Highlights
- A small but promising clinical trial tested a known diabetes drug and intranasal insulin in patients with mild cognitive impairment (MCI) for 4 weeks
- The results showed improvements in multiple indicators including cognition, brain white matter integrity, cerebral blood flow
- Tau protein which signifies neurodegeneration was lower, GFAP protein which indicates brain injury or inflammation was also lower
- The study while promising, was small and needs to be sufficiently powered to be statistically significant
Some diabetes drugs have shown promise in brain health improvement
Researchers in the Wake Forest University school of medicine, wanted to test the diabetes drug empagliflozin in patients with MCI because it has been proposed to improve insulin sensitivity and blood vessel function in the central nervous system (CNS). In preclinical animal models, it was shown to reduce amyloid-β plaques, lower brain blood vessel injury and inflammation, and notably show improved memory. The other drug that was tested was intranasal insulin which when given through the nose goes directly into the CNS (i.e., brain). A previous study had shown that insulin given this way for four months, improved glucose metabolism in the brain and even longer 12-month treatment improved Alzheimer’s disease and associated biomarkers in the cerebrospinal fluid.
Just four-week treatment led to promising changes
A small group of patients (n=11) with MCI was tested with 10mg empagliflozin once a day and 40-IU Humulin® intranasal 4 times a day for four weeks. Other patients in the trial were tested with just one of the drugs or placebo alone. After 4-weeks or treatment, the two drugs together or insulin alone showed improvement in cognitive scores. Improvement in the integrity of brain white matter and in cerebral blood flow in the regions important for Alzheimer’s disease was also observed.
Lower Tau protein and better brain health biomarkers
Also promising was a reduction in the Alzheimer’s associated Tau protein in the cerebrospinal fluid and a lowering of the protein GFAP, which is associated with brain injury. Indicating that these drugs were influencing improved brain function and potentially lowering the risk of Alzheimer’s disease. A reduction in the biomarkers of overall neuroinflammation was measured both in the CSF and blood.Bigger study in progress?
Overall, the study is small yet promising in that two already approved diabetes drugs holds the promise of potentially slowing down the course of Alzheimer’s disease progression in patients with mild cognitive impairment. Large follow up studies to convincingly prove these findings are needed.
Erichsen J., et. al., A phase 2A/B randomized trial of metabolic modulators intranasal insulin and empagliflozin for MCI and early AD.https://doi.org/10.1002/alz.70704