Neurotoxic Saboteurs: Straws That Break the Hippo’s (Hippocampus) Back Drive Cognitive Impairment and Alzheimer’s Disease.
Neurotoxic Saboteurs: Straws that Break the Hippo’s (Hippocampus) Back Drive Cognitive Impairment and Alzheimer’s Disease.
Neurotox Res. 2013 Jul 3;
Daulatzai MA
Late onset Alzheimer’s disease (AD) is the most common cause of progressive cognitive dysfunction and dementia. Despite considerable progress in elucidating the molecular pathology of this disease, we are not yet close to unraveling its etiopathogenesis. The hippocampus is at the epicenter of cognition being associated with learning and memory. A battery of neurotoxic modifiers has been delineated that may unleash deleterious heterogeneous pathologic impacts. Synergistically they target hippocampus causing its neuronal degeneration, gray matter volume atrophy, and progressive cognitive decline. The neurotoxic factors include aging, stress, depression, hypoxia/hypoxemia, hypertension, diabetes, obesity, alcohol abuse, smoking, malnutrition, and polypharmacy-to name a few. Addressing “upstream pathologies” due to these multiple and heterogeneous neurotoxic modifiers vis-a-vis hippocampal dysfunction is of paramount importance. The downstream-generated inflammatory cytokines, mitochondrial dysfunction, oxidative stress, hypoperfusion, excitotoxicity, amyloid beta, and neurofibrillary tangles may then trigger and sustain neurocognitive pathology. The failure of clinical trials in AD is due in part to this complex multifactorial neurotoxic-pathophysiological labyrinth. The key is to employ appropriate preventive and treatment strategies prior to significant hippocampus damage and its dysfunction. Prevention/reversal of the diverse neurotoxic impacts, delineated here, should be an integral part of therapeutic armamentarium, in order to ameliorate hippocampus dysfunction and to enhance memory in aging, mild cognitive impairment, and AD. Throughout, the paper highlights both the challenges presented by the ever present neurotoxic onslaught, and the opportunities to overcome them. Hence, arresting AD pathogenesis is achievable through early intervention. A targeted approach may ameliorate neurocognitive pathology and attenuate memory deterioration. HubMed – depression
Suicide and Suicidal Ideation Among Bhutanese Refugees – United States, 2009-2012.
MMWR Morb Mortal Wkly Rep. 2013 Jul 5; 62(26): 533-536
During the period February 2009-February 2012, the Office of Refugee Resettlement of the U.S. Department of Health and Human Services reported 16 suicides among the approximately 57,000 Bhutanese refugees who had resettled in the United States since 2008. In 2012, the office requested assistance from CDC and the Massachusetts Department of Public Health’s Refugee Health Technical Assistance Center to identify risk factors that might be associated with suicidal ideation among Bhutanese refugees. In collaboration with the Massachusetts refugee health center, CDC conducted a survey of randomly selected Bhutanese refugees in four U.S. states with large populations of resettled refugees. The results indicated significant associations between ever having expressed suicidal ideation and current self-reported symptoms of mental health disorder (e.g., anxiety, depression, or posttraumatic stress disorder) and postmigration difficulties (e.g., family conflict or inability to find work). The findings highlight the need for development of culturally appropriate community-based interventions for suicide prevention and standard procedures for monitoring and reporting suicides and suicide attempts in the Bhutanese refugee population. HubMed – depression
Early markers of cognitive enhancement: developing an implicit measure of cognitive performance.
Psychopharmacology (Berl). 2013 Jul 3;
Pringle A, Browning M, Parsons E, Cowen PJ, Harmer CJ
There is intense interest in the development of effective cognitive enhancing drugs which would have therapeutic application across a number of neurological and psychological disorders including dementia, schizophrenia and depression. However, development in this area has been limited by the absence of sensitive biomarkers which can be used to detect and refine therapeutic-like action in phase 1 clinical studies. The aim of the present study was therefore to develop a measure of cognition relevant to the action of candidate cognitive enhancers which might be sensitive to pharmacological manipulation in healthy volunteers. Healthy volunteers (n?=?34) were randomised to receive a single dose of modafinil (100 mg) or placebo. Five hours post dose, attentional flexibility in learning was assessed using a novel implicit learning task. Volunteers also completed an auditory digit span task and visual analogue scales (VAS). Modafinil increased alertness as measured by the VAS. In the implicit learning task, modafinil enhanced learning rates in terms of both accuracy and reaction time, suggesting an increase in implicit rule learning. These results suggest that the novel learning task should be explored as a biomarker of early cognitive improvement which could be more sensitive than conventional measures. HubMed – depression