Neuropathological correlates of late-life depression

The relationship between depression and both dementia and cerebrovascular pathology has, for good reason, received much attention from researchers and clinicians alike. Over previous decades, several generations of hypotheses have linked depression to the etiology or pathophysiology of dementia. Similarly, a host of studies have looked at the interplay between cerebrovascular pathology and late-life depression. This has resulted in new concepts of late-life depression, such as vascular depression. The study under evaluation sought to assess the neuropathological correlates of late-life depression by examining brains donated for study by a large sample of participants in the Medical Research Council Cognitive Function and Ageing Study. The study is unique in its large size, representative sample of participants and rigorous exclusion of participants who were demented during their life, using structured interviews to diagnose depression at multiple life stages before death. The results suggest that depression is not associated with cortical pathology of either Alzheimer's dementia or cerebrovascular disease. There were associations with Lewy body pathology and loss of neurons in the hippocampus and other subcortical areas. Although the authors are cautious with regard to drawing firm conclusions, the results suggest that, in the community, depression is not an important etiological factor for the development of the neuropathology of Alzheimer's disease and there was no association with cerebrovascular pathology. Although restricted to only very few subjects, the association with Lewy body pathology warrants further research, as does the association with neuronal loss in the hippocampus.