Altered central and blood glutathione in Alzheimer's disease and mild cognitive impairment: a meta-analysis.

BACKGROUND: Increasing evidence implicates oxidative stress (OS) in Alzheimer disease (AD) and mild cognitive impairment (MCI). Depletion of the brain antioxidant glutathione (GSH) may be important in OS-mediated neurodegeneration, though studies of post-mortem brain GSH changes in AD have been inconclusive. Recent in vivo measurements of the brain and blood GSH may shed light on GSH changes earlier in the disease. AIM: To quantitatively review in vivo GSH in AD and MCI compared to healthy controls (HC) using meta-analyses. METHOD: Studies with in vivo brain or blood GSH levels in MCI or AD with a HC group were identified using MEDLINE, PsychInfo, and Embase (1947-June 2020). Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated for outcomes using random effects models. Outcome measures included brain GSH (Meshcher-Garwood Point Resolved Spectroscopy (MEGA-PRESS) versus non-MEGA-PRESS) and blood GSH (intracellular versus extracellular) in AD and MCI. The Q statistic and Egger's test were used to assess heterogeneity and risk of publication bias, respectively. RESULTS: For brain GSH, 4 AD (AD=135, HC=223) and 4 MCI (MCI=213, HC=211) studies were included. For blood GSH, 26 AD (AD=1203, HC=1135) and 7 MCI (MCI=434, HC=408) studies were included. Brain GSH overall did not differ in AD or MCI compared to HC; however, the subgroup of studies using MEGA-PRESS reported lower brain GSH in AD (SMD [95%CI] -1.45 [-1.83, -1.06], p<0.001) and MCI (-1.15 [-1.71, -0.59], z=4.0, p<0.001). AD had lower intracellular and extracellular blood GSH overall (-0.87 [-1. 30, -0.44], z=3.96, p<0.001). In a subgroup analysis, intracellular GSH was lower in MCI (-0.66 [-1.11, -0.21], p=0.025). Heterogeneity was observed throughout (I2 >85%) and not fully accounted by subgroup analysis. Egger's test indicated risk of publication bias. CONCLUSION: Blood intracellular GSH decrease is seen in MCI, while both intra- and extracellular decreases were seen in AD. Brain GSH is decreased in AD and MCI in subgroup analysis. Potential bias and heterogeneity suggest the need for measurement standardization and additional studies to explore sources of heterogeneity.

It is premature to test older drivers with the SIMARD-MD.

BACKGROUND: A new tool, the SIMARD-MD, has been proposed to help physicians identify cognitively impaired drivers who may be unfit to drive, but little empirical evidence is available to justify its use. We analyzed data from a cohort of older Canadian drivers who had undergone cognitive testing to: (1) correlate the SIMARD-MD with other tools that measure cognition (e.g., trail-making test), (2) identify how many drivers, using published cut-offs on the SIMARD-MD, would be recommended to lose their license, or be considered fit to drive, or be required to undergo further driving assessment, and (3) determine if the SIMARD-MD is biased by level of education as many cognitive tools are. METHODS: Cross-sectional data from 841 drivers aged 70 and over from seven Canadian sites who are enrolled in a 5-year cohort study were used for the analyses. Scores on the SIMARD-MD were correlated with scores on the other cognitive measures. The recommendations that would be made based on the SIMARD-MD scores were based on published cut-off values suggested by the authors of the tool. The impact of education status was examined using linear regression controlling for age. RESULTS: Correlations between the SIMARD-MD and other cognitive measures ranged from .15 to .86. Using published cut-off scores, 21 participants (2.5%) would have been recommended to relinquish their licenses, 428 (50.9%) would have been deemed fit to drive, and 392 (46.6%) would have been required to undergo further testing. We found a difference of 8.19 points (95% CI=4.99, 11.40, p<.001) in favor of drivers with post-secondary education versus those without, representing over 11% of the mean score. DISCUSSION: The SIMARD-MD is unlikely to be valuable to clinicians because it lacks sufficient precision to provide clear recommendations about fitness-to-drive. Recommendations based solely on the SIMARD-MD may place many seniors at risk of losing their transportation mobility or incurring unnecessary stress and costs to prove they are safe to drive. Furthermore, the education bias may create an unwanted structural inequity. Hence, adoption of the SIMARD-MD as a tool to determine fitness-to-drive appears premature.

Gas-containing renal stones.

Emphysematous pyelonephritis is a rare, but potentially lethal, possible sequela of nephrolithiasis, occurring most commonly in diabetic patients. The diagnosis of emphysematous pyelonephritis relies on the radiologic finding of gas in the renal parenchyma. We present the case of a patient with sarcoidosis, diabetes, and obstructing, gas-containing ureteral stones. Gas-containing renal stones are exceedingly rare, but have been linked to serious renal infections. The case management and a brief review of the published reports follow. We propose that gas-containing stones be considered evidence of emphysematous pyelonephritis in certain clinical settings.