Anxiety in late-life depression: Associations with brain volume, amyloid beta, white matter lesions, cognition, and functional ability

Objectives: Late-life depression (LLD) is common and frequently co-occurs with neurodegenerative diseases of aging. Little is known about how heterogeneity within LLD relates to factors typically associated with neurodegeneration. Varying levels of anxiety are one source of heterogeneity in LLD. We examined associations between anxiety symptom severity and factors associated with neurodegeneration, including regional brain volumes, amyloid beta (Aβ) deposition, white matter disease, cognitive dysfunction, and functional ability in LLD. Participants and Measurements: Older adults with major depression (N = 121, Ages 65-91) were evaluated for anxiety severity and the following: brain volume (orbitofrontal cortex [OFC], insula), cortical Aβ standardized uptake value ratio (SUVR), white matter hyperintensity (WMH) volume, global cognition, and functional ability. Separate linear regression analyses adjusting for age, sex, and concurrent depression severity were conducted to examine associations between anxiety and each of these factors. A global regression analysis was then conducted to examine the relative associations of these variables with anxiety severity. Results: Greater anxiety severity was associated with lower OFC volume (β = -68.25, t = -2.18, p =.031) and greater cognitive dysfunction (β = 0.23, t = 2.46, p =.016). Anxiety severity was not associated with insula volume, Aβ SUVR, WMH, or functional ability. When examining the relative associations of cognitive functioning and OFC volume with anxiety in a global model, cognitive dysfunction (β = 0.24, t = 2.62, p =.010), but not OFC volume, remained significantly associated with anxiety. Conclusions: Among multiple factors typically associated with neurodegeneration, cognitive dysfunction stands out as a key factor associated with anxiety severity in LLD which has implications for cognitive and psychiatric interventions.