Immunological associations in familial and non-familial Alzheimer patients and their families.

A number of autoimmune diseases and immune-related conditions were investigated in a series of 100 Alzheimer patients and their families. The group was divided into those who had familial dementia of the Alzheimer type and non-familial dementia of the Alzheimer type. HLA DR3 was associated with the familial dementia of the Alzheimer type patients. Adult exposure to tuberculosis appeared to be a risk factor for familial dementia of the Alzheimer type patients. Autoimmune diseases clustered among the non-familial dementia of the Alzheimer type patients, and also among their relatives. Asthma and infertility were also significantly increased among non-familial dementia of the Alzheimer type relatives. The analysis showed that (1) autoimmunity may be important in the sporadic form of Alzheimer disease; (2) it may be possible to confer a decreased risk for Alzheimer disease among relatives when many autoimmune diseases occur in the family; (3) it may be important to assess environmental risk factors for Alzheimer disease separately in patients with familial and sporadic disease; and (4) the efficacy of drug therapies may be dependent on whether the patients have a familial or sporadic form of Alzheimer disease.

Dementia in Newfoundland: identification of a geographical isolate?

STUDY OBJECTIVE: The aims were (1) to identify from death certificates regions with an increased incidence of dementia mortality; and (2) to determine whether a previously observed excess of patients with Alzheimer disease originating from a small area could be confirmed in a survey of death certificates. DESIGN: The study identified all individuals dying with dementia, recorded on death certificates as an immediate, antecedent, underlying, or contributing cause of death. Rather than the usual residence, the birthplace of these individuals was used to determine regional differences in dementia mortality. A comparison was made of two areas to test the significance of a geographical isolate of persons. To test for a possible genetic component of the excess, an analysis was made of the frequencies of family names. To test for a possible environmental component an analysis was made of standard measurements of drinking water quality. SETTING: The survey data were derived from all 1985 and 1986 deaths in the province of Newfoundland. MEASUREMENTS AND MAIN RESULTS: Based on the current census population, the prevalence of dementia at death for 1985 and 1986 was 34 and 37/100,000. For both years there was a significant excess of persons originating from a small area (95% CI, 1.1-20.7%, and 2.5-20.4%). This excess could not be explained by differences in age, sex, ethnic origin, or by variation in mobility patterns. The study area has a high concentration of aluminium in the drinking water. An analysis of the family names gave inconclusive evidence of a clustering among the dementia cases. CONCLUSIONS: If all contributing causes of death are recorded and the birthplace of individuals is noted, mortality statistics can reveal regional differences in dementia rates. This shows the need to examine areas smaller than census districts to identify subpopulation variation in the prevalence of dementia. Environmental influences can vary substantially in areas relatively close together, as evidenced in measurements of drinking water chemistry. Genetic influences are more likely to be revealed from the birthplace of individuals, which may indicate a common ancestry.

Association between Alzheimer disease and amyotrophic lateral sclerosis?

We report two cases of Alzheimer disease (AD)--one of them familial--in which the patient also had amyotrophic lateral sclerosis (ALS), and one patient with familial AD who had a son with ALS. Three further cases of probable ALS were found in pedigrees of AD reported from the literature. It is proposed that this association is not coincidental, but may suggest an etiological factor in common.

Heterogeneity by cluster analysis techniques of Graves' patients typed for HLA DR and IgG heavy chain markers.

In a previous study we were able to separate, using cluster analysis, 196 patients with Graves' disease evaluated for a large number of clinical and laboratory characteristics, including HLA-A and HLA-B typing into one subset with recurring disease and a high prevalence of ophthalmopathy and another subset with mild disease and little ophthalmopathy. Prevalence of HLA-B8 was much higher in the first as compared to the second group. The present study was undertaken in 117 new patients with Graves' disease, typed for HLA-A, HLA-B, HLA-C and DR antigens and IgG heavy chain markers, to determine whether these characteristics could be used to segregate patients into clinically relevant subsets. There was a greater proportion of Gm fb homozygotes among patients than among controls (chi2 = 4.71, p less than 0.05) as well as individuals with HLA-B8 and DR3, previously documented for this disease. Two patient clusters were identified. In one (C1), there is a high incidence of exophthalmos, recurrence of hyperthyroidism after drug treatment, high titres of anti-thyroglobulin antibody, and an association with other autoimmune (including thyroid) diseases, a tendency for the disease to be familial and the presence of larger goitres. The incidence of HLA-B8 was greater in C1, while HLA-B12 was more frequent in the mild cluster, C2. HLA-DR3 was found to be associated with patients in the severe cluster and HLA-DR2 with patients in the mild cluster.(ABSTRACT TRUNCATED AT 250 WORDS)

A prognostic score for Graves' disease.

We have reanalysed the clinical and laboratory data on 196 individuals with Graves' disease. The consensus of two clustering techniques and a new method of allocating patients to a cluster resulted in two groups of patients, those with a severe and others with a mild disease. The severe disorder is characterized by a high frequency of HLA-B8 and -Al, a low complement level, high titres of circulating immune complex and anti-thyroglobulin antibody, a high lymphocyte transformation index and serum T3 level, a low level of active E-rosettes, large goitres and a high value for the Crooks test. The mild disorder shows a higher frequency of HLA-B12 and an abnormally low absolute lymphocyte number. A weight was calculated for each character according to the relative frequency in the two clusters. A total score could then be calculated for each patient based on their clinical and laboratory findings. There were two distinct distributions of scores corresponding to the two subgroups. This suggests different aetiological factors which may be more easily studied in these more homogeneous groups. Prognostic predictions can be made using the score. The risk of recurrence and the frequency and severity of ophthalmopathy increases dramatically as the score increases. The use of the score in making therapeutic decisions needs to be tested.