List of publications for June 27, 2022
Doherty, J.M.a , Roe, C.M.a , Murphy, S.A.a , Johnson, A.M.b , Fleischer, E.c , Toedebusch, C.D.a , Redrick, T.a , Freund, D.a , Morris, J.C.a d e , Schindler, S.E.a e , Fagan, A.M.a d e , Holtzman, D.M.a d e f , Lucey, B.P.a d f , Babulal, G.M.a g h i
a Department of Neurology, Washington University in St. Louis, St. Louis, MO, USA
b Center for Clinical Studies, Washington University in St. Louis, St. Louis, MO, USA
c Byram Hills High School, NY, NY, United States
d Hope Center for Neurological Disorders, Washington University in St Louis, St. Louis, MO, USA
e Knight Alzheimer’s Disease Research Center, Washington University in St Louis, St. Louis, MO, USA
f Center on Biological Rhythms and Sleep, Washington University in St Louis, St. Louis, MO, USA
g Institute of Public Health, Washington University in St. Louis, St. Louis, United States
h Department of Psychology, Faculty of Humanities, University of Johannesburg, Johannesburg, South Africa
i Department of Clinical Research and Leadership, George Washington University School of Medicine and Health Sciences, DCWA, United States
Alzheimer’s disease (AD) pathology accumulates for decades before the onset of cognitive decline. Cognitively normal individuals with biomarker evidence of AD brain pathology (i.e. biomarker + or preclinical AD) can be differentiated from individuals without AD brain pathology based on naturalistic driving data, such as hard acceleration or braking and speeding, measured using in-vehicle dataloggers. Older adults are at increased risk of injury and death from motor vehicle crashes and driving cessation is also linked to negative health outcomes. Identifying potentially modifiable risk factors that increase driving risk may prolong safe driving in old age. Sleep apnea is associated with adverse driving behaviors across the age span. In this study, we hypothesized that high-risk driving behaviors would be associated with increased sleep apnea severity and AD pathology. We found that higher sleep apnea severity measured by a home sleep apnea test was associated with a higher incidence of adverse driving behaviors even after controlling for multiple confounders (β = 0.24 ± 0.09, p < 0.01). This association was independent of AD biomarker positivity (i.e. increased t-tau/Aβ 42 ratio). Increasing age was associated with a higher likelihood of high-risk driving behaviors in individuals with AD brain pathology (β = 0.12 ± 0.04, p < 0.01), but a lower likelihood in individuals without AD brain pathology (β = -0.06 ± 0.03, p < 0.05). These findings suggest that adverse driving behaviors linked to a higher rate of traffic crashes in older adults are associated with sleep apnea severity and AD pathology even in cognitively unimpaired individuals. Further studies are needed to determine if treatment of sleep apnea decreases high-risk driving behaviors and therefore motor vehicle crashes. © The Author(s) 2022. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: email@example.com.
Alzheimer’s disease; driving; obstructive sleep apnea; older adults
Document Type: Article
Publication Stage: Final
Assessment of Instrumental Activities of Daily Living in Preclinical Alzheimer Disease
(2022) OTJR Occupation, Participation and Health, .
Keleman, A.A., Bollinger, R.M., Wisch, J.K., Grant, E.A., Benzinger, T.L., Ances, B.M., Stark, S.L.
Washington University in St. LouisMO, United States
Questionnaires are used to assess instrumental activities of daily living (IADL) among individuals with preclinical Alzheimer disease (AD). They have indicated no functional impairment among this population. We aim to determine among cognitively normal (CN) older adults with and without preclinical AD whether: (a) performance-based IADL assessment measures a wider range of function than an IADL questionnaire and (b) biomarkers of AD are associated with IADL performance. In this cross-sectional analysis of 161 older adults, participants in studies of AD completed an IADL questionnaire, performance-based IADL assessment, cognitive assessments, and had biomarkers of AD (amyloid, hippocampal volume, brain network strength) assessed within 2 to 3 years. Performance-based IADL scores were more widely distributed compared with the IADL questionnaire. Smaller hippocampal volumes and reduced brain network connections were associated with worse IADL performance. A performance-based IADL assessment demonstrates functional impairment associated with neurodegeneration among CN older adults. © The Author(s) 2022.
cognitive impairment; dementia; instrumental activities of daily living; neuroscience; older adults
Document Type: Article
Publication Stage: Article in Press
The Hydrocephalus Clinical Research Network quality improvement initiative: the role of antibiotic-impregnated catheters and vancomycin wound irrigation
(2022) Journal of Neurosurgery: Pediatrics, 29 (6), pp. 711-718.
Chu, J.a , Jensen, H.b , Holubkov, R.b , Krieger, M.D.a , Kulkarni, A.V.c , Riva-Cambrin, J.d , Rozzelle, C.J.e , Limbrick, D.D., Jr.f , Wellons, J.C., IIIg , Browd, S.R.h , Whitehead, W.E.i , Pollack, I.F.j , Simon, T.D.k , Tamber, M.S.l , Hauptman, J.S.h , Pindrik, J.m , Naftel, R.P.g , McDonald, P.J.n , Hankinson, T.C.o , Jackson, E.M.p , Rocque, B.G.e , Reeder, R.b , Drake, J.M.c , Kestle, J.R.W.q , for the Hydrocephalus Clinical Research Networkr
a Division of Neurosurgery, Children’s Hospital Los Angeles, Department of Neurosurgery, University of Southern California, Los Angeles, CA, United States
b Department of Pediatrics, University of Utah, Salt Lake City, UT, United States
c Division of Neurosurgery, Hospital for Sick Children, University of TorontoON, Canada
d Department of Clinical Neurosciences, University of Calgary, Alberta, Canada
e Section of Pediatric Neurosurgery, Division of Neurosurgery, Children’s Hospital of Alabama, University of Alabama–BirminghamAL, United States
f Department of Neurosurgery, St. Louis Children’s Hospital, Washington University in St. LouisMO, United States
g Division of Pediatric Neurosurgery, Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, TN, United States
h Department of Neurosurgery, University of Washington, Seattle Children’s Hospital, Seattle, WA, United States
i Division of Pediatric Neurosurgery, Department of Neurosurgery, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX, United States
j Division of Neurosurgery, Children’s Hospital of PittsburghPA, United States
k Department of Pediatrics, Children’s Hospital Los Angeles, University of Southern California, Los Angeles, CA, United States
l Department of Surgery, Division of Neurosurgery, British Columbia Children’s Hospital, University of British Columbia, Vancouver, BC, Canada
m Department of Neurosurgery, Nationwide Children’s Hospital, Columbus, OH, United States
n Section of Neurosurgery, Department of Surgery, University of Manitoba, Winnipeg, MB, Canada
o Division of Pediatric Neurosurgery, Department of Neurosurgery, University of Colorado School of Medicine, Aurora, CO, United States
p Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States
q Department of Neurosurgery, University of Utah, Salt Lake City, UT, United States
OBJECTIVE Two previous Hydrocephalus Clinical Research Network (HCRN) studies have demonstrated that compliance with a standardized CSF shunt infection protocol reduces shunt infections. In this third iteration, a simplified protocol consisting of 5 steps was implemented. This analysis provides an updated evaluation of protocol compliance and evaluates modifiable shunt infection risk factors. METHODS The new simplified protocol was implemented at HCRN centers on November 1, 2016, for all shunt procedures, excluding external ventricular drains, ventricular reservoirs, and subgaleal shunts. Procedures performed through December 31, 2019, were included (38 months). Compliance with the protocol, use of antibiotic-impregnated catheters (AICs), and other variables of interest were collected at the index operation. Outcome events for a minimum of 6 months postoperatively were recorded. The definition of infection was unchanged from the authors’ previous report. RESULTS A total of 4913 procedures were performed at 13 HCRN centers. The overall infection rate was 5.1%. Surgeons were compliant with all 5 steps of the protocol in 79.4% of procedures. The infection rate for the protocol alone was 8.1% and dropped to 4.9% when AICs were added. Multivariate analysis identified having ≥ 2 complex chronic conditions (odds ratio [OR] 1.76, 95% confidence interval [CI] 1.26–2.44, p = 0.01) and a history of prior shunt surgery within 12 weeks (OR 1.84, 95% CI 1.37–2.47, p < 0.01) as independent risk factors for shunt infection. The use of AICs (OR 0.70, 95% CI 0.50–0.97, p = 0.05) and vancomycin irrigation (OR 0.36, 95% CI 0.21–0.62, p < 0.01) were identified as independent factors protective against shunt infection. CONCLUSIONS The authors report the third iteration of their quality improvement protocol to reduce the risk of shunt infection. Compliance with the protocol was high. These updated data suggest that the incorporation of AICs is an important, modifiable infection prevention measure. Vancomycin irrigation was also identified as a protective factor but requires further study to better understand its role in preventing shunt infection. ©AANS 2022
cerebrospinal fluid; hydrocephalus; protocol; quality improvement; shunt infection
National Institute of Neurological Disorders and StrokeNINDS1RC1NS068943-01
Document Type: Article
Publication Stage: Final
Clonally expanded CD8 T cells characterize amyotrophic lateral sclerosis-4
(2022) Nature, 606(7916), pp. 945-952
Campisi, L., Chizari, S., Ho, J.S.Y., (…), La Spada, A.R., Marazzi, I.
Amyotrophic lateral sclerosis (ALS) is a heterogenous neurodegenerative disorder that affects motor neurons and voluntary muscle control1. ALS heterogeneity includes the age of manifestation, the rate of progression and the anatomical sites of symptom onset. Disease-causing mutations in specific genes have been identified and define different subtypes of ALS1. Although several ALS-associated genes have been shown to affect immune functions2, whether specific immune features account for ALS heterogeneity is poorly understood. Amyotrophic lateral sclerosis-4 (ALS4) is characterized by juvenile onset and slow progression3. Patients with ALS4 show motor difficulties by the time that they are in their thirties, and most of them require devices to assist with walking by their fifties. ALS4 is caused by mutations in the senataxin gene (SETX). Here, using Setx knock-in mice that carry the ALS4-causative L389S mutation, we describe an immunological signature that consists of clonally expanded, terminally differentiated effector memory (TEMRA) CD8 T cells in the central nervous system and the blood of knock-in mice. Increased frequencies of antigen-specific CD8 T cells in knock-in mice mirror the progression of motor neuron disease and correlate with anti-glioma immunity. Furthermore, bone marrow transplantation experiments indicate that the immune system has a key role in ALS4 neurodegeneration. In patients with ALS4, clonally expanded TEMRA CD8 T cells circulate in the peripheral blood. Our results provide evidence of an antigen-specific CD8 T cell response in ALS4, which could be used to unravel disease mechanisms and as a potential biomarker of disease state.