Remote ischemic conditioning of the brain in dementia patients: protocol for a crossover non-pharmaceutical intervention study

Background and objectives: Brain ischemia is one of the mechanisms causing dementia; this refers to vascular dementia, however its involvement in other forms of dementia cannot be excluded. We will study the potential neuroprotection of ischemia/reperfusion of a peripheral organ or tissue against cerebral I/R injury in people with mild cognitive impairment (percondition) and early and middle stage dementia (postcondition). Subjects and methods: This crossover study will be held with individuals suffering from peripheral arteriopathy that can cause intermittent claudication after structured exercise, thus inducing extensive transient leg’s ischemia. The level of cerebral function will be checked at baseline and after the intervention with cognitive tests, electroencephalography, magnetic resonance imaging, blood tests, immunological examinations, Event Related Potentials and level of proteins of cerebrospinal fluid (only at baseline). We will examine the possible slowing of progression or the improvement of the disease (dementia), we will suggest or exclude possible biomarkers that are transmitted to the process as well as the intracellular mode of action in the target organs, with a study comprising independent samples and comparison groups. Patient recruitment will begin in January 2020, the analysis of primary outcome measures will be completed in August 2021, and the study will finish in December 2021. The study was approved by the Ethical Committee of the “Greek Association of Alzheimer’s Disease and Related Disorders” (Alzheimer Hellas) (Pr Nr 250 / 2019 AI) on November 8, 2019. Outcome measures: Participants’ cognitive function will be assessed by cognitive scales (primary outcome measure), electroencephalography, magnetic resonance imaging, blood tests and immunological examinations, and cognitive induced potentials (secondary outcome measure) at the beginning and at the end of the study. Discussion: This is the first time in the literature that protection of the human brain from dementia of different stages by remote conditioning is investigated. Also innovating is the method that the remote organ ischemia is achieved. The above mentioned strategy of cerebral protection from the initiation or the development of dementia is safe and costless. Trial registration: ClinicalTrials.gov NCT04168021 registered on November 18, 2019.