Abuse of Δ 9 -THC by females during adolescence may produce long-term deficits in complex behavioral processes such as learning, and these deficits may be affected by the presence of ovarian hormones. To assess this possibility, 40 injections of saline or 5.6 mg/kg of Δ 9 -THC were administered i.p. daily during adolescence to gonadally intact or ovariectomized (OVX) female rats, yielding 4 treatment groups (intact/saline, intact/THC, OVX/saline, and OVX/THC). Δ 9 -THC (0.56-10 mg/kg) was then re-administered to each of the 4 groups during adulthood to examine their sensitivity to its disruptive effects. The behavioral task required adult subjects to both learn (acquisition component) different response sequences and repeat a known response sequence (performance component) daily. During baseline (no injection) and control (saline injection) sessions, ovariectomized subjects had significantly higher response rates and lower percentages of error in both behavioral components than the intact groups irrespective of saline or Δ 9 -THC administration during adolescence; the intact group that received Δ 9 -THC had the lowest response rates in each component. Upon re-administration of Δ 9 -THC, the groups that received adolescent ovariectomy alone, adolescent Δ 9 -THC administration alone, or both treatments were found to be less sensitive to the rate-decreasing effects, and more sensitive to the error-increasing effects of Δ 9 -THC than the control group (i.e., intact subjects that received saline during adolescence). Neurochemical analyses of the brains from each adolescent-treated group indicated that there were also persistent effects on cannabinoid type-1 (CB-1) receptor levels in the hippocampus and striatum that depended on the brain region and the presence of ovarian hormones. In addition, autoradiographic analyses of the brains from adolescent-treated, but behaviorally-naïve, subjects indicated that ovariectomy and Δ 9 -THC administration produced effects on receptor coupling in some of the same brain regions. In summary, chronic administration of Δ 9 -THC during adolescence in female rats produced long-term effects on operant learning and performance tasks and on the cannabinoid system that were mediated by the presence of ovarian hormones, and that altered their sensitivity to Δ 9 -THC as adults.

stimates from the coronavirus disease 2019 pandemic suggest that about 20% of adults with COVID-19 are hospitalized, and in approximately 20% of those, severe acute respiratory failure develops that requires life-support treatments such as invasive mechanical ventilation. 1,2 Results of research from before the COVID-19 pandemic suggest that most of these adults with critical illness will survive to hospital discharge. 3,4 Survival, for many, will come with a legacy of new or worsening deficits in physical, 5 mental, 6,7 or cognitive health in the months to years after hospital discharge. 8,9 Post-intensive care syndrome has become the agreedupon term for these new or worsening health problems that can persist beyond an acute hospitalization for serious illness. 8 The psychosocial outcomes in survivors of critical illness include high rates of clinically significant anxiety, 10 depression, 11 and posttraumatic stress symptoms. 12 Related, many survivors are unable to return to work 13 and thereby suffer financial consequences that further the distress of survivors and their loved ones 14 ; income loss by both the survivor and family members who curtail work to serve as caregivers

OBJECTIVES Research estimates that a significant percentage of individuals with Mild Cognitive Impairment (MCI) experience functional difficulties. In addition to reduced accuracy on measures of everyday function, cross-sectional research has demonstrated that speed of performing instrumental activities of daily living (IADLs) is slowed in individuals with MCI. The present study investigated whether baseline and longitudinal changes in speed and accuracy of IADL performance differed between persons with MCI and cognitively normal peers. DESIGN Linear mixed models were used to estimate group differences in longitudinal performance on measures of IADLs. SETTING Assessments were conducted at university and medical research centers. PARTICIPANTS The sample consisted of 80 participants with MCI and 80 control participants who were enrolled in the Alzheimer’s Disease Research Center’s Measuring Independent Living in the Elderly Study (MILES). MEASUREMENTS IADL speed and accuracy were directly assessed using selected domains of the Financial Capacity Instrument, the Timed IADL assessment, and driving-related assessments (Useful Field of View, Road Sign Test). RESULTS Individuals with MCI performed worse on speed and accuracy measures of IADLs in comparison to cognitively normal peers and demonstrated significantly steeper rates of decline over 3 years in either speed or accuracy in all domains assessed. CONCLUSION Both speed and accuracy of performance on measures of IADL are valuable indices for early detection of functional change in MCI. The performance pattern may reflect a trade-off between speed and accuracy that can guide clinical recommendations for maintaining patient independence.

Background Cognitive processing speed is important for performing everyday activities in persons with mild cognitive impairment (MCI). However, its role in daily function has not been examined while simultaneously accounting for contributions of Alzheimer’s disease (AD) risk biomarkers. We examine the relationships of processing speed and genetic and neuroimaging biomarkers to composites of daily function, mobility, and driving. Method We used baseline data from 103 participants on the MCI/mild dementia spectrum from the Applying Programs to Preserve Skills trial. Linear regression models examined relationships of processing speed, structural magnetic resonance imaging (MRI), and genetic risk alleles for AD to composites of performance-based instrumental activities of daily living (IADLs), community mobility, and on-road driving evaluations. Results In multivariable models, processing speed and the brain MRI neurodegeneration biomarker Spatial Pattern of Abnormality for Recognition of Early Alzheimer’s disease (SPARE-AD) were significantly associated with functional and mobility composite performance. Better processing speed and younger age were associated with on-road driving ratings. Genetic risk markers, left hippocampal atrophy, and white matter lesion volumes were not significant correlates of these abilities. Processing speed had a strong positive association with IADL function (p < .001), mobility (p < .001), and driving (p = .002). Conclusions Cognitive processing speed is strongly and consistently associated with critical daily functions in persons with MCI in models including genetic and neuroimaging biomarkers of AD risk. SPARE-AD scores also significantly correlate with IADL performance and mobility. Results highlight the central role of processing speed in everyday task performance among persons with MCI/mild dementia.