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), phosphorylat-
ed tau (P-tau), and total tau (T-tau) with time to nursing home placement (NHP) and life expectan-
cy 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 ab-
normal 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 sex-
and-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 survi-
val time. However, the biomarkers reflect the central pathophysiologies of AD. In particular, patho-
logic tau is associated with more advanced disease, younger age at onset, and earlier death.
High tau levels in cerebrospinal fluid predict nursing home placement and rapid progression in Alzheimer’s disease
