Midlife alcohol consumption and later life cognitive impairment: Light drinking is not protective and APOE genotype does not change this relationship.

INTRODUCTION: Much debate exists about the role of light to moderate alcohol intake and subsequent cognitive function. The apolipoprotein E genotype may modify the relationship. METHODS: Using data from the Honolulu-Asia Aging Study, a longitudinal population-based cohort (n = 2,416), Cox proportional hazards regression analyses were performed to measure midlife alcohol intake (average age = 52 years) and later life cognitive function (average age = 87 years) and to explore the role of apolipoprotein E genotype. RESULTS: No protective effect of light drinking (>1 drink/month- 1 drink/day) or moderate drinking (>1-2 drinks/day) was observed in the cohort in adjusted models (HR = 1.013, CI:0.88-1.16; HR = 1.104, CI:0.91-1.34, respectively). Heavy drinking (>2-4 drinks/day) and very heavy drinking (>4 drinks/day) increased the risk for incident moderate cognitive impairment (HR = 1.355, CI:1.09-1.68; HR = 1.462, CI:1.04-2.05, respectively). When examining the relationship by apolipoprotein E ε4 carrier status, a similar dose-response pattern was observed in both groups with higher hazard ratios for those carrying at least one copy of the apolipoprotein E ℇ4 allele. As alcohol level increased, the age at incident moderate cognitive impairment decreased, especially among those with at least one apolipoprotein E ℇ4 allele. DISCUSSION: We did not observe a significant protective effect for light to moderate drinking in midlife and subsequent cognitive impairment in this cohort. Heavy drinking increased the risk for moderate cognitive impairment and decreased the age at incidence, as did carrying at least one allele of the apolipoprotein E ℇ4 gene.

Brain Injury and Later-Life Cognitive Impairment and Neuropathology: The Honolulu-Asia Aging Study.

BACKGROUND: Findings are inconsistent regarding the role of traumatic head injury in the subsequent development of neurologic outcomes. OBJECTIVE: Examine the relationship between head injury and later cognitive impairment. METHODS: A sample of 3,123 Japanese-American men was assessed for history of head injury and evaluated for cognitive impairment using the Cognitive Abilities Screening Instrument (CASI). For a subsample of 676 respondents, neuropathologic results from those with and without head injury were compared. RESULTS: Although the crude model showed an association between history of head injury and later severe cognitive impairment, the relationship lost significance in the adjusted model (OR = 1.320, CI: 0.90-1.93), regardless of time between injury and impairment. Similar to cognitive impairment, hippocampal sclerosis was observed significantly more in the brains of respondents with a history of head injury in the crude model, but the relationship weakened in the adjusted model (OR = 1.462, CI: 0.68-3.12). After adjustment, decedents with a head injury demonstrated marginally higher brain weight (OR = 1.003, CI: 1.00-1.01). CONCLUSION: We did not find a relationship between head injury and subsequent cognitive decline in this cohort. The neuropathology results also displayed no strong association between history of head injury and specific brain lesions and characteristics. These results support other findings in prospective cohorts. However, they could be influenced by the demographic make-up of the sample (male Japanese-Americans) or by the observation that the majority reported only a single head injury.

The CAIDE Dementia Risk Score and the Honolulu-Asia Aging Study.

INTRODUCTION: The CAIDE (Cardiovascular Risk Factors, Aging, and Incidence of Dementia) dementia risk score is based on demographic, genetic, and modifiable risk factors in midlife and has been shown to be predictive of later-life dementia. OBJECTIVE: To test the predictive capacity of the CAIDE dementia risk score among a cohort of Japanese-American men. METHODS: Midlife measures were obtained from a sample of 3,582 Japanese-American men in the Honolulu Heart Program (1965-1968, average age = 53.1 years). A follow-up exam in 1991 (average age = 77.8 years) assessed cognitive impairment using the Cognitive Abilities Screening Instrument (CASI). Severe cognitive impairment was defined as a CASI score <60. RESULTS: In this cohort, the CAIDE dementia risk score demonstrates significant association with later-life severe cognitive impairment (OR = 1.477, 95% CI: 1.39-1.58). However, the area under the receiver-operating characteristic curve c-statistics suggests poor predictive ability (c = 0.645, 95% CI: 0.62-0.67). Using a score cut-point of 10, the accuracy is acceptable (0.82), but the sensitivity is low (0.50). CONCLUSION: While the CAIDE dementia risk score at midlife is associated with later development of cognitive impairment in Japanese-American men, its predictive capacity in this population is weak.

Characterization of antibody binding to three cancer-related antigens using flow cytometry and cell tracking velocimetry.

Proper antibody labeling is a fundamental step in the positive selection/isolation of rare cancer cells using immunomagnetic cell separation technology. Using either a two-step or single-step labeling protocol, we examined a combination of six different antibodies specific for three different antigens (epithelial specific antigen, epithelial membrane antigen, and HER-2/Neu) on two different breast cancer cell lines (HCC1954 and MCF-7). When a two-step labeling protocol was used (i.e., anti-surface marker-fluoroscein-isothiocyanate [FITC] [primary Ab], anti-FITC magnetic colloid [secondary Ab]) saturation of the primary antibody was determined using fluorescence intensity measurements from flow cytometry (FCM). The saturation of the secondary antibody (or saturation of a single-step labeling) was determined using magnetophoretic mobility measurements from cell tracking velocimetry (CTV). When the maximum magnetophoretic mobility was the primary objective, our results demonstrate that the quantities necessary for antibody saturation with respect to fluorescence intensity were generally higher than those recommended by the manufacturer. The results demonstrate that magnetophoretic mobility varies depending on the types of cell lines, primary antibodies, and concentration of secondary magnetic colloid-conjugated antibody. It is concluded that saturation studies are a vital preparatory step in any separation method involving antibody labeling, especially those that require the specificity of rare cell detection.

Helicobacter pylori: consensus and controversy.

Helicobacter pylori is uniquely adapted to colonize the human stomach. Infection leads to a range of subclinical and clinical outcomes that depend on properties of the infecting strain, the host, and the environment. Eradication therapy is indicated for infected persons who develop peptic ulcer disease or gastric lymphoma or who are beginning long-term treatment with nonsteroidal anti-inflammatory drugs. However, treatment may worsen gastroesophageal reflux disease and increase the risk of esophageal cancer. H. pylori infections can be diagnosed noninvasively and can be eradicated with approximately 85% success by a variety of multidrug, 7-14-day regimens. Unfortunately, antibiotic resistance is affecting treatment effectiveness in the United States and abroad. A more complete understanding of the variation in H. pylori pathogenesis should lead to clearer recommendations about treatment for infected persons who have neither peptic ulcer disease nor gastric lymphoma.