Optimizing clinical phenotyping to better delineate the complex relationship between type 2 diabetes and Alzheimer’s disease

Alzheimer’s disease (AD) is the most common form of dementia, and its prevalence is increasing rapidly. According to the Alzheimer’s Association, over 5 million adults in the United States over the age of 65 years currently have AD, and this number is expected to exceed 13 million by 2050 in the absence of novel, preventative strategies. Epidemiologic studies have implicated the presence of type 2 diabetes mellitus (T2DM) specifically at midlife as a key modifiable risk factor for AD, and AD may increase risk of dysglycemia and T2DM. However, data have been inconsistent with regard to the magnitude of AD risk attributable to T2DM, and the pathways underlying this apparent relationship remain poorly understood. Elucidating the impact of T2DM on AD risk and progression requires greater attention to the myriad facets of T2DM pathophysiology, its comorbid conditions, and attendant treatment modalities, all of which may differentially impact the relationships among T2DM, cognitive decline, and AD. This mini‐review will summarize the discrete facets of T2DM that may influence AD risk and highlight the importance of careful clinical phenotyping in both epidemiologic and interventional studies to better delineate the key pathways and mechanisms linking T2DM and AD.