Postmortem brain studies of older drivers killed in car accidents indicate that many had Alzheimer disease (AD) neuropathologic changes. We examined whether AD biomarkers are related to driving performance among cognitively normal older adults. Individuals with normal cognition, aged 65+ years, and driving at least once per week, were recruited. Participants (N=129) took part in clinical assessments, a driving test, and positron emission tomography imaging with Pittsburgh compound B (PIB) and/or cerebrospinal fluid (CSF) collection. General linear models tested whether the number of driving errors differed as a function of each of the biomarker variables (mean cortical binding potential for PIB, and CSF Aβ42, tau, ptau181, tau/Aβ42, ptau181/Aβ42). Higher ratios of CSF tau/Aβ42, ptau181/Aβ42, and PIB mean cortical binding potential, were associated with more driving errors (P<0.05). Preclinical AD may have subtle cognitive and functional effects, which alone may go unnoticed. However, when combined, these changes may impact complex behaviors such as driving.
*Charles F. and Joanne Knight Alzheimer’s Disease Research Center
Departments of †Neurology
¶¶Pathology and Immunology
¶Center for Clinical Studies
#Division of Biostatistics, Washington University School of Medicine, St. Louis, MO
§The Rehabilitation Institute of St. Louis
††The Alzheimer’s Disease & Memory Disorders Center, Alpert Medical School of Brown University
‡‡Rhode Island Hospital, Providence, Rhode Island
Supported by the National Institute on Aging (R01AG043434, R01AG43434-03S1, P50AG005681, P01AG003991, P01AG026276, and K12 HD001459), Fred Simmons and Olga Mohan, the Farrell Family Research Fund, and the Charles and Joanne Knight Alzheimer’s Research Initiative of the Washington University Knight Alzheimer’s Disease Research Center (ADRC). Imaging facilities were supported by the Washington University Institute of Clinical and Translational Sciences Grant UL1TR000448 from the National Center for Advancing Translational Sciences of the National Institutes of Health. Imaging analyses used the services of the Neuroimaging Informatics and Analysis Center, supported by National Institutes of Health Grant 5P30NS048056.
C.M.R. receives funding from NIH Grants R01AG043434, R01AG43434-03S1, P50AG005681, P01AG003991, and P01AG026276. P.P.B. receives funding from the Missouri Department of Transportation and NIMH/OBSSR R01MH099011; Board Membership: American Occupational Therapy Board and Specialty Certification (BASC); Consultant: Traffic Injury Research Foundation (TIRF). D.M.H. receives funding from R01AG043434, P01AG026276, P01AG003991, and R01AG049369. N.G. receives funding from NIH K12HD001459, P01AG026276, R01AG043434, U01AG045390, and U54NS092089-01, Tau Consortium and has participated or is currently participating in clinical trials of antidementia drugs sponsored by the following companies: Bristol Myers Squibb, Eli Lilly/Avid Radiopharmaceuticals, Janssen Immunotherapy, Novartis, Pfizer, Wyeth, SNIFF (The Study of Nasal Insulin to Fight Forgetfulness) study, and A4 (the anti-amyloid treatment in asymptomatic Alzheimer’s disease) trial. G.M.B. receives funding from NIH grants R01AG043434 and R01AG43434-03S1. A.J. is funded by R01AG043434, Missouri Department of Transportation, Department of Defense. S.F. is funded by NIH Grants: SP01AG02627610, SR01AG03411905, SR01AG03865104, U01AG016976, 2UF1AG03243807, 2P50AG00569132, 5P0AG00568132, and 5R01AG043434. C.X. is funded by NIH Grants P50AG005681, U01AG16975, P01NS074969, P01AG026276, R01AG038651, R01AG034119, P01AG02676 (supplement), PO1AG0399131, UFAG032438, and R01AG043434; DIAN TU CT Clinical Trial Funds; and Grant A214296S from the Bright Focus Foundation. E.A.G. is funded by P50AG05681, P01AG03991, and P01AG26276. B.R.O. receives funding for clinical trials and instrument development from Eli Lilly, Avid, Merck, TauRx, Biogen, Long Term Care Group, the Alzheimer’s Disease Cooperative Study, and the Alzheimer’s Therapeutic Research Institute. He is a consultant for Accera and Amgen. He has received honoraria for CME programs from the American Academy of Neurology, MedScape, and the National Highway Traffic and Safety Administration. He is funded by NIH Grant R03AG046472 and Alzheimer’s Association Grant NPSASA-15-362133. D.M.H. receives funding from C2N Diagnostics SAB, Genentech SAB, and Neurophage SAB. He is a consultant for AbbVie. His lab receives Grants from the NIH, the JPB Foundation, Cure Alzheimer’s Fund, the Tau Consortium, Eli Lilly, and C2N Diagnostics. T.L.S.B. is funded by NIH Grants # P50AG005681, UF1AG032438, U01AG042791, 2P01AG003991, P01AG026276, R01AG043434, U54 MH091657, and the Barnes-Jewish Hospital Foundation. A.M.F. receives funding from R01AG043434, P50AG005681, P01AG003991, P01AG026276, and UF1AG032438. She is on the scientific advisory boards of IBL International and Roche and is a consultant for AbbVie, Novartis, and DiamiR. D.B.C. receives research funding from the NIH (R01AG043434), the Missouri Department of Transportation, The Rehabilitation Institute of St. Louis, and State Farm and has Consulting Relationship with The Traffic Injury Research Foundation, Medscape, and the AAA Foundation for Traffic Safety. J.C.M. and his family do not own stock or have equity interest (outside of mutual funds or other externally directed accounts) in any pharmaceutical or biotechnology company. J.C.M. has participated or is currently participating in clinical trials of antidementia drugs sponsored by the following companies: Janssen Immunotherapy, Pfizer, Eli Lilly/Avid Radiopharmaceuticals, SNIFF (The Study of Nasal Insulin to Fight Forgetfulness) study, and A4 (The Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease) trial. J.C.M. has served as a consultant for Lilly USA, and Charles Dana Foundation. He receives research support from Eli Lilly/Avid Radiopharmaceuticals and is funded by NIH Grants # P50AG005681, P01AG003991, P01AG026276, and UF1AG032438. The remaining authors declare no conflicts of interest.
Reprints: Catherine M. Roe, PhD, 660 S. Euclid Avenue, Campus Box 8111, St. Louis, MO 63110 (e-mail: firstname.lastname@example.org).
Received December 30, 2015
Accepted March 8, 2016