Plasma and cerebrospinal fluid ABeta42 for the differential diagnosis of Alzheimer's disease dementia in participants diagnosed with any dementia subtype in a specialist care setting.

BACKGROUND: Dementia is a syndrome that comprises many differing pathologies, including Alzheimer's disease dementia (ADD), vascular dementia (VaD) and frontotemporal dementia (FTD). People may benefit from knowing the type of dementia they live with, as this could inform prognosis and may allow for tailored treatment. Beta-amyloid (1-42) (ABeta42) is a protein which decreases in both the plasma and cerebrospinal fluid (CSF) of people living with ADD, when compared to people with no dementia. However, it is not clear if changes in ABeta42 are specific to ADD or if they are also seen in other types of dementia. It is possible that ABeta42 could help differentiate ADD from other dementia subtypes. OBJECTIVES: To determine the accuracy of plasma and CSF ABeta42 for distinguishing ADD from other dementia subtypes in people who meet the criteria for a dementia syndrome. SEARCH METHODS: We searched MEDLINE, and nine other databases up to 18 February 2020. We checked reference lists of any relevant systematic reviews to identify additional studies. SELECTION CRITERIA: We considered cross-sectional studies that differentiated people with ADD from other dementia subtypes. Eligible studies required measurement of participant plasma or CSF ABeta42 levels and clinical assessment for dementia subtype. DATA COLLECTION AND ANALYSIS: Seven review authors working independently screened the titles and abstracts generated by the searches. We collected data on study characteristics and test accuracy. We used the second version of the 'Quality Assessment of Diagnostic Accuracy Studies' (QUADAS-2) tool to assess internal and external validity of results. We extracted data into 2 x 2 tables, cross-tabulating index test results (ABeta42) with the reference standard (diagnostic criteria for each dementia subtype). We performed meta-analyses using bivariate, random-effects models. We calculated pooled estimates of sensitivity, specificity, positive predictive values, positive and negative likelihood ratios, and corresponding 95% confidence intervals (CIs). In the primary analysis, we assessed accuracy of plasma or CSF ABeta42 for distinguishing ADD from other mixed dementia types (non-ADD). We then assessed accuracy of ABeta42 for differentiating ADD from specific dementia types: VaD, FTD, dementia with Lewy bodies (DLB), alcohol-related cognitive disorder (ARCD), Creutzfeldt-Jakob disease (CJD) and normal pressure hydrocephalus (NPH). To determine test-positive cases, we used the ABeta42 thresholds employed in the respective primary studies. We then performed sensitivity analyses restricted to those studies that used common thresholds for ABeta42. MAIN RESULTS: We identified 39 studies (5000 participants) that used CSF ABeta42 levels to differentiate ADD from other subtypes of dementia. No studies of plasma ABeta42 met the inclusion criteria. No studies were rated as low risk of bias across all QUADAS-2 domains. High risk of bias was found predominantly in the domains of patient selection (28 studies) and index test (25 studies). The pooled estimates for differentiating ADD from other dementia subtypes were as follows: ADD from non-ADD: sensitivity 79% (95% CI 0.73 to 0.85), specificity 60% (95% CI 0.52 to 0.67), 13 studies, 1704 participants, 880 participants with ADD; ADD from VaD: sensitivity 79% (95% CI 0.75 to 0.83), specificity 69% (95% CI 0.55 to 0.81), 11 studies, 1151 participants, 941 participants with ADD; ADD from FTD: sensitivity 85% (95% CI 0.79 to 0.89), specificity 72% (95% CI 0.55 to 0.84), 17 studies, 1948 participants, 1371 participants with ADD; ADD from DLB: sensitivity 76% (95% CI 0.69 to 0.82), specificity 67% (95% CI 0.52 to 0.79), nine studies, 1929 participants, 1521 participants with ADD. Across all dementia subtypes, sensitivity was greater than specificity, and the balance of sensitivity and specificity was dependent on the threshold used to define test positivity. AUTHORS' CONCLUSIONS: Our review indicates that measuring ABeta42 levels in CSF may help differentiate ADD from other dementia subtypes, but the test is imperfect and tends to misdiagnose those with non-ADD as having ADD. We would caution against the use of CSF ABeta42 alone for dementia classification. However, ABeta42 may have value as an adjunct to a full clinical assessment, to aid dementia diagnosis.

Endovascular intervention to treat spontaneous carotid-cavernous fistula in a patient with Ehlers-Danlos Syndrome with an access site anatomical variant.

Vascular Ehlers-Danlos Syndrome (vEDS) is a rare and potentially life-threatening inherited connective tissue disorder. Patients with vEDS can present with spontaneous arterial dissections and ruptured aneurysms. There are previous reports of large artery dissections and vessel rupture following conventional catheter diagnostic angiography. We present the case of a patient with vEDS who had a spontaneous carotid-cavernous fistula (CCF) and visceral aneurysms, associated with a normal variant of corona mortis. A CCF was successfully treated with a transvenous approach with detachable coils.

Dopamine in major depressive disorder: A systematic review and meta-analysis of in vivo imaging studies.

BACKGROUND: Major depressive disorder (MDD) is a leading cause of global disability. Several lines of evidence implicate the dopamine system in its pathophysiology. However, the magnitude and consistency of the findings are unknown. We address this by systematically reviewing in vivo imaging evidence for dopamine measures in MDD and meta-analysing these where there are sufficient studies. METHODS: Studies investigating the dopaminergic system using positron emission tomography or single photon emission computed tomography in MDD and a control group were included. Demographic, clinical and imaging measures were extracted from each study, and meta-analyses and sensitivity analyses were conducted. RESULTS: We identified 43 studies including 662 patients and 801 controls. Meta-analysis of 38 studies showed no difference in mean or mean variability of striatal D2/3 receptor availability (g = 0.06, p = 0.620), or combined dopamine synthesis and release capacity (g = 0.19, p = 0.309). Dopamine transporter (DAT) availability was lower in the MDD group in studies using DAT selective tracers (g = -0.56, p = 0.006), but not when tracers with an affinity for serotonin transporters were included (g = -0.21, p = 0.420). Subgroup analysis showed greater dopamine release (g = 0.49, p = 0.030), but no difference in dopamine synthesis capacity (g = -0.21, p = 0.434) in the MDD group. Striatal D1 receptor availability was lower in patients with MDD in two studies. CONCLUSIONS: The meta-analysis indicates striatal DAT availability is lower, but D2/3 receptor availability is not altered in people with MDD compared to healthy controls. There may be greater dopamine release and lower striatal D1 receptors in MDD, although further studies are warranted. We discuss factors associated with these findings, discrepancies with preclinical literature and implications for future research.

Early motor resonance differentiates schizophrenia patients from healthy subjects and predicts social cognition performance.

BACKGROUND: Diminished motor resonance (facilitation of motor potentials during action observation) is possibly related to social cognition deficits in schizophrenia. Adequate social cognition requires the successful moment-to-moment appraisal of social stimuli over a temporal window. However, similar changes in motor resonance with successive action observation stimuli are unknown. We compared the time-course of motor resonance evoked during successive action observation stimuli between schizophrenia patients (antipsychotic-naïve and medicated) and healthy subjects and examined its association with social cognition performance. METHOD: Fifty-four schizophrenia patients (33 antipsychotic-naive) and 45 healthy subjects underwent 10-recordings (T1 to T10) of cortical reactivity, using two single (sp)- and two paired-pulse (pp) transcranial magnetic stimulation (TMS) paradigms, while they observed goal-directed actions and a static image. They also underwent comprehensive social cognition assessments. RESULTS: Sp-motor resonance revealed a significant quadratic time effect (initial fall and then rise) in patients and healthy subjects [F=12.21, P=0.001]. Such a pattern was not observed for pp-motor resonance. We categorized motor resonance as early (T1-T3), middle (T4-T7) and late (T8-T10) based on pair-wise comparisons. Early, but not middle or late sp-motor resonance was reduced in antipsychotic naïve patients compared to the medicated patients and healthy subjects (F=3.41, P=0.037). Social cognition composite score had significant correlations with both early sp-motor resonance (r=0.34, P=0.01) and early pp-motor resonance (r=0.314, P=0.02) in the combined patient group. CONCLUSIONS: Motor resonance time-courses did not vary across groups. The magnitude of early motor resonance was reduced in the antipsychotic-naïve schizophrenia group, compared to healthy subjects. Early phase motor resonance was associated with social cognition deficits in patients.

Prevalence and determinants of metabolic syndrome in patients with schizophrenia: A systematic review and meta-analysis of Indian studies.

INTRODUCTION: Several authors have studied prevalence of metabolic syndrome (Met-S) in schizophrenia patients. Studies conducted in Indian scenario have shown conflicting results. Community based studies reported extremely low prevalence of metabolic syndrome in contrast to hospital based studies reporting higher rates. In this systematic review we summarize results of studies conducted in India and discuss possible reasons for these discrepancies. METHODS: Literature search was conducted with keywords metabolic, schizophrenia and India in PubMed, Google Scholar, and Science Direct database. Studies assessing prevalence of metabolic syndrome using IDF or NCEP-ATP III criteria, conducted in hospital and community setting were included. RESULTS: Fourteen studies conducted in hospital setting and two studies conducted in community were included for analysis. Pooled prevalence of Met-S in patients with schizophrenia was 29.83%. Pooled prevalence in community based studies was 10.81% significantly lower than in hospital based studies 33.05%. Overall meta-analysis of studies with case control design showed an OR 3.03 for prevalence in cases compared to controls. Except in one study conducted in a rural community, all other studies reported higher prevalence of Met-S in schizophrenia patients compared to controls. Drug-naïve patients had a pooled prevalence of 11.86%. CONCLUSION: In India, prevalence rates of Met-S in schizophrenia patients are comparable to the rates reported in western studies. Community based studies highlight a significantly lower prevalence compared to hospital studies. More community based studies will enhance our understanding of prevalence and determinants of Met-S in patients with schizophrenia.