Longitudinal Changes in Anger, Anxiety, and Fatigue Are Associated with Cerebrospinal Fluid Biomarkers of Alzheimer\u27s Disease

Alzheimer\u27s disease (AD) studies in cognitively normal (CN) older adults aged≥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 (Aβ 42/Aβ 40, t-Tau/Aβ 42, p-Tau/Aβ 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