Journal
JOURNAL OF NEUROLOGY
Volume 269, Issue 9, Pages 4817-4835Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s00415-022-11119-6
Keywords
Type 2 diabetes; Intranasal insulin; Cognition; Gait; Brain blood flow; Aging
Categories
Funding
- National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (NIDDK) [R01DK103902, FDA IND 107690]
- Harvard Catalyst-The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health) [UL1TR002541]
- Harvard University and its affiliated academic healthcare centers
- Bagsvaerd, Denmark through an independent ISS grant [ISS-001063]
- Medtronic Inc., Northridge CA, USA [NERP15-031]
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This study investigated the long-term effects of intranasal insulin (INI) on cognition and gait in older individuals, with and without type 2 diabetes mellitus (T2DM). The results showed that INI treatment improved walking speed and cerebral blood flow in T2DM participants, while controls exhibited improved executive functioning and verbal memory. These findings suggest the potential of INI in treating T2DM and age-related functional decline.
Background This study aimed at assessing the long-term effects of intranasal insulin (INI) on cognition and gait in older people with and without type 2 diabetes mellitus (T2DM). Methods Phase 2 randomized, double-blinded trial consisted of 24 week treatment with 40 IU of INI (Novolin (R) R, off-label use) or placebo (sterile saline) once daily and 24 week follow-up. Primary outcomes were cognition, normal (NW), and dual-task (DTW) walking speeds. Of 244 randomized, 223 completed baseline (51 DM-INI, 55 DM-Placebo, 58 ControlINI, 59 Control-Placebo; 109 female, 65.8 +/- 9.1; 50-85 years old); 174 completed treatment (84 DM, 90 Controls); 156 completed follow-up (69 DM). Results DM-INI had faster NW (similar to 7 cm/s; p = 0.025) and DTW on-treatment (p = 0.007; p = 0.812 adjusted for baseline difference) than DM-Placebo. Control-INI had better executive functioning on-treatment (p = 0.008) and post-treatment (p = 0.007) and verbal memory post-treatment (p = 0.004) than Control-Placebo. DM-INI increased cerebral blood flow in medio-prefrontal cortex (p < 0.001) on MRI. Better vasoreactivity was associated with faster DTW (p < 0.008). In DM-INI, plasma insulin (p = 0.006) and HOMA-IR (p < 0.013) decreased post-treatment. Overall INI effect demonstrated faster walking (p = 0.002) and better executive function (p = 0.002) and verbal memory (p = 0.02) (combined DM-INI and Control-INI cohort, hemoglobin A1c-adjusted). INI was not associated with serious adverse events, hypoglycemic episodes, or weight gain. Conclusion There is evidence for positive INI effects on cognition and gait. INI-treated T2DM participants walked faster, showed increased cerebral blood flow and decreased plasma insulin, while controls improved executive functioning and verbal memory. The MemAID trial provides proof-of-concept for preliminary safety and efficacy and supports future evaluation of INI role to treat T2DM and age-related functional decline. [GRAPHICS] .
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