Alzheimer's disease: Genetic aspects and associated clinical disorders

TLDR

The study examined genetic factors and related clinical disorders in 68 consecutive patients with early‑onset Alzheimer’s disease (≤70 years). Early‑onset Alzheimer’s disease showed strong familial aggregation of dementia (25 % of families, 14 % cumulative incidence at 75 years), an elevated rate of Down syndrome among relatives, and a higher prevalence of thyroid disease in affected women, while no excess of hematological cancers or abnormal parental age was observed.

Abstract

Abstract Genetic aspects and associated clinical disorders were studied in a consecutive series of 68 men and women in whom Alzheimer's disease appeared at or before age 70. Secondary cases of dementia were found in 17 (25%) of the families, affecting 22 of the probands' siblings and parents. The cumulative incidence of Alzheimer's disease in these relatives was approximately 14% at age 75. An increased frequency of Down's syndrome was observed among relatives of the probands: a rate of 3.6 per 1, 000, as compared with an expected rate of 1.3 per 1, 000. A history of thyroid disease was established in 9 (19.6%) of the 46 female probands, a frequency greater than that reported in the general population. There was no excess of hematological malignancies among the blood relatives, and parental age at the time of birth of the probands did not differ from the norm. The results of this study indicate that early‐onset Alzheimer's disease is associated with a genetic factor manifested in a substantial familial aggregation of dementia, a probable excess of Down's syndrome in the probands' relatives, and a possible association with thyroid dysfunction in women with this form of dementia.