Depressive symptoms are associated with differential cognitive and neuroanatomical alterations in young and older adults

ObjectiveDepression is a heterogeneous disorder. The purpose of this article is to examine the contribution of age to this heterogeneity by characterizing the associations of depressive symptoms with cognitive performance and brain structure across the lifespan. MethodsThe authors analyzed demographic variables (age, gender, education), affective measures (Hospital Anxiety and Depression Scale), and cognitive assessments (The Addenbrookes Cognitive Examination Revised) from the Cambridge Centre for Ageing Neuroscience (Cam-CAN) cohort (N=2591, age 18-99). A subset of this cohort (N=647) underwent structural MRI, which was used for voxel-based brain morphometry. ResultsA linear regression model revealed a significant interaction between age and depression score, indicating that depression-related cognitive dysfunction is more severe in older adults. A comparison of different cognitive domains showed that this effect was consistent across all tested domains but significantly more prominent for fluency. A complementary voxel-based morphometry analysis, based on similar regression models, revealed age by depression interactions in several brain regions, demonstrating preferential age-related reduction in grey matter volume in the left and right hippocampi in older adults. The reciprocal contrast revealed preferential reduction in grey matter in the left superior frontal gyrus, left middle frontal gyrus, and left superior parietal lobule in younger adults. ConclusionsThese findings indicate that the associations of depression with cognitive performance and brain structure are age-dependent, suggesting that the neuropathological mechanisms underlying depression may differ between young and older adults. Recognizing these differences will support the development of better diagnostic tools and therapeutic interventions for depression across the lifespan.