Cognitive Processing Speed Is Strongly Related to Driving Skills, Financial Abilities, and Other Instrumental Activities of Daily Living in Persons With Mild Cognitive Impairment and Mild Dementia.

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.

Feasibility of Videophone-Assisted Neuropsychological Testing For Intensive Care Unit Survivors.

BACKGROUND: Most hospitals lack neuropsychologists, and this lack has hampered the conduct of large-scale, multicenter clinical trials to evaluate the effect of interventions on long-term cognition in patients in intensive care units (ICUs). OBJECTIVE: To evaluate the feasibility of videophone-assisted neuropsychological testing administered by using an inexpensive high-definition web camera and a laptop. METHODS: This prospective, single-center observational study, conducted at a tertiary care academic hospital, included ICU survivors aged 18 years or older. Participants were seated in a quiet room with a proctor who provided neuropsychological testing forms and addressed technical difficulties. The neuropsychological rater was in a room 100 yd (90 m) from the participant. Skype was used for videoconferencing via a wireless connection. After the testing session was completed, participants completed surveys. RESULTS: In April 2017, 10 ICU survivors (median age, 63 years; range, 51-73 years) were enrolled. All indicated that "Videophone-assisted neuropsychological testing is reasonable to use in research studies." When asked "What made the videophone-assisted cognitive testing difficult?" 1 participant (10%) reported occasionally becoming frustrated with the testing because the wireless internet speed was slower than usual and reduced the resolution of visual stimuli. Three participants (30%) reported difficulty with the line orientation task because the lines were "shaky" and the images were "hard to see." CONCLUSION: Videophone-assisted neuropsychological testing is feasible for evaluating cognition in multicenter studies of ICU patients. Feedback provided will be used to refine this telemedicine approach to neuropsychological testing.

Mild Cognitive Impairment and Changes in Everyday Function Over Time: The Importance of Evaluating Both Speed and Accuracy.

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 the 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. MEASUREMENTS: Instrumental activities of daily living 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 three 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.

Cognitive function in adults aging with fabry disease: a case-control feasibility study using telephone-based assessments.

We examined the feasibility of recruiting US adults ≥45 years old with Fabry disease (FD) for telephone assessments of cognitive functioning. A case-control design matched each FD participant on age, sex, race, and education to four participants from a population-based study. Fifty-four participants with FD age 46-72 years were matched to 216 controls. Standardized cognitive assessments, quality of life (QOL), and medical histories were obtained by phone, supplemented by objective indices of comorbidities. Normalized scores on six cognitive tasks were calculated. On the individual tasks, scores on list recall and semantic fluency were significantly lower among FD participants (p-values < 0.05), while scores on the other four tasks did not differ. After averaging each participant's normalized scores to form a cognitive composite, we examined group differences in composite scores, before and after adjusting for multiple covariates using generalized estimating equations. The composite scores of FD cases were marginally lower than controls before covariate adjustments (p = 0.08). QOL and mental health variables substantially attenuated this finding (p = 0.75), highlighting the influence of these factors on cognition in FD. Additional adjustment for cardiovascular comorbidities, kidney function, and stroke had negligible impact, despite higher prevalence in the FD sample. Telephone-based cognitive assessment methods are feasible among adults with FD, affording access to a geographically dispersed sample. Although decrements in discrete cognitive domains were observed, the overall cognitive function of older adults with FD was equivalent to that of well-matched controls before and after accounting for multiple confounding variables.

Long-term behavioral and pharmacodynamic effects of delta-9-tetrahydrocannabinol in female rats depend on ovarian hormone status.

Abuse of Δ9-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 Δ9-THC were administered i.p. daily during adolescence to gonadally intact or ovariectomized (OVX) female rats, yielding four treatment groups (intact/saline, intact/THC, OVX/saline, and OVX/ THC). Δ9-THC (0.56-10 mg/kg) was then re-administered to each of the four 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, OVX subjects had significantly higher response rates and lower percentages of error in both behavioral components than the intact groups irrespective of saline or Δ9-THC administration during adolescence; the intact group that received Δ9-THC had the lowest response rates in each component. Upon re-administration of Δ9-THC, the groups that received adolescent ovariectomy alone, adolescent Δ9-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 Δ9-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 Δ9-THC administration produced effects on receptor coupling in some of the same brain regions. In summary, chronic administration of Δ9-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 Δ9-THC as adults.

A duck delta1 crystallin double loop mutant provides insight into residues important for argininosuccinate lyase activity.

Delta-crystallin is directly related to argininosuccinate lyase (ASL), and catalyzes the reversible hydrolysis of argininosuccinate to arginine and fumarate. Two delta-crystallin isoforms exist in duck lenses, delta1 and delta2, which are 94% identical in amino acid sequence. Although the sequences of duck delta2-crystallin (ddeltac2) and duck delta1-crystallin (ddeltac1) are 69 and 71% identical to that of human ASL, respectively, only ddeltac2 has maintained ASL activity. Domain exchange experiments and comparisons of various delta-crystallin structures have suggested that the amino acid substitutions in the 20's (residues 22-31) and 70's (residues 74-89) loops of ddeltac1 are responsible for the loss of enzyme activity in this isoform. To test this hypothesis, a double loop mutant (DLM) of ddeltac1 was constructed in which all the residues that differ between the two isoforms in the 20's and 70's loops were mutated to those of ddeltac2. Contrary to expectations, kinetic analysis of the DLM found that it was enzymatically inactive. Furthermore, binding of argininosuccinate by the DLM, as well as the ddeltac1, could not be detected by isothermal titration calorimetry (ITC). To examine the conformation of the 20's and 70's loops in the DLM, and to understand why the DLM is unable to bind the substrate, its structure was determined to 2.5 A resolution. Comparison of this structure with both wild-type ddeltac1 and ddeltac2 structures reveals that the conformations of the 20's and 70's loops in the DLM mutant are very similar to those of ddeltac2. This suggests that the five amino acid substitutions in domain 1 which lie outside of the two loop regions and which are different in the DLM, and ddeltac2, must be important enzymatically. The structure of the DLM in complex with sulfate was also determined to 2.2 A resolution. This structure demonstrates that the conformational changes of the 280's loop and domain 3, previously observed in ddeltac1, also occur in the DLM upon sulfate binding, reinforcing the hypothesis that these events may occur in the active ddeltac2 protein during catalysis.