Choline alphoscerate activity in cerebrovascular disease: preclinical and clinical evidence

Background: Cholinergic precursors increasing choline availability and acetylcholine synthesis/release may represent a therapeutic strategy for countering cognitive impairment occurring in adult-onset dementia disorders. Choline alphoscerate (GPC) is the acetylcholine precursor with larger clinical evidence in the treatment of cognitive decline in aging and Alzheimer’s Disease (AD). Aims: The present study was designed to highlight the effects of GPC from preclinical to clinical point of view. Methods: spontaneously hypertensive rats (SHR), taken as a model of hypertension-related cerebrovascular injury, were treated with GPC (150mg/Kg/die) to assess the cerebroprotective activity of the compound. In ASCOMALVA trial, AD patients with cerebrovascular damage were treated with donepezil + GPC or + placebo. After three years of treatment 113 patients were examined by MRI and neuropsychologically. Results: SHR brain compared to normotensive rats showed a decrease of neurons and gliosis with signs of neuroinflammation. These changes were countered by GPC treatment. In AD patients, analysis of hippocampus and amygdala grey matter revealed a progressive reduction in the volume of these two areas more pronounced in the group treated with donepezil alone compared to the donepezil + GPC group. These morphological data were confirmed by a better outcome in neuropsychological testing in the GPC treated patients. Conclusions: Preclinical data suggest that the compound could have protective effects. The same probably occurs by combining GPC with donepezil in clinics. Collectively these data suggest that the addition of a cholinergic precursor to standard cholinesterase inhibitor therapy may prolong/increase the effectiveness of cholinergic therapies in AD patients with the cerebrovascular injury