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

<title>Abstract</title> <p>Affective symptoms, such as depression, anxiety and apathy, are highly prevalent in cognitively impaired Lewy body disease (LBD) groups, including Parkinson’s disease dementia and dementia with Lewy bodies. Despite their association with cognitive decline, their underlying neuropathological mechanisms, in the context of cognitive impairment, remain unclear. This systematic review examines the neural correlates of affective symptoms in cognitively impaired LBD based on anatomical, functional, metabolic and neurotransmitter imaging studies. 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. Substantial heterogeneity in imaging techniques, study protocols and cohort characteristics limited direct comparisons between studies. Some evidence implicated changes to intrinsic brain networks, such as default mode and salience networks, in affective symptom manifestation in cognitively impaired LBD, providing a potential neuropathological connection between neuropsychiatric and cognitive decline. Other studies highlighted changes within cortico-striato-limbic pathways typically associated with psychiatric disorders. However, half of the studies reported no significant findings, and only dopaminergic imaging was repeated in more than one study within the same clinical subgroup. This limited and heterogeneous evidence base constrains development of clear mechanistic models regarding affective symptoms in LBD cognitive impairment. This review emphasises the need for more targeted, hypothesis-driven research to understand these underlying mechanisms and inform future therapeutic strategies.</p>