Moreover, we will show that depression can be diagnosed in the older patient and that it can be differentiated from normal aging. Importantly, a variety of treatments have been demonstrated to be safe and efficacious in the elderly, and long-term treatment might be indicated. Onset and course of depression Depression in late life is a very heterogeneous condition. Onset may be early in life with the course recurrent from a first episode earlier in adulthood, or the onset of the first episode may be late in life. In general, compared with patients of the same age with recurrent Inhibitors,research,lifescience,medical depression, those

patients with the first onset of depression in late life are likely to have a less satisfactory response to treatment and a more chronic course. There are significant brain changes in depression: frontal and temporal lobe atrophy,11,12 periventricular and subcortical deep white matter hyperintensities,13 and significantly decreased metabolism in a variety Inhibitors,research,lifescience,medical of brain regions (dorsolateral prefrontal cortex, inferior

frontal cortex, basal ganglia).14 Many of these changes are associated with normal aging as well. Late-onset depression often is associated with a variety of brain abnormalities, such as ventriculomegaly Inhibitors,research,lifescience,medical and white matter hyperintensities, and with cognitive impairments. Recent research has uncovered important sources of clinical and biological heterogeneity within late-life-onset depression, and subgroups with distinctive patterns Inhibitors,research,lifescience,medical of clinical presentations, course, mechanisms, and outcomes have been identified.15-17 The association between depression and cognitive impairment has been well established, though the direction of causality has been disputed, as has the methodology of assessment.18,19 There does seem to be general agreement, however, that late-life depression with cognitive impairment that is reversed by antidepressant

treatment is, more often than not, a predictor of the development of an irreversible dementia such as Alzheimer’s disease or Volasertib datasheet vascular dementia.20 Converging findings implicate vascular Inhibitors,research,lifescience,medical disease in the pathogenesis of one particular subgroup. Geriatric depression is often comorbid Thymidine kinase with vascular disorders and is accompanied by lesions in the basal ganglia and prefrontal areas of the brain. The clinical profile of depression in patients with vascular disease is often characterized by motor retardation, lack of insight, and impairment of executive functions. This clinical presentation suggests that dysfunction of frontal brain systems is a possible contributing factor to depression in late life.21-24 It also suggests that treatment for cerebrovascular disease may have preventive implications for latelife-onset depression. The article by Alexopoulos and colleagues in this issue of Dialogues in Clinical Neuroscience addresses this specific topic.