Silvana Prando

Localized cerebral blood flow reductions in patients with heart failure: a study using 99mTc-HMPAO SPECT.

Background and Purpose. Reduced resting global cerebral blood flow has been previously detected in association with heart failure (HF), but it is not clear whether there are brain regions that could be specifically affected by those brain perfusion deficits. The authors used a fully automated, voxel‐based image analysis method to investigate, across the entire cerebral volume, the presence of resting regional cerebral blood flow (rCBF) abnormalities in HF patients compared to healthy controls. Methods. rCBF was evaluated with 99m Tc‐single‐photon emission computed tomography in 17 HF patients (New York Heart Association functional class II or III) and 18 elderly healthy volunteers. Voxel‐based analyses of rCBF data were conducted using the statistical parametric mapping software. Results. Significant rCBF reductions in HF patients relative to controls (P < .05, corrected for multiple comparisons) were detected in 2 foci, encompassing, respectively, the left and right precuneus and cuneus and the right lateral temporoparietal cortex and posterior cingulated gyrus. In the HF group, there was also a significant direct correlation between the degree of cognitive impairment as assessed using the Cambridge Mental Disorders of the Elderly Examination and rCBF on a voxel cluster involving the right posterior cingulate cortex and precuneus, located closely to the site where between‐group rCBF differences had been identified. Conclusions. These preliminary findings indicate that posterior cortical areas of the brain may be particularly vulnerable to brain perfusion reductions associated with HF and sug est that functional deficits in these regions might be relevant to the pathophysiology of the cognitive impairments presented by HF patients.

Changes in Neuropsychological Tests and Brain Metabolism After Bariatric Surgery

CONTEXT The mechanisms by which obesity alters the cerebral function and the effect of weight loss on the brain have not been completely clarified. OBJECTIVE The objective of the study was to assess the effect of bariatric surgery on the cognitive function and cerebral metabolism. DESIGN Seventeen obese women were studied prior to and 24 weeks after bariatric surgery using neuropsychological tests and positron emission tomography. SETTING The study was conducted in a reference center for the treatment of obesity of a Brazilian public university. PARTICIPANTS Thirty-three women paired by age and level of education made up two groups: 17 severely obese patients and 16 lean patients. They did not have diabetes mellitus or a family history of dementia. MAIN OUTCOME MEASURES Comparison of performance in neuropsychological tests and cerebral metabolism of the obese women before and after bariatric surgery was measured. The results found at the two moments were compared with those of the women of normal weight. RESULTS Women with a mean age of 40.5 years and mean body mass index of 50.1 kg/m(2) when compared with women with mean body mass index of 22.3 kg/m(2) showed increased cerebral metabolism, especially in the posterior cingulate gyrus (P < .004). No difference was found between the groups for the neuropsychological tests. After 24 weeks the cerebral metabolism of the obese women was lower, similar to the lean women, and there was an improvement of executive function, accompanying changes of metabolic and inflammatory parameters. CONCLUSIONS Obese women may have increased cerebral metabolism when compared with women of normal weight, and this appears to reverse after weight loss induced by bariatric surgery, accompanied by improved executive function.

Association between major depressive symptoms in heart failure and impaired regional cerebral blood flow in the medial temporal region: a study using 99m Tc-HMPAO single photon emission computerized tomography (SPECT)

BACKGROUND AND PURPOSE Depressive symptoms are frequently associated with heart failure (HF), but the brain mechanisms underlying such association are unclear. We hypothesized that the presence of major depressive disorder (MDD) emerging after the onset of HF would be associated with regional cerebral blood flow (rCBF) abnormalities in medial temporal regions previously implicated in primary MDD, namely the hippocampus and parahippocampal gyrus. METHOD Using 99mTc-SPECT, we measured rCBF in 17 elderly MDD-HF patients, 17 non-depressed HF patients, and 18 healthy controls, matched for demographic variables. Group differences were investigated with Statistical Parametric Mapping. RESULTS Significant rCBF reductions in MDD-HF patients relative to both non-depressed HF patients and healthy controls were detected in the left anterior parahippocampal gyrus and hippocampus (ANOVA, p=0.008 corrected for multiple comparisons) and the right posterior hippocampus and parahippocampal gyrus (p=0.005 corrected). In the overall HF group, there was a negative correlation between the severity of depressive symptoms and rCBF in the right posterior hippocampal/parahippocampal region (p=0.045 corrected). CONCLUSIONS These findings are consistent with the notion that the medial temporal region is vulnerable to brain perfusion deficits associated with HF, and provide evidence that such functional deficits may be specifically implicated in the pathophysiology of MDD associated with HF.

Effects of Aerobic Training on Cognition and Brain Glucose Metabolism in Subjects with Mild Cognitive Impairment

BACKGROUND Aerobic training (AT) is a promising intervention for mild cognitive impairment (MCI). OBJECTIVE To evaluate the effects of AT on cognition and regional brain glucose metabolism (rBGM) in MCI patients. METHODS Subjects performed a twice-a-week, moderate intensity, AT program for 24 weeks. Assessment with ADAS-cog, a comprehensive neuropsychological battery, and evaluation of rBGM with positron emission tomography with 18F-fluorodeoxyglucose ([18F]FDG-PET) were performed before and after the intervention. Aerobic capacity was compared using the maximal oxygen consumption VO2max (mL/Kg/min). [18F]FDG-PET data were analyzed on a voxel-by-voxel basis with SPM8 software. RESULTS Forty subjects were included, with a mean (M) age of 70.3 (5.4) years and an initial Mini-Mental State Exam score of 27.4 (1.7). Comparisons using paired t-tests revealed improvements in the ADAS-cog (M difference: -2.7 (3.7), p <  0.001) and VO2max scores (M difference: 1.8 (2.0) mL/kg/min, p <  0.001). Brain metabolic analysis revealed a bilateral decrease in the rBGM of the dorsal anterior cingulate cortex, pFWE = 0.04. This rBGM decrease was negatively correlated with improvement in a visuospatial function/attentional test (rho =-0.31, p = 0.04). Several other brain areas also showed increases or decreases in rBGM. Of note, there was an increase in the retrosplenial cortex, an important node of the default mode network, that was negatively correlated with the metabolic decrease in the dorsal anterior cingulate cortex (r =-0.51, p = 0.001). CONCLUSION AT improved cognition and changed rBGM in areas related to cognition in subjects with MCI.

Brain metabolism and cerebrospinal fluid biomarkers profile of non-amnestic mild cognitive impairment in comparison to amnestic mild cognitive impairment and normal older subjects

IntroductionMild cognitive impairment (MCI) is classically considered a transitional stage between normal aging and dementia. Non-amnestic MCI (naMCI) patients, however, typically demonstrate cognitive deficits other than memory decline. Furthermore, as a group, naMCI have a lower rate of an eventual dementia diagnosis as compared to amnestic subtypes of MCI (aMCI). Unfortunately, studies investigating biomarker profiles of naMCI are scarce. The study objective was to investigate the regional brain glucose metabolism (rBGM) with [18F]FDG-PET and cerebrospinal fluid (CSF) biomarkers in subjects with naMCI as compared to a control group (CG) and aMCI subjects.MethodsNinety-five patients were included in three different groups: naMCI (N = 32), aMCI (N = 33) and CG (N = 30). Patients underwent brain MRI and [18F]FDG-PET. A subsample (naMCI = 26, aMCI = 28) also had an assessment of amyloid-β, tau, and phosphorylated tau levels in the CSF.ResultsBoth MCI groups had lower rBGM in relation to the CG in the precuneus. Subjects with naMCI showed decreased right prefrontal metabolism as well as higher levels of CSF amyloid-β relative to aMCI subjects.ConclusionWhile amnestic MCI subjects showed a biomarker profile classically related to MCI due to Alzheimer’s disease, naMCI patients illustrated a decrease in both prefrontal hypometabolism and higher CSF amyloid-β levels relative to the aMCI group. These biomarker findings indicate that naMCI is probably a heterogeneous group with similar precuneus hypometabolism compared to aMCI, but additional frontal hypometabolism and less amyloid-β deposition in the brain. Clinical follow-up and reappraisal of biomarkers of the naMCI group is needed to determine the outcome and probable etiological diagnosis.

Long-term lithium treatment reduces glucose metabolism in the cerebellum and hippocampus of nondemented older adults: an [¹⁸F]FDG-PET study.

Lithium modulates several intracellular pathways related to neuroplasticity and resilience against neuronal injury. These properties have been consistently reported in experimental models, and involve the up-regulation of neurotrophic response and autophagy, and down-regulation of apoptosis, oxidative stress, and inflammation. Clinical and epidemiological studies in bipolar disorder show that acute treatment with lithium increases plasma concentrations of brain-derived neurotrophic factor, and long-term treatment lowers the risk of dementia. Neuroimaging studies indicate that lithium use is further associated with increased cortical thickness and larger hippocampal volumes. The objective of the present study was to evaluate whether these neurobiological properties of lithium reflect in increased regional brain glucose metabolism, as shown by [(18)F]FDG-PET. Participants (n = 19) were nondemented older adults recruited at the end point of a controlled trial addressing clinical and biological effects of lithium in a sample of patients with amnestic mild cognitive impairment. Twelve patients who had received low-dose lithium carbonate for 4 years were compared to seven matched controls. Chronic lithium treatment was not associated with any significant increase in brain glucose metabolism in the studied areas. Conversely, we found a significant reduction in glucose uptake in several clusters of the cerebellum and in both hippocampi. These findings were not associated with any clinical evidence of toxicity. The clinical implications of the present findings need to be clarified by future controlled studies, particularly in the light of the potential use of lithium as a disease-modifying treatment approach for certain neurodegenerative disorders, namely, Alzheimers disease and amyotrophic lateral sclerosis.

Early postnatal rat ventricle resection leads to long-term preserved cardiac function despite tissue hypoperfusion

One‐day‐old mice display a brief capacity for heart regeneration after apex resection. We sought to examine this response in a different model and to determine the impact of this early process on long‐term tissue perfusion and overall cardiac function in response to stress. Apical resection of postnatal rats at day 1 (P1) and 7 (P7) rendered 18 ± 1.0% and 16 ± 1.3% loss of cardiac area estimated by magnetic resonance imaging (MRI), respectively (P > 0.05). P1 was associated with evidence of cardiac neoformation as indicated by Troponin I and Connexin 43 expression at 21 days postresection, while in the P7 group mainly scar tissue replacement ensued. Interestingly, there was an apparent lack of uniform alignment of newly formed cells in P1, and we detected cardiac tissue hypoperfusion for both groups at 21 and 60 days postresection using SPECT scanning. Direct basal cardiac function at 60 days, when the early lesion is undetectable, was preserved in all groups, whereas under hemodynamic stress the degree of change on LVDEP, Stroke Volume and Stroke Work indicated diminished overall cardiac function in P7 (P < 0.05). Furthermore, the End‐Diastolic Pressure–Volume relationship and increased interstitial collagen deposition in P7 is consistent with increased chamber stiffness. Taken together, we provide evidence that early cardiac repair response to apex resection in rats also leads to cardiomyocyte neoformation and is associated to long‐term preservation of cardiac function despite tissue hypoperfusion.

Methods for quantification of cerebral glycolytic metabolism using 2-deoxy-2-[18 F]fluoroglucose in small animals

Introduction: The use of the same imaging and quantification techniques in small animals and clinical studies presents the opportunity for direct translational research in drug discovery and development, in neuropharmacological basis of neurological and psychiatric diseases, and in optimization of drug therapy. Thus, positron emission tomography (PET) studies in rodents can bridge the gap between pre-clinical and clinical research. The aim should be to find a method with capability to measure, without compromising accuracy, glucose distribution in the structures of the brain, which can also be used in pathological situations and with applicability for other substances than glucose analogue. Methods: This is a systematic review of several assessment techniques available, including visual and quantitative methods that enable the investigation of the transport mechanisms and enzymes involved in glucose metabolism in the brain. In addition to the ex vivo methods, PET with glucose analogues allows in vivo analyses using qualitative, semiquantitative and quantitative methods. Results: These techniques provide different results, and the applicability of a specific method is related to the purpose of the study and the multiple factors that may interfere in the process. Conclusion: This review provides a solid background of tools and quantification methods for medical physicists and other professionals interested in cerebral glycolytic metabolism quantification in experimental animals. It also addresses the main factors related to animals, equipment and techniques that are used, as well as how these factors should be understood to better interpret the results obtained from experiments.

Differences in biomarker profiles of people with amnestic and nonamnestic mild cognitive impairment

opportunities to characterize and evaluate AD. However, the correspondence between ADAD and the far more prevalent sporadic AD (sAD) requires elucidation. Methods: We analyzed functional connectivity in multiple brain networks in a cross-sectional cohort of ADAD (N1⁄487) and sAD (N1⁄4507) participants using resting state functional connectivity magnetic resonance imaging (rs-fcMRI). For both types of AD, we quantified rs-fcMRI changes in five resting state networks (RSNs) with respect to progressing clinical dementia rating (CDR) using general linear mixed models with factors CDR, AD type, and CDR€ı,’€ıVAD type interaction. In the ADAD group, we investigated rs-fcMRI changes with respect to years from expected onset of symptoms. We also related rs-fcMRI differences to genetic mutation type (presenilin 1, presenilin 2, amyloid precursor protein). Results: rs-fcMRI decreases with advancing clinical status were similar for both forms of AD in multiple RSNs. However, it is possible that ADAD causes more rapid loss with respect to CDR than sAD in certain RSNs. Within ADAD participants, functional connectivity in multiple RSNs was lower in individuals closer to their expected age of onset of symptoms. Within cognitively normal ADAD participants (N1⁄433), mutation-specific effects may occur in particular RSNs. Conclusions: rsfcMRI can elucidate specific AD subtypes and may help evaluate future therapeutic interventions.

Evaluation of cerebral perfusion changes through SPECT in people with mild Alzheimer's disease after a cognitive rehabilitation program

Background: Efficient and broadly available therapeutic interventions are urgently needed for Alzheimer’s Disease (AD). The impact of non-pharmacologic therapies on the course of AD has been object of discussion, wh ether they may or may not have an important role in the management of the disease. However, it is still challenging to quantify and describe the results of those approaches under a neurobiological interpretation. Functional neuroimaging methods, such as single photon emission computed tomography (SPECT), may be useful to evaluate the impact of Cognitive Rehabilitation Programs (CRP) in AD. Our goal was to analyze and quantify the possible changes of CRP in regional cerebral blood flow (rCBF) in patients withmild AD, using technetium-99m-ethyl cysteinate dimer (99mTc-ECD) SPECT, and compare the results with those of placebo (sham intervention). Methods: It was included 14 patients (pts) with mild AD (CDR1⁄4 0.5 and 1) receiving standard pharmacological treatment. They were divided in two groups: Group I comprised by six pts who joined a cognitive and functional training program, having 60 minutes sessions twice a week for 3 months (24 sessions) and Group II of eight pts who joined 60 minutes placebo entertainment activities twice a week for the same period of time. All underwent brain SPECT imaging before and after the intervention. Data were compared in a voxel by voxel basis with the Statistical Parametric Mapping (SPM8) software. Results: Pts characteristics were (mean 6SD): mean age (yr) 1⁄4 7466; schooling (yr) 1⁄4 864; MMSE Scores 1⁄4 2463. No difference between groups was observed in the above mentioned parameters.SPM analysis of the baseline SPECT showed no difference between groups (p uncorrected>0.05). CRP did not produce any significant changes in rCBF in the present sample of patients, in comparison to the placebo group. Conclusions: Our preliminary results suggest that SPECT was not able to show any change in brain relative perfusion after 3 months of CRP in comparison to a placebo group.