Longitudinal Changes in Anger, Anxiety, and Fatigue Are Associated with Cerebrospinal Fluid Biomarkers of Alzheimer's Disease

Alzheimer's disease (AD) studies in cognitively normal (CN) older adults age >= 65 suggest depression is associated with molecular biomarkers (imaging and cerebrospinal fluid [CSF]). This study used linear mixed models (covariance pattern model) to assess whether baseline CSF biomarkers (A beta(42)/A beta(40), t-Tau/A beta(42) , p-Tau/A beta(42)) predicted changes in non-depressed mood states in CN older adults (N= 248), with an average of three follow-up years. Participants with higher levels of CSF biomarkers developed more anger, anxiety, and fatigue over time compared to those with more normal levels. Non-depressed mood states in preclinical AD may be a prodrome for neuropsychiatric symptoms in symptomatic AD.