Introduction Alzheimer s disease AD is a chronic neurodegene

Introduction Alzheimer’s disease (AD) is a chronic neurodegenerative disease and the most common cause of dementia, accounting for over 50% of individuals affected [1]. This disease is characterized by progressive memory impairment and cognitive decline interfering with daily life activities. The most common early symptom of AD is difficulty remembering recent events. The symptoms of patients with advancing disease can include executive dysfunction, disorientation, problems with language, mood swings, behavioral changes and impaired self-care [2]. Age-standardized prevalence for individuals aged over 60 years varied between 5% and 7% in most world regions [3]. An estimated 35.6 million people lived with dementia worldwide in 2010, with numbers expected to almost double every 20 years [3]. AD has a long preclinical phase of several decades and the most important risk factor for AD is increasing age. Impaired vascular health has been shown to be another major risk factor for cognitive decline and interventions for cardiovascular risk may therefore improve cognitive health at the population level [4,5]. Other lifestyle-related factors, such as obesity, diabetes, smoking, diet, physical and mental inactivity, have been suggested to play a role in dementia, and potential preventive measures related to these risk factors should be investigated [6]. AD is neuropathologically defined by neuronal loss and the accumulation of extracellular amyloid β-peptide (Aβ)-containing plaques and intracellular hyperphosphorylated tau protein-containing neurofibrillary tangles in the order NSC127716 [7]. The accumulation of abnormally folded Aβ and tau proteins in amyloid plaques and neuronal tangles, respectively, appear to be causally associated with the neurodegeneration in AD [8]. However, a linear causality between amyloid and tau and AD seems to be too simplistic an assumption made by the original amyloid hypothesis [9]. The cognitive decline in AD is associated with progressive synaptic dysfunction and neuronal atrophy, mainly in the neocortex, limbic system and subcortical brain areas [7]. The etiology of AD is unknown, but both genetic and environmental risk factors have been suggested to be involved. Genome-wide association studies have shown more than 20 genetic loci to be associated with the risk of AD [10]. The identified AD risk genes are related to lipid and cholesterol processing, inflammatory responses and the immune system. The majority of these genes affect Aβ production and clearance, emphasizing the special role of this pathway in the pathogenesis of AD. Carriers of the presenilin 1 mutation have the highest risk of AD [10]. Another major susceptibility gene is the apolipoprotein E (ApoE) gene which is related to sporadic late-onset AD, the epsilon 4 (E4) variant of ApoE was found to increase the risk for AD [10]. Curative therapies for AD are not available and supportive care plays an important role in the treatment of patients with AD. Symptomatic treatments providing temporary alleviation of the symptoms of AD without modifying the disease progression include drugs such as acetylcholinesterase inhibitors and the glutamate antagonist memantine [1]. Most of these drugs offer at best a moderate symptomatic effect. Other therapeutic strategies focus on anti-amyloid approaches, including active and passive immunization, γ-secretase and β-secretase inhibitors, and antiaggregation drugs [1]. A further understanding of the etiopathogenesis of AD is needed in order to develop disease-modifying therapies which can prevent, delay or treat the symptoms of AD. Type 2 diabetes and insulin resistance are the main lifestyle-related risk factors for AD. Lifestyle-modifying approaches including diet and physical exercise may show beneficial effects in the prevention and early treatment of AD. The accumulation of Aβ and the development of AD have been proposed to be related to dietary factors. For example, the findings of a Dutch study suggested that diets rich in saturated fat and cholesterol increase the risk of several types of dementia [11]. However, a subsequent 6-year follow-up of the same study population found no correlation between fat consumption and dementia [12]. Another large study of elderly participants found only weak trends between cognitive decline and the intake of saturated fat and cholesterol as assessed using a food questionnaire [13].