4.4.0.0 Cog­ni­tive Im­pair­ment/‍Dementia

Di­a­betes is as­so­ci­at­ed with a significant­ly in­creased risk and rate of cog­ni­tive de­cline and an in­creased risk of de­men­tia (32,33). A re­cent meta-‍anal­y­sis of prospec­tive ob­ser­va­tion­al stud­ies in peo­ple with di­a­betes showed 73% in­creased risk of all types of de­men­tia, 56% in­creased risk of Alzheimer de­men­tia, and 127% in­creased risk of vas­cu­lar de­men­tia com­pared with in­di­vid­u­als with­out di­a­betes (34). The re­verse is also true: peo­ple with Alzheimer de­men­tia are more like­ly to de­vel­op di­a­betes than peo­ple with­out Alzheimer de­men­tia. In a 15-year prospec­tive study of com­mu­ni­ty-‍dwelling peo­ple >60 years of age, the pres­ence of di­a­betes at base­line significant­ly in­creased the age- and sex-‍ad­just­ed in­ci­dence of all-‍cause de­men­tia, Alzheimer de­men­tia, and vas­cu­lar de­men­tia com­pared with rates in those with nor­mal glu­cose tol­er­ance (35).

Hy­per­glycemia

In those with type 2 di­a­betes, the de­gree and du­ra­tion of hy­per­glycemia are re­lat­ed to de­men­tia. More rapid cog­ni­tive de­cline is as­so­ci­at­ed with both in­creased A1C and longer du­ra­tion of di­a­betes (34). The Ac­tion to Con­trol Car­dio­vas­cu­lar Risk in Di­a­betes (AC­CORD) study found that each 1% high­er A1C level was as­so­ci­at­ed with lower cog­ni­tive func­tion in in­di­vid­u­als with type 2 di­a­betes (36). How­ev­er, the AC­CORD study found no dif­fer­ence in cog­ni­tive out­comes in par­tic­i­pants ran­dom­ly as­signed to in­ten­sive and stan­dard glycemic con­trol, sup­porting the rec­om­men­da­tion that in­ten­sive glu­cose con­trol should not be ad­vised for the im­provement of cog­ni­tive func­tion in in­di­vid­u­als with type 2 di­a­betes (37).

Hy­po­glycemia

In type 2 di­a­betes, se­vere hy­po­glycemia is as­so­ci­at­ed with re­duced cog­ni­tive func­tion, and those with poor cog­ni­tive func­tion have more se­vere hy­po­glycemia. In a long-‍term study of older pa­tients with type 2 di­a­betes, in­di­vid­u­als with one or more record­ed episode of se­vere hy­po­glycemia had a step­wise in­crease in risk of de­men­tia (38). Like­wise, the AC­CORD trial found that as cog­ni­tive func­tion de­creased, the risk of se­vere hy­po­glycemia in­creased (39). Tai­lor­ing glycemic ther­a­py may help to pre­vent hy­po­glycemia in in­di­vid­u­als with cog­ni­tive dysfunc­tion.

Nu­tri­tion

In one study, ad­her­ence to the Mediter­ranean diet corre­lat­ed with im­proved cog­ni­tive func­tion (40). How­ev­er, a re­cent Cochrane re­view found insufficient ev­i­dence to rec­om­mend any di­etary change for the pre­vention or treat­ment of cog­ni­tive dysfunc­tion (41).

Statins

A sys­tematic re­view has re­ported that data do not sup­port an ad­verse ef­fect of statins on cog­ni­tion (42). The U.S. Food and Drug Ad­min­is­tra­tion post-­mar­ket­ing surveil­lance databas­es have also re­vealed a low re­port­ing rate for cog­ni­tive-‍re­lat­ed ad­verse events, in­clud­ing cog­ni­tive dysfunc­tion or de­men­tia, with statin ther­a­py, sim­i­lar to rates seen with other com­monly pre­scribed car­dio­vas­cu­lar med­i­ca­tions (42). There­fore, fear of cog­ni­tive de­cline should not be a bar­ri­er to statin use in in­di­vid­u­als with di­a­betes and a high risk for car­dio­vas­cu­lar dis­ease.