Development of Apathy, Anxiety, and Depression in Cognitively Unimpaired Older Adults: Effects of Alzheimer's Disease Pathology and Cognitive Decline

BACKGROUND: The impact of Alzheimer's disease (AD) pathology and cognitive deficits on longitudinal neuropsychiatric symptoms is unclear, especially in early disease stages. METHODS: Cognitively unimpaired older adults (N = 356) enrolled in the prospective Swedish BioFINDER study were examined. Neuropsychiatric assessments encompassed the Apathy Evaluation Scale and the Hospital Anxiety and Depression Scale, performed biennially (together with tests of global cognition) for up to 8 years. Biomarkers were measured in cerebrospinal fluid or plasma at baseline. Magnetic resonance imaging quantified white matter lesions. We used linear mixed-effect models to test associations between baseline AD biomarkers (for annyloid-beta [A beta], tau, and neurodegeneration) and white matter lesions with longitudinal neuropsychiatric symptoms (apathy, anxiety, and depressive symptoms). We also tested associations between changes in cognition and changes in neuropsychiatric symptoms. Finally, we tested if change in cognition mediated the effects of different brain pathologies on neuropsychiatric symptoms. RESULTS: A beta pathology at baseline was associated with increasing levels of apathy (beta = -0.284, p = .005) and anxiety (beta = -0.060, p = .011) longitudinally. More rapid decline of cognition over time was related to increasing levels of apathy. The effects of baseline A beta pathology on longitudinal apathy were partly mediated by changes in cognitive performance (proportion mediated 23%). CONCLUSIONS: A beta pathology may drive the development of both apathy and anxiety in very early stages of AD, largely independent of cognitive change. The effect of A beta on apathy is only partially conveyed by worse cognition. Together, these findings highlight certain neuropsychiatric symptoms as early manifestations of AD.

Automated summary

This study found that AD pathology in early stages of the disease is associated with the development of apathy and anxiety, independent of cognitive changes. The effects of A beta pathology on apathy are partially mediated by changes in cognitive performance.