Objectives/Introduction: Major Depressive Disorder is associated age-related medical conditions (e.g., diabetes
mellitus type II, Alzheimer’s disease) that frequently manifest at an earlier age, contributing to excess and premature
mortality. The foregoing observation provides the impetus to further refine potential mechanisms and molecular pathways
subserving these disorders in order to more effectively treat these clinical populations by aiming to reduce and prevent
cognitive impairment as well as downstream neurodegeneration.
Methods: A review of computerized databases was performed to identify original studies that investigated the impact of the
independent and comorbid association of major depressive disorder and type II diabetes mellitus on cognitive function and
conversion to Alzheimer’s disease. English-written articles were selected for review based on the adequacy of sample size,
the use of standardized diagnostic instruments, and validated assessment measures.
Results: Individuals with persistent neuropsychiatric illness account for a disproportionate overall burden of disability
mediated largely by decrements in cognitive performance. Mixed results from epidemiological and clinical studies suggest
that insulin may mediate and/or moderate risk for cognitive dysfunction in subsets of individuals. Moreover, physiological
changes, such as insulin resistance and the activation of neuroimmunoinflammatory systems result in glial and
Conclusion: Disturbances in the metabolic milieu exert a neurotoxic effect on the central nervous system and poses a
hazard to other organ systems.