Acute stress impairs memory retrieval and facilitates the induction of long-term depression (LTD) in the hippocampal CA1 region of the adult rodent brain. However, whether such alterations in synaptic plasticity cause the behavioral effects of stress is not known. Here, we report that two selective inhibitors of the induction or expression of stress-enabled, N-methyl-D-aspartate receptor-dependent hippocampal LTD also block spatial memory retrieval impairments caused by acute stress. Additionally, we demonstrate that facilitating the induction of hippocampal LTD in vivo by blockade of glutamate transport mimics the behavioral effects of acute stress by impairing spatial memory retrieval. Thus, the present study demonstrates that hippocampal LTD is both necessary and sufficient to cause acute stressinduced impairment of spatial memory retrieval and provides a new perspective from which to consider the nature of cognitive deficits in disorders whose symptoms are aggravated by stress.glutamate transporter ͉ interference peptide ͉ synaptic plasticity ͉ water maze ͉ corticosterone C ognitive functions such as learning and memory are greatly affected by stress. Memory retrieval in humans is especially vulnerable to acute psychological stress (1) or cortisol treatment (2), effects caused in part by alterations in medial temporal lobe function (3). In rodents, acute stress or administration of glucocorticoids disrupts the retrieval of hippocampal-dependent spatial memory (4). Furthermore, stress and glucocorticoids have a profound influence on the physiology of the hippocampal CA1 region by inhibiting long-term potentiation (LTP) (5-7) and enabling long-term depression (LTD) (7,8), the two most well characterized forms of synaptic plasticity and proposed cellular substrates for learning and memory (9, 10). However, it remains to be established whether the alterations in either LTP or LTD caused by stress contribute to the stress-induced impairment of spatial memory retrieval.Considerable experimental evidence supports the role of hippocampal LTP in spatial memory (11)(12)(13)(14), and theoretical accounts of associative memory, based on neural network models, suggest that a balance between LTP and LTD may underlie efficient memory storage (10, 15). By using two recently developed specific inhibitors of LTD (16, 17), the present experiments assess the role of LTD in the spatial memory retrieval deficits induced by acute stress and provide strong evidence for a role of hippocampal LTD in mediating this aspect of acute stress-induced impairment of cognitive function in adult rats. ResultsBlocking the Induction of LTD Prevents the Stress-Induced Impairment of Spatial Memory Retrieval. It is well accepted that the induction of hippocampal CA1 homosynaptic LTD depends on the N-methyl-D-aspartate subtype of glutamate receptors (NMDARs) (10), which are heteromeric complexes of NR1 subunits and at least one type of NR2 subunit (NR2A-D) (18). Converging evidence supports the hypothesis that the subunit composition of NMDARs may c...

Digital technology is transforming the development of drugs for Alzheimer's disease and was the topic of the Alzheimer's Association's Research Roundtable on its May 23–24, 2017 meeting. Research indicates that wearable devices and unobtrusive passive sensors that enable the collection of frequent or continuous, objective, and multidimensional data during daily activities may capture subtle changes in cognition and functional capacity long before the onset of dementia. The potential to exploit these technologies to improve clinical trials as both recruitment and retention tools as well as for potential end points was discussed. The implications for the collection and use of large amounts of data, lessons learned from other related disease areas, ethical concerns raised by these new technologies, and regulatory issues were also covered in the meeting. Finally, the challenges and opportunities of these new technologies for future use were discussed.

BackgroundOnline health information is unregulated and can be of highly variable quality. There is currently no singular quantitative tool that has undergone a validation process, can be used for a broad range of health information, and strikes a balance between ease of use, concision and comprehensiveness. To address this gap, we developed the QUality Evaluation Scoring Tool (QUEST). Here we report on the analysis of the reliability and validity of the QUEST in assessing the quality of online health information.MethodsThe QUEST and three existing tools designed to measure the quality of online health information were applied to two randomized samples of articles containing information about the treatment (n = 16) and prevention (n = 29) of Alzheimer disease as a sample health condition. Inter-rater reliability was assessed using a weighted Cohen’s kappa (κ) for each item of the QUEST. To compare the quality scores generated by each pair of tools, convergent validity was measured using Kendall’s tau (τ) ranked correlation.ResultsThe QUEST demonstrated high levels of inter-rater reliability for the seven quality items included in the tool (κ ranging from 0.7387 to 1.0, P < .05). The tool was also found to demonstrate high convergent validity. For both treatment- and prevention-related articles, all six pairs of tests exhibited a strong correlation between the tools (τ ranging from 0.41 to 0.65, P < .05).ConclusionsOur findings support the QUEST as a reliable and valid tool to evaluate online articles about health. Results provide evidence that the QUEST integrates the strengths of existing tools and evaluates quality with equal efficacy using a concise, seven-item questionnaire. The QUEST can serve as a rapid, effective, and accessible method of appraising the quality of online health information for researchers and clinicians alike.Electronic supplementary materialThe online version of this article (10.1186/s12911-018-0668-9) contains supplementary material, which is available to authorized users.

ObjectiveTo assess the availability, readability, and privacy-related content of the privacy policies and terms of agreement of mental health apps available through popular digital stores.Materials and methodsPopular smartphone app stores were searched using combinations of keywords “track” and “mood” and their synonyms. The first 100 apps from each search were evaluated for inclusion and exclusion criteria. Apps were assessed for availability of a privacy policy (PP) and terms of agreement (ToA) and if available, these documents were evaluated for both content and readability.ResultsMost of the apps collected in the sample did not include a PP or ToA. PPs could be accessed for 18% of iOS apps and 4% of Android apps; whereas ToAs were available for 15% of iOS and 3% of Android apps. Many PPs stated that users' information may be shared with third parties (71% iOS, 46% Android).DiscussionResults demonstrate that information collection is occurring with the majority of apps that allow users to track the status of their mental health. Most of the apps collected in the initial sample did not include a PP or ToA despite this being a requirement by the store. The majority of PPs and ToAs that were evaluated are written at a post-secondary reading level and disclose that extensive data collection is occurring.ConclusionOur findings raise concerns about consent, transparency, and data sharing associated with mental health apps and highlight the importance of improved regulation in the mobile app environment.

Online social media is widespread, easily accessible and attracts a global audience with a widening demographic. As a large proportion of adults now seek health information online and through social media applications, communication about health has become increasingly interactive and dynamic. Online health information has the potential to significantly impact public health, especially as the population gets older and the prevalence of dementia increases. However, little is known about how information pertaining to age-associated diseases is disseminated on popular social media platforms. To fill this knowledge gap, we examined empirically: (i) who is using social media to share information about dementia, (ii) what sources of information about dementia are promoted, and (iii) which dementia themes dominate the discussion. We data-mined the microblogging platform Twitter for content containing dementia-related keywords for a period of 24 hours and retrieved over 9,200 tweets. A coding guide was developed and content analysis conducted on a random sample (10%), and on a subsample from top users’ tweets to assess impact. We found that a majority of tweets contained a link to a third party site rather than personal information, and these links redirected mainly to news sites and health information sites. As well, a large number of tweets discussed recent research findings related to the prediction and risk management of Alzheimer’s disease. The results highlight the need for the dementia research community to harness the reach of this medium and its potential as a tool for multidirectional engagement.

Background: Technology has multiple potential applications to dementia from diagnosis and assessment to care delivery and supporting ageing in place. Objectives: To summarise key areas of technology development in dementia and identify future directions and implications. Method: Members of the US Alzheimer’s Association Technology Professional Interest Area involved in delivering the annual pre-conference summarised existing knowledge on current and future technology developments in dementia. Results: The main domains of technology development are as follows: (i) diagnosis, assessment and monitoring, (ii) maintenance of functioning, (iii) leisure and activity, (iv) caregiving and management. Conclusions: The pace of technology development requires urgent policy, funding and practice change, away from a narrow medical approach, to a holistic model that facilitates future risk reduction and prevention strategies, enables earlier detection and supports implementation at scale for a meaningful and fulfilling life with dementia.

Glutathione (GSH), the major endogenous antioxidant produced by cells, can modulate the activity of N-methyl-D-aspartate receptors (NMDARs) through its reducing functions. During aging, an increase in oxidative stress leads to decreased levels of GSH in the brain. Concurrently, aging is characterized by calcium dysregulation, thought to underlie impairments in hippocampal NMDAR-dependent long-term potentiation (LTP), a form of synaptic plasticity thought to represent a cellular model for memory.Here we show that orally supplementing aged mice with N-acetylcysteine, a precursor for the formation of glutathione, reverses the L-type calcium channel-dependent LTP seen in aged animals to NMDAR-dependent LTP. In addition, introducing glutathione in the intrapipette solution during whole-cell recordings restores LTP obtained in whole-cell conditions in the aged hippocampus. We conclude that aging leads to a reduced redox potential in hippocampal neurons, triggering impairments in LTP.

Gene therapy research is advancing rapidly, and hopes of treating a large number of brain disorders exist alongside ethical concerns. Most surveys of public attitudes toward these ethical issues are already dated and the content of these surveys has been researcher-driven. To examine current public perceptions, we developed an online instrument that is responsive and relevant to the latest research about ethics, gene therapy, and the brain. The 16-question survey was launched with the platform Amazon Mechanical Turk and was made available to residents of Canada and the United States. The survey was divided into six themes: (1) demographic information, (2) general opinions about gene therapy, (3) medical applications of gene therapy, (4) identity and moral/belief systems, (5) enhancement, and (6) risks. We received and analyzed responses from a total of 467 participants. Our results show that a majority of respondents (>90%) accept gene therapy as a treatment for severe illnesses such as Alzheimer disease, but this receptivity decreases for conditions perceived as less severe such as attention deficit hyperactivity disorder (79%), and for nontherapeutic applications (47%). The greatest area of concern for the application of gene therapy to brain conditions is the fear of not receiving sufficient information before undergoing the treatment. The main ethical concerns with enhancement were the potential for disparities in resource allocation, access to the procedure, and discrimination. When comparing these data with those from the 1990s, our findings suggest that the acceptability of gene therapy is increasing and that this trend is occurring despite lingering concerns over ethical issues. Providing the public and patients with up-to-date information and opportunities to engage in the discourse about areas of research in gene therapy is a priority.