Assessing cognition in people with severe mental disorders in low- and middle-income countries: a systematic review of assessment measures

Background

Cognitive difficulties are common in people with severe mental disorders (SMDs) and various measures of cognition are of proven validity. However, there is a lack of systematic evidence regarding the psychometric properties of these measures in low- and middle-income countries (LMICs).

Objective

To systematically review the psychometric properties of cognitive measures validated in people with SMDs in LMICs.

Methods

We conducted a systematic review of the literature by searching from four electronic databases. Two authors independently screened studies for their eligibility. Measurement properties of measures in all included studies were extracted. All eligible measures were assessed against criteria set for clinical and research recommendations. Results are summarized narratively and measures were grouped by measurement type and population.

Results

We identified 23 unique measures from 28 studies. None of these was from low-income settings. Seventeen of the measures were performance-based. The majority (n = 16/23) of the measures were validated in people with schizophrenia. The most commonly reported measurement properties were: known group, convergent, and divergent validity (n = 25/28). For most psychometric property, studies of methodological qualities were found to be doubtful. Among measures evaluated in people with schizophrenia, Brief Assessment of Cognition in Schizophrenia, Cognitive Assessment Interview, MATRICS Consensus Cognitive Battery, and CogState Schizophrenia Battery were with the highest scores for clinical and research recommendation.

Conclusions

Studies included in our review provide only limited quality evidence and future studies should consider adapting and validating measures using stronger designs and methods. Nonetheless, validated assessments of cognition could help in the management and allocating therapy in people with SMDs in LMICs.

     

Activation of nuclear factor kappa B and mitogen activated protein kinases in psoriatic arthritis before and after etanercept treatment

OBJECTIVE: To study activation of intracellular pathways depending on nuclear factor kappa B (NFkappaB) and mitogen activated kinases (MAPK) in the synovium of patients with psoriatic arthritis before and after treatment with etanercept. METHODS: Synovial biopsies were obtained by needle arthroscopy of the knee in 9 patients with active psoriatic arthritis before the initiation of etanercept. Follow-up biopsies were taken in the same knee after 6 months. Synovitis was studied by histology. Pathway activation was studied by immunofluorescense for phosphorylated ERK, phosphorylated p38, phosphorylated JNK or phosphorylated inhibitor of kappa B (IkappaBalpha) using digital image analysis. RESULTS: Histological severity scores were significantly reduced after etanercept treatment. Activation of NFkappaB signaling was found in the lining layer, and in infiltrating and peri-vascular cells in the sublining zone. Activated p38 was present in both lining and sublining layer. In the sublining layer, positive cells were found in inflammatory infiltrates, in perivascular zones and in the endothelium. Activated ERK was mainly present in the sublining layer, both in mononuclear cell infiltrates and perivascularly. Occasional positive cells were found in the lining layer. Activation of JNK was recognized in cells of the lining layer, in some of the sublining cell infiltrates and the perivascular compartment. CONCLUSIONS: Etanercept therapy resulted in a significant decrease in NFkappaB, JNK and ERK, but not in p38 activation. Persistent activation of these pathways, albeit reduced, may trigger positive feedback loops and flares of arthritis after cessation of etanercept.     

LAG-3 regulates CD8+ T cell accumulation and effector function in murine self- and tumor-tolerance systems

Lymphocyte activation gene-3 (LAG-3) is a cell-surface molecule with diverse biologic effects on T cell function. We recently showed that LAG-3 signaling is important in CD4+ regulatory T cell suppression of autoimmune responses. Here, we demonstrate that LAG-3 maintains tolerance to self and tumor antigens via direct effects on CD8+ T cells using 2 murine systems. Naive CD8+ T cells express low levels of LAG-3, and expression increases upon antigen stimulation. Our data show increased levels of LAG-3 protein on antigen-specific CD8+ T cells within antigen-expressing organs or tumors. In vivo antibody blockade of LAG-3 or genetic ablation of the Lag-3 gene resulted in increased accumulation and effector function of antigen-specific CD8+ T cells within organs and tumors that express their cognate antigen. Most notably, combining LAG-3 blockade with specific antitumor vaccination resulted in a significant increase in activated CD8+ T cells in the tumor and disruption of the tumor parenchyma. A major component of this effect was CD4 independent and required LAG-3 expression by CD8+ T cells. Taken together, these data demonstrate a direct role for LAG-3 on CD8+ T cells and suggest that LAG-3 blockade may be a potential cancer treatment.