Early Detection of Brain Pathology Suggestive of Early AD Using Objective Evaluation of FDG-PET Scans

The need for early detection of AD becomes critical as disease-modifying agents near the marketplace. Here, we present results from a study focused on improvement in detection of metabolic deficits related to neurodegenerative changes consistent with possible early AD with statistical evaluation of FDG-PET brain images. We followed 31 subjects at high risk or diagnosed with MCI/AD for 3 years. 15 met criteria for diagnosis of MCI, and five met criteria for AD. FDG-PET scans were completed at initiation and termination of the study. PET scans were read clinically and also evaluated objectively using Statistical Parametric Mapping (SPM). Using standard clinical evaluation of the FDG-PET scans, 11 subjects were detected, while 18 were detected using SPM evaluation. These preliminary results indicate that objective analyses may improve detection; however, early detection in at-risk normal subjects remains tentative. Several FDA-approved software packages are available that use objective analyses, thus the capacity exists for wider use of this method for MCI/AD

The Metal-Poor Halo of the Andromeda Spiral Galaxy (M31)

We present spectroscopic observations of red giant branch (RGB) stars over a large expanse in the halo of the Andromeda spiral galaxy (M31), acquired with the DEIMOS instrument on the Keck II 10-m telescope. Using a combination of five photometric/spectroscopic diagnostics -- (1) radial velocity, (2) intermediate-width DDO51 photometry, (3) Na I equivalent width (surface gravity sensitive), (4) position in the color-magnitude diagram, and (5) comparison between photometric and spectroscopic [Fe/H] estimates -- we isolate over 250 bona fide M31 bulge and halo RGB stars located in twelve fields ranging from R = 12-165kpc from the center of M31 (47 of these stars are halo members with R > 60 kpc). We derive the photometric and spectroscopic metallicity distribution function of M31 RGB stars in each of these fields. The mean of the resulting M31 spheroid (bulge and halo) metallicity distribution is found to be systematically more metal-poor with increasing radius, shifting from = -0.47+/-0.03 (sigma = 0.39) at R = -0.94+/-0.06 (sigma = 0.60) at R ~ 30 kpc to = -1.26+/-0.10 (sigma = 0.72) at R > 60 kpc, assuming [alpha/Fe] = 0.0. These results indicate the presence of a metal-poor RGB population at large radial distances out to at least R = 160 kpc, thereby supporting our recent discovery of a stellar halo in M31: its halo and bulge (defined as the structural components with R^{-2} power law and de Vaucouleurs R^{1/4} law surface brightness profiles, respectively) are shown to have distinct metallicity distributions. If we assume an alpha-enhancement of [alpha/Fe] = +0.3 for M31's halo, we derive = -1.5+/-0.1 (sigma = 0.7). Therefore, the mean metallicity and metallicity spread of this newly found remote M31 RGB population are similar to those of the Milky Way halo.Comment: Accepted for publication in ApJ on May 4th, 2006 (submitted on Jan 30, 2006). 16 pages, 13 figures, 3 table

Language Disorder in Progressive Supranuclear Palsy and Corticobasal Syndrome: Neural Correlates and Detection by the MLSE Screening Tool.

Background: Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) affect speech and language as well as motor functions. Clinical and neuropathological data indicate a close relationship between these two disorders and the non-fluent variant of primary progressive aphasia (nfvPPA). We use the recently developed Mini Linguistic State Examination tool (MLSE) to study speech and language disorders in patients with PSP, CBS, and nfvPPA, in combination with structural magnetic resonance imaging (MRI). Methods: Fifty-one patients (PSP N = 13, CBS N = 19, nfvPPA N = 19) and 30 age-matched controls completed the MLSE, the short form of the Boston Diagnostic Aphasia Examination (BDAE), and the Addenbrooke's Cognitive Examination III. Thirty-eight patients and all controls underwent structural MRI at 3 Tesla, with T1 and T2-weighted images processed by surface-based and subcortical segmentation within FreeSurfer 6.0.0 to extract cortical thickness and subcortical volumes. Morphometric differences were compared between groups and correlated with the severity of speech and language impairment. Results: CBS and PSP patients showed impaired MLSE performance, compared to controls, with a similar language profile to nfvPPA, albeit less severe. All patient groups showed reduced cortical thickness in bilateral frontal regions and striatal volume. PSP and nfvPPA patients also showed reduced superior temporal cortical thickness, with additional thalamic and amygdalo-hippocampal volume reductions in nfvPPA. Multivariate analysis of brain-wide cortical thickness and subcortical volumes with MLSE domain scores revealed associations between performance on multiple speech and language domains with atrophy of left-lateralised fronto-temporal cortex, amygdala, hippocampus, putamen, and caudate. Conclusions: The effect of PSP and CBS on speech and language overlaps with nfvPPA. These three disorders cause a common anatomical pattern of atrophy in the left frontotemporal language network and striatum. The MLSE is a short clinical screening tool that can identify the language disorder of PSP and CBS, facilitating clinical management and patient access to future clinical trials

Language impairment in progressive supranuclear palsy and corticobasal syndrome

Abstract: Although commonly known as movement disorders, progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) may present with changes in speech and language alongside or even before motor symptoms. The differential diagnosis of these two disorders can be challenging, especially in the early stages. Here we review their impact on speech and language. We discuss the neurobiological and clinical-phenomenological overlap of PSP and CBS with each other, and with other disorders including non-fluent agrammatic primary progressive aphasia and primary progressive apraxia of speech. Because language impairment is often an early and persistent problem in CBS and PSP, there is a need for improved methods for language screening in primary and secondary care, and more detailed language assessments in tertiary healthcare settings. Improved language assessment may aid differential diagnosis as well as inform clinical management decisions

Language impairment in progressive supranuclear palsy and corticobasal syndrome

Abstract: Although commonly known as movement disorders, progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) may present with changes in speech and language alongside or even before motor symptoms. The differential diagnosis of these two disorders can be challenging, especially in the early stages. Here we review their impact on speech and language. We discuss the neurobiological and clinical-phenomenological overlap of PSP and CBS with each other, and with other disorders including non-fluent agrammatic primary progressive aphasia and primary progressive apraxia of speech. Because language impairment is often an early and persistent problem in CBS and PSP, there is a need for improved methods for language screening in primary and secondary care, and more detailed language assessments in tertiary healthcare settings. Improved language assessment may aid differential diagnosis as well as inform clinical management decisions

Anterior temporal lobe is necessary for efficient lateralised processing of spoken word identity.

In the healthy human brain, the processing of language is strongly lateralised, usually to the left hemisphere, while the processing of complex non-linguistic sounds recruits brain regions bilaterally. Here we asked whether the anterior temporal lobes, strongly implicated in semantic processing, are critical to this special treatment of spoken words. Nine patients with semantic dementia (SD) and fourteen age-matched controls underwent magnetoencephalography and structural MRI. Voxel based morphometry demonstrated the stereotypical pattern of SD: severe grey matter loss restricted to the anterior temporal lobes, with the left side more affected. During magnetoencephalography, participants listened to word sets in which identity and meaning were ambiguous until word completion, for example PLAYED versus PLATE. Whereas left-hemispheric responses were similar across groups, patients demonstrated increased right hemisphere activity 174-294 msec after stimulus disambiguation. Source reconstructions confirmed recruitment of right-sided analogues of language regions in SD: atrophy of anterior temporal lobes was associated with increased activity in right temporal pole, middle temporal gyrus, inferior frontal gyrus and supramarginal gyrus. Overall, the results indicate that anterior temporal lobes are necessary for normal and efficient lateralised processing of word identity by the language network.The study was primarily funded by the MRC Cognition and Brain Sciences Unit with additional support from the Cambridge NIHR Biomedical Research Centre (the views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care). TEC was supported by the Association of British Neurologists, the Patrick Berthoud Charitable trust, and the NIHR. YS was supported by the Medical Research Council (MC-A060-5PQ90), Lundbeck Foundation (R164-2013-15801, project 18690), Danish Council for Independent Research (6110-00486, project 23776), HSE Basic Research Program and the RF Academic Excellence Project '5-100'. JBR was supported by the Wellcome Trust (103838), and the Medical Research Council (MC-A060-5PQ30 & SUAG/004 RG91365)

Red cell and platelet transfusions in neonates: a population based study

Objectives: Reports of neonatal transfusion practices have focused predominantly on premature neonates admitted to neonatal intensive care units (NICU), however little is known about transfusion among other neonates. This study aimed to describe the use of blood products among all neonates. Design: Linked population-based birth and hospital discharge data from New South Wales (NSW), Australia was used to determine rates of blood product transfusion in the first 28 days of life. The study included all livebirths ≥23 weeks’ gestation in NSW between 2001 and 2011. Results: Between 2001-2011, 5326 of 989,491 live born neonates received a blood product transfusion (5.4 per 1000 births). Transfusion rates were 4.8 per 1000 for red cells, 1.3 per 1000 for platelets and 0.3 per 1000 for exchange transfusion. High transfusion rates were seen in neonates with prior in-utero transfusion (631/1000), congenital anomaly requiring surgery (440/1000) or haemolytic disorder (106/1000). Among transfused infants, 7% received transfusions in a hospital without a NICU. Of those transfused, 64% were born ≤32 weeks gestation (n=3384, 255/1000 births), with 96% of these receiving red cells. 36% were born >32 weeks gestation (n= 1942, 1.98/1000 births), with 76% receiving red cells and 38% receiving platelets. Conclusions: In this population based study, high transfusion rates were seen in neonates with haemolytic disorders or requiring surgery, as well as in those born preterm. Thirty-six percent of neonates who received blood products were born >32 weeks gestation and 7% were transfused in hospitals without a NICU.NHMRC, AR

Age of blood and adverse outcomes in a maternity population

BACKGROUND In recent times there has been debate around whether longer storage time of blood is associated with increased rates of adverse outcomes following transfusion. It is unclear whether results focused on cardiac or critically ill patients apply to a maternity population. This study investigates whether older blood is associated with increased morbidity and readmission in women undergoing obstetric transfusion. STUDY DESIGN AND METHODS Women giving birth in hospitals in New South Wales, Australia between July 2006‐December 2010 were included in the study population if they had received between 1‐4 red cell units during the birth admission. Information on women’s characteristics, transfusions and outcomes were obtained from 5 routinely collected datasets including blood collection, birth and hospitalisation data. Generalised propensity score methods were used to determine the effect of age of blood on rates of severe morbidity and readmission, independent of confounding factors. RESULTS Transfusion data were available for 2990 women, with a median age of blood transfused of 20 days (interquartile range 14,27 days). There were no differences in the age of blood transfused between women with and without severe morbidity (21 (14,28) vs 22 (15,30) days), and in women readmitted or not (22 (14,28) vs 22 (16,30) days). After considering potential confounding factors, no relationship was found between the age of blood transfused and rates of severe morbidity and readmission. CONCLUSION Among women receiving low volume transfusions during a birth admission, there was no evidence of increased rates of adverse outcomes following transfusion with older blood.NHMRC, Australian Red Cross, NSW Clinical Excellence Commission, AR