Genetic vs Environmental Factors in the Causation of Alzheimer’s Disease

Abstract & Commentary

Source: Pedersen NL, et al. How heritable is Alzheimer’s disease late in life? Findings from Swedish twins. Ann Neurol. Early view online.

The availability of comprehensive records of public health in Scandinavian countries is a major advantage in working out epidemiological studies. This has enabled the assessment of the role of genetics vs environmental contributions to diseases ranging from schizophrenia to Alzheimer’s disease (AD). The present study of Swedish twins including many older than 80 now suggests that the genetic component of AD may be less than previously thought. The current study, which had an average of 5 years of follow-up, was notable for the large number of twin pairs older than 80. There were 297 out of a total of 662 initially enrolled. Pedersen and associates found that among 221 pairs of monozygotic twins, 21 had 1 sibling afflicted with AD and 5 had both siblings with the disease, for a concordance rate of 32.2%. The corresponding figures for 329 dizygotic twins were 42 discordant pairs and only 2 concordant pairs, for an overall concordance rate of 8.7%. They then performed structural modeling of the genetic vs environmental contributions and found that the genetic contribution to AD in the sample was 48%. This is considerably lower than the prior estimates in which the genetic risk was felt to be as high as 75%. A major difference in this study is that it was based on incident cases rather than prevalent cases, which provide only a snapshot of cases at a given time. Incident cases refer to those arising during the course of the study period. Subjects older than 80 did not have significantly greater environmental risk relative to those younger than 80.

Commentary

These findings are of interest since they suggest that environmental factors may play a larger role in AD than previously suggested. Pedersen et al note that it would be important to identify further genetic factors that place individuals at risk. They, however, point out that modulation of environmental risk factors may play an equally important role. These include such commonly cited risk factors as vitamin B12 deficits, elevated homocysteine, drug-induced decrements, recent head trauma, and cerebral ischemic disease. — M. Flint Beal

Dr. Beal, Professor and Chairman; Department of Neurology; Cornell University Medical College New York, NY, is Editor of Neurology Alert.

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