**1. Introduction**

Ascorbic acid (AA; Vitamin C) is a remarkable water-soluble antioxidant concentrated predominately in citrus fruits, strawberries and vegetables (e.g., spinach and broccoli) and found in

many supplement formulations (LPI Micronutrient Information Center). The adequate functioning of the human organism in general, and of the brain in particular, is highly dependent on AA, but humans are completely dependent on dietary sources due to the evolutionary process leaving us a gene incapable of producing the enzyme gulonolactone oxidase needed to yield AA from glucose [1]. Thus, humans require a constant stream of AA from the diet and rely on robust "carrier" transport and "barrier" integrity mechanisms to meet the brain's demand. AA is the most powerful water-soluble antioxidant of the organism, and key to preventing oxidative lipid damage in biological systems [2]. It forms the first line of antioxidant defence under many types of oxidizing conditions. It can rapidly intercept free radicals in the aqueous phase before they attack lipids [3]. As an antioxidant, AA also provides protection against oxidative stress-induced cellular damage by neutralization of lipid hydroperoxyl (LHP) radicals and by protecting proteins from alkylation by electrophilic lipid peroxidation activity [4].

Several pathological processes can involve the production of free radicals, antioxidant depletion, oxidative and nitrosative stress including vascular disease and cognitive impairments seen in aging older adults (Dementia of Alzheimer's type). Dementia, with its most prevalent form, Alzheimer's disease (AD), is characterized by an insidious progressive nature that usually begins with memory deficits followed by disturbances in other cognitive domains that eventually reach a level that impacts functions of daily life. Age–related dementias also disrupt the family unit, which must often scramble to meet day-to-day care requirements to compensate for loss of independence. The economic conditions associated with this phenomenon of disability and dependence is an enormous and pressing threat to public health. The major risk factor for dementia and AD remains to be advanced age; therefore the projected impact of AD can be estimated by frequency in strata of the population. For example, in the US about 14% of the older adult population age 65 and older carry a diagnosis of dementia and age 85 and older is about 47%. In either case, these cohort effects will stress the value of anti-AD strategies while general practitioners, geriatricians, neurologists and health care professionals all around the globe are projected to face over 115 million people with dementia from all causes by 2050 [5].

The pathological hallmarks of AD include a loss in synaptic function and accumulation of extracellular amyloid-β plaques and intraneuronal neurofibrillary tangles. Oxidative stress displays chronological primacy in the onset of AD, and in its prephase, mild cognitive impairment (MCI) [6–9]. Thus, preventive therapy that is safe and effective for reducing oxidative damage seen early in neurodegenerative disorders and applied before the onset of dementia is a public health priority.

This overview will focus on the biological rationale for the avoidance of AA deficiency in the promotion of healthy brain aging. We include discussion on the biochemistry and transport of AA, much of which has been clarified through basic research using genetically modified mouse models, and also the clinical studies designed to better understand the influence over cognitive health in our aging populations.
