Serum estradiol and risk of stroke in elderly men.

OBJECTIVE: To determine if levels of serum estradiol and testosterone can predict stroke in a population-based sample of elderly men. METHODS: Serum 17beta estradiol and testosterone were measured in 2,197 men aged 71 to 93 years who participated in the Honolulu-Asia Aging Study from 1991 to 1993. All were free of prevalent stroke, coronary heart disease, and cancer. Participants were followed to the end of 1998 for thromboembolic and hemorrhagic events. RESULTS: During the course of follow-up, 124 men developed a stroke (9.1/1,000 person-years). After age adjustment, men in the top quintile of serum estradiol (> or =125 pmol/L [34.1 pg/mL]) experienced a twofold excess risk of stroke vs men whose estradiol levels were lower (14.8 vs 7.3/1,000 person-years, p < 0.001). Among the lower quintiles, there were little differences in the risk of stroke. Findings were also significant and comparable for bioavailable estradiol and for thromboembolic and hemorrhagic events. After additional adjustment for hypertension, diabetes, adiposity, cholesterol concentrations, atrial fibrillation, and other characteristics, men in the top quintile of serum estradiol continued to have a higher risk of stroke vs those whose estradiol levels were lower (relative hazards = 2.2; 95% CI = 1.5 to 3.4, p < 0.001). Testosterone was not related to the risk of stroke. CONCLUSIONS: High levels of serum estradiol may be associated with an elevated risk of stroke in elderly men.

Elevated cortical zinc in Alzheimer disease.

OBJECTIVE: To determine whether changes in brain biometals in Alzheimer disease (AD) and in normal brain tissue are tandemly associated with amyloid beta-peptide (Abeta) burden and dementia severity. METHODS: The authors measured zinc, copper, iron, manganese, and aluminum and Abeta levels in postmortem neocortical tissue from patients with AD (n = 10), normal age-matched control subjects (n = 14), patients with schizophrenia (n = 26), and patients with schizophrenia with amyloid (n = 8). Severity of cognitive impairment was assessed with the Clinical Dementia Rating Scale (CDR). RESULTS: There was a significant, more than twofold, increase of tissue zinc in the AD-affected cortex compared with the other groups. Zinc levels increased with tissue amyloid levels. Zinc levels were significantly elevated in the most severely demented cases (CDR 4 to 5) and in cases that had an amyloid burden greater than 8 plaques/mm(2). Levels of other metals did not differ between groups. CONCLUSIONS: Brain zinc accumulation is a prominent feature of advanced Alzheimer disease (AD) and is biochemically linked to brain amyloid beta-peptide accumulation and dementia severity in AD.

Brain lesions on MRI and endogenous sex hormones in elderly men.

We investigated the association between MRI detected brain lesions and levels of endogenous sex hormones in Japanese-American men aged 74-95 years. Logistic regression was used to estimate the association (OR (95% CI)) of MRI outcome with tertiles of bioavailable testosterone, 17beta estradiol and sex hormone binding globulin (SHBG). There was a significantly increased risk for cerebral atrophy in the highest tertile of testosterone (3.1 (1.2-7.8)) compared to the lowest. We also found that men with the highest estradiol had a higher risk of lacunes (1.92 (1.1-3.2)). These relationships did not change with adjustment for the other sex hormones, cardiovascular risk factors, or other brain lesions. In contrast, men with the highest SHBG had a lower risk both of cerebral atrophy and lacunes, after adjusting for sex hormones and cardiovascular risk factors. There were no associations between sex hormones and hippocampal atrophy, white matter lesions, and large infarcts. Because the levels of hormone were measured close in time to the acquisition of the MRI, these associations may reflect neurodegeneration in brain regions regulating hormone levels.

CSF Abeta 42 levels correlate with amyloid-neuropathology in a population-based autopsy study.

OBJECTIVE: To investigate the relationship of amyloid neuropathology to postmortem CSF Abeta 42 levels in an autopsy sample of Japanese American men from the population-based Honolulu-Asia Aging Study. METHODS: In 1991, participants were assessed and diagnosed with dementia (including subtype) based on published criteria. At death CSF was obtained from the ventricles. Neuritic plaques (NP) and diffuse plaques in areas of the neocortex and hippocampus were examined using Bielschowsky silver stains. Cerebral amyloid angiopathy (CAA) was measured by immunostaining for beta4 amyloid in cerebral vessels in the neocortex. Neuropathologically confirmed AD was diagnosed using Consortium to Establish a Registry for Alzheimer's Disease criteria. In 155 autopsy samples, log transformed linear regression models were used to examine the association of NP and CAA to Abeta 42 levels, controlling for clinical dementia severity, time between diagnosis and death, age at death, brain weight, hours between death and collection of CSF, education, and APOE genotype. RESULTS: Higher numbers of NP in the neocortex (p trend = 0.001) and in the hippocampus (p trend = 0.03) were strongly associated with lower levels of Abeta 42. Individuals with CAA had lower Abeta 42 levels (beta coefficient = -0.48; 95% CI -0.9, -0.1). Compared to participants with a diagnosis of clinical dementia, those with pathologically confirmed AD had lower Abeta 42 levels (beta coefficient = -0.74; 95% CI -1.4, -0.1). CONCLUSION: The current study suggests that lower Abeta 42 levels reflect neuropathologic processes implicated in amyloid-related pathologies, such as NP and CAA.