Neuroimaging of affective symptoms in Lewy body dementia: A systematic review

Background Affective symptoms, such as depression, anxiety and apathy, are highly prevalent in Lewy body diseases (LBDs), including both Parkinson’s disease and dementia with Lewy bodies. Despite their association with cognitive decline, their underlying neuropathological mechanisms, in the context of cognitive impairment, remain poorly understood. This systematic review examines the neural correlates of affective symptoms in cognitively impaired LBD based on anatomical, functional, metabolic and neurotransmitter imaging studies. Methods Literature searches conducted using PubMed, PsychINFO and Web of Science, identified eighteen eligible studies, including 785 participants, that included assessments of depression, anxiety or apathy; an acceptable method of neuroimaging; and participants with a diagnosis of LBD and evidence of cognitive impairment. A narrative synthesis of their findings is provided. Results Significant heterogeneity in imaging techniques, study protocols and cohort characteristics were identified. Half of the studies did not report significant findings, and only dopaminergic imaging was used by more than one study within the same clinical subgroup. Some evidence highlights involvement of intrinsic brain networks, such as the default mode and salience networks, in affective symptom manifestation. Additionally, two studies found associations between affective symptoms and cholinergic denervation, providing a potential neuropathological connection between neuropsychiatric and cognitive decline in LBD. Conclusions The paucity of studies, and heterogeneity within them, significantly hinder the development of robust hypotheses regarding the neuropathology of affective symptoms in LBD cognitive impairment. This review therefore emphasises the need for more targeted research to understand these underlying mechanisms to inform future therapeutic strategies.