Circulating neurodegenerative brain injury markers and hip fracture and fall hospitalizations: the Cardiovascular Health Study
Year: 2025
Type: article
Study design: Observational Study
Abstract: Individuals with dementia have a heightened hip fracture and fall risk but whether markers of brain injury are associated with hip fracture and falls is unknown. We tested the hypothesis that higher circulating brain injury markers were associated with increased risk of hip fracture and fall hospitalizations. Brain injury markers were measured in 2141 participants (mean age 77.9 yr; 60% women). Brain injury markers included neurofilament light chain (NfL), a marker of axonal injury; glial fibrillary acidic protein (GFAP), a marker of astrocytic injury; total Tau, whose many functions include neuron microtubule stabilization; and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), a major protein of neurons. Incident hip fractures and hospitalizations for falls were identified through participant report and confirmed with medical records or medicare claims. Hazard ratios were computed for a doubling exposure (log2 transformed brain injury marker) using multivariable-adjusted Cox models. After a median follow-up of 11 yr, 304 incident hip fractures and 284 incident fall hospitalizations occurred. Doubling of GFAP and NfL were associated with a 22% (p = .048) and 42% (p < .001) higher risk of hip fracture, respectively. Additional adjustment for cognitive function, gait speed, grip strength, inflammatory markers, and depressive symptoms had no effect on results. Models that adjusted for all 4 brain markers showed that only NfL was independent of the other markers. Neurofilament light chain was also associated with a 47% increase risk of hospitalization for falls. There was no association of total Tau or UCH-L1 with hip fracture or falls. GFAP was also unrelated to fall hospitalizations. Neurofilament light chain was independently associated with an incident risk of hip fracture and fall hospitalizations. These results suggest that subclinical degrees of brain injury may contribute to falls and hip fracture. Future research is needed to test whether the association between NfL and hip fracture is independent of falls.
DOI: 10.1093/jbmr/zjaf155
Institutions: University of Pittsburgh, University of Washington, Minneapolis VA Health Care System, Minneapolis VA Medical Center, Kaiser Permanente, Emory University, Augusta University, University of California, Davis, Brigham and Women's Hospital, Harvard University, Beth Israel Deaconess Medical Center
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1023702118, G1101846420, G1220223050, G125972088, G1261314546, CORONARY HEART DISEASE AND STROKE, CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84, G1549444152, CORONARY HEART DISEASE AND STROKE, G2194386449, CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84, G2391884931, G247538147, G2553531566, CORONARY HEART DISEASE &STROKE IN THE ELDERLY, G270907595, G2800149121, ACTIVE Phase III: JHU Field Site, G3045517347, G3220743633, G3256118428, G34347772, CHS research resources for the cardiovascular health of older adults, G3762349130, CENTRAL BLOOD ANALYSIS LABORATORY FOR CHS, G423252844, G4276072587, G5479317095, G581887176, G585648573, CHS Events Follow-up Study, G6226795708, G624497702, G6566566152, G659495149, CHS-Transition Phase, G7176672723, Osteoporotic Fractures in Men_MrOS Renewal_Birmingham, G870119955, G8827260454, Training in the Epidemiology of Aging, Cardiovascular Epidemiology Training Program, Infrastructure for mentored access to CHS data and specimens, G905887895
OpenAlex ID: W4415516496