Mild cognitive impairment and major depressive disorder are associated with molecular senescence abnormalities in older adults.

Introduction The biological mechanisms linking mild cognitive impairment (MCI) and major depressive disorder are not well understood. We investigated whether molecular senescence changes in older adults are associated with a history of major depressive disorder (MDD) or MCI. Methods We included 371 participants: 167 with MCI; 62 cognitively normal with a history of MDD; 97 with MDD+MCI; and 45 cognitively unimpaired (CU) without a history of MDD. The candidate Senescence-Associated Secretory Phenotype (SASP) biomarkers were measured in the plasma using a customized LUMINEX assay. Results The MDD+MCI group had a higher SASP index than the other groups (P < .001). A higher SASP index was significantly associated with worse global cognitive performance, executive dysfunction, slower processing speed, and episodic memory deficits. Discussion Our study suggests that increased molecular changes are associated with cognitive impairment in older adults with MDD and indicate that accelerated biological aging is an underlying feature of MDD.