The current review systematically documents the role of g-amino-butyric acid (GABA) in different aspects of fear memoryFacquisition and consolidation, reconsolidation, and extinction, and attempts to resolve apparent contradictions in the data in order to identify the function of GABA A receptors in fear memory. First, numerous studies have shown that pre-and post-training administration of drugs that facilitate GABAergic transmission disrupt the initial formation of fear memories, indicating a role for GABA A receptors, possibly within the amygdala and hippocampus, in the acquisition and consolidation of fear memories. Similarly, recent evidence indicates that these drugs are also detrimental to the restorage of fear memories after their reactivation. This suggests a role for GABA A receptors in the reconsolidation of fear memories, although the precise neural circuits are yet to be identified. Finally, research regarding the role of GABA in extinction has shown that GABAergic transmission is also disruptive to the formation of newly acquired extinction memories. We argue that contradictions to these patterns are the result of variations in (a) the location of drug infusion, (b) the dosage of the drug and/or (c) the time point of drug administration. The question of whether these GABA-induced memory deficits reflect deficits in retrieval is discussed. Overall, the evidence implies that the processes mediating memory stability consequent to initial fear learning, memory reactivation, and extinction training are dependent on a common mechanism of reduced GABAergic neurotransmission.

Type 2 diabetes (diabetes) is characterized by accelerated cognitive decline and higher dementia risk. Controversy exists regarding the impact of metformin, which is associated with both increased and decreased dementia rates. The objective of this study was to determine the association of metformin use with incident dementia and cognitive decline over 6 years in participants with diabetes compared with those not receiving metformin and those without diabetes. RESEARCH DESIGN AND METHODSA prospective observational study was conducted of N 5 1,037 community-dwelling older participants without dementia aged 70-90 years at baseline (the Sydney Memory and Ageing Study). Exclusion criteria were dementia, major neurological or psychiatric disease, or progressive malignancy. Neuropsychological testing measured cognitive function every 2 years; a battery of tests measured executive function, memory, attention/speed, language, and visuospatial function individually. These were used to determine the measure of global cognition. Incident dementia was ascertained by a multidisciplinary panel. Total brain, hippocampal, and parahippocampal volumes were measured by MRI at baseline and 2 years (n 5 526). Data were analyzed by linear mixed modeling, including the covariates of age, sex, education, BMI, heart disease, hypertension, stroke, smoking, and apolipoprotein E«4 carriage. RESULTSOf n 5 1,037, 123 had diabetes; 67 received metformin (DM1MF) and were demographically similar to those who did not (DM-noMF) and participants without diabetes (no-DM). DM1MF had significantly slower global cognition and executive function decline compared with DM-noMF. Incident dementia was significantly higher in DM-noMF compared with DM1MF (odds ratio 5.29 [95% CI 1.17-23.88]; P 5 0.05). CONCLUSIONSOlder people with diabetes receiving metformin have slower cognitive decline and lower dementia risk. Large randomized studies in people with and without diabetes will determine whether these associations can be attributed to metformin.

BackgroundCapacity building strategies are widely used to increase the use of research in policy development. However, a lack of well-validated measures for policy contexts has hampered efforts to identify priorities for capacity building and to evaluate the impact of strategies. We aimed to address this gap by developing SEER (Seeking, Engaging with and Evaluating Research), a self-report measure of individual policymakers’ capacity to engage with and use research.MethodsWe used the SPIRIT Action Framework to identify pertinent domains and guide development of items for measuring each domain. Scales covered (1) individual capacity to use research (confidence in using research, value placed on research, individual perceptions of the value their organisation places on research, supporting tools and systems), (2) actions taken to engage with research and researchers, and (3) use of research to inform policy (extent and type of research use). A sample of policymakers engaged in health policy development provided data to examine scale reliability (internal consistency, test-retest) and validity (relation to measures of similar concepts, relation to a measure of intention to use research, internal structure of the individual capacity scales).ResultsResponse rates were 55% (150/272 people, 12 agencies) for the validity and internal consistency analyses, and 54% (57/105 people, 9 agencies) for test-retest reliability. The individual capacity scales demonstrated adequate internal consistency reliability (alpha coefficients > 0.7, all four scales) and test-retest reliability (intra-class correlation coefficients > 0.7 for three scales and 0.59 for fourth scale). Scores on individual capacity scales converged as predicted with measures of similar concepts (moderate correlations of > 0.4), and confirmatory factor analysis provided evidence that the scales measured related but distinct concepts. Items in each of these four scales related as predicted to concepts in the measurement model derived from the SPIRIT Action Framework. Evidence about the reliability and validity of the research engagement actions and research use scales was equivocal.ConclusionsInitial testing of SEER suggests that the four individual capacity scales may be used in policy settings to examine current capacity and identify areas for capacity building. The relation between capacity, research engagement actions and research use requires further investigation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12961-016-0162-8) contains supplementary material, which is available to authorized users.

Background: Hypertension is an established risk factor for stroke and vascular dementia but recent meta-analyses examining the association between Alzheimer's disease (AD) and hypertension have found no significant association. These metaanalyses included short term studies starting in late life which may have obscured the real effect of midlife hypertension. Objective: To examine the association of AD with midlife hypertension, by including only studies with a sufficiently long follow up duration. Methods: Relevant studies were found by searches of MEDLINE, EMBASE, and PubMed. Study outcomes were grouped by measures of blood pressure and definition of hypertension (e.g., systolic hypertension > 140 mmHg or > 160 mmHg). We assessed pooled effect estimates using random effects models and heterogeneity of pooled estimates through the I 2 statistic. Results: Literature search found 3,426 publications of which 7 were eligible studies. There was a significant association between systolic hypertension (>160 mm Hg) and AD (HR 1.25, 95CI 1.06 -1.47, p = 0.0065). Similarly, for systolic hypertension > 140 mm Hg, there was a smaller but still significant association (HR 1.18, 95CI 1.02 -1.35, p = 0.021). For diastolic hypertension, all four studies found no significant associations between diastolic hypertension and AD, and these data could not be pooled due to heterogeneity in reporting. Conclusions: Our study found that midlife stage 1 and stage 2 systolic hypertension is associated with increased risk of AD by 18 and 25%, respectively, although no association was found for diastolic hypertension. It is likely that assertive control of systolic hypertension starting in midlife is important to preventing AD.

BackgroundEvidence-informed policymaking is more likely if organisations have cultures that promote research use and invest in resources that facilitate staff engagement with research. Measures of organisations’ research use culture and capacity are needed to assess current capacity, identify opportunities for improvement, and examine the impact of capacity-building interventions. The aim of the current study was to develop a comprehensive system to measure and score organisations’ capacity to engage with and use research in policymaking, which we entitled ORACLe (Organisational Research Access, Culture, and Leadership).MethodWe used a multifaceted approach to develop ORACLe. Firstly, we reviewed the available literature to identify key domains of organisational tools and systems that may facilitate research use by staff. We interviewed senior health policymakers to verify the relevance and applicability of these domains. This information was used to generate an interview schedule that focused on seven key domains of organisational capacity. The interview was pilot-tested within four Australian policy agencies. A discrete choice experiment (DCE) was then undertaken using an expert sample to establish the relative importance of these domains. This data was used to produce a scoring system for ORACLe.ResultsThe ORACLe interview was developed, comprised of 23 questions addressing seven domains of organisational capacity and tools that support research use, including (1) documented processes for policymaking; (2) leadership training; (3) staff training; (4) research resources (e.g. database access); and systems to (5) generate new research, (6) undertake evaluations, and (7) strengthen relationships with researchers. From the DCE data, a conditional logit model was estimated to calculate total scores that took into account the relative importance of the seven domains. The model indicated that our expert sample placed the greatest importance on domains (2), (3) and (4).ConclusionWe utilised qualitative and quantitative methods to develop a system to assess and score organisations’ capacity to engage with and apply research to policy. Our measure assesses a broad range of capacity domains and identifies the relative importance of these capacities. ORACLe data can be used by organisations keen to increase their use of evidence to identify areas for further development.Electronic supplementary materialThe online version of this article (doi:10.1186/s12961-015-0069-9) contains supplementary material, which is available to authorized users.