Agitation and impulsivity in mid and late life as possible risk markers for incident dementia

To identify knowledge gaps regarding new-onset agitation and impulsivity prior to onset of cognitive impairment or dementia the International Society to Advance Alzheimer's Research and Treatment Neuropsychiatric Syndromes (NPS) Professional Interest Area conducted a scoping review. Extending a series of reviews exploring the pre-dementia risk syndrome Mild Behavioral Impairment (MBI), we focused on late-onset agitation and impulsivity (the MBI impulse dyscontrol domain) and risk of incident cognitive decline and dementia. This scoping review of agitation and impulsivity pre-dementia syndromes summarizes the current biomedical literature in terms of epidemiology, diagnosis and measurement, neurobiology, neuroimaging, biomarkers, course and prognosis, treatment, and ongoing clinical trials. Validations for pre-dementia scales such as the MBI Checklist, and incorporation into longitudinal and intervention trials, are needed to better understand impulse dyscontrol as a risk factor for mild cognitive impairment and dementia.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.Daniel Bateman receives support from the Indiana University Richard M. Fairbanks Chair of Aging Research, the Indiana University Cornelius and Yvonne Pettinga Chair of Medicine, and funding from the National Institute on Aging (NIA) grants K23AG059914 and P30AF10133. Sascha Gill receives funding from a University of Calgary Graduate Student Research Award. Sophie Hu receives funding from a Cana dian Institute of Health Research (CIHR) Master’s Research Award. Erin Foster: none. Myuri Ruthirakuhan receives funding from a CIHR Doctoral Research Award. Allis Sellek receives funding from Alzheimer Foundation of Costa Rica. Moyra Mortby receives support from the Australian National Health and Medical Research Council (NHMRC) and Australian Research Council (ARC) Dementia Research Development Fellowship #1102028. Veronika Matušková receives support from MH CZ – DRO, Motol University Hospital, Prague, Czech Republic 00064203 and Czech Ministry of Health grant 16-27611A. Kok Pin Ng: none. Rawan Tarawneh receives support from the Ohio State University Chronic Brain Injury Discovery Themes. Yvonne Freund-Levi:none. Sanjeev Kumar receives research support from Brain and Behavior Foundation, National institute on Ageing, BrightFocus Foundation, Brain Canada, Canadian Institute of Health Research, Centre for Ageing and Brain Health Innovation, Weston Brain Institute, and Centre for Mental Health and Addiction Foundation and University of Toronto. Serge Gauthier receives support from the CIHR, Weston, and the National Institutes of Health (NIH). Paul Rosenberg receives funding from the National Institute on Aging (NIA) grants R01AG049872 and R01 AG054771. Fabricio Ferreira de Oliveira has a grant from FAPESP - The State of São Paulo Research Foundation (grant #2015/10109-5). Devangere Devanand: none. Clive Ballard: none. Zahinoor Ismail has received funding from Alzheimer’s Society of Calgary via the Hotchkiss Brain Institute.published version, accepted version (12 month embargo), submitted versio

The ASEAN Secretariat and Legal Issues Arising From ASEAN Charter

There are three major issues embodied in the new ASEAN Charter. They are. Legal personality of ASEAN, previlages and immunities and dispute settlement mechanism. This article elaborates recent development of those three legal issues, as new legal tasks that ASEAN Secretariat has to carry out as the ASEAN Charter start to be entry into force. Nonetheless, ASEAN Secretariat faces many obstacles ahead particularly in building its human resources and seeking of the legal experts to carry the tasks which must be undertaken by the ASEAN Secretariat

ASEAN measures in combating piracy and other maritime crimes

10.4337/9781781006849.00015Piracy and International Maritime Crimes in ASEAN: Prospects for Cooperation139-16

Targeting norepinephrine in mild cognitive impairment and Alzheimer's disease.

peer reviewedThe Alzheimer's disease (AD) epidemic is a looming crisis, with an urgent need for new therapies to delay or prevent symptom onset and progression. There is growing awareness that clinical trials must target stage-appropriate pathophysiological mechanisms to effectively develop disease-modifying treatments. Advances in AD biomarker research have demonstrated changes in amyloid-beta (Aβ), brain metabolism and other pathophysiologies prior to the onset of memory loss, with some markers possibly changing one or two decades earlier. These findings suggest that amyloid-based therapies would optimally be targeted at the earliest clinically detectable stage (such as mild cognitive impairment (MCI)) or before. Postmortem data indicate that tau lesions in the locus coeruleus (LC), the primary source of subcortical norepinephrine (NE), may be the first identifiable pathology of AD, and recent data from basic research in animal models of AD indicate that loss of NE incites a neurotoxic proinflammatory condition, reduces Aβ clearance and negatively impacts cognition - recapitulating key aspects of AD. In addition, evidence linking NE deficiency to neuroinflammation in AD also exists. By promoting proinflammatory responses, suppressing anti-inflammatory responses and impairing Aβ degradation and clearance, LC degeneration and NE loss can be considered a triple threat to AD pathogenesis. Remarkably, restoration of NE reverses these effects and slows neurodegeneration in animal models, raising the possibility that treatments which increase NE transmission may have the potential to delay or reverse AD-related pathology. This review describes the evidence supporting a key role for noradrenergic-based therapies to slow or prevent progressive neurodegeneration in AD. Specifically, since MCI coincides with the onset of clinical symptoms and brain atrophy, and LC pathology is already present at this early stage of AD pathogenesis, MCI may offer a critical window of time to initiate novel noradrenergic-based therapies aimed at the secondary wave of events that lead to progressive neurodegeneration. Because of the widespread clinical use of drugs with a NE-based mechanism of action, there are immediate opportunities to repurpose existing medications. For example, NE transport inhibitors and NE-precursor therapies that are used for treatment of neurologic and psychiatric disorders have shown promise in animal models of AD, and are now prime candidates for early-phase clinical trials in humans