CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
Editor: Deborah Sesok-Pizzini, MD, MBA, chief medical officer, Labcorp Diagnostics, Burlington, NC, and adjunct professor, Department of Clinical Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
Contribution of markers of neurodegeneration and hypercholesterolemia to dementia risk
October 2022—Cardiovascular health is often linked to dementia, and compelling evidence indicates that there are modifiable risk factors for dementia, knowledge of which may also benefit vascular health. In previous studies, hypercholesterolemia and cardiovascular pathology were associated with the apolipoprotein E (APOE) ε4 genotype and cognitive function. In this study, the authors examined whether blood biomarkers of neurodegeneration help explain the link between hypercholesterolemia and cognitive decline. They analyzed such biomarkers as glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and phosphorylated tau 181 (p-tau181) to determine if they were associated with dementia risk based on varying levels of total cholesterol and the APOE ε4 genotype. The authors selected these markers because they have been associated with dementia or cerebrovascular disease, or both. They used a nested case-control study design within a population-based cohort, which included 768 older adults (261 dementia cases and 507 randomly selected controls) who were followed for up to 17 years. The authors measured GFAP, NfL, and p-tau181 in baseline blood samples and categorized the results as high (quartile 4) or low (quartiles 1–3). They then used logistic regression analyses and spline regression models for dose-response analysis. The authors also calculated the receiver operating characteristic curves for cholesterol levels. The results of regression analyses showed that the odds of a dementia diagnosis were significantly higher among study participants with high baseline levels of markers of neurodegeneration and high levels of total cholesterol than among those with low levels of total cholesterol. This pattern was especially evident with GFAP and NfL, for which the odds ratios among those with high total cholesterol were 5.10 and 2.96, respectively. The odds ratios for those with low total cholesterol were 2.44 and 1.15, respectively. Of interest, APOE ε4 genotype also impacted the strength of the associations with biomarker patterns, but this varied by biomarker and type of dementia. No significant association was seen with p-tau181. The authors concluded that in the general population, blood GFAP and NfL are better predictors of dementia than p-tau181, and their links to dementia risk are highly amplified by hypercholesterolemia, depending on the APOE ε4 genotype. The authors propose that future studies include subgroups with low- and high-density lipoprotein cholesterol and other vascular risk factors, such as hypertension and diabetes mellitus.
Perna L, Mons U, Stocker H, et al. Joint contribution of markers of neurodegeneration and hypercholesterolemia to dementia risk. Available as a medRxiv preprint. https://doi.org/10.1101/2022.01.16.22269370
Correspondence: Dr. Laura Perna at laura_perna@psych.mpg.de
Diagnostic value of various urine tests for UTI
Urinary tract infections are common and have numerous causes, including indwelling catheters and underlying chronic health conditions. Clinical symptoms and biochemical testing results should be used in combination to diagnose such infections. Urinary tract infections (UTIs) that are treated insufficiently or reoccur may become chronic infections that significantly impact a person’s health. UTIs generally are divided into upper urinary tract infections (pyelonephritis) and lower UTIs (cystitis, urethritis). Most clinicians use a urine dipstick test to initially diagnose the infection. However, this method may not be sufficient to complete the diagnosis. Current urine-analysis and detection methods include the use of visual measurements, urine analyzer instruments, sediment microscopy, bacterial culture, and routine urine dry chemical methods. The authors performed a meta-analysis to compare the effectiveness of various urine-analysis and detection methods. They searched the databases of PubMed, Embase, Cochrane Library, SpringerLink, CNKI, and Wanfang from inception to December 2021. The authors then assigned two reviewers to independently screen the literature according to the inclusion and exclusion criteria outlined in their study. The Cochrane Collaboration and Meta-DiSc were used to calculate the combined sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR−), and diagnostic ratio of each type of diagnostic test addressed in the literature and draw summary receiver operating characteristic curves. The study focused on 14 documents. The results showed significant statistical differences between urine sediment microscopy, the urine erythrocyte test, quantitative determination of urinary protein composition, and determination of urinary enzymes. The authors also found that when analyzing red and white blood cells in UTIs, urine dry chemistry was superior to automated urinalysis in terms of area under the curve, sensitivity, and specificity. The data further showed that when analyzing urine bacteria, combining urine dry chemistry and quantitative urine culture results led to significantly better specificity, sensitivity, positive predictive value, and negative predictive value compared to the use of urine dipstick alone. The authors noted that despite the small number of papers included in the analysis, the study demonstrated that automated urinalysis and urine dry chemistry methods have a high degree of accuracy. However, these methods need to be combined with urine sediment microscopy and urine culture for a definitive diagnosis. These detection methods can lead to an early diagnosis of UTI, resulting in appropriate treatment to prevent chronic UTI infection.