Alzheimer's, Parkinson's Don't Show Familial Relationship

Could it be that the two most common neurodegenerative disorders—Parkinson's disease and Alzheimer's disease—share common origins?

Some evidence suggests that they might. For example, as many as one-fourth of Alzheimer's patients develop Parkinsonian symptoms, and patients with rapidly progressing Parkinson's have more than an eightfold increased risk of developing Alzheimer's compared with patients with slowly progressing Parkinson's (Psychiatric News, October. 19, 2001; June 20, 2003).

A new, large study, however, argues that the two illnesses are not related—or at least, not genetically related. It found no evidence of an increased risk of Alzheimer's in some 2,500 relatives of patients with Parkinson's compared with some 2,300 relatives of similar persons without Parkinson's, thus arguing against a common genetic cause for the two diseases.

One of the primary investigators was Karen Marder, M.D., a professor of neurology at Columbia University. Results appeared in the July Archives of Neurology.

Some 500 persons with Parkinson's disease were recruited from the Center for Parkinson's Disease and Other Movement Disorders of the Columbia Presbyterian Medical Center in New York City and also from a neurology clinic serving persons in northern Manhattan. About 400 other individuals were recruited by random-digit dialing and matched with the Parkinson's subjects on age, gender, and ethnicity.

Each subject was given the Mini-Mental State Examination. Anyone screening positive for dementia on this exam was excluded from the study. The reason the researchers excluded anyone who screened positive for dementia was to guard against subjects providing inaccurate information about whether their relatives had Alzheimer's disease. The researchers admitted in their study report, however, that by eliminating some subjects who had both Parkinson's and Alzheimer's, they could not “explore the incidence of Alzheimer's disease in relatives of patients with Parkinson's disease with dementia.”

The subjects with Parkinson's disease were then given a structured family history interview to learn whether some 2,500 of their first-degree relatives had Alzheimer's. The researchers also tried to obtain a second interview by telephone with each first-degree relative of a subject to confirm what the subject had reported, regardless of whether the subject said that the relative had Alzheimer's. And if the first-degree relative had died or was unable to provide information, the researchers tried to contact another informant to verify what the subject had said.

A similar protocol was followed to learn if any of the approximately 2,300 first-degree relatives of control subjects had Alzheimer's disease.

A total of 61 first-degree relatives (2.4 percent) of patients with Parkinson's were found to have Alzheimer's, while 52 first-degree relatives of control subjects (2.3 percent) were found to have the illness.

The risk of Alzheimer's was thus not increased in relatives of Parkinson's subjects compared with relatives of control subjects.

The researchers also compared the incidence of Alzheimer's in the relatives of subjects who had developed Parkinson's at age 50 or younger with the incidence of Alzheimer's in relatives of matching control subjects. The investigators' rationale was that early onset of a disorder often signals a genetic origin. But again, they found no significantly increased risk of Alzheimer's in the relatives of Parkinson's subjects.

Thus, it looks as though Parkinson's disease and Alzheimer's disease do not share a common genetic origin, Marder and her team concluded. “This is also consistent with the lack of overlap in currently known genetic causes of Parkinson's disease and Alzheimer's disease,” they pointed out.

“The evidence appears quite convincing,” Walter Kukull, Ph.D., of the National Alzheimer's Coordinating Center at the University of Washington, wrote in an accompanying editorial. Yet there are several limitations to the study, he cautioned. For instance, as mentioned above, relatives of persons who had both Parkinson's and Alzheimer's were not included in the study, which may have skewed results. In other words, if such relatives had been included, then perhaps the researchers might have found that Parkinson's and Alzheimer's are genetically related. Also, the family history interview method that was used in the study is rather low in sensitivity. (However, as the researchers pointed out in their report, they“ tried to maximize sensitivity by collecting a second informant report....”)

The study was supported by federal grants and by the Parkinson's Disease Foundation.

An abstract of the report, “Lack of Familial Aggregation of Parkinson Disease and Alzheimer Disease,” is posted online at<http://archneur.ama-assn.org/cgi/content/abstract/61/7/1033>.▪

Arch Neurol 2004 61 1033