Faculty Peer Reviewed
In the headlines this week, The New York Times featured an article describing a test capable of identifying biomarkers in cerebrospinal fluid to diagnose patients with Alzheimer’s disease. This article is based on a study that was published this week in the Archives of Neurology. Previously, Alzheimer’s disease could only be diagnosed based on clinical suspicion until a definite diagnosis was available with autopsy. In the study by De Meyer et al., researchers measured levels of A1-42, total tau, and P-Tau181P and used mixture modeling approaches to apply these markers in the diagnosis of Alzheimer’s disease. Reduced levels of A1-42 and increased levels of P-Tau181P were considered hallmarks of Alzheimer’s disease. This data was first validated on the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database, which includes normal participants, patients with mild cognitive impairment, and patients with a diagnosis of early Alzheimer’s disease. In the ADNI database, the biomarkers were identified not only in 90% of patients with Alzheimer’s disease and 72% of patients with moderate cognitive impairment, but also in 36% of normal participants. Analysis showed that these biomarkers had 90% sensitivity and 64% specificity for an Alzheimer’s diagnosis. Validation of the findings was achieved using both a Belgian database of autopsy-proven Alzheimer’s disease and another group of patients initially diagnosed with mild cognitive impairment who later developed Alzheimer’s disease. Sensitivity was 94% in the autopsy-verified Alzheimer’s disease specimens. In the prospectively studied chort, the markers showed 100% sensitivity in patients with moderate cognitive impairment who were clinically progressing towards Alzheimer’s disease over a 5-year follow-up period. However, this group of patients does not have a pathology-confirmed diagnosis of Alzheimer’s disease. The authors suggest that this test may be used in patients prior to the development of clinical features of Alzheimer’s disease. The New York Times feature of this study brings up the issue of using a diagnostic test for a disease with limited treatment options, significant consequences, and no cure.
An article in JAMA addressed the increasing incidence of diabetic retinopathy as our population ages and the prevalence of diabetes increases. Zhang et al. analyzed data from 2005-2008 to summarize the prevalence and risk factors associated with diabetic retinopathy among adults aged 40 years and older. This retrospective review used National Health and Nutrition Examination Surveys 2005-2008 (NHANES), which are surveys of 6797 adults aged 40 years and older from the National Center for Health Statistics. The surveys were of the general US population, and the diagnosis of diabetes was defined from self-reporting of a previous clinical diagnosis or hemoglobin A1c 6.5% or greater. Participants of NHANES 2005-2008 had photographs of their eye to diagnose diabetic retinopathy. The study found that the prevalence of diabetic retinopathy among US adults with diabetes was 28.5% (CI 24.9-32.5%). Further analysis found higher rates of diabetic retinopathy in non-Hispanic, black individuals. Male sex, higher hemoglobin A1c, longer duration of diabetes, insulin use, and higher systolic blood pressure were independent risk factors for diabetic retinopathy in multivariate analysis. The authors concluded that the high prevalence of diabetic retinopathy should encourage population-based public health interventions for eye care.
The Lancet featured an epidemiological study describing a new mechanism for antibiotic resistance in India, Pakistan, and the UK. Given our experiences with the problems of MRSA, VRE and ESBL-producing bacteria, there is now concern for new Enterobacteriaceae resistance to carbapenem antibiotics. The New Delhi Metallo-beta-lactamase 1 (NDM-1) is responsible for the resistance of this family of gram negative rods including Escherichia coli, Klebsiella pneumoniae, and Proteus spp. to carbapenems. Researchers identified Enterobacteriaceae isolates from India, Pakistan, Bangladesh, and UK and found that NDM-1 was present in E. coli and K. pneumoniae isolates that were resistant to all antibiotics except tigecycline and polymyxin. The study found that 1% of all carbapenem-resistant Enterobacteriaceae from Chennai were NDM-1 positive. In the UK, 37 Enterobacteriaceae isolates with the NDM-1 enzyme were found; an additional 73 isolates were analyzed from different parts of India and Pakistan. With the surge of ESBL producing gram negative bacteria, we continue to depend on carbapenems for antibiotic therapy so resistance to this class of antibiotics would present a significant global health problem. This study represents yet another alarm about the perils of indiscriminant antibiotic usage.
Also addressing antibiotic resistance, an article in JAMA assessed the current state of health care-associated invasive MRSA infections, including MRSA bacteremia, pneumonia, skin or soft tissue infection, bone or joint infection, urinary tract infection, and endocarditis. This large retrospective review used data from the CDC’s Emerging Infections Program/Active Bacterial Core surveillance system between 2005 and 2008. This program tracks data from 9 different metropolitan areas. On a positive note, this study found decreased rates of invasive health care-associated MRSA with a 28% and 17% decrease in hospital-onset and health care-associated community onset MRSA infections during this time period.
In this week’s NEJM, a Perspective article by Dr. Ofri of NYU School of Medicine addressed the growing use of quality measures to assess physician performance. Dr. Ofri explains that providing medical care involves many factors including aspects of a doctor-patient relationship that lab results may not take into account.
Dr. Jhaveri, MD is a third year resident at NYU Langone Medical Center
Peer reviewed by Michael Poles, MD, Section Editor, Clinical Correlations
Image of Dr. Alois Alzheimer courtesy of Wikemedia Commons.
 Kolata G. Spinal-Fluid Test is Found to Predict Alzheimer’s. The New York Times. 2010 Aug 9. http://www.nytimes.com/2010/08/10/health/research/10spinal.html?scp=2&sq=alzheimer’s&st=cse”&HYPERLINK
 De Meyer G, Shapiro F, Vanderstichele H, et al. Diagnosis-Independent Alzheimer Disease Biomarker Signature in Cognitively Normal Elderly People. Arch Neurol. 2010;67:949-956. http://archneur.ama-assn.org/cgi/content/abstract/67/8/949
 Zhang X, Saaddine JB, Chou CF, et al. Prevalence of diabetic retinopathy in the United States, 2005-2008. JAMA. 2010;304:649-656. http://archneur.ama-assn.org/cgi/content/abstract/67/8/949
 Kumarasamy KK, Toleman MA, Walsh TR, et al. Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study. Lancet Infect Dis. 2010. http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(10)70143-2/abstract
 Kallen AJ, Mu Y, Bulens S, et al. Health care-associated invasive MRSA infections, 2005-2008. JAMA. 2010;304:641-648. http://jama.ama-assn.org/cgi/content/full/304/6/641
 Ofri D. Quality Measures and the Individual Physician. NEJM. 2010;363:606-608. http://www.nejm.org/doi/full/10.1056/NEJMp1006298