CSF biomarkers of alzheimer disease

Objectives: To test whether CSF Alzheimer disease biomarkers (β-amyloid 42 [Aβ₄₂], tau, phosphorylated tau at threonine₁₈₁ [ptau181], Ptau/Aβ₄₂, and ptau181/Aβ₄₂) predict future decline in noncognitive outcomes among individuals cognitively normal at baseline. Methods: Longitudinal data from participants (N 5 430) who donated CSF within 1 year of a clinical assessment indicating normal cognition and were aged 50 years or older were analyzed. Mixed linear models were used to test whether baseline biomarker values predicted future decline in function (instrumental activities of daily living), weight, behavior, and mood. Clinical Dementia Rating Sum of Boxes and Mini-Mental State Examination scores were also examined. Results: Abnormal levels of each biomarker were related to greater impairment with time in behavior(p<0.035) and mood (p<0.012) symptoms, and more difficulties with independent activities of daily living (p<0.012). However, biomarker levels were unrelated to weight change with time (p>0.115). As expected, abnormal biomarker values also predicted more rapidly changing Mini-Mental State Examination (p<0.041) and Clinical Dementia Rating Sum of Boxes (p<0.001) scores compared with normal values. Conclusions: CSF biomarkers among cognitively normal individuals are associated with future decline in some, but not all, noncognitive Alzheimer disease symptoms studied. Additional work is needed to determine the extent to which these findings generalize to other samples.