Plasma homocysteine levels and Alzheimer's Disease: A systematic review

Objective. To systematically review studies published in English on the relationship between plasma total homocysteine (Hcy) levels and the clinical and/or postmortem diagnosis of Alzheimer's disease (AD) in subjects who are over 60 years old.^ Method. Medline, PubMed, PsycINFO and Academic Search Premier, were searched by using the keywords "homocysteine", "Alzheimer disease" and "dementia", and "cognitive disorders". In addition, relevant articles in PubMed using the "related articles" link and by cross-referencing were identified. The study design, study setting and study population, sample size, the diagnostic criteria of the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and the Alzheimer's Disease and Related Disorders Association (ADRDA), and description of how Hcy levels were measured or defined had to have been clearly stated. Empirical investigations reporting quantitative data on the epidemiology of the relationship between plasma total Hcy (exposure factor) and AD (outcome) were included in the systematic review.^ Results. A total of 7 studies, which included a total of 2,989 subjects, out of 388 potential articles met the inclusion criteria: four case control and three cohort studies were identified. All 7 studies had association statistics, such as the odds ratio (OR), the relative rates (RR), and the hazard ratio (HR) of AD, examined using multivariate and logistic regression analyses. Three case - comparison studies: Clarke et al. (1998) (OR: 4.5, 95% CI.: 2.2 - 9.2); McIlroy et al. (2002) (OR: 2.9, 95% CI.: 1.00–8.1); Quadri et al. (2004) (OR: 3.7, 95% CI.: 1.1 - 13.1), and two cohort studies: Seshadri et al. (2002) (RR: 1.8, 95% CI.: 1.3 - 2.5); Ravaglia et al. (2005) (HR: 2.1, 95% CI.: 1.7 - 3.8) found a significant association between serum total Hcy and AD. One case-comparison study, Miller et al. (2002) (OR: 2.2, 95% C.I.: 0.3 -16), and one cohort study, Luchsinger et al. (2004) (HR: 1.4, 95% C.I.: 0.7 - 2.3) failed to reject H0.^ Conclusions. The purpose of this review is to provide a thorough analysis of studies that examined the relationship between Hcy levels and AD. Five studies showed a positive statistically significant association between elevated total Hcy values and AD but the association was not statistically significant in two studies. Further research is needed in order to establish evidence of the strong, consistent association between serum total Hcy and AD as well as the presence of the appropriate temporal relationship. To answer these questions, it is important to conduct more prospective studies that examine the occurrence of AD in individuals with and without elevated Hcy values at baseline. In addition, the international standardization of measurements and cut-off points for plasma Hcy levels across laboratories is a critical issue to be addressed for the conduct of future studies on the topic.^

Performance of HbA1c for classifying diabetes and diagnostic threshold for diabetes among the Mexican American border community

Objective. In 2009, the International Expert Committee recommended the use of HbA1c test for diagnosis of diabetes. Although it has been recommended for the diagnosis of diabetes, its precise test performance among Mexican Americans is uncertain. A strong “gold standard” would rely on repeated blood glucose measurement on different days, which is the recommended method for diagnosing diabetes in clinical practice. Our objective was to assess test performance of HbA1c in detecting diabetes and pre-diabetes against repeated fasting blood glucose measurement for the Mexican American population living in United States-Mexico border. Moreover, we wanted to find out a specific and precise threshold value of HbA1c for Diabetes Mellitus (DM) and pre-diabetes for this high-risk population which might assist in better diagnosis and better management of patient diabetes. ^ Research design and methods. We used CCHC dataset for our study. In 2004, the Cameron County Hispanic Cohort (CCHC), now numbering 2,574, was established drawn from randomly selected households on the basis of 2000 Census tract data. The CCHC study randomly selected a subset of people (aged 18-64 years) in CCHC cohort households to determine the influence of SES on diabetes and obesity. Among the participants in Cohort-2000, 67.15% are female; all are Hispanic. ^ Individuals were defined as having diabetes mellitus (Fasting plasma glucose [FPG] ≥ 126 mg/dL or pre-diabetes (100 ≤ FPG < 126 mg/dL). HbA1c test performance was evaluated using receiver operator characteristic (ROC) curves. Moreover, change-point models were used to determine HbA1c thresholds compatible with FPG thresholds for diabetes and pre-diabetes. ^ Results. When assessing Fasting Plasma Glucose (FPG) is used to detect diabetes, the sensitivity and specificity of HbA1c≥ 6.5% was 75% and 87% respectively (area under the curve 0.895). Additionally, when assessing FPG to detect pre-diabetes, the sensitivity and specificity of HbA1c≥ 6.0% (ADA recommended threshold) was 18% and 90% respectively. The sensitivity and specificity of HbA1c≥ 5.7% (International Expert Committee recommended threshold) for detecting pre-diabetes was 31% and 78% respectively. ROC analyses suggest HbA1c as a sound predictor of diabetes mellitus (area under the curve 0.895) but a poorer predictor for pre-diabetes (area under the curve 0.632). ^ Conclusions. Our data support the current recommendations for use of HbA1c in the diagnosis of diabetes for the Mexican American population as it has shown reasonable sensitivity, specificity and accuracy against repeated FPG measures. However, use of HbA1c may be premature for detecting pre-diabetes in this specific population because of the poor sensitivity with FPG. It might be the case that HbA1c is differentiating the cases more effectively who are at risk of developing diabetes. Following these pre-diabetic individuals for a longer-term for the detection of incident diabetes may lead to more confirmatory result.^