Prospective study of risk factors for Alzheimer's disease: results at 7.5 years.

OBJECTIVE: The primary goal of this study was to evaluate increased platelet membrane fluidity as a putative risk factor for Alzheimer's disease and its relationship to the APOE epsilon4 genotype. METHOD: This report describes the results of a prospective, longitudinal study of 330 initially asymptomatic, first-degree relatives of probands with Alzheimer's disease. RESULTS: Nine incident cases of Alzheimer's disease were detected during the first 2,220 subject-years of the follow-up period. Age, increased platelet membrane fluidity, and the APOE epsilon4 allele made significant independent contributions to the risk of developing Alzheimer's disease, while sex and years of education did not. Increased platelet membrane fluidity was associated with incident Alzheimer's disease cases between the ages of 64 and 71, while the epsilon4 allele was associated with incident Alzheimer's disease cases from age 64 until at least age 80. CONCLUSIONS: These results indicate that increased platelet membrane fluidity is not produced by the APOE epsilon4 allele. Instead, increased platelet membrane fluidity and the epsilon4 allele appear to make significant independent contributions to the risk of developing Alzheimer's disease among the first-degree relatives of patients with this disorder. Moreover, the age ranges over which these risk factors operate appear to be different.

Prospective study of increased platelet membrane fluidity as a risk factor for Alzheimer's disease: results at 5 years.

OBJECTIVE: The primary goal of this study was to evaluate increased platelet membrane fluidity as a putative risk factor for Alzheimer's disease. METHOD: This report describes the initial results of a prospective, longitudinal study of 330 initially asymptomatic, first-degree relatives of probands with Alzheimer's disease. RESULTS: Five incident cases of Alzheimer's disease were detected during the first 1,582 subject-years of the follow-up period. The age-specific incidence of Alzheimer's disease was several-fold higher than corresponding figures that were obtained in two prospective community studies. Most important, both age and increased platelet membrane fluidity made significant independent contributions to the risk of developing Alzheimer's disease. CONCLUSIONS: These results validate age and a family history of Alzheimer's disease as risk factors for this disorder and provide the first prospective evidence of increased platelet membrane fluidity as a biological risk factor for Alzheimer's disease.

Ethanol's fluidizing effects on RBC membranes from children at risk for alcoholism.

The fluidizing effects of ethanol on membrane fluidity at 37 degrees C have been assessed using steady-state anisotropy measurements in both children at high risk for developing alcoholism and control children. Erythrocyte membranes were labeled with 1,6-diphenyl-1,3,5-hexatriene (DPH) and fluidity measurements recorded by steady-state fluorescence anisotropy for three ethanol concentrations--0, 0.5 M, and 1.0 M. The in vitro fluidizing effects of acute ethanol treatment by concentration were clearly shown in both groups. However, RBC membranes taken from children at high risk for developing alcoholism showed no significant differences in baseline membrane fluidity or to the fludizing effects of ethanol.

Risk factors for stroke as predictors of platelet membrane fluidity in Alzheimer's disease.

We have previously reported that increased platelet membrane fluidity identifies a subgroup of patients with Alzheimer's disease who have distinct clinical features including an earlier age of symptomatic onset, a more rapidly progressive cognitive decline, and a decreased prevalence of focal electroencephalographic findings. In the current study, these patients also exhibited a decreased prevalence of risk factors for stroke compared with patients who had normal platelet membrane fluidity. Our findings suggest that the platelet membrane abnormality describes a clinical subgroup of patients with Alzheimer's disease who are less likely to have coexisting cerebrovascular disease than the remaining patients who meet clinical consensus criteria for probable Alzheimer's disease.

[Theodor Billroth and Johannes Brahms--friendship between two giants]. / Theodor Billroth a Johannes Brahms--priatel'stvo dvoch velikánov.

The study portrays the exceptional personality of Theodor Billroth and his friendship with Johannes Brahms. Billroth who laid the foundation of modern abdominal surgery by performing his pioneer operations was also an excellent musician and connoisseur of the arts. His enthusiasm for the music of Brahms and Brahms' respect for Billroth, his knowledge and musical instinct, were the basis of a mutual intensive relationship. The paper describes the productive period of a 30-year friendship of the two great men, presenting basic bibliographic data and an outline of their work.

Cognitive function and platelet membrane fluidity in Alzheimer's disease.

Increased platelet membrane fluidity, as reflected by a decrease in the fluorescence anisotropy of diphenylhexatriene in labeled membranes, identifies a clinically distinct subgroup of approximately 50% of patients at our center who meet NINCDS-ADRDA clinical criteria for Alzheimer's disease. In the current study, we compared the cognitive impairments of patients in this subgroup to those observed in the residual subgroup of patients with Alzheimer's disease who had normal platelet membrane fluidity. No significant differences in the number or distribution of deficits in six cognitive domains were observed between the two subgroups. However, in the subgroup with increased platelet membrane fluidity, there were significantly more patients who exhibited dissociation of deficits on tests related to left and right parietal lobe function than in the residual subgroup. Moreover, the cases with dissociation of deficits consisted almost entirely of patients with deficits on tests reflecting left parietal lobe function and no deficit on tests of right parietal lobe function.

Longitudinal study of platelet membrane fluidity in Alzheimer's disease.

Increased platelet membrane fluidity identifies a prominent subgroup of patients with Alzheimer's disease who exhibit distinct clinical features. In the current longitudinal study, the stability of this membrane characteristic was determined for 15 patients with Alzheimer's disease and 10 healthy elderly controls over a 1-year follow-up period.

Familial risk of dementia associated with a biologic subtype of Alzheimer's disease.

Increased platelet membrane fluidity is a stable familial trait that identifies a prominent subgroup of patients with Alzheimer's disease. Patients in this subgroup have distinct clinical features, including an early age at symptomatic onset and a rapidly progressive course. The morbid risk of Alzheimer's-type dementia was studied in 421 first-degree relatives of 43 patients who met current consensus criteria for probable Alzheimer's disease and 47 healthy controls. Relatives of patients showed an approximate 50% (90- to 95-year) lifetime risk of dementia, regardless of the platelet membrane phenotype of the respective proband, which was over four times the control value. However, relatives of patients with increased platelet membrane fluidity who developed dementia exhibited symptoms significantly earlier than relatives of patients with normal platelet membrane fluidity. Alternative genetic models that describe the relationship of platelet membrane fluidity and Alzheimer's disease are discussed.

Electroencephalographic correlates of increased platelet membrane fluidity in Alzheimer's disease.

Increased platelet membrane fluidity is a stable, familial characteristic that describes a clinically distinct subgroup of patients with Alzheimer's disease. In the current study, electroencephalograms (EEGs) from 49 patients with probable Alzheimer's disease were subjected to visual and computerized spectral analysis. Only three (14.3%) of 21 patients in the subgroup with increased platelet membrane fluidity exhibited focal EEG abnormalities, while 12 (42.9%) of 28 of the residual subgroup exhibited focal EEG findings, a threefold difference. This difference in EEG profile provides further validation of these two subgroups and suggests that the subgroup with increased fluidity is less heterogeneous than the residual group.

Family study of platelet membrane fluidity in Alzheimer's disease.

The fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene in labeled platelet membranes, an index of membrane fluidity, identifies a prominent subgroup of patients with Alzheimer's disease who manifest distinct clinical features. In a family study, the prevalence of this platelet membrane abnormality was 3.2 to 11.5 times higher in asymptomatic, first-degree relatives of probands with Alzheimer's disease than in neurologically healthy control subjects chosen without regard to family history of dementia. The pattern of the platelet membrane abnormality within families was consistent with that of a fully penetrant autosomal dominant trait. Thus, this abnormality of platelet membranes may be an inherited factor that is related to the development of Alzheimer's disease.

Platelet membrane fluidity identifies a clinical subtype of Alzheimer's disease.

1. The fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH) in labeled platelet membranes, an index of membrane fluidity, identifies a prominent subgroup (approx. 50%) of patients with Alzheimer's disease who manifest distinct clinical features. 2. We review an integrated series of studies that explore both the clinical significance of this finding and the biological basis for the platelet membrane alteration.