Human hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D), an autosomal dominant form of cerebral amyloid angiopathy (CAA), is characterized by extensive amyloid deposition in the small leptomeningeal arteries and cortical arterioles, which lead to an early death of those afflicted in their fifth or sixth decade. Immunohistochemical and biochemical studies have indicated that the amyloid subunit in HCHWA-D is antigenically related to and homologous in sequence with the amyloid beta protein isolated from brains of patients with Alzheimer's disease and Down syndrome. The amyloid beta protein is encoded by the amyloid beta protein precursor (APP) gene located on chromosome 21. Restriction fragment length polymorphisms detected by the APP gene were used to examine whether this gene is a candidate for the genetic defect in HCHWA-D. The data indicate that the APP gene is tightly linked to HCHWA-D and therefore, in contrast to familial Alzheimer's disease, cannot be excluded as the site of mutation in HCHWA-D.

We have studied the 6-month follow-up attitudes of 63 individuals, after predictive testing for Huntington disease (HD). Reducing uncertainty (81%) and family planning (60%) were the major reasons for taking the test. Twenty-four individuals were diagnosed as having an increased risk (+/- 98%), and 39 a decreased risk (+/- 2%). Among those with an increased risk, denial or minimization of the ultimate impact of the increased risk result was observed. Most of them (84%) rated their current life situation, at the very least, as being good. Twenty-one percent of individuals with an increased risk who originally planned to have a family, decided to refrain from having children. Sixty percent of those with increased risk who still wished to have children, would choose to have prenatal testing. In most individuals with increased risk, the test result did not increase the previously expected control over their own future. Half of the partners of persons with increased risk acknowledged the burden of the future disease. Half had no one in whom they could confide. They showed loyalty to the denial and avoidance reactions of their spouses. Half of the individuals with decreased risk denied the impact of the result, as reflected by absence of relief, and emotional numbness. A third of persons with decreased risk experienced involvement with problems of affected relatives. We found that 20% of all participants were discontented with the support given by their general practitioner, who is normally regarded as being the most significant professional for aftercare. Our findings suggest that the perpetuation

1) The more that applicants suffered from intrusive feelings about HD and tried to avoid HD-related situations, prior to the test, the greater the chance that they will experience this 6 months after the test if they proved to be at increased risk; 2) the more that both individuals with increased risk and those with decreased risk who suffered from the threat of having HD tried to avoid HD-related situations prior to the test and the less satisfied they were with available support, the greater the probability that they will show avoidance behavior after the test; 3) the more pessimistic that individuals with increased risk as well as those with decreased risk were about their future prior to the test, the more they avoided HD-related situations and the more dissatisfied they were about their available support (pretest), the greater the probability that they will become depressive and suicidal. Psychological adjustment was also studied as a function of a) intrusion/denial-avoidance pattern over time and b) healthy mental functioning/future expectancies. Most individuals with increased risk (86%) seem to cope well thus far, although this was based largely on strong psychological defenses and dependent on satisfactory relationships.(ABSTRACT TRUNCATED AT 250 WORDS)

The age at onset and duration of illness were studied in patients with Huntington's disease in the Leiden Roster which at 1 July 1990 contained 2787 patients. Of 1106 patients, 800 deceased and 306 alive, the age at onset was known. The median duration was 16-2 (range 2-45) years. In contrast to the current opinion, the median duration was independent of the age of onset. The median duration in juvenile Huntington's disease was 17'1 years, which is much longer than reported in the literature, and comparable with the categories for the age of onset of 20-34 and 35-49 years. Only in the group where onset was over 50 years of age was the median duration somewhat shorter (15.6 years), which can be ascribed to unrelated causes of death. As age of onset and duration of illness are not related, at least two mechanisms to determine the clinical course have to be postulated: one for age of onset and another for duration of illness. Duration was shorter for males, especially for those with an affected father. ( Neurol Neurosurg Psychiatry 1993;56:98-100)

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