Targeting Neuroplasticity for the Management of Pain and Agitation in Alzheimer’s Disease via Bergamot Nanotherapy

Alzheimer’s disease (AD) accounts for 50–70% of cases of dementia worldwide and is a social burden to the affected population. Although several pathogenetic hypotheses have been proposed, evidence favoring the role of aberrant neuroplasticity in the development of the neuropsychiatric symptoms associated with dementia is increasing. Specifically, agitation is resistant to treatment and affects the quality of life, also because of the lack of safe and effective treatment for AD. Alterations in pain processing due to plastic modifications occur during aging and neurodegeneration. Up to 80% of AD patients have chronic pain due to age-related comorbidities that are misdiagnosed and remain unattended due to a lack of self-reporting because of communication hindrance, which also contributes to the development of agitation. Here, we reported a strategy to target altered neuroplasticity for treating pain and agitation by applying bergamot essential oil with evidence for in-vivo analgesic effects on neuropathic and inflammatory pain preclinical models. Bergamot was engineered in a nanotechnology delivery system, NanoBEO, which provides the opportunity to investigate its efficacy in the NCT04321889 randomized, double-blind, placebo-controlled clinical trial BRAINAID. This trial can provide a rational basis for safe and effective treatment to alleviate agitation and pain, thus improving the quality of life of people suffering from AD.