Brain Structure and Function Related to Depression in Alzheimer's Disease: Contributions from Neuroimaging Research

The development of minimally invasive in vivo methods for imaging the brain has allowed for unprecedented advancement in our understanding of brain-behavior relationships. Structural, functional, and multimodal neuroimaging techniques have become more sophisticated in detecting structural and physiological abnormalities that may underlie various affective disorders and neurological illnesses such as depression in Alzheimer's disease (AD). In general, neuroimaging studies of depression in AD investigate whether depression is associated with damage to structures in specific neural networks involving frontal and subcortical structures or with functional disruption of cortical neural systems. This review provides an overview of how various imaging modalities have contributed to our understanding of the neurobiology of depression in AD. At present, the literature does not conclusively support any specific pathogenesis for depression, and it is not clear whether patients with AD and depression have histopathological and neurochemical characteristics that contribute to mood symptoms that are different from cognitively intact individuals with depression. Neuroimaging studies suggest that atrophy of temporal or frontal structures, white matter lesions in frontal lobe or subcortical systems, reduced activity in dorsolateral frontal cortex, or small vessel cerebrovascular disease may be associated with depression in AD. Conceptual, clinical, and methodological challenges in studying this relationship are discussed. Further work is needed to understand the specific brain structures, relevant white matter tracts, and interactions among them that are most important. This review concludes with potential directions for future research.