografía digital cuantitativa. El estudio en Macaca fascicularis se realizó en animales control y tratados con el tóxico 1-metil-4-fenil-1,2,3,6-tetrahidropiridina (MPTP). Resultados. En ambas especies se obtuvieron imágenes de gran calidad donde se observó una alta captación de 11C-(+) DTBZ en el estriado. La cuantificación se realizó mediante la creación de imágenes paramétricas y el cálculo del potencial de unión (BP). La medida del BP en la población control de ratas arrojó un valor de 1,10 ± 0,16 (media ± error estándar [EE]), mientras que los estriados dañados con 6-OHDA mostraron una captación disminuida en función del grado de la lesión. Las imágenes obtenidas con 18F-DOPA no fueron aptas para el análisis al no discriminar los estriados, mientras que el estudio mediante autorradiografía digital cuantitativa confirmó la elevada afinidad de la 11C-(+)DTBZ por estas estructuras. En monos, el valor final de BP fue de 1,31 y 1,06 mientras que el tratamiento con MPTP disminuyó la captación en un 40 %. Conclusiones. La calidad de las imágenes PET y la disminución de la captación en las lesiones con 6-OHDA y MPTP indican que la 11C-(+)DTBZ es un radiotrazador adecuado para el estudio de la inervación dopaminérgica en estas especies animales.

The aim of this study was to investigate the changes in the cerebral blood flow that took place in normal subjects during an auditory attention paradigm which included automatic and controlled processing components.Participants consisted in 10 normal subjects who were submitted to medical, neuropsychological and neuroimaging evaluation. PET was used to carry out an exploration of each subject in the four experimental conditions: basal, listening to clicks (A), counting while listening to clicks (C+A) and counting without listening to clicks (C).During the condition involving counting while listening to clicks (automatic processing) the subjects displayed a significant increase in the activation of the bilateral precentral convolutions, left dorsolateral prefrontal cortex (DLPFC), left inferior and superior frontal convolutions, left supplementary motor area and the left superior and inferior temporal convolution. During the condition involving counting without listening to clicks (controlled processing), the subjects activated the right precentral convolution, bilateral DLPFC, the right supplementary motor area, anterior cingulate and right inferior parietal convolution.The results obtained support the suggestion that regions such as the DLPFC and the inferior parietal convolution play a part in attentional tasks in which the subject is required to make an effort to carry out the controlled processing of information.

Se evaluaron 34 pacientes con enfermedad de Alzheimer (EA) probable (EA leve = 16; EA moderada = 18) y 12 controles mediante un estudio semicuantitativo de SPECT con 99mTc-HMPAO y la batería de tests neuropsicológicos CERAD. Resultados: La hipoperfusión temporal (p < 0,01) y los tests de memoria (p < 0,001) permitieron diferenciar los controles de los pacientes con EA leve. En estos pacientes se observaron también correlaciones significativas (p < 0,05) entre: test de recuerdo diferido-hipoperfusión temporal, test de aprendizaje-hipoperfusión temporoparietal y frontal y praxis visuoconstructiva-hipoperfusión temporal posterior. Los pacientes con EA moderada mostraron, respecto a la EA leve, una mayor hipoperfusión temporal (p < 0,01), parietal y frontal (p < 0,05), junto a un empeoramiento de la praxis (p < 0,001) y los test de memoria (p < 0,05). Conclusiones: La SPECT y la evaluación neuropsicológica permiten distinguir entre controles y pacientes con estadios leve y moderado de la EA, existiendo una estrecha correlación entre ambos métodos desde las etapas iniciales de la enfermedad.

To corroborate the hypothesis of hypofrontality in schizophrenia and to study the relationship between positive/negative symptoms (measured by the positive and negative syndrome scale [PANSS]) and regional cortical blood flow (rCBF), both at rest and during the Wisconsin Card Sorting Test (WCST) performance (activation).We compared a control group (n = 18) to a group of patients with schizophrenia (n = 21) in terms of rCBF, measured by single photon emission computed tomography (SPECT).We found significantly higher left-frontal- CBF (during the WCST performance and at rest) and right-frontal-CBF (only at rest) in control subjects. Only the control group showed a right-frontal-CBF increase during activation. Only the patients group showed a significant right-occipital-CBF increase during the activation. We observed a positive significant correlation between the PANSS-P score and the left- frontal index at rest. Some negative symptoms such as difficulty in abstract thinking (N5) and lack of spontaneity and flow of conversation (N6) are associated to low frontal blood flow at rest. Affective blunting (N1) is associated to low left-frontal blood flow during activation.Our data support the hypothesis of hypofrontality, at rest and during activation, which means the incapacity of schizophrenic patients to increase the frontal CBF while performing the WCST (activation). Schizophrenia positive symptoms are associated to high left-frontal blood flow.

Brain single photon emission computed tomography (SPECT) with 99mTc-HMPAO is a diagnostic tool for evaluating regional cerebral blood flow. Recently, the diagnostic possibilities of the method are being investigated in some neurologic disorders, such as cerebrovascular accidents, seizures and dementia. This work has been carried out with 54 subjects, 9 healthy volunteers and 45 patients (31 dementia and 14 epileptics), in order to evaluate gammagraphic patterns and the utility of cortico/cerebellar activity indexes. An interesting diagnostic finding is a significant decrease (p less than 0.001) in perfusion of temporoparietal regions in the patients with Alzheimer's disease in relation with the healthy volunteers' group. We have not found significant changes in perfusion in the group of epileptic patients during the interictal phase. We conclude emphasizing the interest of the SPECT in the differential diagnosis of dementia.

Contains fulltext : 229556.pdf (Publisher’s version ) (Closed access) Various biomarkers are available to support the diagnosis of neurodegenerative diseases in clinical and research settings. Among the molecular imaging biomarkers, amyloid-PET, which assesses brain amyloid deposition, and (18)F-fluorodeoxyglucose ((18)F-FDG) PET, which assesses glucose metabolism, provide valuable and complementary information. However, uncertainty remains regarding the optimal timepoint, combination, and an order in which these PET biomarkers should be used in diagnostic evaluations because conclusive evidence is missing. Following an expert panel discussion, we reached an agreement on the specific use of the individual biomarkers, based on available evidence and clinical expertise. We propose a diagnostic algorithm with optimal timepoints for these PET biomarkers, also taking into account evidence from other biomarkers, for early and differential diagnosis of neurodegenerative diseases that can lead to dementia. We propose three main diagnostic pathways with distinct biomarker sequences, in which amyloid-PET and (18)F-FDG-PET are placed at different positions in the order of diagnostic evaluations, depending on clinical presentation. We hope that this algorithm can support diagnostic decision making in specialist clinical settings with access to these biomarkers and might stimulate further research towards optimal diagnostic strategies.