Cobalt and titanium levels in the brain are associated with Alzheimer’s disease pathology but not cognition: A study of older adults with and without total joint replacement

Alzheimer's disease (AD) and total joint arthroplasty are prevalent and often concomitant in older adults, but an etiologic link is debated. Since wear particles are an inevitable side product of total joint arthroplasty (TJA), we hypothesized that older adults with TJA agglomerate higher-than-normal concentrations of implant alloy elements caused by the dissemination of debris from the implants, resulting in a pathological reaction. A cross-sectional analysis was conducted among 701 autopsied participants of an ongoing longitudinal cohort (Memory and Aging Project (MAP)) of whom postmortem neuropathologic data was available and implant-related metals (cobalt, titanium) were quantified in four brain regions by inductively coupled mass-spectrometry. MAP participants are enrolled without known dementia at baseline and followed annually for cognitive assessments using 19-test battery. In the analytical sample, 229 had TJA (total hip arthroplasty, total knee arthroplasty, and total shoulder arthroplasty) and n = 472 had no total joint. Due to a higher likelihood of cobalt release in total hip arthroplasty, the TJA group was subdivided into a hip (n = 146) and a knee/shoulder (n = 83) group. We used regression and linear mixed-effects models, adjusted for demographics and apolipoprotein E ε4 status, to examine associations between metals, AD pathology and cognitive decline. Cobalt content of brain tissue was 8.9 % higher in the total hip arthroplasty group than in the no-TJA group (p = 0.003). Cobalt-containing particles were identified within brain tissue using scanning electron microscopy. In the inferior temporal cortex, cobalt was positively associated (p = 0.0004) and titanium was negatively associated (p = 0.038) with amyloid-beta load, but had no association with cognition. These results warrant monitoring the potential impact of metal implant debris on brain health. STATEMENT OF SIGNIFICANCE: This study is of great clinical significance because Alzheimer's disease (AD) and total joint arthroplasty (TJA)-the end-stage treatment of osteoarthritis-affect large and overlapping groups in our aging population. There is limited knowledge about the relationship between the prominent TJA implant metals cobalt and titanium and the pathogenesis of AD. This study shows that Co28Cr6Mo and Ti6Al4V implant alloy particles-most likely from a subset of total hip replacements with accelerated wear or tribocorrosion-can disseminate to the brain and be associated with increased cobalt and titanium concentrations. Cobalt was associated with greater AD pathology in the inferior-temporal cortex, even after correction for other known AD risk factors. However, there was no correlation with cognitive decline. Titanium was negatively associated with AD pathology, but titanium oxide appeared to be abundant in the brain from sources other than joint replacements.