Functional Neuroanatomy Correlates of Worry in Older Adults

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Severe worry, a transdiagnostic symptom particularly pernicious for the health of older adults, is associated with increased risk of conversion from mild cognitive impairment to Alzheimer's disease, and with increased risk of stroke and other cardiovascular events. Severe worry, defined as intense, uncontrollable worry associated with interruption in functioning and reduced quality of life, is surprisingly prevalent in the community, with 20% of older adults reporting severe worry. While there are no studies regarding the lifespan incidence of severe worry, we can draw inferences based on the incidence of Generalized Anxiety Disorder (GAD), for which up to half of the cases are late-onset. These data suggest a particularly heavy burden of severe worry loaded in the second half of life, pointing toward an increasing role for the neuropathologic changes of aging. Identifying neural mechanisms for late-life worry is a crucial step for understanding why worry crops up in the latter part of life, and for eventually improving treatment. Our team has made significant headway in this regard. Through her K23 award, which was focused on the neuroanatomy of late-life GAD, the PI has shown that neural markers of worry differ across ages. Preliminary results indicate that older worriers have impaired functional connectivity both at rest and during worry reappraisal. In addition to documenting age-related brain pathology, our preliminary findings may explain why current treatment choices, such as cognitive-behavioral therapy, which relies on worry reappraisal to interrupt the worry loop, have proven less effective in reducing worry severity in older adults and may actually be counterproductive. However, the examination of the neural architecture underlying worry has garnered relatively little attention, especially with regard to the mechanism underlying essential processes such as worry induction and reappraisal. This project will test a mechanistic model anchored in systems neuroscience and aimed at characterizing the functional neuroanatomy of severe worry in older adults. We focus on the roles of three canonical brain networks: 1) the network subserving the “resting” state, a time when many worriers would worry naturally [the Default Mode], 2) the network involved in the detection of environmentally salient, often threatening information, ideally allowing us to anchor the neural features of worry in the RDoC's threat reactivity categories [the Salience Network], and 3) the network active during cognitive efforts to reappraise worry [the Executive Control]. We will characterize the specificity of this model for aging, by testing the moderating effect of brain aging, as measured by white matter disease. The phenomenological layout of worry from everyday reactions to stress to anxious perseveration, together with the distribution of worry across various disorders, makes this investigation fit ideally within the RDoC framework. We plan to recruit a stratified sample of 160 participants (age 50 to 85) representing a wide range of worry severity. As NIMH moves away from DSM categorical disorders, identifying the neural basis of pathological transdiagnostic features, such as worry, will be of increasing importance for developing targeted interventions. 1