Metabolic Modulators Show Promise in Early Alzheimer Disease
Intranasal insulin and the diabetes drug empagliflozin were safe and demonstrated positive effects on memory, brain health, and brain blood flow in patients with mild cognitive impairment (MCI) and early Alzheimer disease (AD), according to results from a phase 2A/B trial published in Alzheimer’s & Dementia.
“Our study suggests that targeting metabolism can change the course of Alzheimer disease,” said corresponding author and lead investigator Suzanne Craft, PhD, of the Wake Forest University School of Medicine, Winston-Salem, North Carolina, in a news release.
The 4-week trial included 47 older adults with MCI or early AD. Participants were randomized to receive either intranasal insulin, empagliflozin, both intranasal insulin and empagliflozin, or placebo.
For the primary outcome of treatment-related adverse events, events were mild and similar across treatment groups, according to the study.
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Secondary and exploratory outcomes, meanwhile, suggested different benefits with each medication. Intranasal insulin improved performance on the modified Preclinical Alzheimer Cognitive Composite-5, modulated cerebral blood flow and fractional anisotropy, and reduced plasma glial fibrillary acidic protein, researchers reported.
Empagliflozin, meanwhile, lowered cerebrospinal fluid tau, reduced neurogranin and vascular makers associated with disease progression, and modulated cerebral blood flow. The drug also increased high-density lipoprotein, demonstrating a beneficial metabolic effect even in patients without diabetes.
Both agents influenced multiple immune and inflammatory markers in cerebrospinal fluid and blood, the research team reported, suggesting the medications offer protective immune response while easing inflammation. Intranasal insulin specifically affected proteins in the nasal-olfactory plexus, a recently discovered pathway connecting waste clearance in the brain with immune systems throughout the body.
“We plan to build on these promising results with larger, longer studies in people with early and preclinical Alzheimer disease,” Dr Craft said. “Because empagliflozin or intranasal insulin improved tau tangles, cognition, neurovascular health and immune function, we believe these treatments could offer real therapeutic potential, either on their own or in combination with other Alzheimer’s therapies.”
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