Non-invasive vagus nerve stimulation

Non-invasive VNS (nVNS) does not require a surgical procedure to implant an electrode. nVNS devices are portable and can stimulate the vagus nerve indirectly through the skin of neck or ear (85–87). nVNS is less expensive, carries a lower risk, and is more convenient than iVNS.

Two small trials have shown iVNS may enhance cognitive function in patients with AD (21, 22). In Sweden, researchers enrolled 10 patients with AD (22). Each patient received surgery to implant a pulse generator, which deliver programmable signals to the left-side tenth cranial nerve. The initial settings were frequency 20 Hz, pulse width 500 μs, and current 0.25 mA. The stimulation was on for 30 s followed by a pause for 5 min. After 3 months of treatment, they found the response rates were 70% (seven of 10 patients) on the ADAS-Cog and 90% (nine of 10 patients) on the MMSE. Moreover, 6 months after the iVNS treatment, response rate was still 70% on the ADAS-Cog, and 70% on the MMSE. Adverse effects of invasive VNS were transient and mild.

Therefore, based on these promising findings, the same research team recruited another seven patients with AD. The researchers followed up these total 17 patients for at least 1 year (21). They found that 1 year after iVNS treatment, the score of the ADAS-Cog in seven patients did not decline or even increase, while the score of the MMSE in 12 patients did not decline or even improve compared with baseline. These two small trials revealed that invasive VNS was well-tolerated and improved specific cognitive functions in MMSE and ADAS-Cog after 1 year and 3 months of treatment, respectively.

Non-invasive VNS may affect cognition through the same neural pathway. Until now, no trial with non-invasive NVS in AD has been published in PubMED or registered at clinicaltrials.gov. Further studies of non-invasive VNS in patients with AD are required.