Dementing illnesses, including Alzheimer disease (AD), are major sources of morbidity and mortality that affect more than several hundred millions of persons in the increasingly aging society of developed and developing countries. Efforts to develop strategies to delay and prevent the onset of the potentially devastating illnesses are now ongoing worldwide.
The pathology of AD is complex and involves numerous pathways including defective beta-amyloid (Aβ) protein metabolism, abnormalities of glutamatergic, adrenergic, serotonergic and dopaminergic neurotransmission. The pathways are said to involve inflammatory, oxidative and hormonal pathways.1 Even though the precise cause of AD is unknown, it is clear that genetic factors play a major role. However, the four genes that have been identified so far are linked to less than 10% of total AD cases, and there are numerous familial cases that are not linked to any of the genes. On the other hand, non-genetic factors also play extremely important roles in the pathophysiology of AD, epigenetic components of neurons such as mitochondria, proteasomes and post-translation protein modifications (processing of amyloid precursor protein to Aβ and hyperphosphorylation of tau), rather than nuclear genes, are primary targets for the actions of diverse groups of neurotoxins.2
During the last decades, researchers have found several risk factors for the development of AD and other dementing illnesses. Among them, lifestyle-related factors such as exercise and nutrition have received increasing attention. Some longitudinal studies and randomized trials have suggested that exercise enhances cognitive functioning of elderly individuals, whereas other studies have failed to observe such benefits.3–6
Only recently, several encouraging studies have been conducted. A recent investigation has demonstrated that exercise and environmental enrichment lead to reduction in amyloid deposit in AD-like transgenic mice.7 Additionally, the administration of docosahexaenoic acid (DHA) also succeeded in reducing amyloid deposits in similar mice.8 Furthermore, it has been reported that the benefit of donepezil in delaying the progression of mild cognitive impairment (MCI) to AD was evident during 1-year follow-up.9 All of these studies inspire us to develop effective interventions including lifestyle changes that might prevent the onset of human AD.
In order to provide sound interventions against the development of AD, it is indispensable to evaluate in detail the putative risk factors for AD, especially modifiable lifestyle related factors. Thus, in this article, we will review recent findings regarding nutrition as possible method of AD prevention. The main issues dealt with in the review and their putative mechanisms are shown in the Table 1.
|Dietary fat: Omega-3 fatty acids (EPA, DHA)|
|neural function including neurotransmission, membrane fluidity, ion channel and enzyme regulation and gene expression|
|Diabetes: Glucose, Insulin|
|1 glucose regulatory mechanisms can also affect amyloid precursor protein (APP)|
|2 the insulin degrading enzyme can break down Aβ as well as insulin|
|3 insulin also reduces intracellular accumulation of Aβ by accelerating APP trafficking|
|Antioxidants: Vitamin C, E, beta-carotene|
|to reduce reactive oxygen species (ROS) causing the neuronal degeneration in AD|
|putative antioxidant properties and to reduce the aggregation of the Aβ|
|Green tea, melatonin, miscellaneous|