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While the majority of dementias are sporadic, many diseases causing dementia can also occur on a familial basis. Some of these show an autosomal or sex linked inheritance, In others, [...]

Byline: E.K. Warrington (1), S.K. Agnew (1), A.M. Kennedy (1), M.N. Rossor (1) Keywords: Key words Neuropsychology; Familial Alzheimer's disease Abstract: Patients with familial Alzheimer's disease and a subset known to have presenilin mutations were compared with sporadic cases on a comprehensive battery of cognitive tests. These included measures of memory, intelligence, language and perception. The three group were very comparable, in terms of severity, on global measures of dementia. However, their profiles/patterns of cognitive impairment differed in two respects the group with sporadic Alzheimer's disease were significantly more impaired on tests of object naming and object perception than either the group with familial Alzheimer's disease or group with familial Alzheimer's disease and presenilin mutations, yet they scored at a significantly higher level on the measure of verbal intelligence. This study provides further evidence of the heterogeneity of the disease process. Author Affiliation: (1) Dementia Research Group, Department of Clinical Neurology, Institute of Neurology, Queen Square, London, WC1 3BG, UK, Tel.: +44-20-78 37 36 11, ext 36 39, Fax: +44-20-72 09 01 82, GB Article note: Received: 25 April 2000 / Received in revised form: 26 June 2000 / Accepted: 14 July 2000

The majority of cases of Alzheimer's disease (AD) occur sporadically. However, there are some families in which Alzheimer's disease seems to be passed from generation to generation as an inherited trait. Although these cases of familial Alzheimer's disease (FAD) constitute only a small minority, they may provide important clues to the development of the disease in general. Furthermore, there has been some suggestion that even in the sporadic cases which are not, strictly speaking, inherited, there may still be a strong contribution of an individual's genetic makeup to the ultimate development of AD. A study was undertaken to explore in greater detail the mode of inheritance of FAD. Seventy affected family groups were studied, consisting of 541 affected and 1,066 unaffected offspring of parents with AD. Such studies are complicated by the fact that unaffected offspring may simply not be old enough to develop the symptoms of AD, and any investigation of the inheritance of the disorder must use statistical methods to take this possibility into account. Overall, a rate of Alzheimer's disease of 64 percent (by age 87) was observed for the children of parents with FAD. This figure is slightly higher than the 50 percent which would be expected if the disorder were randomly passed from generation to generation as a dominant trait. However, when the families were grouped by average age of onset, a different pattern emerged. By defining 'early-onset' AD as disease symptoms beginning before the age of 58, it was found that the statistics of FAD differed for early- and late-onset disease. In families with early-onset FAD, the rate among offspring of affected parents was 53 percent, very close to the theoretically expected 50 percent. In contrast, among the late-onset families, in which disease symptoms first appeared after the age of 58, the rate of disease among offspring of affected parents was 86 percent, significantly higher. These observations suggest that the early-onset disease may be inherited as a simple dominant trait, while the late-onset disease may have a more complicated mode of inheritance which is not yet understood. (Consumer Summary produced by Reliance Medical Information, Inc.)