Using the A/T/N Framework to Examine Driving in Preclinical AD

Catherine M Roe, Ganesh M Babulal, Sarah H Stout, Brian R Ott, David B Carr, Monique M Williams, Tammie L S Benzinger, Anne M Fagan, David M Holtzman, Beau M Ances, John C Morris, Catherine M Roe, Ganesh M Babulal, Sarah H Stout, Brian R Ott, David B Carr, Monique M Williams, Tammie L S Benzinger, Anne M Fagan, David M Holtzman, Beau M Ances, John C Morris

Abstract

The A/T/N classification system is the foundation of the 2018 NIA-AA Research Framework and is intended to guide the Alzheimer disease (AD) research agenda for the next 5–10 years. Driving is a widespread functional activity that may be particularly useful in investigation of functional changes in pathological AD before onset of cognitive symptoms. We examined driving in preclinical AD using the A/T/N framework and found that the onset of driving difficulties is most associated with abnormality of both amyloid and tau pathology, rather than amyloid alone. These results have implications for participant selection into clinical trials and for the application time of interventions aimed at prolonging the time of safe driving among older adults with preclinical AD.

Keywords: biomarkers; driving; preclinical Alzheimer disease.

Conflict of interest statement

Conflicts of Interest/Disclosures Dr. Roe reports no disclosures. Dr. Babulal reports no disclosures. Ms. Stout reports no disclosures. Dr. Ott reports that neither he nor his family owns stock or has equity interest (outside of mutual funds or other externally directed accounts) in any pharmaceutical or biotechnology company. Dr. Ott has participated or is currently participating in clinical trials of antidementia drugs sponsored by the following companies: Janssen, Eli Lilly/Avid, Merck, AbbVie, Biogen, and TauRx. Dr. Ott has served as a consultant for Accera and Amgen. He also receives research support from Long Term Care Group. Dr. Williams reports no disclosures. Dr. Benzinger reports that neither she nor her family owns stock or has equity interest (outside of mutual funds or other externally directed accounts) in any pharmaceutical or biotechnology company. Dr. Benzinger is currently participating in clinical trials of antidementia drugs from Eli Lilly and Company, Biogen, and Janssen. She receives research support from Eli Lilly/Avid Radiopharmaceuticals, including provision of the PET tracer florbetapir used in this study, and precursor for the tracer flortaucipir, used in this study and is funded by NIH grants # P50AG005681; P01AG003991; P01AG026276 and UF01AG032438. Dr. Fagan is on the scientific advisory boards of IBL International, Roche Diagnostics and AbbVie and is a consultant for Biogen, Araclon/Grifols and DiamiR. Dr. Fagan reports no conflicts of interest. Dr. Holtzman receives funding from C2N Diagnostics SAB, Genentech SAB, and Proclara SAB. He is a consultant for AbbVie and Glaxosmithkline. His lab receives grants from the NIH, the JPB Foundation, Cure Alzheimer’s Fund, the Tau Consortium, Eli Lilly, and C2N Diagnostics. Dr. Holtzman reports no conflicts of interest. Dr. Ances reports no disclosures.

Figures

Figure 1
Figure 1
Time from baseline in years to receiving a Marginal or Fail rating as a function of A/T/N parent group membership. Numbers below the X-axis indicate the number of participants at risk at that time.
Figure 2
Figure 2
Time from baseline in years to receiving a Marginal or Fail rating as a function of A/T/N parent group membership, including participants with suspected non-Alzheimer’s pathophysiology (SNAP). Numbers below the X-axis indicate the number of participants at risk at that time.

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