New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Chronic intracerebroventricular infusion of b-amyloid (1-40) results in a selective loss of neuropeptides in addition to a reduction in choline acetytransferase activity in the cortical mantle and hippocampus in the rat

Neuropeptides: Structure and Function in Biology and Behavior: Part 8. Poster Paperslink_to_subscribed_fulltex

Antibiotics and Mortality in Patients with Lower Respiratory Infection and Advanced Dementia

Objectives: To describe long-term mortality rate and to assess associations between mortality rate and antibiotic treatment of lower respiratory infection in patients with advanced dementia; antibiotic treatment allocation was independent of mortality risk-leaving less room for biased associations than in previous multicenter observational studies. Design: Prospective study (2004-2009). Multilevel Cox proportional hazard analyses with adjustment for mortality risk were used to assess associations between antibiotics and mortality using time-dependent covariates. Setting: A US Department of Veterans Affairs nursing home. Participants: Ninety-four residents with advanced dementia who developed 109 episodes. Measurements: Survival, treatment, mortality risk, illness severity, fluid intake, and several other patient characteristics. Results: Ten-day mortality was 48%, and 6-month mortality was 74%. Antibiotics were used in 77% of episodes. Overall, antibiotics were not associated with mortality rate (Hazard Ratio [HR] 0.70, Confidence Interval [CI] 0.38-1.30); however, antibiotics were associated with reduced 10-day mortality rate (HR 0.51, CI, 0.30-0.87; rate after 10 days: 1.5, CI 0.42-5.2). Benefit from antibiotics was less likely with inadequate fluid intake, and when experiencing the first episode. Conclusion: In our sample of male nursing home residents with advanced dementia and lower respiratory infection, mortality was substantial despite antibiotic treatment. Antibiotics prolonged life but in many cases only for several days. Treatment decisions should take into account that antibiotics may delay death but may also prolong the dying process, indicating a need for accurate prediction of mortality and study of characteristics that may alter effectiveness of antibiotics. © 2012 American Medical Directors Association, Inc

The department of veterans affairs gulf war veterans’ illnesses biorepository: Supporting research on gulf war veterans’ illnesses

Aims: To introduce a resource supporting research on Gulf War illness (GWI) and related disorders, the Gulf War Veterans’ Illnesses Biorepository (GWVIB). Methods: Gulf War era veterans (GWVs) are recruited nationally and enrolled via telephone and email/postal mail. Enrolled veterans receive annual telephone and mail follow-up to collect health data until their passing. A postmortem neuropathological examination is performed, and fixed and frozen brain and spinal cord samples are banked to support research. Investigators studying GWI and related disorders may request tissue and data from the GWVIB. Results: As of September 2021, 127 GWVs from 39 states were enrolled; 60 met the criteria for GWI, and 14 met the criteria for chronic multisymptom illness (CMI). Enrollees have been followed up to six years. Postmortem tissue recoveries were performed on 14 GWVs. The most commonly found neuropathologies included amyotrophic lateral sclerosis, chronic traumatic encephalopathy, and Lewy body disease. Tissue was of good quality with an average RNA integrity number of 5.8 (SD = 1.0) and ≥4.8 in all of the cases. Discussion: The availability of health data and high-quality CNS tissue from this well-characterized GWV cohort will support research on GWI and related disorders affecting GWVs. Enrollment is ongoing. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]