The goal of this review is to examine the clinical studies on d-cycloserine, a partial glutamatergic N-methyl-D-aspartate agonist, as an augmentation strategy for exposure procedures during cognitive ...behavioral therapy for anxiety disorders. Although cognitive behavioral therapy and anxiolytic medications are more effective than placebo for treating anxiety disorders, there is still considerable room for further improvement. Traditional combination strategies typically yield disappointing results. However, recent studies based on translational research have shown promise to augment the neural circuitry underlying fear extinction with pharmacological means. We discuss the current state of the literature, including inconsistencies of findings and issues concerning the drug mechanism, dosing, and dose timing. D-cycloserine is a promising combination strategy for cognitive behavioral therapy of anxiety disorders by augmenting extinction learning. However, there is also evidence to suggest that d-cycloserine can facilitate reconsolidation of fear memory when exposure procedures are unsuccessful.
Sleep is important for physical and mental health. Latinx individuals are thought to experience worse sleep and associated health outcomes, resulting in health disparities. There is a dearth of ...research on the factors (e.g., employment status, age at immigration) that predict poor sleep among Latinx immigrants. The present study aimed to (1) examine the link between demographic factors, immigration-related factors, and acculturation stress, and sleep, and (2) identify factors that either attenuate or intensify the link between acculturation stress and sleep among Latinx immigrants in the US South, an immigrant-hostile area that is home to an increasing Latinx population that remains understudied. Hierarchical regressions were used to analyze data from 391 Latinx adult immigrants, examining the link between demographic factors, immigration-related factors, acculturation stress, and two sleep variables (sleep quality, difficulty falling asleep). Employment status and age at immigration were examined as moderators of the link between acculturation stress and sleep. Data were collected through in-person surveys. Regressions showed that acculturation stress was significantly linked to worse sleep quality (
β
= 0.30,
p
= 0.001) and more difficulty falling asleep (
β
= 0.41,
p
< 0.001), while controlling for participant characteristics. Younger age at immigration (
β
= − 0.14,
p
= 0.005) and being unemployed (
β
= − 0.13,
p
= 0.006) were associated with more difficulty falling asleep. Age at immigration intensified the relationship between acculturation stress and sleep quality (
β
= 0.14,
p
= 0.005), difficulty falling asleep (
β
= 0.15,
p
= 0.002). Reducing acculturation stress is a meaningful intervention focus, with important implications for sleep health, particularly for recent Latinx immigrants. Age at immigration and employment status are also important factors to consider when designing targeted interventions.
Background
Cognitive impairment is a common and debilitating symptom of Parkinson's disease (PD), and its etiology is likely multifactorial. One candidate mechanism is circadian disruption. Although ...there is evidence of circadian abnormalities in PD, no studies have directly assessed their association with cognitive impairment.
Objectives
Investigate whether circadian rest‐activity rhythm is associated with cognitive function in PD independently of sleep.
Methods
Thirty‐five participants with PD wore wrist actigraph monitors and completed sleep diaries for 7 to 10 days, then underwent neuropsychological testing. Rest‐activity rhythm was characterized using nonparametric circadian rhythm analysis of actigraphy data. Objective sleep parameters were also estimated using actigraphy data. Hierarchical regression models assessed the independent contributions of sleep and rest‐activity rhythm to cognitive performance.
Results
Less stable day‐to‐day rest‐activity rhythm was associated with poorer executive, visuospatial, and psychomotor functioning, but not with memory. Hierarchical regressions showed that interdaily stability's contribution to cognitive performance was independent of sleep's contributions. Whereas sleep contributed to executive function, but not psychomotor or visuospatial performance, rest‐activity rhythm stability significantly contributed to variance in all three of these domains, uniquely accounting for 14.4% to 17.6% of their performance variance.
Conclusions
Our findings indicate that circadian rest‐activity rhythm is associated with cognitive impairment independently of sleep. This suggests the possible utility of rest‐activity rhythm as a biomarker for circadian function in PD. Future research should explore interventions to stabilize behavioral rhythms in order to strengthen circadian function, which, in turn, may reduce cognitive impairment in PD.
Inhibition is an important component of many cognitive functions, including memory. For example, the retrieval-induced forgetting (RIF) effect occurs when extra practice with some items from a study ...list inhibits the retrieval of the nonpracticed items relative to a baseline condition that does not involve extra practice. Although counterintuitive, the RIF phenomenon may be important for resolving interference by inhibiting potentially competing retrieval targets. Neuroimaging studies suggest that the hippocampus and prefrontal cortex are involved in the RIF effect, but controlled lesion studies have not yet been performed. We developed a rodent model of the RIF training procedure and trained control rats and rats with temporary inactivation of the hippocampus or medial prefrontal cortex (mPFC). Rats were trained on a list of odor cues, presented in cups of digging medium with a buried reward, followed by additional practice trials with a subset of the cues. We then tested the rats' memories for the cues and their association with reward by presenting them with unbaited cups containing the test odorants and measuring how long they persisted in digging. Control rats exhibited a robust RIF effect in which memory for the nonpracticed odors was significantly inhibited. Thus, extra practice with some odor cues inhibited memory for the others, relative to a baseline condition that involved an identical amount of training. Inactivation of either the hippocampus or the mPFC blocked the RIF effect. We also constructed a computational model of a representational learning circuit to simulate the RIF effect. We show in this model that "sideband suppression" of similar memory representations can reproduce the RIF effect and that alteration of the suppression parameters and learning rate can reproduce the lesion effects seen in our rats. Our results suggest that the RIF effect is widespread and that inhibitory processes are an important feature of memory function.
Abstract Introduction There is little information on patient-driven noncompliance of adjuvant therapies and its consequences. Methods This retrospective study compares clinical, pathological features ...and outcomes of breast cancer patients who were compliant to recommended radiation, chemotherapy, and hormonal therapies to those who were noncompliant. Results Noncompliance rates for chemotherapy, radiation, and tamoxifen were 31 of 421 (7%), 30 of 855 (4%), and 294 of (37%) respectively. Old age was associated with noncompliance to chemotherapy and radiation, but younger women tend to be more often noncompliant to tamoxifen. Noncompliance with chemotherapy or radiation did not significantly affect 5-year local and distant disease-free survival rates. Noncompliance with tamoxifen was associated with decreased 5-year local and distant disease-free survivals (87% versus 96%, 76% versus 87%, respectively, P < .001). Conclusion Noncompliance with tamoxifen is the most common, resulting in significantly increased risk of local and distant disease recurrence.
Parkinson’s disease (PD) is a neurodegenerative disorder associated with motor disturbance and non-motor symptoms (NMS). Although NMS such as sleep and circadian disruption, cognitive impairment, and ...mood disturbance are prevalent and debilitating, treatments are limited, owing to lack of knowledge about their etiologies and interactions. This project comprised two studies of NMS in mild to moderate idiopathic PD without dementia. The hypothesis of Study 1 was that disruption of rest-activity circadian rhythm contributes to cognitive impairment in PD independently of sleep disruption. Thirty-five participants underwent 7-10 days of actigraphy monitoring, which provided estimates of sleep and circadian functioning, and then neuropsychological testing. Hierarchical regression showed that circadian interdaily stability predicted executive function, visuospatial function, and psychomotor speed, though not memory, independently of sleep. Sleep efficiency independently predicted executive but not other cognitive function. Study 2 examined daily temporal associations between sleep, subjective cognition, and mood (anxiety, positive affect) in PD. Twenty participants used a smartphone app to engage in 14 days of ecological momentary assessment (EMA) of daytime symptoms and subjective sleep quantity and quality. They wore actigraphs for objective sleep assessment. The hypothesis was that sleep quality would predict cognition and mood. Multilevel modeling indicated that subjective sleep quality was bidirectionally associated with mood on a day-to-day basis (i.e., last night’s perceived sleep affected today’s mood, which in turn will affect tonight’s sleep). There was also a trend for subjective sleep quality to predict the next day’s subjective cognitive function. Objective sleep was not associated with any daytime symptoms. Study 1 provided the first evidence that circadian rhythm contributes to cognition in PD independently of sleep. Study 2 indicated that, on a daily timescale, subjective sleep is relevant to mood and possibly cognition in PD, whereas objective sleep is either insufficiently sensitive or not relevant. Together these findings support the use of EMA to investigate small-timescale interactions among NMS, and present circadian rhythms and sleep perception as intervention targets for improving cognition and mood, and ultimately for enhancing quality of life in PD.
PDF
