LAUSR

OBJECTIVE The objectives of this review are to explore the neuronal pathways and cellular and molecular mechanisms involved in both healthy and impaired cognitive function and to discuss the role of nootropics, in particular, those with cholinergic activity, as promising interventions to preserve and/or improve cognitive performance in patients in the symptomatic pre-dementia stage, known as mild cognitive impairment (MCI). MATERIALS AND METHODS Papers were retrieved by a PubMed search, using different combinations of keywords (e.g., cognitive function AND aging AND nootropics), without limitations in terms of publication date or language. RESULTS Nootropics modulate the activities of specific brain pathways involving neurotransmitters and neuromodulators that have distinct roles in the cognitive processes. The nootropic L-a-glyceryl-phosphoryl-ethanolamine (L-a GPE), by virtue of its action as a phospholipid (PL) precursor and acetylcholine (Ach) donor, targets neural stem cell aging, cholinergic depletion, oxidative stress and microglia activation, loss of entorhinal cortex neurons, and reduced hippocampal volume. Cognitive reserve levels may be linked to the resilience and adaptability of the brain to cope with age-related cognitive decline. L-a GPE may contribute to cognitive reserve preservation via its neuronal well-being promoting action. CONCLUSIONS The substantial burden of age-related cognitive decline demands effective long-term and well-tolerated interventions aimed at maximizing the span of effective functioning. The use of inappropriate medication may lower cognitive reserve, thus hastening the onset of symptomatic AD, while the use of nootropics, such as L-a GPE may contribute to cognitive reserve preservation via its neuronal well-being promoting action.