Psychotic Alzheimer\u27s disease is associated with gender-specific tau phosphorylation abnormalities

Converging evidence suggests that psychotic Alzheimer\u27s disease (AD + P) is associated with an acceleration of frontal degeneration, with tau pathology playing a primary role. Previous histopathologic and biomarker studies have specifically implicated tau pathology in this condition. To precisely quantify tau abnormalities in the frontal cortex in AD + P, we used a sensitive biochemical assay of total tau and 4 epitopes of phospho-tau relevant in AD pathology in a postmortem sample of AD + P and AD - P. Samples of superior frontal gyrus from 26 AD subjects without psychosis and 45 AD + P subjects with psychosis were analyzed. Results of enzyme-linked immunosorbent assay demonstrate that AD + P females, but not males, had significantly higher levels of phosphorylated tau in the frontal cortex. In males, but not females, AD + P was associated with the presence of alpha-synuclein pathology. These results support a gender dissociation of pathology in AD + P. The design of future studies aimed at the elucidation of cognitive and/or functional outcomes; regional brain metabolic deficits; or genetic correlates of AD + P should take gender into consideration. (C) 2014 Elsevier Inc. All rights reserved

Proceedings from the Ice Hockey Summit III: Action on Concussion

The Ice Hockey Summit III provided updated scientific evidence on concussions in hockey to inform these five objectives: 1) describe sport-related concussion (SRC) epidemiology, 2) classify prevention strategies, 3) define objective, diagnostic tests, 4) identify treatment, and 5) integrate science and clinical care into prioritized action plans and policy. Our action plan evolved from 40 scientific presentations. The 155 attendees (physicians, athletic trainers, physical therapists, nurses, neuropsychologists, scientists, engineers, coaches, and officials) voted to prioritize these action items in the final Summit session. 1) Establish a national and international hockey data base for SRC at all levels, 2) eliminate body checking in Bantam youth hockey games, 3) expand a behavior modification program (Fair Play) to all youth hockey levels, 4) enforce game ejection penalties for fighting in Junior A and professional hockey leagues, 5) establish objective tests to diagnose concussion at point of care (POC), and 6) mandate baseline testing to improve concussion diagnosis for all age groups. Expedient implementation of the Summit III prioritized action items is necessary to reduce the risk, severity, and consequences of concussion in the sport of ice hockey

Proceedings from the Ice Hockey Summit III: Action on Concussion

Objectives The Ice Hockey Summit III provided updated scientific evidence on concussions in hockey to inform these five objectives: (1) describe sport related concussion (SRC) epidemiology, (2) classify prevention strategies, (3) define objective, diagnostic tests, (4) identify treatment and (5) integrate science and clinical care into prioritized action plans and policy. Methods Our action plan evolved from 40 scientific presentations. The 155 attendees (physicians, athletic trainers, physical therapists, nurses, neuropsychologists, scientists, engineers, coaches and officials) voted to prioritize these action items in the final Summit session. Results (1) establish a national and international hockey data base for SRCs at all levels; (2) eliminate body checking in Bantam youth hockey games; (3) expand a behavior modification program (Fair Play) to all youth hockey levels; (4) enforce game ejection penalties for fighting in Junior A and professional hockey leagues; (5) establish objective tests to diagnose concussion at point of care (POC); and (6) mandate baseline testing to improve concussion diagnosis for all age groups. Conclusions Expedient implementation of the Summit III prioritized action items is necessary to reduce the risk, severity and consequences of concussion in the sport of ice hockey

Psychosis in Alzheimer\u27s Disease is Associated with Frontal Metabolic Impairment and Accelerated Decline in Working Memory: Findings from the Alzheimer\u27s Disease Neuroimaging Initiative

Objective: An ascendant body of evidence suggests that Alzheimer disease with psychosis (AD+P) is a distinct variant of illness with its own genetic diathesis and a unique clinical course. Impaired frontal lobe function has been previously implicated in AD+P. The current exploratory study, presented in two parts, evaluates both the regional brain metabolic and psychometric correlates of psychosis in a longitudinal sample of subjects with AD, made available by the Alzheimer\u27s Disease Neuroimaging Initiative (ADNI). Methods: In Part 1 of the study, 21 ADNI participants with AD who developed psychotic symptoms during the study but were not psychotic at baseline were matched with 21 participants with AD who never became psychotic during the study period, and mean brain [F-18]fluorodeoxyglucose positron emission tomography (FDG-PET) Cerebral metabolic rate for glucose (CMRgl) by regions of interest (ROIs) were compared Additionally, 39 participants with active psychosis at the time of image acquisition were matched with 39 participants who were never psychotic during the study period, and mean brain FDG-PET CMRgl by sROI were compared. In Part 2 of the study, 354 ADNI participants with AD who were followed for 24 months with serial psychometric testing were identified, and cognitive performance and decline were evaluated for correlation with psychotic symptoms. Results: Part 1: There were no regional brain metabolic differences between those with AD destined to become psychotic and those who did not become psychotic. There was a significant reduction in mean orbitofrontal brain metabolism in those with active psychosis. Part 2: Over the course of study follow-up, psychosis was associated with accelerated decline in functional performance as measured by the Functional Assessment Questionnaire, the Mini-Mental State Examination, and Forward Digit Span. Conclusion: In a sample drawn from the ADNI dataset, our exploratory FDG-PET findings and longitudinal cognitive outcomes support the hypofrontality model of AD+P. Focal frontal vulnerability may mediate the accelerated decline seen in AD+P

Pathogenic tau species drive a psychosis-like phenotype in a mouse model of Alzheimer\u27s disease

Psychotic Alzheimer\u27s disease (AD + P) is a rapidly progressive variant of AD associated with an increased burden of frontal tau pathology that affects up to 50% of those with AD, and is observed more commonly in females. To date, there are no safe and effective medication interventions with an indication for treatment in this condition, and there has been only very limited exploration of potential animal models for preclinical drug development. Pathogenic tau is over represented in the frontal cortex in AD + P, especially in females. In order to develop a candidate animal model of AD + P, we employed a tau mouse model with a heavy burden of frontal tau pathology, the rTg(tauP301L)4510 mouse, hereafter termed rTg4510. We explored deficits of prepulse inhibition of acoustic startle (PPI), a model of psychosis in rodents, and the correlation between pathogenic phospho-tau species associated with AD + P and PPI deficits in female mice. We found that female rTg4510 mice exhibit increasing PPI deficits relative to littermate controls from 4.5 to 5.5 months of age, and that these deficits are driven by insoluble fractions of the phospho-tau species pSer396/404, pSer202, and pThr231 found to be associated with human AD + P. This preliminary data suggests the utility of the rTg4510 mouse as a candidate disease model of human female AD + P. Further work expanded to include both genders and other behavioral outcome measures relevant to AD + P is necessary. (C) 2014 Elsevier B.V. All rights reserved

A Call to Restructure Psychiatry General and Subspecialty Training

Dire shortages of psychiatrists with special expertise in geriatrics, substance abuse, forensics, and psychosomatics create barriers to care for populations with complex mental disorders and pose a significant public health concern. To address these disparities in access to care, we propose streamlining graduate medical education to increase efficiency and enhance cost-effectiveness while simultaneously increasing the number of psychiatric subspecialists in these key areas. We propose that trainees interested in subspecialties complete their general training in 3 years, while meeting ACGME required milestones, and then utilize their 4th year to complete subspecialty fellowship training. Eligible trainees would then qualify for psychiatry subspecialty certification and general psychiatry ABPN certification at the end of 4 years