Insulin resistance is a state where cells in the body have an impaired ability to respond to insulin. Metabolic conditions associated with insulin resistance, such as diabetes, are well-known risk factors for mild cognitive impairment and Alzheimer’s disease [1]. No studies have examined whether intranasal insulin can prevent Alzheimer’s disease or other dementias. Systematic reviews of multiple small studies suggest that intranasal insulin may improve certain types of cognitive function in healthy individuals [2; 3], and meta-analyses have found that there may be cognitive benefits of intranasal insulin administration in individuals with mild cognitive impairment [4]. However, findings have not been consistent across studies. Larger and longer studies are needed to fully understand the effects of intranasal insulin in healthy individuals, people with diseases like type 2 diabetes, and those with mild cognitive impairment.
APOE4 carriers: Some studies have looked at whether APOE4 carriers respond differently to intranasal insulin than non-carriers, but the results are not consistent between studies [4; 5; 6; 7]. The effects of intranasal insulin may be different based on sex, the type of insulin used, or whether people use intranasal insulin just once or consistently over days or weeks. For instance, some very preliminary data suggest that long-acting insulin detemir could have more benefit for APOE4 carriers [7], whereas regular insulin may have more benefit for non-carriers [8]. More work is needed to test these initial findings. Larger, longer-term clinical trials can help answer these questions.
For more information on what the APOE4 gene allele means for your health, read our APOE4 information page.
For Dementia Patients
Multiple studies show abnormal insulin signaling in brain tissue of patients with Alzheimer’s disease [9; 10; 11; 12]. Insulin signaling may be especially impaired in patients with both type 2 diabetes and Alzheimer’s disease [13], though insulin signaling can also be impaired in brain tissue from patients with Alzheimer’s disease and no history of diabetes [11].
Multiple systematic reviews and meta-analyses looking at several small trials have found that intranasal insulin may help improve cognitive function or daily functioning in patients with mild cognitive impairment or dementia, though there may be nuance in what type of insulin is best for different patients [4; 14; 15]. For instance, some studies on the acute effects of intranasal insulin in patients with mild cognitive impairment and Alzheimer’s disease suggest that intranasal insulin may improve some aspects of memory in APOE4 non-carriers and has no effect (or may be detrimental) to APOE4 carriers [5; 6; 16]. Other studies report regular, but not long-acting, intranasal insulin improved memory in patients with Alzheimer’s when given for one to four months, including one study of 104 patients [8; 17; 18]. On the other hand, a 21-day treatment with high dose long-acting intranasal insulin improved memory in APOE4 carriers but made memory worse in APOE4 non-carriers [7]; there was no impact of the lower dose on memory. Together, these results suggest that the dosing, duration, type of insulin, and genetics of the patient all may influence the effect of intranasal insulin on memory.
A larger study that ran for more than a year tried to confirm the effects of regular insulin in patients with Alzheimer’s disease but was unable to do so due to malfunction of the intranasal device [19]. Researchers ran another 4-week study in 47 patients with mild cognitive impairment or early Alzheimer’s disease, this time with an intranasal device they confirmed worked. The early results from this trial support the potential cognitive benefits of regular intranasal insulin in patients with mild cognitive impairment and early Alzheimer’s disease [20]. Future studies are needed to see whether these findings have real benefit for patients and their families.
