Perioperative Assessment of Cerebellar Masses and the Potential for Cerebellar Cognitive Affective Syndrome.

The cerebellum was long perceived to be a region of limited importance with primary functions in the regulation of motor control. A degree of its functional topography in motor modulation has been traditionally appreciated. However, an evolving body of evidence supports its role in a range of cognitive processes, including executive decision making, language, emotional processing, and working memory. To this end, numerous studies of cerebellar stroke syndromes as well as investigations with functional magnetic resonance imaging and diffusion tensor imaging have given clinicians a better model of the functional topography within the cerebellum and the essential lanes of communication with the cerebrum. With this deeper understanding, neurosurgeons should integrate these domains into the perioperative evaluation and postoperative rehabilitation of patients with cerebellar tumors. This review aims to discuss these understandings and identify valuable tools for implementation into clinical practice.

Can 11C-PiB-PET Relative Delivery R1 or 11C-PiB-PET Perfusion Replace 18F-FDG-PET in the Assessment of Brain Neurodegeneration?

BACKGROUND: Pittsburgh Compound B (PiB) positron emission tomography (PET) is used to visualize in vivo amyloid plaques in the brain. Frequently the PiB examinations are complemented with a fluorodeoxyglucose (FDG) PET scan to further assess neurodegeneration. OBJECTIVE: Our goal is to identify alternative correlates of FDG images by assessing which kinetic methods originate PiB derived relative delivery ratio (R1) images that can be correlated with the FDG images, and to compare them with PiB perfusion (pPiB) images obtained from the early-phase of PiB acquisition. METHODS: We selected 52 patients with cognitive impairment who underwent a dynamic PiB and FDG acquisitions. To compute the R1 images, two simplified reference tissue models (SRTM and SRTM2) and two multi-linear reference tissue models (MRTM and MRTM2) were used. The pPiB images were obtained in two different time intervals. RESULTS: All six types of images were of good quality and highly correlated with the FDG images (mean voxelwise within-subjects r > 0.92). The higher correlation was found for FDG-R1(MRTM). Regarding the voxelwise regional correlation, the higher mean all brain correlations was r = 0.825 for FDG-R1(MRTM) and statistically significant in the whole brain analysis. CONCLUSION: All R1 and pPiB images here tested have potential to assess the metabolic impact of neurodegeneration almost as reliably as the FDG images. However, this is not enough to validate these images for a single-subject analysis compared with the FDG image, and thus they cannot yet be used clinically to replace the FDG image before such evaluation.

Assessment of the Autonomic Response in Alzheimer's Patients During the Execution of Memory Tasks: A Functional Thermal Imaging Study.

BACKGROUND: Alzheimer's disease (AD) is a form of dementia characterized by failure of memory that becomes more severe with the progression of the disease. The Free and Cued Selective Reminding Test (FCSRT) is a clinical test used to evaluate such a deficit. However, since the cognitive performances could depend also on the psychophysiological state of the individual, it is important to monitor that state through the peripheral autonomic activity during the execution of the test. Thermal infrared imaging has been used for this kind of assessment in order to preserve the free and unbiased interaction between doctor and patient, thanks to the contactless features of the technique. OBJECTIVE: To investigate whether the variation of facial temperature parameters during the FCSRT is indicative of different autonomic states in the early AD with respect to healthy controls (HC). RESULTS: At a group level, a greater sympathetic activity for the HC with respect to AD during the execution of the test was found, indicative of a suppression of anxiety associated with the performances of the FCSRT in AD patients. CONCLUSION: These results indicate that AD and HC may present different autonomic activity associated with the execution of a cognitive task, thus suggesting a different modulation of high-cognition and emotion network.

Longitudinal assessment of chemotherapy-induced changes in brain and cognitive functioning: A systematic review.

In addition to the burden of a life-threatening diagnosis, cancer patients are struggling with adverse side-effects from cancer treatment. Chemotherapy has been linked to an array of cognitive impairments and alterations in brain structure and function ("chemobrain"). In this review, we summarized the existing evidence that evaluate the changes in cognitive functioning and brain with chemotherapy, as assessed using structural and functional MRI-based techniques in a longitudinal design. This review followed the latest PRISMA guidelines using Embase, Medline, PsychINFO, Scopus, and Web of Science databases with date restrictions from 2012 to 2017. Fourteen research articles met the key inclusion criteria: (i) the studies involved adult cancer patients (mean age ≥ 18); (ii) the use of chemotherapy in the treatment of cancer; (iii) pre-post assessment of behavioral and brain-based outcomes; and (iv) abstracts written in English. Effect sizes of subjective and objective cognitive impairments from the reviewed studies were estimated using Cohen's d or z-scores. We calculated percentage of mean change or effect sizes for main neuroimaging findings when data were available. Strength of the correlations between brain alterations and cognitive changes was obtained using squared correlation coefficients. Small to medium effect sizes were shown? on individual tests of attention, processing speed, verbal memory, and executive control; and medium effect sizes on self-report questionnaires. Neuroimaging data showed reduced grey matter density in cancer patients in frontal, parietal, and temporal regions. Changes in brain function (brain activation and cerebral blood flow) were observed with cancer across functional networks involving (pre)frontal, parietal, occipital, temporal, and cerebellar regions. Data from diffusion-weighted MRI suggested reduced white matter integrity involving the superior longitudinal fasciculus, corpus callosum, forceps major, and corona radiate, and altered structural connectivity across the whole brain network. Finally, we observed moderate-to-strong correlations between worsening cognitive function and morphological changes in frontal brain regions. While MRI is a powerful tool for detection of longitudinal brain changes in the 'chemobrain', the underlying biological mechanisms are still unclear. Continued work in this field will hopefully detect MRI metrics to be used as biomarkers to help guide cognitive treatment at the individual cancer patient level.

A 10-minute measure of global cognition: Validation of the Brief Cognitive Assessment Tool for Schizophrenia (B-CATS).

INTRODUCTION: Schizophrenia is marked by a global cognitive impairment that contributes significantly to chronic disability and unemployment. As new treatments are developed for cognition in schizophrenia, clinicians require easily administered instruments to assess cognition. We previously developed a very brief cognitive battery (Bell et al., 2005). The Brief Cognitive Assessment Tool for Schizophrenia (B-CATS) was developed specifically to provide clinicians with a way to assess cognition in their patients with schizophrenia. Here, we report the results of a validity study comparing B-CATS to a larger neurocognitive battery, the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) battery. METHODS: Outpatients with schizophrenia (N=91) were administered the B-CATS and the non-overlapping tests of the MATRICS battery at two time points separated by 1month. They were also administered the UCSD Performance-based Skills Assessment-Brief (UPSA-B), a measure of functional capacity. RESULT: The B-CATS has an administration time of approximately 10min. It demonstrates good test-retest reliability and internal consistency. It correlates 0.76 (p<0.01) with the MATRICS battery. The shorter B-CATS and the MATRICS battery correlate with the UPSA-B at 0.50 and 0.58 respectively. CONCLUSION: A 10-minute version of the B-CATS correlates highly with the "gold standard" neurocognitive battery that has an administration time of over 60min. Both measures correlate moderately with a measure of functional capacity. This brief battery was designed to allow clinicians to monitor cognitive change and better inform treatment decisions.

The Role of Neuroimaging in the Assessment of the Cognitively Impaired Elderly.

This article reviews the current diagnostic tools that are available for structural, functional, and molecular imaging of the brain, summarizing some of the key findings that have been reported in individuals diagnosed with Alzheimer disease, mild cognitive impairment, prodromal AD, or other prevalent dementias. Given recent advances in the development of amyloid PET tracers, current guidelines for the use of amyloid PET imaging in patients with cognitive complaints are reviewed. In addition, data addressing the potential value of amyloid PET imaging in the clinical setting are highlighted.

Quantitative assessment of white matter injury in preterm neonates: Association with outcomes.

OBJECTIVE: To quantitatively assess white matter injury (WMI) volume and location in very preterm neonates, and to examine the association of lesion volume and location with 18-month neurodevelopmental outcomes. METHODS: Volume and location of WMI was quantified on MRI in 216 neonates (median gestational age 27.9 weeks) who had motor, cognitive, and language assessments at 18 months corrected age (CA). Neonates were scanned at 32.1 postmenstrual weeks (median) and 68 (31.5%) had WMI; of 66 survivors, 58 (87.9%) had MRI and 18-month outcomes. WMI was manually segmented and transformed into a common image space, accounting for intersubject anatomical variability. Probability maps describing the likelihood of a lesion predicting adverse 18-month outcomes were developed. RESULTS: WMI occurs in a characteristic topology, with most lesions occurring in the periventricular central region, followed by posterior and frontal regions. Irrespective of lesion location, greater WMI volumes predicted poor motor outcomes (p = 0.001). Lobar regional analysis revealed that greater WMI volumes in frontal, parietal, and temporal lobes have adverse motor outcomes (all, p < 0.05), but only frontal WMI volumes predicted adverse cognitive outcomes (p = 0.002). To account for lesion location and volume, voxel-wise odds ratio (OR) maps demonstrate that frontal lobe lesions predict adverse cognitive and language development, with maximum odds ratios (ORs) of 78.9 and 17.5, respectively, while adverse motor outcomes are predicted by widespread injury, with maximum OR of 63.8. CONCLUSIONS: The predictive value of frontal lobe WMI volume highlights the importance of lesion location when considering the neurodevelopmental significance of WMI. Frontal lobe lesions are of particular concern.

The Diagnostic and Prognostic Value of Neuropsychological Assessment in Memory Clinic Patients.

BACKGROUND: Neuropsychological testing has long been embedded in daily clinical practice at memory clinics but the added value of a complete neuropsychological assessment (NPA) to standard clinical evaluation is unknown. OBJECTIVE: To evaluate the added diagnostic and prognostic value of NPA to clinical evaluation only in memory clinic patients. METHODS: In 221 memory clinic patients of a prospective cohort study, clinical experts diagnosed clinical syndrome (subjective cognitive impairment (SCI), mild cognitive impairment (MCI), or dementia) and etiology (Alzheimer's disease (AD) or no AD), and provided a prognosis of disease course (decline or no decline) before and after results of NPA were made available. The reference standard was a panel consensus based on all clinical information at baseline and up to 2 follow-up assessments. RESULTS: With NPA data available, clinicians changed their initial syndromal diagnosis in 22% of patients, and the etiological diagnosis as well as the prognosis in 15%. This led to an increase in correctly classified cases of 18% for syndromal diagnosis, 5% for etiological diagnosis, and 1% for prognosis. NPA data resulted in the largest improvement in patients initially classified as SCI (syndrome: 93.3% (n = 14) correctly reclassified, etiology: net reclassification improvement [NRI] = 0.61, prognosis: NRI = 0.13) or MCI (syndrome: 89.3% (n = 23) correctly reclassified, etiology: NRI = 0.17, prognosis: NRI = 0.14), while there was no improvement in patients with dementia (syndrome: 100% (n = 1) correctly reclassified, etiology: NRI = -0.05, prognosis: NRI = -0.06). Overall, inclusion of NPA in the diagnostic process increased confidence in all diagnoses with 6-7%. CONCLUSION: Administration of a complete NPA after standard clinical evaluation has added value for diagnosing cognitive syndrome and its underlying etiology in patients regarded as non-demented based on the first clinical impression.

Iron Deposition Is Positively Related to Cognitive Impairment in Patients with Chronic Mild Traumatic Brain Injury: Assessment with Susceptibility Weighted Imaging.

BACKGROUND: This study aimed to evaluate the usability of SWI in assessment of brain iron to detect cognitive dysfunction in patients with chronic mild traumatic brain injury (mTBI). METHODS: 39 patients with mTBI and 37 normal controls were given the Mini-Mental State Examination (MMSE) and underwent SWI scanning at least 6 months after injury. Angle radian values were calculated with phase images. The angle radian values were compared between groups using analysis of covariance, and their association with MMSE scores was analyzed using Spearman correlations. RESULTS: Significantly higher angle radian values (p < 0.05) were found in the head of the caudate nucleus, the lenticular nucleus, the hippocampus, the thalamus, the right substantia nigra, the red nucleus, and the splenium of the corpus callosum (SCC) in the mTBI group, compared to the control group. MMSE scores were negatively correlated with angle radian values in the right substantia nigra (r = -0.685, p < 0.001). CONCLUSIONS: Patients with chronic mTBI might have abnormally high accumulations of iron, and their MMSE scores are negatively associated with angle radian values in the right substantia nigra, suggesting a role of SWI in the assessment of cognitive impairments of these patients.

Assessment of cognitive function in adult patients with hemorrhagic moyamoya disease who received no surgical revascularization.

BACKGROUND AND PURPOSE: Due to controversial surgical treatment for hemorrhagic moyamoya disease (MMD), a large proportion of these patients chose conservative treatment. The aim of this study was to assess cognitive function in adult patients with hemorrhagic MMD who received no surgical revascularization. METHODS: Twenty-six adult hemorrhagic MMD patients with only intraventricular hemorrhage (IVH) confirmed by positive computed tomography and magnetic resonance imaging scan, 20 patients with spontaneous IVH whose digital subtraction angiography results were negative, and 30 healthy controls were identified and matched for age, gender, education background and living area. Cognitive function was evaluated by Montreal Cognitive Assessment (MoCA). The non-parametric test was used for comparisons among the three groups. RESULTS: No patient was confirmed cognitive dysfunction at the initial screening. Twenty-four (92%) cases presented mild cognitive impairment (MCI) after 1 year. All the cases demonstrated MCI after 2 years. The difference between cases and healthy controls was statistically significant at the second screening (P = 0.000) and the third screening (P = 0.000), as was that between cases and patients with spontaneous IVH at the second screening (P = 0.000) and the third screening (P = 0.000). In addition, there were significant decreases in all MoCA subscores (P = 0.000) with special regards to delayed recall, visual space and executive function in cases compared with the other two groups. Moreover, significant differences were found in the subgroups of smoking (P = 0.021) and Suzuki angiographic classification of MMD (P = 0.030). CONCLUSIONS: Cognitive impairment is a long-term complication for adult hemorrhagic MMD patients who underwent conservative treatment.

The use of CT in dementia.

Neuroimaging has become part of the required investigations when assessing a patient with dementia. In this brief paper, we summarize the role of computed tomography (CT) in the routine work-up in dementia and provide some information about the role of the CT scan in the field of dementia research. Although CT is far less sensitive than magnetic resonance imaging (MRI) in detecting changes associated with cognitive impairment, it may still have a role in this regard. This role is mainly that of detecting secondary, sometimes treatable causes of cognitive impairment, such as intracranial masses. In this sense, CT should be seen as a first-line tool. Possible advantages of CT are lower cost; shorter acquisition time, making it more adaptable to patients with poor compliance; and the possibility that it can be performed in patients with metal devices, such as a pacemaker. The role of CT in the field of dementia research is very restricted in comparison to that of MRI, and is limited to the structural assessment of vascular lesions, and to a lesser extent, to that of degenerative changes, particularly when using specific slicing.

Cerebral microhemorrhage and brain ß-amyloid in aging and Alzheimer disease.

OBJECTIVES: Incidental cerebral microhemorrhage (MH) is frequently found in older individuals scanned with susceptibility-weighted MRI (SWI) or gradient-recalled echo MRI. MH have been linked with ß-amyloid (Aß) deposition using (11)C-Pittsburgh compound B (PiB) PET in Alzheimer disease (AD) and cerebral amyloid angiopathy (CAA). We hypothesized that Aß deposition in asymptomatic elderly individuals is associated with lobar MH (LMH). METHODS: This was a cross-sectional study of 84 elderly healthy controls (HC), 28 subjects with mild cognitive impairment (MCI), and 26 subjects with probable AD who underwent 3-T SWI and (11)C-PiB PET. (11)C-PiB cortical binding was quantified normalized to cerebellar cortex (standardized uptake value ratio [SUVR]) and scans classified as positive (PiB+) or negative (PiB-) by visual inspection. MH were manually counted and categorized by region and as lobar or nonlobar. RESULTS: LMH were present in 30.8% of AD, 35.7% of MCI, and 19.1% of HC. The prevalence of LMH among PiB+ subjects was similar, regardless of clinical classification (AD 30.8%, MCI 38.9%, HC 41.4%, p > 0.7). HC with LMH had significantly higher mean neocortical SUVR (1.7 ± 0.5) than HC without LMH (1.3 ± 0.3, p ± 0.01). In HC, there was a positive correlation between number of LMH and SUVR, and between LMH and age. In HC, PiB+ (odds ratio [OR] 7.3, 95% confidence interval [CI] 1.6-33.7, p = 0.01) and age (OR 1.2, 95% CI 1.03-1.3, p = 0.02) both independently predicted the occurrence of LMH using logistic regression. CONCLUSION: Asymptomatic Aß deposition in older adults is strongly associated with LMH.

Width of the third ventricle assessed by transcranial sonography can monitor brain atrophy in a time- and cost-effective manner--results from a longitudinal study on 500 subjects.

Ventricular width and its enlargement over time are discussed as promising markers for preclinical brain atrophy. The aim of our study was to define whether brain atrophy can reliably be monitored by transcranial ultrasound (TCS). In a prospective longitudinal trial over 5years, 500 healthy persons were examined by a standardized protocol with TCS in addition to an extensive cognitive testing using the Consortium to Establish a Registry of Alzheimer's Disease - Neuropsychological Testing (CERAD-NP). TCS displayed the third ventricle in 96% of all cases at the follow-up with a high intra-individual reproducibility and excellent inter-rater coefficient (0.992). The mean diameter of the third ventricle in subjects with a cognitive decline was significantly wider (6mm±2) than in subjects with normal cognitive testing results (4.6mm±1.8). We demonstrated that the width of the third ventricle, as a marker of brain atrophy can reliably be monitored by using TCS as a non-invasive, time- and cost-effective method. We provide evidence that the assessed width of the third ventricle can differentiate between subjects with a normal cognitive performance and subjects with a cognitive decline. TCS may be a useful screening tool in the early diagnosis of cognitive decline.

Comparing fludeoxyglucose F18-PET assessment of regional cerebral glucose metabolism and [11C]dihydrotetrabenazine-PET in evaluation of early dementia and mild cognitive impairment.

OBJECTIVE: To compare assessment of regional cerebral metabolic changes with [(11)C]dihydrotetrabenazine (DTBZ)-positron emission tomography (PET) measurement of regional cerebral blood flow (K(1)) and fludeoxyglucose F18 (FDG)-PET measurement of regional cerebral glucose uptake (CMR(glc)) in a clinically representative sample of subjects with mild dementia and mild cognitive impairment (MCI). DESIGN: [(11)C]Dihydrotetrabenazine-PET K(1) and FDG-PET CMR(glc) measurements were performed. SETTING: University-based cognitive disorders clinic. PARTICIPANTS: Fifty subjects with either mild dementia (Mini-Mental State Examination score > or = 18) or MCI. Their results were compared with those of 80 normal control subjects. MAIN OUTCOME MEASURES: The DTBZ-PET regional K(1) and FDG-PET CMR(glc) measurements were compared with standard correlation analysis. The overall patterns of DTBZ-PET K(1) and FDG-PET CMR(glc) deficits were assessed with stereotaxic surface projections (SSPs) of parametric images. RESULTS: The DTBZ-PET regional K(1) and FDG-PET CMR(glc) measurements were highly correlated, both within and between subjects. The SSP maps of deficits in DTBZ-PET regional K(1) and FDG-PET CMR(glc) measurements were markedly similar. The DTBZ-PET K(1) SSP maps exhibited a mild decrease in sensitivity relative to FDG-PET CMR(glc) maps. CONCLUSIONS: Both DTBZ-PET K(1) and FDG-PET CMR(glc) measurements provide comparable information in assessment of regional cerebral metabolic deficits in mild dementia and MCI. Blood flow measures can assess regional cerebral metabolism deficits accurately in mild dementia and MCI. Blood flow assessments of regional cerebral metabolic deficits can be combined with tracer binding results to improve utility of PET imaging in mild dementia and MCI.

Visual assessment of [(11)C]PIB PET in patients with cognitive impairment.

PURPOSE: The aim of this study was to evaluate the visual assessment of positron emission tomography images of N-[methyl-11C]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole ([11C]PIB) in a patient population with mild to moderate memory impairment or dementia. METHODS: We compared the visual ratings of two readers using kappa statistics and correlated the results of visual and quantitative region of interest (ROI) analyses. The one reader had good experience in evaluating PIB images and the other had little previous experience. The sensitivity and specificity of the visual assessment was determined using quantitative data from 18 healthy controls previously examined: [11C]PIB uptake was considered as abnormal if it was more than 2 SD above the mean of the healthy subjects. RESULTS: The evaluation of visual classification as "normal" or "abnormal" showed good interobserver agreement (kappa = 0.90). There was a clear correlation between visual and quantitative analysis (r = 0.47-0.79, p < 0.001). The most difficult visually assessed brain area was the putamen (kappa = 0.11; correlation with quantitative analysis: reader A r = 0.22; reader B r = 0.60). CONCLUSION: Our study shows that visual evaluation of [(11)C]PIB images conforms with quantitative analyses also in a clinical patient population supporting the feasibility of visual evaluation in clinical settings.

Assessment of mental deterioration with the Cognitive Abilities Screening Instrument (CASI) and glucose hypometabolism in Alzheimer's disease: the Osaki-Tajiri Project.

The Cognitive Abilities Screening Instrument (CASI) is a screening test for dementia consisting of 9 domains. We investigated the relationships between CASI domain scores and cerebral glucose metabolism (CMRglc) as shown by positron emission tomography. Fifteen patients with very mild Alzheimer's disease (AD) and 15 with mild AD were studied using the [(18)F]fluoro-deoxyglucose method. The 9 CASI domains were classified into four clusters (recent memory, frontal cortex cluster, posterior cortex cluster, and orientation). Using the region of interest method, the recent memory cluster was correlated with the bilateral hippocampal CMRglc, the frontal cortex cluster was correlated with the bilateral anterior and right inferior frontal CMRglc, the posterior cortex cluster was correlated with the bilateral temporo-parieto-occipital and occipital CMRglc, and the orientation cluster was correlated with the left anterior frontal CMRglc (Spearman's correlations). The use of statistical parametric mapping showed that most CASI domains were correlated with CMRglc of the left frontal lobe, the temporal lobe, and the angular gyrus. These findings show that the mental dysfunction assessed using CASI in AD patients has a neurobiological basis.

Transcranial Doppler blood flow assessment in patients with mild heart failure: correlates with neuroimaging and cognitive performance.

Cardiac output and cerebral perfusion are reduced in patients with advanced stages of heart failure. Our aim was to determine whether cerebral blood flow velocity measured by transcranial Doppler ultrasonography was reduced in outpatients with mild heart failure in comparison to controls and, if so, whether this reduction was related to cognitive performance and abnormalities of the brain diagnosed by magnetic resonance imaging.

Frontal assessment battery and brain perfusion image in Parkinson's disease.

The objective was to compare brain perfusion image using 3-dimensional stereotactic surface projection analysis of N-isopropyl-p-123I iodoamphetamine single photon emission computed tomography between Parkinson's disease patients with a high frontal assessment battery score and those with a low frontal assessment battery score. Thirty nondemented patients with Parkinson's disease were studied. Patients were divided into 2 groups: a high-scoring group whose frontal assessment battery score was 12 or more and a low-scoring group whose frontal assessment battery score was 11 or less. The high-scoring group included 21 patients, and the low-scoring group included 9 patients. They underwent N-isopropyl-p-123I iodoamphetamine single photon emission computed tomography, and we analyzed the data by the 3-dimensional stereotactic surface projection method. Results showed that left inferior parietal lobule and left supramarginal gyrus perfusion of the low-scoring group were significantly decreased compared with the high-scoring group. It is concluded that patients with Parkinson's disease may have frontal lobe dysfunction, but the decreased frontal assessment battery score may be caused not by progressed frontal lobe dysfunction but by parietal lobe dysfunction added to their preexisting frontal lobe impairment.