Dementia and CSF-biomarkers for Alzheimer's disease predict mortality after acute hip fracture.

Abstract

Mortality is high after an acute hip fracture (AHF) surgery. Are cognitive impairment and/or altered levels of Alzheimer's Disease (AD)-biomarkers in cerebrospinal fluid (CSF) predictors of mortality in AHF-patients, as retrospective studies indicate? Prospective single-center study including 373 AHF-patients, operated in spinal anesthesia. Cognitive status was evaluated by clinical dementia rating (CDR); CSF was analyzed for AD-biomarker concentrations (total tau (T-tau), phosphorylated tau (P-tau), amyloid beta ratio (Aβ42/Aβ40). CDR and biomarker levels were related to mortality up to one-year post-surgery, using univariate logistic regression analysis. Survival analyses showed that mortality was associated to the degree of dementia. In the entire patient cohort 30-, 90-, and 365-day mortality rates were 7.2%, 15.5%, and 25.5%, respectively, but only 2.7%, 5.5%, and 12.6%, for cognitively intact vs 16.3%, 31.7%, and 42.3% for demented patients (OR=2.2-2.8 [CI=1.6-4.9]; P=.0001). High CSF T-tau (OR=1.19 [CI=1.05-1.33]; P=.004) and low Aβ42/Aβ40-ratio (OR=0.85 [CI=0.74-0.97]; P=.017) were associated with increased 90-day mortality. Analysis of 4 subgroups (Cognitive impairment ± and Biomarkers ±) showed significant associations of dementia and CSF biomarker concentrations to mortality after an AHF. Even cognitively intact patients presenting with abnormal AD-biomarkers showed an increased 90-day mortality which, however, was statistically insignificant. Cognitive impairment and altered CSF biomarker concentrations indicative of AD pathology can predict increased mortality in patients with an AHF, and so probably even before clinical dementia diagnosis by early biomarker analysis; a notion that may have substantial clinical implications by improving perioperative treatment and postoperative rehabilitation.