Abstract
Cerebrospinal Fluid (CSF) biomarkers are associated with conversion from mild cognitive impairment to Alzheimer's Disease (AD), but their predictive value for later end-points has been less evaluated with inconsistent results. We investigated potential relationships between CSF amyloid-β1-42 (Aβ42), Phosphorylated tau (P-tau), and Total tau (T-tau) with time to Nursing Home Placement (NHP) and life expectancy after diagnosis. This prospective observational study included 129 outpatients clinically diagnosed with mild-to-moderate AD who underwent a lumbar puncture. The CSF biomarkers were analysed with xMAP technology. Dates of institutionalisation and death were recorded. After 20 years of follow-up, 123 patients (95%) were deceased. The participants with abnormal P-tau and T-tau (A+ T+ (N)+) died earlier than those with normal P-tau/abnormal T-tau (A+ T- (N)+) (mean, 80.5 vs. 85.4 years). Linear associations were demonstrated between lower Aβ42 and shorter time to NHP (p = 0.017), and higher P-tau and younger age at death (p = 0.016). No correlations were detected between survival after AD diagnosis and CSF biomarkers. In sexand- age-adjusted Cox regression models, higher P-tau and T-tau were independent predictors of shorter lifespan after diagnosis. In multivariate Cox models, older age and lower baseline cognitive status, but not elevated tau, significantly precipitated both institutionalisation and death. These findings suggest that CSF biomarker levels plateau in the dementia phase of AD, which may limit their possible relationships with clinical end-points, such as NHP and survival time. However, the biomarkers reflect the central pathophysiologies of AD. In particular, pathologic tau is associated with more advanced disease, younger age at onset, and earlier death.
Highlights
After a long neurodegenerative disease process with decreasing cognitive ability and a continuous loss of instrumental and basic activities of daily living (ADL) performance, patients with Alzheimer’s disease (AD) reach the end-points of nursing home placement (NHP) and death [1]
In multivariate Cox models, older age and lower baseline cognitive status, but not elevated tau, significantly precipitated both institutionalisation and death. These findings suggest that Cerebrospinal Fluid (CSF) biomarker levels plateau in the dementia phase of Alzheimer’s Disease (AD), which may limit their possible relationships with clinical end-points, such as Nursing Home Placement (NHP) and survival time
There is an enhanced interest in the tau protein and its role in pathophysiology, and clinical trials of immunization with anti-tau antibodies are ongoing. In this longitudinal study in a routine clinical setting, we found that the individuals with both pathologic tau and neuronal injury died at a younger age than those without pathologic tau but with neurodegeneration, suggesting a subtype of AD with earlier onset and a more aggressive disease
Summary
After a long neurodegenerative disease process with decreasing cognitive ability and a continuous loss of instrumental and basic activities of daily living (ADL) performance, patients with Alzheimer’s disease (AD) reach the end-points of nursing home placement (NHP) and death [1]. Factors affecting both the institutionalisation process and survival in AD are complex and depend on socio-demographic and clinical features. A previous study demonstrated that the CSF levels of phosphorylated tau (P-tau) and total tau (T-tau) become pathological later in the course of AD compared with amyloid-β1-42 (Aβ42) [10]. Cerebrospinal Fluid (CSF) biomarkers are associated with conversion from mild cognitive impairment to Alzheimer’s Disease (AD), but their predictive value for later end-points has been less evaluated with inconsistent results
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
