P&S Journal: Winter 1995, Vol.15, No.1
Alzheimer's and Down's Syndrome
Women under age 35 who give birth to babies with Down's syndrome are five times more likely to develop Alzheimer's disease in later life than mothers of children with other developmental disorders, according to a study led by Dr. Nicole Schupf, associate research scientist at the Gertrude Sergievsky Center for the Study of Nervous System Disorders at P&S, and conducted with Dr. Richard Mayeux, director of the Sergievsky Center. Dr. Schupf also heads the epidemiology laboratory at the New York State Institute for Basic Research in Developmental Disabilities.
Other studies have suggested that families with a history of Alzheimer's disease are more likely to produce children with Down's syndrome. But this study marked the first investigation of an association between the parental origin of trisomy-a condition in which women produce eggs with an extra chromosome-and risk of Alzheimer's disease, a degenerative disease of the central nervous system that affects memory processes.
"After age 35, the incidence of Down's syndrome increases dramatically with increasing maternal age," the authors wrote in The Lancet last summer. "For older mothers the increased risk of bearing a child with Down's syndrome may be influenced by normal aging, but a special susceptibility factor in younger mothers, perhaps involving an accelerated aging process, could lead to the birth of a child with Down's syndrome and to an increased risk of Alzheimer's disease in the mother and her relatives." This model of accelerated aging implies that an increased frequency of Alzheimer's should be observed primarily in mothers whose Down's syndrome births occurred when they were 35 years old or younger.
The researchers studied two groups of adults identified through the Developmental Disabilities Profile, a computerized data base maintained by the New York State Office of Mental Retardation and Developmental Disabilities. One group consisted of 96 adults with Down's syndrome and their families. The second group consisted of 80 adults with other forms of mental retardation and their families.
Study investigators used an extensive questionnaire to determine age, sex, level of education, family history of dementia, and risk of dementia. Those reporting a family history of dementia completed a second questionnaire asking for a more detailed history of symptoms and age at onset of dementia and a history of stroke, alcoholism, psychiatric disorders, seizures, syphilis, or other conditions that might result in dementia. Only parents without a history of stroke or other dementing conditions were considered as cases of Alzheimer's disease.
As predicted by the researchers, significant risk of dementia emerged only among mothers who were 35 years or younger when their child with Down's syndrome was born. Risk of dementia was the same among fathers of individuals with Down's syndrome and fathers of controls.
"We suggest that the mixed results of previous studies are due to a dilution of the 'at risk' pool by inclusion of paternal relatives and relatives of mothers who were older than 35 years of age at Down's syndrome birth, who do not have an increased risk of Alzheimer's," the authors wrote. "Further research may show that documenting the maternal family history of Alzheimer's disease can provide useful information for improving primary prevention of Down's syndrome."