Age or age of onset: which is the best criterion to classify late-life depression?

In late-life depression (LLD), several differences between patients whose first episode is reported after age 65 (late-onset depression, LOD) and those with early-onset depression (EOD) might reflect the effects of brain ageing. To test this hypothesis, we analysed the impact of current age and age at illness onset on a number of clinical and cognitive manifestations in 438 outpatients with major depressive disorder aged >60 years, treated with venlafaxine for 12 weeks. When compared to the EOD group, patients with LOD were older ( P  < 0.00001) and associated with lower depression severity ( P  = 0.0029), lower global cognitive functioning [Mini-Mental State Examination (MMSE): P  = 0.0001; Repeatable Battery for the Assessment of Neuropsychological Status: immediate memory, P  = 0.0009, and delayed memory, P  < 0.00001; Delis-Kaplan Executive Function System measuring executive functions: Trail-Making Test (TMT) - P  = 0.0004 and Colour-Word Interference Test, Inhibition - P  = 0.0063], and more dyskinesias (Abnormal Involuntary Movement Scale: P  = 0.0006). After controlling for its interactions with age of onset, current age was inversely correlated with Montgomery Åsberg Depression Rating Scale scores at baseline ( P  < 0.00001) and week 12 ( P  = 0.0066), MMSE ( P  < 0.00001), delayed memory ( P  < 0.00001), and TMT ( P  = 0.0021). Age of onset predicted impairment in immediate ( P  = 0.023) and delayed memory ( P  = 0.0181), and dyskinesias ( P  = 0.0006). Although most features of LLD are related to ageing rather than to late-onset, LOD is a possible separate diagnostic entity characterised by memory dysfunction and increased liability to movement disorders.