Depression in late life, cognitive decline and white matter pathology in two clinico-pathologically investigated...

We report two cases of late life depression who became progressively more resistant to treatment, developed cognitive impairment, and began to exhibit neurological abnormalities and evidence of vascular disease. A discussion of the clinical features of the cases is accompanied by reports of neuropathology and neuroimaging findings. Extensive white matter lesions were present on computed tomography in both patients, and basal ganglia infarcts were seen in one. Neuropathology revealed evidence of cerebral atrophy, demyelination and white matter lesions in addition to cerebrovascular and generalised vascular disease. Neither patient exhibited Alzheimer pathology outwith the norm for their age. We believe this to be the first report of neuropathological findings in depression with white matter changes.

The pathological basis of white matter lesions and their relationship to depression, its age of onset and clinical features is addressed in relation to the cases described. Pathological investigation of white matter lesions has not previously been carried out in depression and hypotheses regarding their nature in this illness are based on extrapolation from research in a variety of other disorders. The association of depression with vascular risk factors is considered, as is the relationship between depression and cognitive deficits. There is a need for further investigation in this area.