The Relationship Between Gait Task Performance and Plasma Biomarkers for Alzheimer’s Disease in Cognitively Unimpaired Older Adults and Patients with Mild Cognitive Impairment

Jordan Sergio,1,2,* Ashley Price,1,2,* Peter J Snyder,1,3 Savannah A Doster,1,2 Maeve Durkin,1,2 Jennifer R Strenger,4 Louisa I Thompson,2,5 Megan Stradtman,2,5 Stuart Sinoff,6 Jessica Alber1,2 1George & Anne Ryan Institute for Neuroscience, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island, USA; 2Butler Hospital Memory & Aging Program, Warren Alpert Medical School of Brown University, Providence, RI, USA; 3Department of Neurology, Alpert Medical School of Brown University, Providence, RI, USA; 4Postbaccalaureate Premedical Program, Bryn Mawr College, Bryn Mawr, PA, USA; 5Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University, RI, USA; 6Neuroscience Institution, Morton Plant Hospital, BayCare Medical Group, Clearwater, FL, USA*These authors contributed equally to this workCorrespondence: Jessica Alber, George & Anne Ryan Institute for Neuroscience, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, 130 Flagg Road, Kingston, RI, 0288, USA, Email [email protected]: The Timed Up and Go (TUG) is a 20-foot gait assessment, with TUG-dual task (DT) serial subtractions to determine dual-task cost. Alzheimer’s disease (AD) risk is established using plasma biomarkers and APOE genotyping.Methods: We investigated: 1) TUG/TUG-DT differences between AD low-risk cognitively unimpaired (CU) older adults (N = 74), AD high-risk CU older adults (N = 87), and mild cognitively impaired (MCI) older adults (N = 33) and 2) the relationship between TUG/TUG-DT performance and plasma biomarkers. One hundred and ninety-four older adults ages 55– 80 completed TUG/TUG-DT, a fasting blood draw, and APOE genotyping. Scores on the Clinical Dementia Rating Scale (CU = 0; CI = ≥ 0.5) and Montreal Cognitive Assessment (CU ≥ 24; CI = ≤ 23) determined whether participants were placed into the CU low-risk, CU high-risk, or MCI groups. Risk level for CU participants were assessed by APOE genotyping. Those participants who carried at least one copy of the APOE ϵ4 allele were designated to the high-risk group (n = 87). Participants with no APOE ϵ4 allele were assigned to the low-risk group (n = 75).Results: MCI participants took longer to perform the TUG than CU participants (p < 0.001). CU high-risk and MCI group performed similarly on step counts, while the CU low-risk took significantly fewer steps (p< 0.001). Speed predicted whether someone was below an AD-risk threshold for pTau217 in CU participants (n = 150). Exploratory generalized additive models showed plasma biomarkers predicted gait metrics in CU groups.Conclusion: Step count may be more sensitive, compared to speed alone, in identifying those in preclinical AD stages. Gait metrics (speed and efficiency) played a key role as a clinical manifestation of early AD pathophysiology determined by blood-based biomarker concentration. Combining these assessments offers a multidimensional, cost-effective approach for preclinical-AD screening and potential early intervention.Keywords: blood biomarkers, timed up and go, gait metrics, pTau217, pTau181