CSF level of β-amyloid peptide predicts mortality in Alzheimer's disease

ObjectiveAlzheimer's disease (AD) is the sixth leading cause of death, with an average survival estimated between 5 and 10years after diagnosis. Despite recent advances in diagnostic criteria of AD, few studies have used biomarker-based diagnostics to determine the prognostic factors of AD. We investigate predictors of death and institutionalization in a population of AD patients with high probability of AD physiopathology process assessed by positivity of three CSF biomarkers.MethodsThree hundred twenty-one AD patients with abnormal values for CSF beta-amyloid peptide (A42), tau, and phosphorylated tau levels were recruited from a memory clinic-based registry between 2008 and 2017 (Lariboisiere hospital, Paris, France) and followed during a median period of 3.9years. We used multivariable Cox models to estimate the hazard ratio (HR) of death and institutionalization for baseline clinical data, genotype of the apolipoprotein E (APOE), and levels of CSF biomarkers.ResultsA total of 71 (22%) patients were institutionalized and 57 (18%) died during the follow-up. Greater age, male sex, lower MMSE score, and lower CSF A42 level were associated with an increased risk of mortality. One standard deviation lower CSF A42 (135pg/mL) was associated with a 89% increased risk of death (95% CI=1.25-2.86; p=0.002). This association was not modified by age, sex, education, APOE epsilon 4, and disease severity. There was no evidence of an association of tau CSF biomarkers with mortality. None of the CSF biomarkers were associated with institutionalization.ConclusionsLower CSF A42 is a strong prognostic marker of mortality in AD patients, independently of age or severity of the disease. Whether drugs targeting beta-amyloid peptide could have an effect on mortality of AD patients should be investigated in future clinical trials.