Serotonin signaling suppresses generation of amyloid-β (Aβ) in vitro and in animal models of Alzheimer’s disease (AD). We show that in an aged transgenic AD mouse model (APP/PS1 plaque-bearing mice), the antidepressant citalopram, a selective serotonin reuptake inhibitor (SSRI), decreased Aβ in brain interstitial fluid (ISF) in a dose-dependent manner. Growth of individual amyloid plaques was assessed in plaque-bearing mice that were chronically administered citalopram. Citalopram arrested the growth of pre-existing plaques and reduced the appearance of new plaques by 78%. In healthy human volunteers, citalopram’s effects on Aβ production and Aβ concentrations in cerebrospinal fluid (CSF) were measured prospectively using stable-isotope labeling kinetics (SILK), with CSF sampling during acute dosing of citalopram. Aβ production in CSF was slowed by 37% in the citalopram group compared to placebo. This change was associated with a 38% decrease in total CSF Aβ concentrations in the drug-treated group. The ability to safely decrease Aβ concentrations is potentially important as a preventive strategy for AD. This study demonstrates key target engagement for future AD prevention trials.
Compromised postural balance is a common manifestation of multiple sclerosis (MS). Effective quantitative methods of assessing postural imbalance are needed to help clinicians evaluate progression of this impairment. The primary objective of this study was to compare postural balance in MS patients and healthy controls using a standard screening tool, the Berg Balance Scale (BBS), as well as a more technically sophisticated device, the NeuroCom SMART Balance Master (NeuroCom International, Inc, Clackamas, OR). The study participants consisted of 14 individuals diagnosed with MS and 10 healthy controls. Each participant was assessed with the BBS and also underwent six different balance tests using the NeuroCom, most comprising several subcomponent measures. Assessment with the BBS showed significantly more postural instability in the MS group than in the control group (P < .05). Testing with the NeuroCom showed significantly more postural instability in the MS group than in the control group on two of the six tests (four specific balance measures) (P < .05). Moderate-to-high correlations (0.50–0.80) were found between the postural assessments using the standard BBS and the NeuroCom balance tests for the MS group. These results indicate that the BBS is an effective screening instrument for balance problems in people with MS.
The acute and chronic effects of whole-body vibration (WBV) on balance, postural stability, and mobility were evaluated in 21 women with relapsing-remitting multiple sclerosis (MS) randomly assigned to control (n = 9) or experimental (n = 12) groups. To assess acute responses, outcome variables were assessed before and immediately after a session of WBV (five 30-second bouts of vibration; frequency 30 Hz; amplitude 3 mm; 1-minute rest intervals) during their first visit (week 1) using field (Timed-Up and Go; 500-m walk; Berg Balance Scale) and laboratory tests (NeuroCom Balance Master and EquiTest System—Sensory Organization Test, Adaptation Test, Limits of Stability, Modified Clinical Test for Sensory Integration of Balance, Unilateral Stance, Tandem Walk, Step/Quick Turn). Acute responses were also measured after their fifth visit for only the Adaptation and Sensory Organization tests. For the chronic responses, participants were exposed to the WBV protocol once a week, for a total of 5 weeks, and then at week 5, were reassessed with the Adaptation and the Sensory Organization tests. Neither acute nor chronic exposure to the WBV protocols used in this study resulted in significant improvements (P > .05) in balance, postural stability, or mobility as assessed by either field or laboratory tests. However, based on promising results from other studies that have used WBV with other clinical populations, either alone or in conjunction with exercise, additional studies that increase the dose of vibration exposure, both acutely and chronically, should be conducted in patients with MS.
OBJECTIVE: Chest CT is being increasingly utilized for potential lung donor assessment. However, the efficacy of CT in this setting remains unknown. We hypothesize that chest CT imaging independently impacts the decision-making process in donor lung utilization.
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