Risk factors for Alzheimer's

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Much has been learned about Alzheimer disease (AD) since Alois Alzheimer first described it more than a century ago, but to date no consensus has been reached on its etiology, no universally accepted preventive interventions have become available, and treatments are only minimally effective. Although a considerable amount of research is underway, much of it is as yet inconclusive and often mired in significant methodologic challenges. Meanwhile, the number of persons afflicted with AD has been steadily increasing. For the United States alone, estimates have been as high as 5 million in 2007, up from 4 million.Risk factors for AD are notoriously difficult to isolate as they interact with each other in a variety of ways. As a result, the outcomes of different studies are sometimes hard to reconcile and frequently require further clarification. Moreover, there is no uniform method of reporting (eg, prevalence, incidence, and lifetime risk), further complicating comparison of study outcomes. Nevertheless, 2 risk factors have become firmly established: chronologic age and positive family history.

Chronologic age has emerged as a crucially important risk factor, not only in itself but also, as we will see, through its interactions with a variety of other risk factors. For example, in a recent collaborative study carried out in 8 European countries, the pooled AD incidence rate per 1000 person-years rose from 1.2 to 9.1 and 35.3 for ages 65 to 69, 75 to 79, and 85 to 89 years, respectively. In the United States, the current prevalence of AD is estimated as 2%, 19%, and 42% for age groups 65 to 74, 75 to 84, and 85+ years, respectively.

Positive family history of AD is another risk factor for AD, independent of any identified genetic factors. It is generally reported that a person with at least 1 first-degree relative with dementia has 2 to 4 times the lifetime risk of developing AD compared with someone without such a relative. These estimates may be sensitive to age structure and other modeling issues, such as the uncertainty of the diagnosis of AD/dementia in long-deceased relatives, and conversely, the inability to classify relatives who did not live through the age of risk as clearly free of AD/dementia. Moreover, although positive family history increases the risk for developing AD, this effect may diminish with age and may be minimal or absent after the age of 85 years. Other studies point to a different interaction effect of chronologic age and positive family history. The age at which the first-degree relative with AD (proband) manifests the symptoms of AD [age at onset (AAO)] may itself be a risk factor for the development of AD. The younger the proband's AAO, the greater the genetic risk for the relatives, regardless of the age of the relatives themselves.

Within the group of first-degree relatives, the highest risk is faced by persons who have an identical twin with AD. The study of twins (identical or monozygotic and fraternal or dizygotic) offers a unique opportunity to explore the relative contributions of genetic and other influences to the risk of developing AD. In the largest twin study to date, the Swedish twin study, heritability of AD was estimated to be 58%, with nongenetic risk factors playing an important role (nonshared environmental influences 23%, shared environmental influences 19%). In addition, twin studies clearly document that even in concordant twins (ie, both twins develop AD) there can be differences in AAO of as much as 16 years, indicating that the effects of both chronologic age and positive family history vary significantly as they interact with other risk factors. http://ovidsp.tx.ovid.com/spa/ovidweb.cgi?QS2

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