WashU weekly Neuroscience publications

Tau PET in autosomal dominant Alzheimer’s disease: relationship with cognition, dementia and other biomarkers
(2019) Brain : a journal of neurology, 142 (4), pp. 1063-1076. Cited 1 time.

Gordon, B.A.^{a b c d} , Blazey, T.M.^a , Christensen, J.^a , Dincer, A.^a , Flores, S.^a , Keefe, S.^a , Chen, C.^a , Su, Y.^e , McDade, E.M.^{b f} , Wang, G.^f , Li, Y.^f , Hassenstab, J.^{b d f} , Aschenbrenner, A.^{b f} , Hornbeck, R.^a , Jack, C.R.^g , Ances, B.M.^{b c f} , Berman, S.B.^h , Brosch, J.R.ⁱ , Galasko, D.^j , Gauthier, S.^k , Lah, J.J.^l , Masellis, M.^m , van Dyck, C.H.ⁿ , Mintun, M.A.^o , Klein, G.^p , Ristic, S.^q , Cairns, N.J.^{b c f} , Marcus, D.S.^a , Xiong, C.^{b r} , Holtzman, D.M.^{b c f} , Raichle, M.E.^{a c f} , Morris, J.C.^{b f} , Bateman, R.J.^{b c f} , Benzinger, T.L.S.^{a b}

^a Mallinckrodt Institute of Radiology, Washington University in St. LouisMO, United States
^b Knight Alzheimer’s Disease Research Center, Washington University in St. Louis MO, United States
^c Hope Center for Neurological Disorders, St. Louis, MO, United States
^d Department of Psychological and Brain Sciences, Washington University in St. Louis MO, United States
^e Banner Health, United States
^f Department of Neurology, Washington University in St. Louis MO, United States
^g Department of Radiology, Mayo Clinic, Rochester, MN, United States
^h Department of Neurology, University of Pittsburgh, Pittsburgh, PA, United States
ⁱ Department of Neurology, Indiana University, Indianapolis, IN, United States
^j Department of Neurosciences, University of California, San Diego, CA, United States
^k Departments of Psychiatry, Neurology and Neurosurgery, Medicine, McGill University, Montreal, Canada
^l Department of Neurology, Emory University, Atlanta, GA, United States
^m Division of Neurology, Sunnybrook Health Sciences Centre; Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute; Department of Medicine, University of Toronto, Toronto, ON, Canada
ⁿ Alzheimer’s Disease Research Unit, Yale University School of Medicine, New HavenCT, United States
^o Avid Radiopharmaceuticals (A Wholly Owned Subsidiary of Eli Lilly and Company), Philadelphia, PA, United States
^p Roche Pharma Research and Early Development, Basel, Switzerland
^q Roche/Genentech Product Development, Neuroscience, Basel, Switzerland
^r Department of Biostatistics, Washington University in St. LouisMO, United States

Abstract
Tauopathy is a hallmark pathology of Alzheimer’s disease with a strong relationship with cognitive impairment. As such, understanding tau may be a key to clinical interventions. In vivo tauopathy has been measured using cerebrospinal fluid assays, but these do not provide information about where pathology is in the brain. The introduction of PET ligands that bind to paired helical filaments provides the ability to measure the amount and distribution of tau pathology. The heritability of the age of dementia onset tied to the specific mutations found in autosomal dominant Alzheimer’s disease families provides an elegant model to study the spread of tau across the course of the disease as well as the cross-modal relationship between tau and other biomarkers. To better understand the pathobiology of Alzheimer’s disease we measured levels of tau PET binding in individuals with dominantly inherited Alzheimer’s disease using data from the Dominantly Inherited Alzheimer Network (DIAN). We examined cross-sectional measures of amyloid-β, tau, glucose metabolism, and grey matter degeneration in 15 cognitively normal mutation non-carriers, 20 asymptomatic carriers, and 15 symptomatic mutation carriers. Linear models examined the association of pathology with group, estimated years to symptom onset, as well as cross-modal relationships. For comparison, tau PET was acquired on 17 older adults with sporadic, late onset Alzheimer disease. Tau PET binding was starkly elevated in symptomatic DIAN individuals throughout the cortex. The brain areas demonstrating elevated tau PET binding overlapped with those seen in sporadic Alzheimer’s disease, but with a greater cortical involvement and greater levels of binding despite similar cognitive impairment. Tau PET binding was elevated in the temporal lobe, but the most prominent loci of pathology were in the precuneus and lateral parietal regions. Symptomatic mutation carriers also demonstrated elevated tau PET binding in the basal ganglia, consistent with prior work with amyloid-β. The degree of tau tracer binding in symptomatic individuals was correlated to other biomarkers, particularly markers of neurodegeneration. In addition to the differences seen with tau, amyloid-β was increased in both asymptomatic and symptomatic groups relative to non-carriers. Glucose metabolism showed decline primarily in the symptomatic group. MRI indicated structural degeneration in both asymptomatic and symptomatic cohorts. We demonstrate that tau PET binding is elevated in symptomatic individuals with dominantly inherited Alzheimer’s disease. Tau PET uptake was tied to the onset of cognitive dysfunction, and there was a higher amount, and different regional pattern of binding compared to late onset, non-familial Alzheimer’s disease. © The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Author Keywords
Alzheimer’s;  amyloid;  FDG;  flortaucipir;  MRI

Document Type: Article
Publication Stage: Final
Source: Scopus

Cognitive, Emotional, and Physical Functioning as Predictors of Paid Employment in People With Stroke, Traumatic Brain Injury, and Spinal Cord Injury
(2019) The American journal of occupational therapy : official publication of the American Occupational Therapy Association, 73 (2), pp. 7302205010p1-7302205010p15. 

Wong, A.W.K.^a , Chen, C.^b , Baum, M.C.^c , Heaton, R.K.^d , Goodman, B.^e , Heinemann, A.W.^f

^a Alex W. K. Wong, PhD, DPhil, is Assistant Professor, Program in Occupational Therapy and Department of Neurology, Washington University School of Medicine, St. Louis, MO;
^b Saw Swee Hock School of Public Health, National University of Singapore, is Assistant Professor, Singapore
^c M. Carolyn Baum, OTR/L, Program in Occupational Therapy, Washington University School of Medicine, is Professor and Elias Michael Executive Director, St. Louis, MO, United States
^d Department of Psychiatry, University of California, is Professor, San Diego, United States
^e BA, Program in Occupational Therapy, Washington University School of Medicine, is Master of Science in Occupational Therapy Student, St. Louis, MO, United States
^f Department of Physical Medicine and Rehabilitation, Northwestern University Feinberg School of Medicine, Director, Center for Rehabilitation Outcomes Research, Allen W. Heinemann ,is Professor, Chicago, United States

Abstract
OBJECTIVE: Our objective was to examine demographic, cognitive, emotional, and physical factors that predict return to paid employment for people after neurological injury. METHOD: Four hundred eighty adults with stroke (n = 149), traumatic brain injury (n = 155), and spinal cord injury (n = 176) completed an occupational outcome questionnaire and physical, emotional, and cognitive assessments at three rehabilitation facilities. RESULTS: Odds of employment were predicted by being married or partnered, having more education, requiring fewer prompts for task sequencing, and having higher inhibitory control (but were not predicted by specific type of injury). Participants who returned to work within 3 mo were more likely to work with the same employer and to take a full-time position than those who returned later. CONCLUSION: Executive functioning, in particular sequencing and inhibitory control, strongly predicts employment and highlights the importance of cognitive strategy training during occupational therapy with people who have sustained neurological injuries. Copyright © 2019 by the American Occupational Therapy Association, Inc.

Document Type: Article
Publication Stage: Final
Source: Scopus