Early reviews identified over 20 risk factors associated with Alzheimer's disease (AD) including age, familial inheritance, exposure to aluminium, traumatic brain injury (TBI), and associated co-morbidities such as vascular disease and infection. In the light of recent evidence, this review reconsiders these risk factors, identifies those currently regarded as important, and discusses various hypotheses to explain how they may cause AD. Rare forms of early-onset familial AD (EO-FAD) are strongly linked to causal gene mutations, viz. mutations in amyloid precursor protein (APP) and presenilin (PSEN1/2) genes. By contrast, late-onset sporadic AD (LO-SAD) is a multifactorial disorder in which age-related changes, genetic risk factors, such as allelic variation in apolipoprotein E (Apo E) and many other genes, vascular disease, TBI and risk factors associated with diet, the immune system, mitochondrial function, metal exposure, and infection are all implicated. These risk factors may act collectively to cause AD pathology: 1) by promoting the liberation of oxygen free radicals with age, 2) via environmental stress acting on regulatory genes early and later in life ('dual hit' hypothesis), or 3) by increasing the cumulative 'allostatic load' on the body over a lifetime. As a consequence, life-style changes which reduce the impact of these factors may be necessary to lower the risk of AD.

Alzheimer's disease (AD) is a complex and heterogeneous neurodegenerative disorder, classified as either early onset (under 65 years of age), or late onset (over 65 years of age). Three main genes are involved in early onset AD: amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2). The apolipoprotein E (APOE) E4 allele has been found to be a main risk factor for late-onset Alzheimer's disease. Additionally, genome-wide association studies (GWASs) have identified several genes that might be potential risk factors for AD, including clusterin (CLU), complement receptor 1 (CR1), phosphatidylinositol binding clathrin assembly protein (PICALM), and sortilin-related receptor (SORL1). Recent studies have discovered additional novel genes that might be involved in late-onset AD, such as triggering receptor expressed on myeloid cells 2 (TREM2) and cluster of differentiation 33 (CD33). Identification of new AD-related genes is important for better understanding of the pathomechanisms leading to neurodegeneration. Since the differential diagnoses of neurodegenerative disorders are difficult, especially in the early stages, genetic testing is essential for diagnostic processes. Next-generation sequencing studies have been successfully used for detecting mutations, monitoring the epigenetic changes, and analyzing transcriptomes. These studies may be a promising approach toward understanding the complete genetic mechanisms of diverse genetic disorders such as AD.

An estimated 24 million people worldwide have dementia, the majority of whom are thought to have Alzheimer's disease. Thus, Alzheimer's disease represents a major public health concern and has been identified as a research priority. Although there are licensed treatments that can alleviate symptoms of Alzheimer's disease, there is a pressing need to improve our understanding of pathogenesis to enable development of disease-modifying treatments. Methods for improving diagnosis are also moving forward, but a better consensus is needed for development of a panel of biological and neuroimaging biomarkers that support clinical diagnosis. There is now strong evidence of potential risk and protective factors for Alzheimer's disease, dementia, and cognitive decline, but further work is needed to understand these better and to establish whether interventions can substantially lower these risks. In this Seminar, we provide an overview of recent evidence regarding the epidemiology, pathogenesis, diagnosis, and treatment of Alzheimer's disease, and discuss potential ways to reduce the risk of developing the disease.Copyright © 2011 Elsevier Ltd. All rights reserved.

The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of revising the 1984 criteria for Alzheimer's disease (AD) dementia. The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available. We present criteria for all-cause dementia and for AD dementia. We retained the general framework of probable AD dementia from the 1984 criteria. On the basis of the past 27 years of experience, we made several changes in the clinical criteria for the diagnosis. We also retained the term possible AD dementia, but redefined it in a manner more focused than before. Biomarker evidence was also integrated into the diagnostic formulations for probable and possible AD dementia for use in research settings. The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis of AD dementia. Much work lies ahead for validating the biomarker diagnosis of AD dementia.Copyright © 2011. Published by Elsevier Inc.

The author proposes an etiological hypothesis for Alzheimer's disease (malnutrition with or without malabsorption); this may explain clinical and biological phenomena which occur in this disease. A search through the literature revealed that all people suffering from Down's syndrome (and who all develop Alzheimer's disease from forty years of age) also suffer from malnutrition. This hypothesis may explain the anatomical and neurobiochemical perturbations and the inefficacy of choline. Consequent nutritional treatment of the disease is proposed.