Intranasal Insulin Could Help Slow Age-related Cognitive Decline, Suggests a New Study

Treatment with intranasal insulin improved executive function and verbal memory, as well as other measures, in participants with and without type 2 diabetes.

Insulin delivered intranasally (INI) to older persons may slow age-related cognitive decline, according to findings from a small phase 2 proof-of-concept study. The trial found the treatment effective in older adults both with and without type 2 diabetes (T2D).

The research team, from Beth Israel Deaconess Medical Center (BIDMC) and Brigham and Women's Hospital (BWH) in Boston, published its results online April 28, 2022, in the Journal of Neurology.

Study authors, led by Vera Novak, MD, PhD, associate professor of neurology, department of neurology, stroke division, BIDMC, describe brain insulin resistance and impaired insulin signaling as potential common pathways for cognitive decline in aging, diabetes, and Alzheimer disease. They also cite data for the efficacy of INI in improving verbal memory and note the growing interest in using insulin delivered using the intranasal modality as a potential treatment for maintaining cognitive function.

Their trial, Memory Advancement with Intranasal Insulin in Type 2 Diabetes (MemAID), was a prospective, double-blind placebo-controlled phase 2 study designed to assess the long-term effects of INI on cognition in participants with and without diabetes and to evaluate its impacton gait speed, an important indicator of overall health and brain function, according to investigators.

The team recruited patients with and without T2D from clinical research centers at BIDC and Brigham and Women’s Hospital (BWH). Eligible patients were aged 50 to 85 years and able to walk for 6 minutes. Background treatment for patients with T2D comprised diet and noninsulin oral or injectable agents. Participants without T2D that served as controls, had baseline fasting plasma glucose <126 mg/dL and hemoglobin A1c (HbA1c) <6.5%.

Final study enrollment numbered 223 (109 women, mean age [SD] 65 years +/- 9.1).

Pre-treatment assessment included normal and dual task walking speeds, attention, memory and executive function and mood using a battery of validated tests.

Half of the participants with T2D (n=51) and half without T2D (n=58) were treated for 24 weeks with 40 IU of insulin, delivered intranasally via an electronic atomizer once daily. Control group participants were given sterile saline, also delivered intranasally. INI was added to regular daily treatment for T2D participants.

Findings favor INI

After 24 weeks of treatment, report Novak et al, participants with T2D who received INI (DM-INI) demonstrated faster normal walking (~ 7 cm/s; P = .025) and dual task waking during the treatment period (P = .007; P = .812, adjusted for baseline difference) than those with T2D receiving placebo (DM-placebo). The difference remained consistent during the follow up period.

During the treatment period and the 24-week follow-up, the Control-INI participants demonstrated better executive functioning (P = .008, P = .007, respectively) and better verbal memory post-treatment (P = .004) than Control-placebo participants.

Findings from MRI studies showed that T2D-INI treated participants had improved cerebral blood flow in the frontal lobe (P < .001). In this group, both plasma insulin (P = .006) and homeostatic model assessment for insulin resistance (P < .013) decreased during the 24-week follow-up period.

The overall effect of INI, across participants with and without T2D, demonstrated faster walking (P = .002) and better executive function (P = .002) and verbal memory (P = .02). Of interest, investigators pointed out that participants in the Control-INI group with prediabetes demonstrated better executive functioning and memory.

“The consistency of the trends in the data showing better performance on walking speed and cognition for INI-treated participants, especially in those with prediabetes, carries great implication for potential early intervention using INI in this population to prevent or slow down the progression toward Alzheimer Disease’s related dementias,” wrote study authors.

Regarding safety during the study, the researchers found no adverse effects associated with INI after 24 weeks. Importantly, they report, INI had no affect on and did not disrupt injected insulin treatment in those with T2D

“INI-treated diabetic participants had faster walking speed, increased cerebral blood flow and less insulin resistance, while INI-treated controls performed better on executive function and verbal memory tasks,” the researchers concluded.

Novak and her colleagues also stress that the findings, while clinically relevant, warrant further investigation to address unanswered questions. As a proof-of-concept study, the preliminary safety and efficacy findings are intriguing, but issues around optimal dosing and long-term safety remain to be evaluated.

Reference: Novak V, Mantzoros CS, Novak P, et al. MemAID: Memory advancement with intranasal insulin vs. placebo in type 2 diabetes and control participants: a randomized clinical trial. J Neurol. Published online ahead of print April 28, 2022.