Age Stereotypes Influence Subjective Cognitive Decline Via Depression
Silvia Chapman, PhD1, David Weiss, PhD1, Hana M. Broulíková, MSc2, Jillian L Joyce, BSc1, Preeti Sunderaraman, PhD1, Ian W McKeague, PhD1 and Stephanie Cosentino, PhD1, 1Columbia University Medical Center, New York, NY, USA, 2National Institute of Mental Health, Klecany, Czech Republic.
Background: Subjective Cognitive Decline (SCD) is the subjective perception that one’s cognition has declined, before such decline is evident on standard diagnostic testing. Over the past decade, SCD has received increasing attention as a potential feature of preclinical Alzheimer’s disease (AD). The relation between SCD and objective cognition has though been inconsistent, with SCD being frequently associated with other factors such as depression. Social-cognitive factors, particularly an individual’s stereotypes about aging, may also play an in important role in shaping subjective cognition. This study examines if holding negative stereotypes about aging, either implicitly or explicitly, operates with depression to influence SCD.
Method: A total of 100 healthy aging adults were recruited for this study. Participants had a mean age of 71.96 years (SD=7.68), 16.62 years of education (SD=2.21) and were 65 % female. 82 % identified as Caucasian, 11% African-American 3 % Asian and 4 % other. Participants completed SCD questionnaires regarding common cognitive difficulties in memory, language, attention and executive functioning. Depression was measured with the Geriatric Depression Scale. Stereotypes about aging were assessed explicitly (questionnaire on positive and negative stereotypes) and implicitly (reaction-time based implicit association test). Structural equation modelling was used to derive latent variables to represent each SCD, depression, and stereotypes, in order to examine the relation between aging stereotypes and SCD, and to determine whether a potential association was mediated by depression.
Result: Implicit aging stereotypes significantly predicted explicit aging stereotypes (β =.31, p=.003), but neither had a direct effect on SCD (p>.05). Depression was a significant predictor of SCD (β=.57, p<.001) and a significant mediator of the relation between implicit and explicit aging stereotypes and SCD (β =.06, p=.04; β=.20, p=.006).
Conclusion: Individuals' generalized beliefs about older people, both implicitly and explicitly, can have important effects on how SCD is expressed. However, the effects of aging stereotypes on SCD appear to operate only through depression. Future research should examine the mediational role of depression using longitudinal data. Further, the impact of social-cognitive factors should be examined in relation to SCD's accuracy and how it relates to AD biomarkers.
Molsidomine Provides Neuroprotection Against Vincristine-Induced Peripheral Neurotoxicity
Authors: Irina Utkina-Sosunova, Hai Li, Charles Karan, Alessia Chiorazzi, Valentina Carozzi, Serge Przedborski, Guido Cavaletti, and Francesco Lotti.
Chemotherapy-induced peripheral neuropathy (CINP) is the principal dose-limiting adverse reaction of the major frontline chemotherapeutic agents. It can be so devastating that many patients have to drop out of the curative therapy, negatively impacting cancer prognosis. CIPN is refractory to treatment and persists in about 50% of cancer patients limiting their quality of life.
The hallmark of vincristine(VCR) peripheral neurotoxicity is axonopathy that may influence sensory, motor, and autonomous nerves. The underpinning mechanisms of VCR-induced axonopathy remains uncertain. We hypothesize that agents preventing VCR-induced axonopathy will effectively mitigate CIPN symptoms. Based on this premise, we developed a comprehensive drug discovery pipeline to identify small molecules with neuroprotective activity against VCR-induced axonal degeneration. Among the hits identified, SIN-1 chloride (SIN-1) – an active metabolite of molsidomine – prevents VCR-induced axonal loss in both motor and sensory neuronal cultures without compromising VCR anti-cancer potency.
To determine the neuroprotective effect of molsidomine in vivo, we used an extensively validated rat model of VCR-induced peripheral neuropathy. Vincristine (0.2mg/kg/week) was administered via the tail vein for 4 weeks (once per week) and molsidomine (10mg/kg/day or 20mg/kg/day) was given daily orally for 4 weeks, starting the first day of VCR treatment. VCR administration induced severe sensory and motor nerve damage detected with functional tests. Molsidomine administration significantly improves the sensory pain threshold and digital nerve amplitude and velocity in a dose-dependent manner.
This study provides evidence for the neuroprotective properties of molsidomine and opens the window to the usage of this drug as a therapeutic agent in VCR-induced CIPN.