Table 2.
Intranasal insulin improves memory function.
| Subjects | Intranasal insulin duration/dose | Main result | References |
|---|---|---|---|
| Healthy humans | 4 × 40 IU/day, for 8 weeks | Intranasal intake of insulin enhanced long-term declarative memory and positively affected mood in humans without causing systemic side effects like hypoglycaemia. | Benedict et al., 2004 |
| Healthy humans | 4 × 40 IU/day, for 8 weeks; insulin and rapid-acting insulin analog insulin aspart | Declarative memory was improved in insulin and insulin aspart groups compared to placebo group without altering glucose levels. Insulin aspart treated subjects performed even better that those of insulin treated group |
Benedict et al., 2007 |
| Healthy humans | Single dose of regular human insulin 160 IU | Hippocampus-dependent memory and working memory were improved in women where as men did not benefit from acute insulin treatment | Benedict et al., 2008; Krug et al., 2010 |
| MCI and mild AD patients | 20 or 40 IU of insulin acute treatment | Acute intranasal insulin administration improved verbal memory in AD and MCI subjects without the APOE- ε 4 allele | Reger et al., 2006 |
| MCI and AD patients | 10, 20, 40, or 60 IU for 5 days | 10, 20, and 40 IU of insulin improved declarative memory only in APOE-ε 4 negative patients Memory facilitation generally peaked at the 20 IU dose ↑ Aβ42 levels for memory-impaired adults from saline to 10 IU regardless of APOE-ε 4 status Intranasal insulin did not affect peripheral glucose or insulin levels |
Reger et al., 2008a |
| MCI and AD patients | 20 IU BID intranasal insulin treatment for 21 days | Insulin-treated subjects retained more verbal information and improved attention and functional status Insulin treatment raised fasting plasma Aβ40/Aβ42 ratio |
Reger et al., 2008b |
| MCI and mild to moderate AD patients | 20 or 40 IU for 4 months | Treatment with 20 IU of insulin improved delayed memory Both dosages preserved caregiver-rated functional ability and general cognition Unchanged Aβ42 and tau levels after insulin treatment |
Craft et al., 2012 |
| AD patients with ApoE4 allels | Rapid acting insulin | Rapid acting insulin failed to have an acute impact on cognition in ApoE4 carriers with AD | Rosenbloom et al., 2014 |
| MCI and mild AD patients | 20 or 40 IU of insulin detemir for 21 days | High dose (40 IU) improved visuospatial and verbal working memory for all participant High dose improved memory for adults with MCI and AD who were APOE-ε 4 positive patients APOE-ε 4 carriers taking high dose also improved peripheral insulin resistance APOE-ε 4 negative patients taking high dose experiences increased peripheral insulin resistance |
Claxton et al., 2015 |
| S.D. rats—streptozotocin induced AD model | 5 IU for 6 days | Insulin administration significantly reduced the Aβ levels without altering peripheral glucose levels | Subramanian and John, 2012 |
| Streptozotocin induced-rat model of type 2 diabetes |
2U insulin intranasally/4 weeks 6.7 U/kg (s.c.)/4 weeks |
Decreased Akt activation and increased tau phosphorylation and GSK-3β activation was found in T2D rat brains. Intranasal insulin treatment normalized Akt and GSK-3β and reduced tau phosphorylation in diabetic rats s.c. insulin had minimal effect of tau phosphorylation and GSK-3β |
Yang et al., 2013 |
| 3 × Tg-AD mice | 1.75 U/7 days | Intranasal insulin administration restored insulin signaling, ↑ synaptic proteins, and ↓ Aβ40 level and microglia activation in the brains of 3 × Tg-AD mice. Glucose transporters and tau-phosphorylation is unchanged |
Chen et al., 2014c |
| 3 × Tg-AD mice | 1.75 U/7 days Propofol 250 mg/kg (i.p.) |
Insulin treatment attenuated propofol-induced hyperphosphorylation of tau, promoted brain insulin signaling. Resulted in down-regulation of several tau protein kinases, including cyclin-dependent protein kinase 5, calcium/calmodulin-dependent protein kinase II, and c-JunN-terminal kinase and up-regulation of protein phosphatase 2A |
Chen et al., 2014b |