Falls Associate with Neurodegenerative Changes in ATN Framework of Alzheimer’s Disease

Article type: Research Article

Authors: Keleman, Audrey^a | Wisch, Julie K.^b | Bollinger, Rebecca M.^a | Grant, Elizabeth A.^c | Benzinger, Tammie L.^d | Morris, John C.^{b; e} | Ances, Beau M.^{b; d; e; 1; *} | Stark, Susan L.^{a; b; 1}

Affiliations: [a] Program in Occupational Therapy, Washington University in St. Louis, St. Louis, MO, USA | [b] Department of Neurology, Washington University in St. Louis, St. Louis, MO, USA | [c] Department of Biostatistics, Washington University in St. Louis, St. Louis, MO, USA | [d] Department of Radiology, Washington University in St. Louis, St. Louis, MO, USA | [e] Hope Center for Neurological Disorders, Washington University in St. Louis, St. Louis, MO, USA

Correspondence: [*] Correspondence to: Beau Ances, MD, PhD, Department of Neurology, Box 8111, 660 S. Euclid Ave., St. Louis, MO 63110, USA. Tel.: +1 314 747 8423; Fax: +1 314 747 8427; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Background:Behavioral markers for Alzheimer’s disease (AD) are not included within the widely used amyloid-tau-neurodegeneration framework. Objective:To determine when falls occur among cognitively normal (CN) individuals with and without preclinical AD. Methods:This cross-sectional study recorded falls among CN participants (n = 83) over a 1-year period. Tailored calendar journals recorded falls. Biomarkers including amyloid positron emission tomography (PET) and structural and functional magnetic resonance imaging were acquired within 2 years of fall evaluations. CN participants were dichotomized by amyloid PET (using standard cutoffs). Differences in amyloid accumulation, global resting state functional connectivity (rs-fc) intra-network signature, and hippocampal volume were compared between individuals who did and did not fall using Wilcoxon rank sum tests. Among preclinical AD participants (amyloid-positive), the partial correlation between amyloid accumulation and global rs-fc intra-network signature was compared for those who did and did not fall. Results:Participants who fell had smaller hippocampal volumes (p = 0.04). Among preclinical AD participants, those who fell had a negative correlation between amyloid uptake and global rs-fc intra-network signature (R = –0.75, p = 0.012). A trend level positive correlation was observed between amyloid uptake and global rs-fc intra-network signature (R = 0.70, p = 0.081) for preclinical AD participants who did not fall. Conclusion:Falls in CN older adults correlate with neurodegeneration biomarkers. Participants without falls had lower amyloid deposition and preserved global rs-fc intra-network signature. Falls most strongly correlated with presence of amyloid and loss of brain connectivity and occurred in later stages of preclinical AD.

Keywords: Alzheimer’s disease, biomarkers, falls, resting state functional connectivity, volumetrics

DOI: 10.3233/JAD-200192

Journal: Journal of Alzheimer's Disease, vol. 77, no. 2, pp. 745-752, 2020