Health work and skills in the last mile of disease elimination. Experiences from sleeping sickness health workers in South Sudan and DR Congo.

Human African trypanosomiasis (HAT) is considered a highly promising candidate for elimination within the next decade. This paper argues that the experiential knowledge of frontline health workers will be critical to achieve this goal. Interviews are used to explore the ways in which HAT workers understand, maintain, and adjust their skills amidst global and national challenges. We contrast two cases: South Sudan where HAT expertise is scattered and has been repeatedly rebuilt, and the Democratic Republic of Congo (DRC) where specialised mobile detection teams have pro-actively tested people at risk for almost a century. We describe HAT careers where skills are built through participation in HAT technology trials and screening programmes; in the DRC expertise is also supported through formal rotations in screening teams and HAT referral centres for new health workers. As cases fade, de-skilling is a real threat as awareness of populations and authorities diminishes and previously vertical programmes evolve, re-configuring professional development and career paths and associated opportunities for HAT practice. To avoid repeating the mistakes of the 1960s, when elimination also seemed close at hand, we need to recognise that the 'last mile' of elimination hinges on protecting the fragile expertise of frontline health workers.

Out-of-hospital resuscitation of a 3 month old boy presenting with recurrent ventricular fibrillation cardiac arrest: a case report.

A 3 month old boy, with no known health conditions, suffered a sudden collapse at home. On first EMS arrival, ventricular fibrillation (VF) cardiac arrest was identified and resuscitation following UK national guidelines was initiated. He remained in cardiac arrest for over 25 min, during which he received 10 defibrillation shocks, each effective, but with VF reoccurring within a few seconds of each of the first 9. A return of spontaneous circulation (ROSC) was achieved after the 10th shock. The resuscitation was conducted fully in his home, with the early involvement of Advanced Paramedic Practitioners specialising in critical care (APP- CC). Throughout his resuscitation, there remained a strong focus on delivering quality resuscitation in situ, rather than a 'load and go' approach that would have resulted in very early conveyance to hospital with on-going CPR.The patient was subsequently discharged home and is making an excellent recovery. The arrest was later determined to have been caused by a primary arrhythmia as a result of a previously unidentified non-obstructive variant hypertrophic cardiomyopathy.We present data downloaded from the defibrillator used during the resuscitation that illustrates clearly the recurrent nature of his fibrillation.

Frontal lobe functioning during a simple response conflict task in first-episode psychosis and its relationship to treatment response.

Prior functional magnetic resonance imaging (fMRI) studies have investigated the neural mechanisms underlying cognitive control in patients with psychosis with findings of both hypo- and hyperfrontality. One factor that may contribute to inconsistent findings is the use of complex and polyfactorial tasks to investigate frontal lobe functioning. In the current study we employed a simple response conflict task during fMRI to examine differences in brain activation between patients experiencing their first-episode of psychosis (n = 33) and age- and sex-matched healthy volunteers (n = 33). We further investigated whether baseline brain activation among patients predicted changes in symptom severity and treatment response following 12 weeks of controlled antipsychotic treatment. During the task subjects were instructed to press a response button on the same side or opposite side of a circle that appeared on either side of a central fixation point. Imaging data revealed that for the contrast of opposite-side vs. same-side, patients showed significantly greater activation compared with healthy volunteers in the anterior cingulate cortex and intraparietal sulcus. Among patients, greater baseline anterior cingulate cortex, temporal-parietal junction, and superior temporal cortex activation predicted greater symptom reduction and therapeutic response following treatment. All findings remained significant after covarying for task performance. Intact performance on this relatively parsimonious task was associated with frontal hyperactivity suggesting the need for patients to utilize greater neural resources to achieve task performance comparable to healthy individuals. Moreover, frontal hyperactivity observed using a simple fMRI task may provide a biomarker for predicting treatment response in first-episode psychosis.

The Age-Related Perfusion Pattern Measured With Arterial Spin Labeling MRI in Healthy Subjects.

Aim: To analyze age-related cerebral blood flow (CBF) using arterial spin labeling (ASL) MRI in healthy subjects with multivariate principal component analysis (PCA). Methods: 50 healthy subjects (mean age 45.8 ± 18.5 years, range 21-85) had 3D structural MRI and pseudo-continuous ASL MRI at resting state. The relationship between CBF and age was examined with voxel-based univariate analysis using multiple regression and two-sample t-test (median age 41.8 years as a cut-off). An age-related CBF pattern was identified using multivariate PCA. Results: Age correlated negatively with CBF especially anteriorly and in the cerebellum. After adjusting by global value, CBF was relatively decreased with aging in certain regions and relatively increased in others. The age-related CBF pattern showed relative reductions in frontal and parietal areas and cerebellum, and covarying increases in temporal and occipital areas. Subject scores of this pattern correlated negatively with age (R2 = 0.588; P < 0.001) and discriminated between the older and younger subgroups (P < 0.001). Conclusion: A distinct age-related CBF pattern can be identified with multivariate PCA using ASL MRI.

Resting-State Connectivity Biomarkers of Cognitive Performance and Social Function in Individuals With Schizophrenia Spectrum Disorder and Healthy Control Subjects.

BACKGROUND: Deficits in neurocognition and social cognition are drivers of reduced functioning in schizophrenia spectrum disorders, with potentially shared neurobiological underpinnings. Many studies have sought to identify brain-based biomarkers of these clinical variables using a priori dichotomies (e.g., good vs. poor cognition, deficit vs. nondeficit syndrome). METHODS: We evaluated a fully data-driven approach to do the same by building and validating a brain connectivity-based biomarker of social cognitive and neurocognitive performance in a sample using resting-state and task-based functional magnetic resonance imaging (n = 74 healthy control participants, n = 114 persons with schizophrenia spectrum disorder, 188 total). We used canonical correlation analysis followed by clustering to identify a functional connectivity signature of normal and poor social cognitive and neurocognitive performance. RESULTS: Persons with poor social cognitive and neurocognitive performance were differentiated from those with normal performance by greater resting-state connectivity in the mirror neuron and mentalizing systems. We validated our findings by showing that poor performers also scored lower on functional outcome measures not included in the original analysis and by demonstrating neuroanatomical differences between the normal and poorly performing groups. We used a support vector machine classifier to demonstrate that functional connectivity alone is enough to distinguish normal and poorly performing participants, and we replicated our findings in an independent sample (n = 75). CONCLUSIONS: A brief functional magnetic resonance imaging scan may ultimately be useful in future studies aimed at characterizing long-term illness trajectories and treatments that target specific brain circuitry in those with impaired cognition and function.

Integration of routine QA data into mega-analysis may improve quality and sensitivity of multisite diffusion tensor imaging studies.

A novel mega-analytical approach that reduced methodological variance was evaluated using a multisite diffusion tensor imaging (DTI) fractional anisotropy (FA) data by comparing white matter integrity in people with schizophrenia to controls. Methodological variance was reduced through regression of variance captured from quality assurance (QA) and by using Marchenko-Pastur Principal Component Analysis (MP-PCA) denoising. N = 192 (119 patients/73 controls) data sets were collected at three sites equipped with 3T MRI systems: GE MR750, GE HDx, and Siemens Trio. DTI protocol included five b = 0 and 60 diffusion-sensitized gradient directions (b = 1,000 s/mm2 ). In-house DTI QA protocol data was acquired weekly using a uniform phantom; factor analysis was used to distil into two orthogonal QA factors related to: SNR and FA. They were used as site-specific covariates to perform mega-analytic data aggregation. The effect size of patient-control differences was compared to these reported by the enhancing neuro imaging genetics meta-analysis (ENIGMA) consortium before and after regressing QA variance. Impact of MP-PCA filtering was evaluated likewise. QA-factors explained ∼3-4% variance in the whole-brain average FA values per site. Regression of QA factors improved the effect size of schizophrenia on whole brain average FA values-from Cohen's d = .53 to .57-and improved the agreement between the regional pattern of FA differences observed in this study versus ENIGMA from r = .54 to .70. Application of MP-PCA-denoising further improved the agreement to r = .81. Regression of methodological variances captured by routine QA and advanced denoising that led to a better agreement with a large mega-analytic study.

A novel DTI-QA tool: Automated metric extraction exploiting the sphericity of an agar filled phantom.

PURPOSE: To develop a quality assurance (QA) tool (acquisition guidelines and automated processing) for diffusion tensor imaging (DTI) data using a common agar-based phantom used for fMRI QA. The goal is to produce a comprehensive set of automated, sensitive and robust QA metrics. METHODS: A readily available agar phantom was scanned with and without parallel imaging reconstruction. Other scanning parameters were matched to the human scans. A central slab made up of either a thick slice or an average of a few slices, was extracted and all processing was performed on that image. The proposed QA relies on the creation of two ROIs for processing: (i) a preset central circular region of interest (ccROI) and (ii) a signal mask for all images in the dataset. The ccROI enables computation of average signal for SNR calculations as well as average FA values. The production of the signal masks enables automated measurements of eddy current and B0 inhomogeneity induced distortions by exploiting the sphericity of the phantom. Also, the signal masks allow automated background localization to assess levels of Nyquist ghosting. RESULTS: The proposed DTI-QA was shown to produce eleven metrics which are robust yet sensitive to image quality changes within site and differences across sites. It can be performed in a reasonable amount of scan time (~15min) and the code for automated processing has been made publicly available. CONCLUSIONS: A novel DTI-QA tool has been proposed. It has been applied successfully on data from several scanners/platforms. The novelty lies in the exploitation of the sphericity of the phantom for distortion measurements. Other novel contributions are: the computation of an SNR value per gradient direction for the diffusion weighted images (DWIs) and an SNR value per non-DWI, an automated background detection for the Nyquist ghosting measurement and an error metric reflecting the contribution of EPI instability to the eddy current induced shape changes observed for DWIs.

Investigation of superior longitudinal fasciculus fiber complexity in recent onset psychosis.

BACKGROUND: Standard diffusion tensor imaging measures (e.g., fractional anisotropy; FA) are difficult to interpret in brain regions with crossing white-matter (WM) fibers. Diffusion spectrum imaging (DSI) can be used to resolve fiber crossing, but has been difficult to implement in studies of patients with psychosis given long scan times. METHODS: We used four fold accelerated compressed sensing to accelerate DSI acquisition to investigate the superior longitudinal fasciculus (SLF) in 27 (20M/7F) patients with recent onset psychosis and 23 (11M/12F) healthy volunteers. Dependent measures included the number of crossing fiber directions, multi directional anisotropy (MDA), which is a measure sensitive to the anisotropy of the underlying water diffusion in regions of crossing fibers, generalized FA (GFA) computed from the orientation distribution function, FA and tract volume. RESULTS: Patients demonstrated a greater number of crossing WM fibers, lower MDA, GFA and FA in the left SLF compared to healthy volunteers. Patients also demonstrated a reversal in the normal (R>L) asymmetry of crossing fiber directions in the SLF and a lack of normal (L>R) asymmetry in MDA, GFA and FA compared to healthy volunteers. Lower GFA correlated significantly (p<0.05) with worse overall neuropsychological functioning; posthoc tests revealed significant effects with verbal functioning and processing speed. CONCLUSIONS: Our findings provide the first in vivo evidence for abnormal crossing fibers within the SLF among individuals with psychosis and their functional correlates. A reversal in the normal pattern of WM asymmetry of crossing fibers in patients may be consistent with an aberrant neurodevelopmental process.

The impact of self-help groups on pastoral women's empowerment and agency: A study in Nigeria.

While women in pastoralist communities are key stakeholders in the production of milk and dairy products for income generation, they are largely ignored in other areas of development such as health. The need to involve women self-help groups, in pastoralist areas in both animal health and human health development programmes, is essential, particularly given the high incidence of zoonotic diseases in these communities (Maudlin I, Eisler MC and Welburn SC, Philosophical Transactions of the Royal Society B: Biological Sciences, 364(1530):2777-2787, 2009). Understanding the process and impact of social networks on livelihoods is essential for any development programme that aims to prevent and control zoonotic diseases. This study examines the roles and responsibilities of women self-help groups in Kachia Grazing Reserve and Bokkos, Jos Plateau, Nigeria. The findings show that groups promoting social, physical and psychological health strongly motivated women's involvement in self-help groups. Self-help activities showed commitment to effect a change in their livelihoods, despite constraining environmental, cultural and social factors. Engagement of women's self-help groups in livestock development programmes offers a powerful instrument for driving forward the One Health practice in pastoralist communities, promoting human, animal and environmental health and well-being.

Achilles tendon rupture in atypical patient populations.

Rupture of the Achilles tendon is a significant injury, and the likelihood of a good recovery is directly associated with early diagnosis and appropriate referral. Such injuries are commonly assessed and identified by practitioners working in 'minors' areas of emergency departments or urgent care settings. The literature frequently describes rupture of the Achilles tendon as 'typically sport-related' affecting 'middle-aged weekend warriors', but this aetiology accounts for only about 70% of such injuries. Factors such as the natural ageing process, obesity and use of some commonly prescribed medications, can increase the risk of developing a tendinopathy and subsequent rupture, often from a seemingly insignificant incident. However, research suggests that injuries in this patient population are more likely be missed on first examination. This article describes risk factors that should alert clinicians to the possibility of Achilles tendon rupture in 'atypical' patient populations.

Subcortical modulation in auditory processing and auditory hallucinations.

Hearing perception in individuals with auditory hallucinations has not been well studied. Auditory hallucinations have previously been shown to involve primary auditory cortex activation. This activation suggests that auditory hallucinations activate the terminal of the auditory pathway as if auditory signals are submitted from the cochlea, and that a hallucinatory event is therefore perceived as hearing. The primary auditory cortex is stimulated by some unknown source that is outside of the auditory pathway. The current study aimed to assess the outcomes of stimulating the primary auditory cortex through the auditory pathway in individuals who have experienced auditory hallucinations. Sixteen patients with schizophrenia underwent functional magnetic resonance imaging (fMRI) sessions, as well as hallucination assessments. During the fMRI session, auditory stimuli were presented in one-second intervals at times when scanner noise was absent. Participants listened to auditory stimuli of sine waves (SW) (4-5.5kHz), English words (EW), and acoustically reversed English words (arEW) in a block design fashion. The arEW were employed to deliver the sound of a human voice with minimal linguistic components. Patients' auditory hallucination severity was assessed by the auditory hallucination item of the Brief Psychiatric Rating Scale (BPRS). During perception of arEW when compared with perception of SW, bilateral activation of the globus pallidus correlated with severity of auditory hallucinations. EW when compared with arEW did not correlate with auditory hallucination severity. Our findings suggest that the sensitivity of the globus pallidus to the human voice is associated with the severity of auditory hallucination.

Abnormal resting state FMRI activity predicts processing speed deficits in first-episode psychosis.

Little is known regarding the neuropsychological significance of resting state functional magnetic resonance imaging (rs-fMRI) activity early in the course of psychosis. Moreover, no studies have used different approaches for analysis of rs-fMRI activity and examined gray matter thickness in the same cohort. In this study, 41 patients experiencing a first-episode of psychosis (including N=17 who were antipsychotic drug-naive at the time of scanning) and 41 individually age- and sex-matched healthy volunteers completed rs-fMRI and structural MRI exams and neuropsychological assessments. We computed correlation matrices for 266 regions-of-interest across the brain to assess global connectivity. In addition, independent component analysis (ICA) was used to assess group differences in the expression of rs-fMRI activity within 20 predefined publicly available templates. Patients demonstrated lower overall rs-fMRI global connectivity compared with healthy volunteers without associated group differences in gray matter thickness assessed within the same regions-of-interest used in this analysis. Similarly, ICA revealed worse rs-fMRI expression scores across all 20 networks in patients compared with healthy volunteers, with posthoc analyses revealing significant (p<0.05; corrected) abnormalities within the caudate nucleus and planum temporale. Worse processing speed correlated significantly with overall lower global connectivity using the region-of-interest approach and lower expression scores within the planum temporale using ICA. Our findings implicate dysfunction in rs-fMRI activity in first-episode psychosis prior to extensive antipsychotic treatment using different analytic approaches (in the absence of concomitant gray matter structural differences) that predict processing speed.

Seeing scenes: topographic visual hallucinations evoked by direct electrical stimulation of the parahippocampal place area.

In recent years, functional neuroimaging has disclosed a network of cortical areas in the basal temporal lobe that selectively respond to visual scenes, including the parahippocampal place area (PPA). Beyond the observation that lesions involving the PPA cause topographic disorientation, there is little causal evidence linking neural activity in that area to the perception of places. Here, we combined functional magnetic resonance imaging (fMRI) and intracranial EEG (iEEG) recordings to delineate place-selective cortex in a patient implanted with stereo-EEG electrodes for presurgical evaluation of drug-resistant epilepsy. Bipolar direct electrical stimulation of a cortical area in the collateral sulcus and medial fusiform gyrus, which was place-selective according to both fMRI and iEEG, induced a topographic visual hallucination: the patient described seeing indoor and outdoor scenes that included views of the neighborhood he lives in. By contrast, stimulating the more lateral aspect of the basal temporal lobe caused distortion of the patient's perception of faces, as recently reported (Parvizi et al., 2012). Our results support the causal role of the PPA in the perception of visual scenes, demonstrate that electrical stimulation of higher order visual areas can induce complex hallucinations, and also reaffirm direct electrical brain stimulation as a tool to assess the function of the human cerebral cortex.

APOE genotype modulates proton magnetic resonance spectroscopy metabolites in the aging brain.

BACKGROUND: Proton magnetic resonance spectroscopy ((1)H-MRS) studies on healthy aging have reported inconsistent findings and have not systematically taken into account the possible modulatory effect of APOE genotype. We aimed to quantify brain metabolite changes in healthy subjects in relation to age and the presence of the APOE E4 genetic risk factor for Alzheimer's disease. Additionally, we examined these measures in relation to cognition. METHODS: We studied a cohort of 112 normal adults between 50 and 86 years old who were genotyped for APOE genetic polymorphism. Measurements of (1)H-MRS metabolites were obtained in the posterior cingulate and precuneus region. Measures of general cognitive functioning, memory, executive function, semantic fluency, and speed of processing were also obtained. RESULTS: General linear model analysis demonstrated that older APOE E4 carriers had significantly higher choline/creatine and myo-inositol/creatine ratios than APOE E3 homozygotes. Structural equation modeling resulted in a model with an excellent goodness of fit and in which the APOE × age interaction and APOE status each had a significant effect on (1)H-MRS metabolites (choline/creatine and myo-inositol/creatine). Furthermore, the APOE × age variable modulation of cognition was mediated by (1)H-MRS metabolites. CONCLUSIONS: In a healthy aging normal population, choline/creatine and myo-inositol/creatine ratios were significantly increased in APOE E4 carriers, suggesting the presence of neuroinflammatory processes and greater membrane turnover in older carriers. Structural equation modeling analysis confirmed these possible neurodegenerative markers and also indicated the mediator role of these metabolites on cognitive performance among older APOE E4 carriers.

Resting-state fMRI connectivity impairment in schizophrenia and bipolar disorder.

BACKGROUND: Schizophrenia and bipolar disorder share aspects of phenomenology and neurobiology and thus may represent a continuum of disease. Few studies have compared connectivity across the brain in these disorders or investigated their functional correlates. METHODS: We used resting-state functional magnetic resonance imaging to evaluate global and regional connectivity in 32 healthy controls, 19 patients with bipolar disorder, and 18 schizophrenia patients. Patients also received comprehensive neuropsychological and clinical assessments. We computed correlation matrices among 266 regions of interest within the brain, with the primary dependent measure being overall global connectivity strength of each region with every other region. RESULTS: Patients with schizophrenia had significantly lower global connectivity compared with healthy controls, whereas patients with bipolar disorder had global connectivity intermediate to and significantly different from those of patients with schizophrenia and healthy controls. Post hoc analyses revealed that compared with healthy controls, both patient groups had significantly lower connectivity in the paracingulate gyrus and right thalamus. Patients with schizophrenia also had significantly lower connectivity in the temporal occipital fusiform cortex, left caudate nucleus, and left thalamus compared with healthy controls. There were no significant differences among the patient groups in any of these regions. Lower global connectivity among all patients was associated with worse neuropsychological and clinical functioning, but these effects were not specific to any patient group. CONCLUSIONS: These findings are consistent with the hypothesis that schizophrenia and bipolar disorder may represent a continuum of global disconnectivity in the brain but that regional functional specificity may not be evident.

An Open-Label Exploratory Study with Memantine: Correlation between Proton Magnetic Resonance Spectroscopy and Cognition in Patients with Mild to Moderate Alzheimer's Disease.

AIM: To characterize progression of Alzheimer's disease (AD) using proton magnetic resonance spectroscopy ((1)H MRS). METHODS: Eleven subjects with mild to moderate AD underwent neurocognitive testing and single-voxel (1)H MRS from the precuneus and posterior cingulate region at baseline, after 24 weeks of monotherapy with a cholinesterase inhibitor, and after another 24 weeks of combination therapy with open-label memantine and a cholinesterase inhibitor. Baseline metabolites [N-acetylaspartate (NAA), myo-inositol (mI), choline (Cho), and creatine (Cr)] and their ratios in AD subjects were compared with those of an age-matched control group of 28 cognitively normal subjects. RESULTS: AD subjects had significantly higher mI/Cr and lower NAA, NAA/Cr, NAA/Cho, and NAA/mI. Baseline Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) scores significantly correlated with NAA/Cr, mI/Cr, and NAA/mI. There was an increase in mI and a decrease in NAA/mI, but no significant change in other metabolites or ratios, or neurocognitive measures, when memantine was added to a cholinesterase inhibitor. CONCLUSION: Metabolite ratios significantly differed between AD and control subjects. Baseline metabolite ratios correlated with function (ADCS-ADL). There was an increase in mI and a decrease in NAA/mI, but no changes in other metabolites, ratios, or cognitive measures, when memantine was added to a cholinesterase inhibitor.

Feature-based interpolation of diffusion tensor fields and application to human cardiac DT-MRI.

Diffusion tensor interpolation is an important issue in the application of diffusion tensor magnetic resonance imaging (DT-MRI) to the human heart, all the more as the points representing the myocardium of the heart are often sparse. We propose a feature-based interpolation framework for the tensor fields from cardiac DT-MRI, by taking into account inherent relationships between tensor components. In this framework, the interpolation consists in representing a diffusion tensor in terms of two tensor features, eigenvalues and orientation, interpolating the Euler angles or the quaternion relative to tensor orientation and the logarithmically transformed eigenvalues, and reconstructing the tensor to be interpolated from the interpolated eigenvalues and tensor orientations. The results obtained with the aid of both synthetic and real cardiac DT-MRI data demonstrate that the feature-based schemes based on Euler angles or quaternions not only maintain the advantages of Log-Euclidean and Riemannian interpolation as for preserving the tensor's symmetric positive-definiteness and the monotonic determinant variation, but also preserve, at the same time, the monotonicity of fractional anisotropy (FA) and mean diffusivity (MD) values, which is not the case with Euclidean, Cholesky and Log-Euclidean methods. As a result, both interpolation schemes remove the phenomenon of FA collapse, and consequently avoid introducing artificial fiber crossing, with the difference that the quaternion is independent of coordinate system while Euler angles have the property of being more suitable for sophisticated interpolations.

Thalamo-striatal diffusion reductions precede disease onset in prion mutation carriers.

Human prion diseases present substantial scientific and public health challenges. They are unique in being sporadic, infectious and inherited, and their pathogen is distinct from all other pathogens in lacking nucleic acids. Despite progress in understanding the molecular structure of prions, their initial cerebral pathophysiology and the loci of cerebral injury are poorly understood. As part of a large prospective study, we analysed early diffusion MRI scans of 14 patients with the E200K genetic form of Creutzfeldt-Jakob Disease, 20 healthy carriers of this mutation that causes the disease and 20 controls without the mutation from the same families. Cerebral diffusion was quantified by the Apparent Diffusion Coefficient, and analysed by voxel-wise statistical parametric mapping technique. Compared to the mutation-negative controls, diffusion was significantly reduced in a thalamic-striatal network, comprising the putamen and mediodorsal, ventrolateral and pulvinar thalamic nuclei, in both the patients and the healthy mutation carriers. With disease onset, these diffusion reductions intensified, but did not spread to other areas. The caudate nucleus was reduced only after symptomatic onset. These findings indicate that cerebral diffusion reductions can be detected early in the course of Creutzfeldt-Jakob Disease, and years before symptomatic onset in mutation carriers, in a distinct subcortical network. We suggest that this network is centrally involved in the pathogenesis of Creutzfeldt-Jakob Disease, and its anatomical connections are sufficient to account for the common symptoms of this disease. Further, we suggest that the abnormalities in healthy mutation-carrying subjects may reflect the accumulation of abnormal prion protein and/or associated vacuolation at this time, temporally close to disease onset.

The functional neuroanatomy of geriatric depression.

OBJECTIVE: Positron Emission Tomography (PET) studies of cerebral glucose metabolism have demonstrated sensitivity in evaluating the functional neuroanatomy of treatment response variability in depression, as well as in the early detection of functional changes associated with incipient cognitive decline. The evaluation of cerebral glucose metabolism in late life depression may have implications for understanding treatment response variability, as well as evaluating the neurobiological basis of depression in late life as a risk factor for dementia. METHODS: Sixteen patients with geriatric depression and 13 comparison subjects underwent resting PET studies of cerebral glucose metabolism, as well as magnetic resonance (MR) imaging scans to evaluate brain structure. RESULTS: Cerebral glucose metabolism was elevated in geriatric depressed patients relative to comparison subjects in anterior (right and left superior frontal gyrus) and posterior (precuneus, inferior parietal lobule) cortical regions. Cerebral atrophy (increased cerebrospinal fluid [CSF] and decreased grey and white matter volumes) were observed in some of these regions, as well. Regional cerebral metabolism was positively correlated with severity of depression and anxiety symptoms. CONCLUSIONS: In contrast to decreased metabolism observed in normal aging and neurodegenerative conditions such as Alzheimer's disease, cortical glucose metabolism was increased in geriatric depressed patients relative to demographically matched controls, particularly in brain regions in which cerebral atrophy was observed, which may represent a compensatory response.