Intranasal insulin stabilized or improved cognition and function and preserved cerebral metabolic rate of glucose in brain regions affected by Alzheimer’s disease, concluded researchers from a phase II trial. But more and larger trials are needed before any conclusions can be drawn, they also cautioned.
Insulin is important to normal brain function, and reduced insulin levels may contribute to Alzheimer’s disease, researchers noted. To examine the effects of intranasal insulin in adults with amnestic mild cognitive impairment or Alzheimer’s disease, researchers conducted a randomized, double-blind, placebo-controlled trial in a VA medical center.
The intent-to-treat sample consisted of 104 adults with amnestic mild cognitive impairment (n=64) or mild to moderate Alzheimer’s disease (n=40) defined as Clinical Dementia Rating scores of 0.5-1 and Mini-Mental State Examination scores greater than 15.
Participants received nasally delivered placebo (n=30), 20 IU of insulin (n=36), or 40 IU of insulin (n=38) for four months. Researchers assessed delayed story recall score and the Dementia Severity Rating Scale score, and secondary measures included scores on tests for general cognition and functionality.
A subset of participants underwent lumbar puncture (n=23) and positron emission tomography with fludeoxyglucose F 18 (n=40) before and after treatment. Results appeared online Sept. 12 in the Archives of Neurology.
Treatment with 20 IU of insulin improved delayed memory (P less than .05), and the 20 and 40 IU insulin doses preserved caregiver-rated functional ability (P less than .01). Both insulin doses also preserved general cognition for younger patients and functional abilities for adults with Alzheimer’s disease (P less than .05).
Physiologically, insulin has an effect on beta-amyloid peptides. Insoluble beta-amyloids deposit themselves in the brain in Alzheimer’s patients, and soluble beta-amyloids also have toxic effects on brain synapses. Insulin modulates the levels of beta-amyloids and protects against their detrimental effects on synapses.
Results from spinal tap samples found that biomarkers did not change for insulin-treated participants as a group. But, in exploratory analyses, changes in memory and function were associated with changes with beta-amyloid 42 and in its ratio to tau proteins. Placebo-assigned participants showed decreased fludeoxyglucose F 18 uptake in the parietotemporal, frontal, precuneus, and cuneus regions and insulin-minimized progression.
ACP member Jason Karlawish, MD, an Alzheimer’s researcher at the University of Pennsylvania, told the New York Times that the results were provocative, but preliminary. Larger and longer trials are needed to support initial results and detect any adverse effects that might happen.
In the meantime, some advances in Alzheimer’s disease detection, especially in biomarkers, has left some internists in a dilemma. They can detect a disease earlier, but they can’t treat it. ACP Internist examines how to handle this in is September cover story.
*This blog post was originally published at ACP Internist*