Elsevier

The Lancet

Volume 377, Issue 9770, 19–25 March 2011, Pages 1019-1031
The Lancet

Seminar
Alzheimer's disease

https://doi.org/10.1016/S0140-6736(10)61349-9Get rights and content

Summary

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.

Section snippets

Epidemiology

The cost of caring for the increasing number of people with dementia continues to rise and thus accurate estimates of dementia prevalence are needed. Recent systematic reviews of epidemiological studies have provided comprehensive estimates of dementia prevalence. A WHO report1 estimated that dementia contributed 11·2% of years spent living with a disability in people over 60 years old—more than stroke, cardiovascular disease, and cancer. In 2005, Alzheimer's Disease International convened an

Pathogenesis

The two core pathological hallmarks of Alzheimer's disease are amyloid plaques and neurofibrillary tangles. The amyloid cascade hypothesis suggests that deposition of amyloid β (Aβ) triggers neuronal dysfunction and death in the brain (figure 1). In the original hypothesis, this neuronal dysfunction and death was thought to be a toxic effect of the total amyloid load. As knowledge of pathological changes in Alzheimer's disease increased, research focused on more specific alterations in Aβ

Diagnosis and biomarkers

An accurate diagnosis of dementia enables the detection of potentially treatable disorders that contribute to cognitive impairment, such as depression, vitamin deficiencies, and hypothyroidism, and allows patients and their families to plan their future life and finances, including advance directives and optimum treatment and care. With the prospect of development of disease-modifying drugs, early and accurate diagnosis and the ability to provide a prognosis is essential. Improvement of

Treatment

To effectively treat Alzheimer's disease, patients and families should be involved as soon as the diagnosis is made. The ability of patients to correctly use money, medications, transportation, and home appliances should be assessed, and information, services, and support should be provided to help patients and their families to live well with dementia. Concomitant medical conditions and polypharmacy can exacerbate cognitive decline and increase the risk of cerebrovascular disease and therefore

Risk and protective factors

At present, reduction of the risk of developing Alzheimer's disease depends mostly upon lifestyle changes and improved treatment or prevention of medical conditions that confer additional risk. A database of that assess environmental risk factors for Alzheimer's disease is available online. There is a large amount of data about potential risk factors for Alzheimer's disease, including age,2 genetics,13 and head injury.108 Here, we focus on modifiable risk factors. Table 4 summarises the

Search strategy and selection criteria

We searched the Cochrane library (1990–January, 2010), Medline (1990–January, 2010), and Embase (1990–January, 2010) for terms associated with the epidemiology, pathogenesis, diagnosis, treatment, and modifiable risk factors for Alzheimer's disease. For epidemiology we used the following terms: “prevalence OR incidence OR rates OR frequency” AND “dementia, Alzheimer's disease”. In the first instance we preferred systematic reviews and Delphi consensus. For pathogenesis, we used the terms “genes

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