Significant differences between early and late onset depression suggest different aetiological mechanisms, in accordance with a theory of "cerebrovascular" depression of late onset. Greater duration of depressive symptoms, signs and treatment does not appear to have a measurable impact on white matter signal in MRI scans.

Executive function and processing speed appear to represent important cognitive deficits in late-life depression, which contribute to deficits in other domains, and are related to reductions in anisotropy in frontal tracts.

The present work strongly supports the hypothesis that white matter abnormalities in frontal-subcortical and limbic networks play a key role in LLD even in the absence of changes in resting functional connectivity and gray matter. Factors that could contribute to the lack of significant differences in gray matter and functional connectivity measures, including current symptom severity, medication status, and age of participants with LLD, are discussed.

Subtle biases in the processing of emotional information may exist in the unaffected first-degree relatives of those with depression. As such, this may represent a familial vulnerability factor to developing a depressive illness.

Overall, the results were compatible with the vascular hypothesis, and provided some support for the glucocorticoid cascade hypothesis.