Gemma Cuberas-Borrós

A two-year follow-up of cognitive deficits and brain perfusion in Mild Cognitive Impairment and mild Alzheimer’s disease

The 15-Objects Test (15-OT) provides useful gradation of visuoperceptual impairment from normal aging through Alzheimers disease (AD) and correlates with temporo-parietal perfusion. The objectives of this study were to analyze progression of 15-OT performance in mild cognitive impairment (MCI) and AD, and its correlates with cognition and single photon emission computerized tomography (SPECT), as well as to examine neuropsychological and SPECT differences between the MCI patients who developed AD and those who did not. From the initial 126 participants (42/group), 38 AD, 39 MCI, and 38 elderly controls (EC) were reassessed (SPECT: 35 AD, 33 MCI, 35 EC) after two years. The progression of cognitive and SPECT scores during this period was compared between groups, and baseline data between converters and non-converters. The 15-OT was the only measure of progression that differed between the three groups; worsening scores on 15-OT were associated with worsening in verbal and visual retention, and decreased perfusion on left postsubicular area. In the MCI patients, cerebral perfusion fell over the two years in medial-posterior cingulate and fronto-temporo-parietal regions; AD showed extensive changes involving almost all cerebral regions. No SPECT changes were detected in controls. At baseline, the MCI patients who developed AD differed from non-converters in verbal recognition memory, but not in SPECT perfusion. In conclusion, SPECT and 15-OT appear to provide a potential measure to differentiate between normal aging, MCI, and AD. Worsening on 15-OT was related to decreased perfusion in postsubicular area; but further longitudinal studies are needed to determine the contribution of 15-OT as a predictor of AD from MCI.

Quantitative evaluation of striatal I-123-FP-CIT uptake in essential tremor and parkinsonism.

Aim: The aim of this study was to quantitatively evaluate the striatal uptake in 3 groups of patients: essential tremor (ET), drug-induced parkinsonism (DIP), and Parkinson disease (PD), using a voxel-based methodology and volumes of interests (VOIs) analysis. Patients and Method: Sixty patients from the Neurology Department Movement Disorders outpatient clinic in a tertiary hospital with I-123-FP-CIT SPECT were selected. After a clinical follow-up period of 2 years, a final clinical diagnosis of DIP was established for 20 patients (first group); 20 patients were diagnosed with ET (second group), and the third group was made up of 20 patients with a qualitatively pathologic SPECT who were diagnosed with PD. Once processed, DIP studies were spatially normalized to Montreal Neurologic Institute space and an average image was computed to create an I-123-FP-CIT SPECT template using statistical parametric mapping (SPM). Then all the I-123-FP-CIT images from all groups (DIP, ET, and PD) were registered to the new template. VOIs were defined in a digital atlas in Montreal Neurologic Institute space (caudate nucleus, putamen, and occipital cortex). Finally, mean counts were extracted from all VOIs and putamen-occipital and caudate-occipital ratios were computed. Analysis of variance tests were performed with all ratios. A SPM study of patterns evaluated the efficacy of the automated technique to determine whether the significant differences among groups corresponded to the same regions that the method purported to evaluate. Results: The analysis of variance test revealed significant differences between DIP and ET as compared with PD, both in the putamen and in the caudate nucleus. There were significant differences between DIP and ET populations only in the putamen but not in the caudate. The SPM found a lower uptake in the PD group in comparison with the ET and DIP groups. Therefore, in the organic parkinsonism cases, the most significant changes in uptake decrease were found in the putamen nuclei when compared with the DIP and the ET cases. No significant changes were observed between the ET and DIP groups. Conclusions: This study provides a fairly simple, reproducible, and useful methodology to be applied in everyday practice to quantify the studies of dopamine transporters using FP-CIT. We present the different ratios for putamen and caudate nucleus for 3 different groups with FP-CIT images. We obtained an optimal discrimination threshold value between the reference population and the pathologic population for the putamen ratio.

Usefulness of Exercise Test and Myocardial Perfusion–Gated Single Photon Emission Computed Tomography to Improve the Prediction of Major Events

Background—The incremental prognostic value of myocardial perfusion–gated single photon emission computed tomography (MPGS) compared with exercise test has not yet been properly evaluated. Methods and Results—Five thousand six hundred seventy-two consecutive patients with known or suspected coronary disease undergoing exercise MPGS between 1997 and 2007 were included. Three-year predictive models for total death and death from cardiovascular causes or acute myocardial infarction (ie, major cardiovascular events [MCE]) were built using Cox-regression modeling, including only the clinical information. Then the exercise and MPGS information was sequentially added. The added discriminative ability of exercise test information and MPGS was assessed by net reclassification improvement and integrated discrimination improvement. The increase in predictive ability of exercise information for death and MCE was high as assessed by net reclassification improvement (0.199 and 0.263) and integrated discrimination improvement (0.042 and 0.021). The only variable of MPGS associated with total death was ejection fraction (hazard ratio, 0.84; 95% confidence interval, 0.79–0.89; P<0.001). Global stress ischemic score emerged as an additional variable associated with MCE (hazard ratio, 1.07; 95% confidence interval, 1.02–1.12; P=0.007). Adding MPGS information barely improved the prognostic value for total death (net reclassification improvement, 0.017; integrated discrimination improvement, 0.013), but it increased for MCE (net reclassification improvement, 0.122; integrated discrimination improvement, 0.033). Conclusions—Adding MPGS information to exercise information does not improve prediction of total death, although it allows a more accurate prediction of MCE.

Cognitive, Genetic, and Brain Perfusion Factors Associated with Four Year Incidence of Alzheimer's Disease from Mild Cognitive Impairment

BACKGROUND There is a range of factors that predict the development of Alzheimers disease (AD) dementia among patients with amnestic mild cognitive impairment (MCI). OBJECTIVES To identify the neuropsychological, genetic, and functional brain imaging data that best predict conversion to AD dementia in patients with amnestic MCI. METHODS From an initial group of 42 amnestic MCI patients assessed with neurological, neuropsychological, and brain SPECT, 39 (25 converters, 14 non-converters) were followed for 4 years, and 36 had APOE ε4 genotyping. Baseline neuropsychological data and brain SPECT data were used to predict which of the MCI patients would develop dementia by the end of the 4 years of observation. RESULTS The MCI patients who had converted to AD dementia had poorer performance on long-term visual memory and Semantic Fluency tests. The MCI subjects who developed dementia were more likely to carry at least one copy of the APOE ε4 allele (Hazard Risk = 4.22). There was lower brain perfusion in converters than non-converters, mainly in postcentral gyrus. An additional analysis of the SPECT data found differences between the MCI subjects and controls in the posterior cingulate gyrus and the basal forebrain. When the brain imaging and neuropsychological test data were combined in the same Cox regression model, only the neuropsychological test data were significantly associated with time to dementia. CONCLUSION Although the presence of reduced brain perfusion in postcentral gyrus and basal forebrain indicated an at-risk condition, it was the extent of memory impairment that was linked to the speed of decline from MCI to AD.

Does reduced [123I]-FP-CIT binding in Huntington's disease suggest pre-synaptic dopaminergic involvement?

OBJECTIVE To evaluate the usefulness of SPECT in assessing damage to the pre-synaptic dopaminergic system in Huntingtons disease (HD) using [(123)I]-FP-CIT (DaTSCAN), a selective radioligand with regulatory approval as the diagnostic test for investigating functional dopaminergic neuron loss in the striatum in Parkinsons disease. METHODS We studied twelve symptomatic HD patients using DaTSCAN/SPECT imaging. [(123)I]-FP-CIT caudate and putamen uptake levels were qualitatively and semi-quantitatively analyzed to assess pre-synaptic damage in the striatal dopamine system. Possible correlations were analyzed between HD severity on the Unified Huntingtons Disease Rating Scale (UHDRS), duration of clinical symptoms, and [(123)I]-FP-CIT/SPECT striatal uptake. RESULTS DaTSCAN/SPECT qualitative analysis showed reduced striatal uptake in eight patients. Semi-quantitative analysis revealed a significant reduction in four. Of these four, uptake reduction was at putamen level in all, and also at caudate level in one. Although we observed no linear correlation between HD severity and reduced striatal [(123)I]-FP-CIT uptake, the patients with the worst UHDRS scores had more severe reductions in radioligand uptake. CONCLUSION This is the first study to use in vivo [(123)I]-FP-CIT/SPECT imaging to confirm prior descriptions using PET of a pre-synaptic dopaminergic system defect in HD.

Prueba de esfuerzo submáxima y atropina en la SPECT de perfusión miocárdica

Introduccion y objetivos El objetivo de este estudio es evaluar la eficacia diagnostica de la tomografia computarizada por emision monofotonica (SPECT) de perfusion miocardica con la administracion de atropina intravenosa al final de una prueba de esfuerzo con insuficiente taquicardizacion. Metodos A 172 pacientes que, a pesar de realizar una prueba ergometrica limitada por sintomas, no alcanzaron un 80% de taquicardizacion, sin presentar angina ni descenso del segmento ST ≥ 1 mm, se les administro 1 mg de atropina intravenosa al final del esfuerzo. A 23 de estos pacientes con criterios de isquemia gammagrafica en la SPECT con atropina, y en el curso de 1 semana, se les practico una segunda SPECT sin la administracion de atropina con la finalidad de comparar la presencia y la gravedad de la isquemia gammagrafica entre los dos estudios (suma puntuacion diferencial [SPD]). Resultados De los 172 pacientes, 75 (43,6%) presentaron angina (n = 56) o descenso del segmento ST (n = 30) con la administracion de atropina. De los 23 pacientes en los que se hicieron ambas pruebas, 8 (35%) tuvieron isquemia (SPD ≥ 2) unicamente en la prueba con atropina. Ademas, la SPD fue significativamente superior en las imagenes de SPECT con atropina (5,6 ± 4,5 frente a 3,1 ± 2,8; p = 0,0001). Conclusiones La administracion de atropina al final de una prueba de esfuerzo insuficiente permite obtener criterios gammagraficos de isquemia en una tercera parte de los casos en que no se habria obtenido sin la administracion del farmaco.

Base de datos de normalidad de la SPECT de perfusión miocárdica en la población española

Resumen Introduccion y objetivos El objetivo de este estudio ha sido crear una base de datos espanola (BDE) de normalidad de la SPECT (single photon emission computed tomography) de perfusion miocardica y compararla con una base de datos de normalidad de poblacion norteamericana. Metodos Se selecciono a 104 voluntarios sanos (45 mujeres, media de edad, 42 ± 14 anos) a los que se practico una SPECT de estres y reposo, procesandose los estudios en el programa comercial 4DM-SPECT. La BDE de normalidad generada para varones y mujeres se comparo con la base de datos de la poblacion norteamericana (70 varones y 60 mujeres) que proporciona el programa 4DM-SPECT. Resultados En la BDE el mayor porcentaje de captacion correspondio a la region lateral-medial, y el menor, a la region septal-basal, tanto en estres como en reposo. En las mujeres el porcentaje de captacion de la region anterior-medial fue significativamente mas bajo que en los varones, mientras que en estos se observo una menor captacion en las regiones inferiores, septal medial y apical con respecto a las mujeres. Los valores de la BDE fueron significativamente mas bajos que los de la 4DMSPECT en la mayoria de las regiones. Conclusiones Se ha creado una base de datos de normalidad espanola para mujeres y varones por separado de la SPECT de perfusion miocardica, y se ha observado que hay diferencias significativas con una base de datos comercial de origen norteamericano que suele utilizarse en estudios semicuantitativos.

Progressive presynaptic dopaminergic deterioration in Huntington disease: a [123I]-FP-CIT SPECT two-year follow-up study.

To illustrate the potential of [I]-FP-CIT SPECT DaTSCAN® in investigating the progression of presynaptic dopaminergic degeneration in Huntington disease (HD), we performed a 2-year follow-up [I]-FP-CIT study on 4 HD patients, evaluating the SPECT imaging based on qualitative and semiquantitative analysis. The mean annual decline in [I]-FP-CIT uptake in caudate and putamen after 2 years of follow-up was 5.8% and 9.6%, respectively. Our findings suggest that [I]-FP-CIT SPECT is useful in investigating the progression of presynaptic dopaminergic degeneration in HD, and may be useful as a disease biomarker, providing an objective method for measuring the effectiveness of future neuroprotective therapies.

Bone scintigraphy and radiolabeled white blood cell scintigraphy for the diagnosis of mandibular osteomyelitis.

The aim of this study was to evaluate the diagnostic efficacy of bone scintigraphy (BS) and radiolabeled white blood cell scintigraphy (WBCS) in detecting septic activity in the flat bones of the jaw. A retrospective analysis was conducted using 38 studies of combined BS plus WBCS: 33 of them 3-phase BS and 36 of them 2-phase WBCS. These studies were performed on 34 patients, 19 women and 15 men with a mean age of 56 years (22–79), who presented with suspected mandibular osteomyelitis, either acute or chronic exacerbation. The results were compared with histologic findings (55%) or with a minimum clinical/radiologic follow-up of 6 months (average, 21 months), when biopsy results were not available. BS showed a sensitivity of 100%, a specificity of 6.7%, a positive predictive value of 62%, and a negative predictive value of 100%. For WBCS, the corresponding values were as follows: 73.7%, 78.6%, 82%, and 69%. Accuracy was 63.2% for BS and 94.7% for WBCS. WBCS has proven to be a useful test for detecting septic activity in the jaw bone, being more effective than BS alone, which under certain circumstances, can return a very high false-positive rate.

Normal Myocardial Perfusion SPECT Database for the Spanish Population

INTRODUCTION AND OBJECTIVES The aims of this study were to create a Spanish database of normal myocardial perfusion SPECT (single-photon emission computed tomography) data, termed the normal Spanish database, and to compare it with a database of normal data from the North American population. METHODS We selected 104 healthy volunteers (45 female, mean age 42+/-14 years) who underwent SPECT during stress and at rest. The findings were analyzed using the 4DM-SPECT commercial software package. The resulting normal Spanish database for males and females was compared with the North American population database (from 70 men and 60 women) provided with the 4DM-SPECT software. RESULTS In the Spanish database, the highest percentage uptake during both stress and rest was observed in medial-lateral region and the lowest, in the basal-septal region. The percentage uptake in the anterior-medial region was significantly lower in women than men, while uptake in the inferior, medial-septal and apical regions was lower in men than women. Data values in the Spanish database were significantly lower for the majority of heart regions than those in the database with the 4DM-SPECT software. CONCLUSIONS A Spanish database of normal myocardial perfusion SPECT data was created and included separate data for men and women. Significant differences were observed between this database and a commercial North American database that is commonly used in semiquantitative studies.