Type 2 diabetes mellitus (T2DM) is associated with impairment of resting-state functional connectivity (rsFC) and cognition. Intranasal insulin (INI) has emerged as potential treatment for T2DM-related cognitive decline. INI treatment has increased perfusion and low-frequency fluctuations in medio-prefrontal cortex (mPFC) . We aimed to evaluate the effect of INI treatment on mPFC rsFC.MemAIDs trial consisted of 24-week of treatment with 40 IU of intranasal insulin (Novolin® R, off label use) or placebo (sterile saline) once daily and 24-week follow-up period. Of 244 randomized participants (115 T2DM and 129 controls, > 50 years old) , T2DM participants (eight INI, three placebo, > 50 years old) completed the baseline and end-of-treatment blood oxygen level dependent (BOLD) fMRI scans.INI treatment increased resting state mPFC-postcentral rsFC (p=0.005) and decreased mPFC-cerebellum rsFC (p<0.001) . The mPFC rsFC changes after INI treatment were different from those from placebo (Figure 1) .INI treatment can modulate resting state connectivity between pre-frontal and sensorimotor cortex and cerebellum, indicating its potential effects on decision making and goal-oriented behaviors. These findings warrant further investigation.


Z.Zhang: None. V.Novak: None. P.Novak: Stock/Shareholder; Moderna, Inc., Novavax, Pfizer Inc., Prothena. C.Mantzoros: Advisory Panel; Novo Nordisk. L.H.Ngo: None. V.Lioutas: None. W.Dai: None.


Funded by NIH-NIDDK (1R01DK103902) , FDA (IND#107690) , Novo Nordisk, Inc. (ISS-001063) , Medtronic Inc. (NERP15-0310) and registered on www.clinicaltrials.gov (NCT02415556.)

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