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There are minimal data directly comparing plasma neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) in aging and neurodegenerative disease research. We evaluated associations of plasma NfL and plasma GFAP with brain volume and cognition in two independent cohorts of older adults diagnosed as clinically normal (CN), mild cognitive impairment (MCI), or Alzheimer’s dementia.
We studied 121 total participants (Cohort 1: n = 50, age 71.6 ± 6.9 years, 78% CN, 22% MCI; Cohort 2: n = 71, age 72.2 ± 9.2 years, 45% CN, 25% MCI, 30% dementia). Gray and white matter volumes were obtained for total brain and broad subregions of interest (ROIs). Neuropsychological testing evaluated memory, executive functioning, language, and visuospatial abilities. Plasma samples were analyzed in duplicate for NfL and GFAP using single molecule array assays (Quanterix Simoa). Linear regression models with structural MRI and cognitive outcomes included plasma NfL and GFAP simultaneously along with relevant covariates.
Higher plasma GFAP was associated with lower white matter volume in both cohorts for temporal (Cohort 1: β = −0.33, p = .002; Cohort 2: β = −0.36, p = .03) and parietal ROIs (Cohort 1: β = −0.31, p = .01; Cohort 2: β = −0.35, p = .04). No consistent findings emerged for gray matter volumes. Higher plasma GFAP was associated with lower executive function scores (Cohort 1: β = −0.38, p = .01; Cohort 2: β = −0.36, p = .007). Plasma NfL was not associated with gray or white matter volumes, or cognition after adjusting for plasma GFAP.
Plasma GFAP may be more sensitive to white matter and cognitive changes than plasma NfL. Biomarkers reflecting astroglial pathophysiology may capture complex dynamics of aging and neurodegenerative disease.
Objective: We evaluated whether memory recall following an extended (1 week) delay predicts cognitive and brain structural trajectories in older adults
Clinically normal older adults (52–92 years old) were followed longitudinally for up to 8 years after completing a memory paradigm at baseline [Story Recall Test (SRT)] that assessed delayed recall at 30 min and 1 week. Subsets of the cohort underwent neuroimaging (N = 134, mean age = 75) and neuropsychological testing (N = 178–207, mean ages = 74–76) at annual study visits occurring approximately 15–18 months apart. Mixed-effects regression models evaluated if baseline SRT performance predicted longitudinal changes in gray matter volumes and cognitive composite scores, controlling for demographics.
Worse SRT 1-week recall was associated with more precipitous rates of longitudinal decline in medial temporal lobe volumes (p = .037), episodic memory (p = .003), and executive functioning (p = .011), but not occipital lobe or total gray matter volumes (demonstrating neuroanatomical specificity; p > .58). By contrast, SRT 30-min recall was only associated with longitudinal decline in executive functioning (p = .044).
Memory paradigms that capture longer-term recall may be particularly sensitive to age-related medial temporal lobe changes and neurodegenerative disease trajectories. (JINS, 2020, xx, xx-xx)
Antimicrobial stewardship programs are effective in optimizing antimicrobial prescribing patterns and decreasing the negative outcomes of antimicrobial exposure, including the emergence of multidrug-resistant organisms. In dialysis facilities, 30%–35% of antimicrobials are either not indicated or the type of antimicrobial is not optimal. Although antimicrobial stewardship programs are now implemented nationwide in hospital settings, programs specific to the maintenance dialysis facilities have not been developed.
To quantify the effect of an antimicrobial stewardship program in reducing antimicrobial prescribing.
Study design and setting
An interrupted time-series study in 6 outpatient hemodialysis facilities was conducted in which mean monthly antimicrobial doses per 100 patient months during the 12 months prior to the program were compared to those in the 12-month intervention period.
Implementation of the antimicrobial stewardship program was associated with a 6% monthly reduction in antimicrobial doses per 100 patient months during the intervention period (P=.02). The initial mean of 22.6 antimicrobial doses per 100 patient months decreased to a mean of 10.5 antimicrobial doses per 100 patient months at the end of the intervention. There were no significant changes in antimicrobial use by type, including vancomycin. Antimicrobial adjustments were recommended for 30 of 145 antimicrobial courses (20.6%) for which there were sufficient clinical data. The most frequent reasons for adjustment included de-escalation from vancomycin to cefazolin for methicillin-susceptible Staphylococcus aureus infections and discontinuation of antimicrobials when criteria for presumed infection were not met.
Within 6 hemodialysis facilities, implementation of an antimicrobial stewardship was associated with a decline in antimicrobial prescribing with no negative effects.
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