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Cerebrospinal Fluid Biomarker Levels as Markers for Nursing Home Placement and Survival Time in Alzheimer’s Disease

[ Vol. 18 , Issue. 7 ]

Author(s):

Carina Wattmo*, Kaj Blennow and Oskar Hansson   Pages 573 - 584 ( 12 )

Abstract:


Background: 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.

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords:

Alzheimer's disease, nursing home placement, mortality, longitudinal study, predictors, CSF biomarkers, AT(N), Tau.

Affiliation:

Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, SE-205 02 Malmö, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, SE-431 80 Mölndal, Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, SE-205 02 Malmö



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