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We examined whether hypertension moderated the effects of apolipoprotein ε4 (APOE ε4) on individual differences in level and change in cognitive functions over a 21-year period using data from the Seattle Longitudinal Study (SLS). A total of 563 nondemented adults ages 32 to 74 years in 1984 (M = 51.06, SD = 12.03) were included in the study. Cognitive performance was assessed spanning 7 domains-verbal comprehension, numeric facility, episodic memory, spatial orientation, inductive reasoning, perceptual speed, and cognitive flexibility-over 4 occasions of measurement at 7-year intervals. Multilevel modeling was used to test the cross-sectional and longitudinal effects of hypertension, APOE, and their interaction, after adjusting for age, gender, and education. APOE and hypertension had additive and interactive effects on select cognitive functions. APOE ε4 carriers had a performance advantage at baseline on reasoning ability, relative to non-ε4 carriers. The additive effect of hypertension on level of cognitive flexibility (i.e., lower performance for hypertensives) was qualified by a significant APOE × Hypertension interaction on the slope. Hypertension moderated the effects of APOE ε4 on the rate of change for cognitive flexibility, such that the presence of the APOE ε4 allele and hypertension was associated with steeper cognitive decline over a 21-year period. A double dose of genetic vascular risk factors accounted for variation in the slope in normal cognitive aging, suggesting that clinical interventions aimed at lowering vascular risk may benefit cognitive health., (PsycINFO Database Record (c) 2014 APA, all rights reserved.)

The Joint Trauma System in Afghanistan, while designed for the care of injured patients, can provide timely, multimodal, coordinated care for nontraumatic medical emergencies as patients are evacuated from theater. To illustrate this, a case of out-of-hospital cardiac arrest is presented. The patient was able to receive all recommended components of postcardiac arrest care in a timely, coordinated manner at four different medical treatment facilities and while traveling over 8,600 miles with critical care provided en route., (Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.)

Objectives: To determine the effects of cognitive training on cognitive abilities and everyday function over 10 years., Design: Ten-year follow-up of a randomized, controlled single-blind trial (Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE)) with three intervention groups and a no-contact control group., Setting: Six U.S. cities., Participants: A volunteer sample of 2,832 persons (mean baseline age 73.6; 26% African American) living independently., Intervention: Ten training sessions for memory, reasoning, or speed of processing; four sessions of booster training 11 and 35 months after initial training., Measurements: Objectively measured cognitive abilities and self-reported and performance-based measures of everyday function., Results: Participants in each intervention group reported less difficulty with instrumental activities of daily living (IADLs) (memory: effect size = 0.48, 99% confidence interval (CI) = 0.12-0.84; reasoning: effect size = 0.38, 99% CI = 0.02-0.74; speed of processing: effect size = 0.36, 99% CI = 0.01-0.72). At a mean age of 82, approximately 60% of trained participants, versus 50% of controls (P < .05), were at or above their baseline level of self-reported IADL function at 10 years. The reasoning and speed-of-processing interventions maintained their effects on their targeted cognitive abilities at 10 years (reasoning: effect size = 0.23, 99% CI = 0.09-0.38; speed of processing: effect size = 0.66, 99% CI = 0.43-0.88). Memory training effects were no longer maintained for memory performance. Booster training produced additional and durable improvement for the reasoning intervention for reasoning performance (effect size = 0.21, 99% CI = 0.01-0.41) and the speed-of-processing intervention for speed-of-processing performance (effect size = 0.62, 99% CI = 0.31-0.93)., Conclusion: Each Advanced Cognitive Training for Independent and Vital Elderly cognitive intervention resulted in less decline in self-reported IADL compared with the control group. Reasoning and speed, but not memory, training resulted in improved targeted cognitive abilities for 10 years., (© 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.)

Objective: To characterize change through 5-year follow-up, associated with training, booster, adherence, and other characteristics., Methods: Sample included all individuals randomly assigned to reasoning training (N = 699). Piecewise latent growth modeling was used to examine trajectory of performance on outcome measures., Results: Training resulted in improved reasoning performance through Year 5. A significant third annual booster effect was one-half the size of the training effect. Training adherence resulted in greater training effects. Higher education, Mini-Mental State Exam (MMSE), better health, and younger age related to higher baseline performance. Higher MMSE was related to larger training effects, larger linear slopes, and smaller booster effects. Significant functional outcomes included a training effect for complex reaction time (CRT), and first annual booster effects for the CRT and observed tasks of daily living., Discussion: Initial training gain was comparable with magnitude of age-related cognitive decline over 5 years with no training. Neither age nor gender predicted training or booster effects, indicating the generality of training effects across age (65-90 years).

Objective: The current study examined a 5-year cognitive change in untrained African American and White participants from the Advanced Cognitive Training in Independent and Vital Elderly (ACTIVE) study., Method: Five-year trajectories of memory, reasoning, visual processing speed/useful field of view, digit-symbol substitution, and vocabulary were investigated. Education, health, gender, age, and retest/practice effects were controlled for, and a missing data pattern mixture approach was used to adjust for dropout effects., Results: After considering age, education, health, and gender, being African American uniquely explained 2% to 7% of the variance in cognitive performance. There were virtually no significant race differences in the rates of change., Discussion: Race-related results in the current study are consistent with previous research suggesting that social advantage factors such as education have a stronger influence on the level of performance than the rate of change. The small remaining effects of being African American on performance levels likely reflect uncontrolled variation in factors like literacy and financial advantage.

Objectives: Salthouse illustrated that among Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) participants, cognitive change accelerated following training. Our goal was to determine if this finding persists net of practice, training, and loss of training gains effects., Methods: We evaluated change over 5 years following cognitive training among older adults (N = 1,659, age 65 to 94)., Results: Reasoning training, but not memory or speed, attenuated aging-related change. Memory gains were maintained, but about half of reasoning and speed gains were lost. Performance differences at the end of the follow-up were equivalent to about 6, 4, and 8 years of aging for memory, reasoning, and speed training, respectively., Discussion: Training can appear to accelerate age-related change, because change over time is coupled with loss of training gains. Our analysis is limited by follow-up that is short for precisely characterizing aging-related change.

Aims: The second most frequently reported post-treatment symptom in cancer survivors are concerns about impaired cognition. Despite numerous studies demonstrating significant impairments in a portion of survivors, information on effective treatments remains an emerging area of research. This study examined the effectiveness of a group-based cognitive rehabilitation intervention in cancer survivors., Main Methods: This study was a randomized, controlled study of a 7-week cognitive rehabilitation intervention delivered in group format. Participants were evaluated with subjective symptom questionnaires and objective neurocognitive tests prior to and following treatment., Key Findings: Twenty-eight participants (mean age 58 years) with a median of 3 years (± 6 years) post-primary/adjuvant treatment and various cancer sites (breast, bladder, prostate, colon, uterine) completed the study. Compared to baseline, the treatment group demonstrated improvements in symptoms of perceived cognitive impairments (p<.01), cognitive abilities (p<.01) and overall quality of life with regard to cognitive symptoms (p<.01) as measured by the FACT-Cog. The treatment group also improved on objective measures of attention (p<.05) and a trend toward improvement on verbal memory. Significant improvement was not observed on all cognitive tests., Significance: A group based cognitive rehabilitation intervention in cancer survivors was effective for improving attention abilities and overall quality of life related to cognition. Results suggest that group based cognitive rehabilitation may be an effective intervention for treating cognitive dysfunction in cancer patients and should be further studied in a larger trial with an active control condition., (© 2013.)

A major goal of animal research is to identify interventions that can promote successful aging and delay or reverse age-related cognitive decline in humans. Recent advances in standardizing cognitive assessment tools for humans have the potential to bring preclinical work closer to human research in aging and Alzheimer's disease. The National Institute of Health (NIH) has led an initiative to develop a comprehensive Toolbox for Neurologic Behavioral Function (NIH Toolbox) to evaluate cognitive, motor, sensory and emotional function for use in epidemiologic and clinical studies spanning 3 to 85 years of age. This paper aims to analyze the strengths and limitations of animal behavioral tests that can be used to parallel those in the NIH Toolbox. We conclude that there are several paradigms available to define a preclinical battery that parallels the NIH Toolbox. We also suggest areas in which new tests may benefit the development of a comprehensive preclinical test battery for assessment of cognitive function in animal models of aging and Alzheimer's disease., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Although aging is associated with changes in brain structure and cognition it remains unclear which specific structural changes mediate individual cognitive changes. Several studies have reported that white matter (WM) integrity, as assessed by diffusion tensor imaging (DTI), mediates, in part, age-related differences in processing speed (PS). There is less evidence for WM integrity mediating age-related differences in higher order abilities (e.g., memory and executive functions). In 165 typically aging adults (age range 54-89) we show that WM integrity in select cerebral regions is associated with higher cognitive abilities and accounts variance not accounted for by PS or age. Specifically, voxel-wise analyses using tract-based spatial statistics (TBSS) revealed that WM integrity was associated with reasoning, cognitive flexibility and PS, but not memory or word fluency, after accounting for age and gender. While cerebral fractional anisotropy (FA) was only associated with PS; mean (MD), axial (AD) and radial (RD) diffusivity were associated with reasoning and flexibility. Reasoning was selectively associated with left prefrontal AD, while cognitive flexibility was associated with MD, AD and RD throughout the cerebrum. Average WM metrics within select WM regions of interest accounted for 18% and 29% of the variance in reasoning and flexibility, respectively, similar to the amount of variance accounted for by age. WM metrics mediated ~50% of the age-related variance in reasoning and flexibility and different proportions, 11% for reasoning and 44% for flexibility, of the variance accounted for by PS. In sum, (i) WM integrity is significantly, but variably, related to specific higher cognitive abilities and can account for a similar proportion of variance as age, and (ii) while FA is selectively associated with PS; while MD, AD and RD are associated with reasoning, flexibility and PS. This illustrates both the anatomical and cognitive selectivity of structure-cognition relationships in the aging brain., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objectives: This study examines cognitive outcomes for alcohol drinking status over time, across cognitive ability and age groups., Methods: Data (1998-2005) from n = 571 Seattle Longitudinal Study participants aged 45+years (middle-aged: 45-64, young-old: 65-75, old-old: 75+) were analyzed to examine the alcohol drinking status effect (e.g., abstinent, moderate (less than seven drinks/week), at-risk (more than eight drinks/week)) on cognitive ability (e.g., memory, reasoning, spatial, verbal number, speed abilities)., Results: Findings indicated that alcohol drinking status was associated with change in verbal ability, spatial ability, and perceptual speed. Decline in verbal ability was seen among alcohol abstainers and moderate alcohol consumers, but at-risk drinkers displayed relative stability. At-risk old-old adults and middle-aged adults (regardless of drinking status), displayed relative stability in spatial ability. Decline in spatial ability was however present among young-old adults across drinking status, and among abstaining and moderate drinking old-old adults. At-risk drinkers showed the most positive spatial ability trajectory. A gender effect in perceptual speed was detected, with women who abstained from drinking displaying the most decline in perceptual speed compared with women that regularly consumed alcohol, and men displaying decline in perceptual speed across drinking status., Discussion: In this study, consuming alcohol is indicative of cognitive stability. This conclusion should be considered cautiously, due to study bias created from survivor effects, analyzing two time points, health/medication change status, and overrepresentation of higher socioeconomic status and white populations in this study. Future research needs to design studies that can make concrete recommendations about the relationship between drinking status and cognition.

This study examines whether midlife change in episodic memory predicts hippocampal volume in old age. From the Seattle Longitudinal Study we retrospectively identified 84 healthy, cognitively normal individuals, age 52 to 87, whose episodic memory had reliably declined (n = 33), improved (n = 28) or remained stable (n = 23) over a 14-year period in midlife (age 43-63). Midlife memory improvement was associated with 13% larger hippocampal volume (p < 0.01) in old age (age 66-87), compared with old age individuals whose midlife episodic memory had either declined or remained stable during midlife. Midlife memory change did not predict total hippocampal volume for those currently in late middle age (age 52-65). The pattern of findings was not modified by gender, apolipoprotein ε4 status, education or current memory performance. Change in midlife memory scores over 14 years, but not any single assessment, predicted hippocampal volumes in old age, emphasizing the importance of longitudinal data in examining brain-cognition relationships. These findings suggest that improvement in memory in midlife is associated with sparing of hippocampal volume in later life., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To determine local doxorubicin levels surrounding radiopaque drug-eluting beads (DEBs) in normal swine liver and kidney following transcatheter arterial chemoembolization. The influence of bead size (70-150 μm or 100-300 μm) was compared with regard to tissue penetration and spatial distribution of the bead, as well as eventual drug coverage (ie, amount of tissue exposed to drug)., Materials and Methods: Radiopaque DEBs were synthesized by suspension polymerization followed by incorporation of iodized oil and doxorubicin. Chemoembolization of swine liver and kidney was performed under fluoroscopic guidance. Three-dimensional tissue penetration of "imageable" DEBs was investigated ex vivo with micro-computed tomography (microCT). Drug penetration from the bead surface and drug coverage was evaluated with epifluorescence microscopy, and cellular localization of doxorubicin was evaluated with confocal microscopy. Necrosis was evaluated with hematoxylin and eosin staining., Results: MicroCT demonstrated that 70-150-μm DEBs were present in more distal arteries and located in a more frequent and homogeneous spatial distribution. Tissue penetration of doxorubicin from the bead appeared similar (∼300 μm) for both DEBs, with a maximum tissue drug concentration at 1 hour coinciding with nuclear localization of doxorubicin. The greater spatial frequency of the 70-150-μm DEBs resulted in approximately twofold improved drug coverage in kidney. Cellular death is predominantly observed around the DEBs beginning at 8 hours, but increased at 24 and 168 hours., Conclusions: Smaller DEBs penetrated further into targeted tissue (ie, macroscopic) with a higher spatial density, resulting in greater and more uniform drug coverage (ie, microscopic) in swine., (Copyright © 2012 SIR. Published by Elsevier Inc. All rights reserved.)

Social activity is typically viewed as part of an engaged lifestyle that may help mitigate the deleterious effects of advanced age on cognitive function. As such, social activity has been examined in relation to cognitive abilities later in life. However, longitudinal evidence for this hypothesis thus far remains inconclusive. The current study sought to clarify the relationship between social activity and cognitive function over time using a coordinated data analysis approach across four longitudinal studies. A series of multilevel growth models with social activity included as a covariate is presented. Four domains of cognitive function were assessed: reasoning, memory, fluency, and semantic knowledge. Results suggest that baseline social activity is related to some, but not all, cognitive functions. Baseline social activity levels failed to predict rate of decline in most cognitive abilities. Changes in social activity were not consistently associated with cognitive functioning. Our findings do not provide consistent evidence that changes in social activity correspond to immediate benefits in cognitive functioning, except perhaps for verbal fluency.

Engagement in cognitively stimulating activities has been considered to maintain or strengthen cognitive skills, thereby minimizing age-related cognitive decline. While the idea that there may be a modifiable behavior that could lower risk for cognitive decline is appealing and potentially empowering for older adults, research findings have not consistently supported the beneficial effects of engaging in cognitively stimulating tasks. Using observational studies of naturalistic cognitive activities, we report a series of mixed effects models that include baseline and change in cognitive activity predicting cognitive outcomes over up to 21 years in four longitudinal studies of aging. Consistent evidence was found for cross-sectional relationships between level of cognitive activity and cognitive test performance. Baseline activity at an earlier age did not, however, predict rate of decline later in life, thus not supporting the concept that engaging in cognitive activity at an earlier point in time increases one's ability to mitigate future age-related cognitive decline. In contrast, change in activity was associated with relative change in cognitive performance. Results therefore suggest that change in cognitive activity from one's previous level has at least a transitory association with cognitive performance measured at the same point in time.

The present study used a coordinated analyses approach to examine the association of physical activity and cognitive change in four longitudinal studies. A series of multilevel growth models with physical activity included both as a fixed (between-person) and time-varying (within-person) predictor of four domains of cognitive function (reasoning, memory, fluency, and semantic knowledge) was used. Baseline physical activity predicted fluency, reasoning and memory in two studies. However, there was a consistent pattern of positive relationships between time-specific changes in physical activity and time-specific changes in cognition, controlling for expected linear trajectories over time, across all four studies. This pattern was most evident for the domains of reasoning and fluency.

Objective: The present study sought to predict changes in everyday functioning using cognitive tests., Methods: Data from the Advanced Cognitive Training for Independent and Vital Elderly trial were used to examine the extent to which competence in different cognitive domains--memory, inductive reasoning, processing speed, and global mental status--predicts prospectively measured everyday functioning among older adults. Coefficients of determination for baseline levels and trajectories of everyday functioning were estimated using parallel process latent growth models., Results: Each cognitive domain independently predicts a significant proportion of the variance in baseline and trajectory change of everyday functioning, with inductive reasoning explaining the most variance (R2 = .175) in baseline functioning and memory explaining the most variance (R2 = .057) in changes in everyday functioning., Discussion: Inductive reasoning is an important determinant of current everyday functioning in community-dwelling older adults, suggesting that successful performance in daily tasks is critically dependent on executive cognitive function. On the other hand, baseline memory function is more important in determining change over time in everyday functioning, suggesting that some participants with low baseline memory function may reflect a subgroup with incipient progressive neurologic disease.

Life span researchers have long been interested in how and why fundamental aspects of human ontogeny differ between cohorts of people who have lived through different historical epochs. When examined at the same age, later born cohorts are often cognitively and physically fitter than earlier born cohorts. Less is known, however, about cohort differences in the rate of cognitive aging and if, at the very end of life, pervasive mortality-related processes overshadow and minimize cohort differences. We used data on 5 primary mental abilities from the Seattle Longitudinal Study (Schaie, 2005) to compare both age-related and mortality-related changes between earlier born cohorts (1886-1913) and later born cohorts (1914-1948). Our models covary for several individual and cohort differences in central indicators of life expectancy, education, health, and gender. Age-related growth models corroborate and extend earlier findings by documenting level differences at age 70 of up to 0.50 SD and less steep rates of cognitive aging on all abilities between 50 and 80 years of age favoring the later born cohort. In contrast, mortality-related models provide limited support for positive cohort differences. The later born cohort showed steeper mortality-related declines. We discuss possible reasons why often reported positive secular trends in age-related processes may not generalize to the vulnerable segment of the population that is close to death and suggest routes for further inquiry., (PsycINFO Database Record (c) 2011 APA, all rights reserved)

Data from the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) trial (N = 2,802) were analyzed to examine whether word list learning predicts future everyday functioning. Using stepwise random effects modeling, measures from the modified administrations of the Hopkins Verbal Learning Test (HVLT) and the Auditory Verbal Learning Test (AVLT) were independently predictive of everyday IADL functioning, problem-solving, and psychomotor speed. Associations between memory scores and everyday functioning outcomes remained significant across follow-up intervals spanning 5 years. HVLT total recall score was consistently the strongest predictor of each functional outcome. Results suggest that verbal memory measures are uniquely associated with both current and future functioning and that specific verbal memory tests like the HVLT and AVLT have important clinical utility in predicting future functional ability among older adults.

Development does not take place in isolation and is often interrelated with close others such as marital partners. To examine interrelations in spousal happiness across midlife and old age, we used 35-year longitudinal data from both members of 178 married couples in the Seattle Longitudinal Study. Latent growth curve models revealed sizeable spousal similarities not only in levels of happiness but also in how happiness changed over time. These spousal interrelations were considerably larger in size than those found among random pairs of women and men from the same sample. Results are in line with life-span theories emphasizing an interactive minds perspective by showing that adult happiness waxes and wanes in close association with the respective spouse. Our findings also complement previous individual-level work on age-related changes in well-being by pointing to the importance of using the couple as the unit of analysis.

Objective: To determine whether limited transportation affects medication adherence in patients with epilepsy., Design: Descriptive, nonexperimental, cross-sectional study., Setting: United States and worldwide, February to April 2007., Patients: 143 patients with epilepsy., Intervention: A 22-item survey was developed to ask patients with epilepsy or their caregivers about the impact of limited transportation on adherence with medications. The survey was placed on Zoomerang.com. An invitation to participate in the survey was sent via e-mail to members of the Epilepsy.com website, and an invitation with a link to the survey was placed on Epilepsy.com., Main Outcome Measures: Whether patients with epilepsy have difficulty picking up prescriptions on time because of transportation problems and whether they felt they would miss fewer doses if transportation was not an issue., Results: 143 individuals with epilepsy completed part or all of the survey. Of patients who were unable to drive, 45% reported that fewer doses would be missed if transportation was not a problem. Patients who were unable to drive had an odds ratio of 4.2 (P < 0.0001) of being unable to get medications on time. No differences were observed in the number of patients missing prescription medications associated with availability of insurance, use of mail service pharmacies, or population size of patients' area of residence. Ability to drive and distance to the pharmacy were the only factors associated with nonadherence., Conclusion: Limited transportation may be a factor in poor medication adherence in patients with epilepsy.

This paper is based on a presentation made during the Indiana Alzheimer Disease Center's Symposium on Mild Cognitive Impairment on April 19, 2008. The results of the ACTIVE study (Advanced Cognitive Training for Independent and Vital Elderly) were presented at the symposium including review of previously published study findings. The ACTIVE study is a multicenter, randomized, controlled clinical trial that has been examining the long-term effectiveness of cognitive training on enhancing mental abilities (memory, reasoning, and attention) and preserving activities of daily living (managing finances, taking medication, using the telephone, and driving) in older adults. Six centers across the eastern United States enrolled nearly 3000 people initially. Participants underwent detailed assessments of mental and functional ability on multiple occasions over several years of follow-up. ACTIVE has shown positive effects of cognitive training at 5 years post-intervention for basic mental abilities, health-related quality of life, and improved ability to perform instrumental activities of daily living (IADL). A subgroup analysis through 2 years of follow-up suggested that subjects with mild cognitive impairment (MCI) did not benefit from memory training; however, they did benefit, to the same degree as cognitively normal participants, from training in reasoning and speed of processing. This finding suggests that MCI may interfere with a person's ability to benefit from some forms of cognitive enhancement. Limitations of ACTIVE and directions for future research are reviewed.

Objective: The current study examines the prevalence of health risk behaviors and their cumulative effects on cardiovascular disease (CVD) among a sample of adults. Age cohort is also examined to determine the role of age in predicting CVD and risky health behaviors., Method: Medical records of a sample of adults from the Seattle Longitudinal Study categorized into one of four age-group cohorts were examined. Data regarding participants' health risk behaviors were examined individually and cumulatively for predicting later CVD diagnosis., Results: The prevalence of CVD increases with age, obesity, and risky medical checkups. Female risky sleepers are more likely to receive a CVD diagnosis than men who report risky sleep patterns (p < .05)., Discussion: A high risk of CVD appears to exist for adults across the life span, and several risky health behaviors also seem to place individuals more at risk for being diagnosed with CVD.

The factor structure and factorial invariance of the Quality of Life in Alzheimer's Disease (QoL-AD) Scale was investigated in a sample of 653 nondemented, community-dwelling older adults, ages 57 to 95 years (M = 71.62, SD = 8.86), from the Seattle Longitudinal Study. The total sample was split into two random halves to explore and confirm the structure of the QoL-AD. Confirmatory factor analyses indicated better fit for a three-factor solution than one- or two-factor solutions. Weak factorial invariance was found for the three-factor solution (Physical, Social, and Psychological Well-being) across age group and gender. These findings may help to establish a baseline quality of life before the onset of any noticeable AD symptoms.

Purpose: To provide an overview of cognitive plasticity concepts and findings from a lifespan developmental perspective., Methods: After an evaluation of the general concept of cognitive plasticity, the most important approaches to study behavioral and brain plasticity are reviewed. This includes intervention studies, experimental approaches, cognitive trainings, the study of facilitating factors for strategy learning and strategy use, practice, and person-environment interactions. Transfer and durability of training-induced plasticity is discussed., Results: The review indicates that methodological and conceptual advances are needed to improve the match between levels of behavioral and brain plasticity targeted in current developmental research and study designs., Conclusions: The results suggest that the emphasis of plasticity studies on treatment effectiveness needs to be complemented by a strong commitment to the grounding of the intervention in a conceptual framework.

The technical challenges of developing combination products were addressed in Part I of this two part article. Part II reviews the preclinical tests and shelf-life testing that are required using drug eluting stents and drug eluting beads as examples. Regulatory considerations and ways to simplify development are also examined.

Cognitive training improves mental abilities in older adults, but the trainability of persons with memory impairment is unclear. We conducted a subgroup analysis of subjects in the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) trial to examine this issue. ACTIVE enrolled 2802 non-demented, community-dwelling adults aged 65 years and older and randomly assigned them to one of four groups: Memory training, reasoning training, speed-of-processing training, or no-contact control. For this study, participants were defined as memory-impaired if baseline Rey Auditory Verbal Learning Test (AVLT) sum recall score was 1.5 SD or more below predicted AVLT sum recall score from a regression-derived formula using age, education, ethnicity, and vocabulary from all subjects at baseline. Assessments were taken at baseline (BL), post-test, first annual (A1), and second annual (A2) follow-up. One hundred and ninety-three subjects were defined as memory-impaired and 2580 were memory-normal. Training gain as a function memory status (impaired vs. normal) was compared in a mixed effects model. Results indicated that memory-impaired participants failed to benefit from Memory training but did show normal training gains after reasoning and speed training. Memory function appears to mediate response to structured cognitive interventions in older adults.

A 25-year-old man presented with complaints of nonpleuritic, substernal chest pain, dyspnea, and decreasing exercise tolerance. His vital signs were normal, with the exception of an oxygen saturation level of 93% while breathing room air. During his assessment, he developed transient left facial droop, left arm and leg weakness, and an ataxic gait, which lasted 15 min then resolved spontaneously. Cardiac enzyme levels were elevated, and an ECG revealed T-wave inversion in leads III, aVF, V1, and V2 with evolving ST-segment elevation in leads V3 through V5. The findings of a CT scan and MRI of the head were negative; a Doppler ultrasound of the right lower extremity revealed a thrombus extending from the common femoral vein to the popliteal vein. Cardiac catheterization revealed no evidence of epicardial coronary artery disease. CT pulmonary angiography revealed bilateral pulmonary emboli. Transesophageal echocardiography (TEE) showed a 4-cm, dumbbell-shaped mass lodged in a patent foramen ovale, confirming the diagnosis of an impending paradoxical embolism. The patient was started on therapy with unfractionated heparin, and his thrombus resolved spontaneously by hospital day 5. An impending paradoxical embolism is rare but should be suspected in anyone presenting with evidence of both venous and arterial emboli. The therapeutic options include anticoagulation, thrombolysis, and surgical embolectomy. We would propose that initial treatment with anticoagulation therapy and following with serial TEEs may be appropriate therapy in an otherwise stable patient, with surgical embolectomy or thrombolysis reserved for the treatment of thrombi that do not resolve with anticoagulation therapy or for patients with clinical deterioration.

Context: Cognitive training has been shown to improve cognitive abilities in older adults but the effects of cognitive training on everyday function have not been demonstrated., Objective: To determine the effects of cognitive training on daily function and durability of training on cognitive abilities., Design, Setting, and Participants: Five-year follow-up of a randomized controlled single-blind trial with 4 treatment groups. A volunteer sample of 2832 persons (mean age, 73.6 years; 26% black), living independently in 6 US cities, was recruited from senior housing, community centers, and hospitals and clinics. The study was conducted between April 1998 and December 2004. Five-year follow-up was completed in 67% of the sample., Interventions: Ten-session training for memory (verbal episodic memory), reasoning (inductive reasoning), or speed of processing (visual search and identification); 4-session booster training at 11 and 35 months after training in a random sample of those who completed training., Main Outcome Measures: Self-reported and performance-based measures of daily function and cognitive abilities., Results: The reasoning group reported significantly less difficulty in the instrumental activities of daily living (IADL) than the control group (effect size, 0.29; 99% confidence interval [CI], 0.03-0.55). Neither speed of processing training (effect size, 0.26; 99% CI, -0.002 to 0.51) nor memory training (effect size, 0.20; 99% CI, -0.06 to 0.46) had a significant effect on IADL. The booster training for the speed of processing group, but not for the other 2 groups, showed a significant effect on the performance-based functional measure of everyday speed of processing (effect size, 0.30; 99% CI, 0.08-0.52). No booster effects were seen for any of the groups for everyday problem-solving or self-reported difficulty in IADL. Each intervention maintained effects on its specific targeted cognitive ability through 5 years (memory: effect size, 0.23 [99% CI, 0.11-0.35]; reasoning: effect size, 0.26 [99% CI, 0.17-0.35]; speed of processing: effect size, 0.76 [99% CI, 0.62-0.90]). Booster training produced additional improvement with the reasoning intervention for reasoning performance (effect size, 0.28; 99% CI, 0.12-0.43) and the speed of processing intervention for speed of processing performance (effect size, 0.85; 99% CI, 0.61-1.09)., Conclusions: Reasoning training resulted in less functional decline in self-reported IADL. Compared with the control group, cognitive training resulted in improved cognitive abilities specific to the abilities trained that continued 5 years after the initiation of the intervention., Trial Registration: clinicaltrials.gov Identifier: NCT00298558.

The use of performance-enhancing and weight-loss supplements is prevalent in the United States, and over the past decade, there has been growing concern with regard to the safety and efficacy of these products. It is well documented that ephedra-based products are associated with adverse reactions, including serious cardiovascular and neurologic injuries. With new restrictions placed on such products, companies are now marketing caffeine-based ephedra-free herbal supplements. Less is known about the potential side effects of these products. We present the case of a 42-year-old, previously healthy man who developed malignant hypertension and hypertensive retinopathy while taking Hydroxycut, a caffeine-based ephedra-free supplement. To our knowledge, this is the first documented case of hypertensive retinopathy associated with the use of Hydroxycut. Given the lack of investigative studies in regard to their safety and efficacy, judicious care should be taken with the use of all herbal supplements, including those designated as ephedra-free.

Purpose: To present the pathologic and pharmacokinetic findings from hepatic embolization in a porcine model comparing doxorubicin-eluting beads with bland embolization and to correlate these findings with in vitro release kinetics., Materials and Methods: Drug-eluting beads (DEB; 100-300 microm and 700-900 microm) loaded with 37.5 mg doxorubicin per milliliter hydrated beads were used to embolize the hepatic artery feeding the left lobe of the liver in young adult Yucatan pigs (n = 5 per group). Control animals underwent embolization with bland beads (100-300 microm; n = 5). Systemic plasma levels of doxorubicin were measured and correlated to in vitro drug release. Blood sampling and histopathologic examination were performed during the 90-day follow-up., Results: All animals underwent successful embolization, and the treatment was well tolerated. Mean volumes of beads administered were 2.0-3.4 mL, with mean doses of 127.5 mg and 78.7 mg of doxorubicin for the 100- to 300-microm and 700- to 900-microm DEB groups, respectively. Gross pathologic examination revealed no effects on organs other than the liver. There was a transient increase in liver enzyme levels, particularly in the groups of animals who underwent embolization with 100- to 300-microm DEB. Histopathologic study showed mostly nonnecrotic changes with bland beads, whereas the effects of DEB were more severe, with large areas of pannecrosis evident with the 100- to 300-microm DEB. Maximum plasma concentrations were 651 ng/mL and 42.8 ng/mL for the 100- to 300-microm and 700- to 900-microm DEB groups, respectively, observed at 1 minute for both groups. Correlation with in vitro data showed a strong linear relationship., Conclusions: Hepatic arterial embolization with DEB was shown to be safe and well tolerated. The locoregional delivery of doxorubicin from DEB caused targeted tissue damage with minimal systemic impact and could be a promising new approach to transarterial chemoembolization of solid tumors.

Research has demonstrated that older adults' cognitive performance can be enhanced via formal intervention, as well as more informal intervention including collaboration or working with a partner. The current study investigated the effects of an inductive reasoning training program adapted for in-home use among older adults assigned to individual training (n = 30), collaborative training (n = 34), or a no-treatment control group (n = 34). The training consisted of 10 sessions, and all participants completed a pretest followed by a post-test 6 weeks later. Findings suggest that older adults could effectively "train themselves" without the guidance of a formal instructor. The results, however, did not indicate immediate added benefit in reasoning performance for collaborative versus individual training using the current reasoning program.

This study examined the association of a performance-based measure of everyday functioning with clinically meaningful outcomes. Elderly participants in a prospective study of dementia were assessed at two occasions on the Everyday Problems Test for Cognitively Challenged Elderly (EPCCE), a performance-based measure of everyday functioning. Older adults who remained cognitively intact performed approximately 0.66 SD units higher on the EPCCE at both occasions than elders rated as impaired, when covarying on age, education, gender, and cognitive status. Relative to the nonimpaired participants, decline in EPCCE performance over a 2-year interval was significantly greater for impaired participants and those participants who transitioned from nonimpaired to impaired over the course of the study. Increased risk of mortality was associated with lower baseline scores and decline in EPCCE performance even after controlling for demographic variables and performance on the Mini-Mental State Examination. Given the clinical importance of identifying "at risk" elders for impairment, the findings from this study provide initial evidence for the predictive utility of performance-based measures of everyday functioning.

Purpose: The purpose of this investigation is to present the in vitro characterization and detailed drug-loading procedure for DC Bead, a microsphere product that can be loaded with chemotherapeutic agents for embolization., Materials and Methods: DC Bead is an embolic microsphere product that is capable of being loaded with anthracycline drugs such as doxorubicin just before administration in a transarterial chemoembolization (TACE) procedure. Beads can be loaded from solutions prepared from doxorubicin powder or the doxorubicin HCl formulation. In this evaluation, bead sizes were measured by optical microscopy with video imaging. Gravimetric analysis demonstrated the effect of drug loading on bead water content, and its consequent impact on bead compressibility was determined. The subsequent deliverability of the beads was assessed by mixing the beads with contrast medium and saline solution and passing the beads through an appropriately sized microcatheter. A T-cell apparatus was used to monitor the in vitro elution of the drug from the beads over a period of 24 hours in various elution media., Results: DC Bead spheres could be easily loaded with doxorubicin to a recommended level of 25 mg/mL of hydrated beads by immersion of the beads in the drug solution for 10-120 minutes depending on microsphere size. Other commercial embolic microspheres were shown not to load doxorubicin to the same extent or release it in the same fashion and were considered unsuitable for local drug delivery. Maximum theoretic capacity for DC Bead was approximately 45 mg/mL. Increase in doxorubicin loading resulted in a concomitant decrease in water content and consequential increase in bead resistance to compression force. Drug loading also resulted in a decrease in the average size of the beads, which was dependent on bead size and drug dose. This did not impact bead delivery at any drug loading level to a maximum of 37.5 mg/mL. Beads 100-700 microm in size could be delivered through 2.7-F microcatheters, whereas the 700-900-microm range required 3-F catheters. Modeling of the kinetics of drug elution from the beads in vitro at a loading dose of 25 mg/mL yielded calculated half-lives of 150 hours for the 100-300-microm range to a maximum of 1,730 hours for the 700-900-microm size range, which was dependent on the ionic strength of the elution medium. For comparison, there was a rapid loss of drug from an unstable Lipiodol emulsion with a half-life of approximately 1 hour., Conclusions: DC Bead can be loaded with doxorubicin to provide an accurate dosage of drug per unit volume of beads. Drug elution is dependent on ion exchange with the surrounding environment and is controlled and sustained, unlike the rapid separation of the drug from Lipiodol. Drug loading has no impact on the handling and deliverability of the beads, making them suitable for superselective TACE.

A battery of 17 neuropsychological tests (including the CERAD battery) and 17 psychometric ability tests were administered to a sample of 499 participants of the Seattle Longitudinal study who had been given the psychometric ability tests seven and 14 years earlier. The neuropsychological tests were projected into a 5-factor psychometric ability space by means of extension analysis. The concurrent regressions of the neuropsychology tests on the psychometric ability tests were then used to estimate neuropsychology test scores from the psychometric ability tests administered in 1984, 1991 and 1998. Neuropsychologists then rated the study participants as either normal, suspect or cognitively impaired in 1998. Changes in estimated test scores were computed over seven and fourteen years. Significant odds ratios between normal and cognitively impaired groups were found for all neuropsychological tests over the proximal period and for most tests over the 14-year period. Similar findings occurred for the odds ratios between the normal and suspect groups for the most proximal 7-year changes.

A technique is described that allows the staining and subsequent visualization of polymers that contain the phosphorylcholine (PC) group. These materials are useful as bulk materials or coatings for the fabrication of medical devices. The staining method employs rhodamine 6G, which can be simply and rapidly applied to the polymer coating and imaged using fluorescence microscopy. The specificity of the staining for the PC polymers makes this technique suitable for the evaluation of a wide range of substrates and provides qualitative information on coating uniformity, coverage and morphology. It can be used to examine the durability of, and defects in, the coating. Statistical analysis of the fluorescent intensity by measuring the pixel value during imaging can allow for the method to be used as a quality control tool.

The Revised Observed Tasks of Daily Living (OTDL-R), a performance-based test of everyday problem solving, was administered to a sample of community-dwelling older adults. The OTDL-R included nine tasks, representing medication use, telephone use, and financial management. The OTDL-R had a desirable range of difficulty and satisfactory internal consistency and showed a relatively invariant pattern of relations between measured tasks and the underlying latent dimensions they represent across White and non-White subsamples. The OTDL-R also correlated significantly with age, education, self-rated health, a paper-and-pencil measure of everyday problem solving, and measures of basic cognitive functioning. Thus, the OTDL-R is a reliable and valid objective measure of everyday problem solving that has great practical utility for assessing performance in diverse populations.

This article reviews key issues regarding the controversy on the direction and magnitude of cohort differences in intelligence. Data from the Seattle Longitudinal Study (SLS) illustrate why differences must be studied across multiple cohorts and multiple chronological ages. Differential cohort patterns for multiple dimensions of intelligence are described. A conceptual framework is suggested for the identification of historical influences important for developmental study of cohort differences.

This article reviews the history, measures and principal findings of the Seattle Longitudinal Study. This study began in 1956 focusing upon age differences and age changes in cognitive abilities. Its sampling frame is a large HMO in the Pacific Northwest. The study has been expanded to investigate various influences on cognitive aging including, cognitive styles, personality traits, life styles, and family environment. Current interest is also in the early detection of risk for dementia. In addition, this article reports original analyses of the relation of personality dimensions to cognitive abilities (both concurrent and longitudinal). While personality remains relatively stable over the adult life span, modest proportions of variance are shared between various personality traits and the cognitive abilities.

Purpose: This study examined the congruence of self-reported medications with computerized pharmacy records., Design and Methods: Pharmacy records and self-reported medications were obtained for 294 members of a state pharmaceutical assistance program who also participated in ACTIVE, a clinical trial on cognitive training in nondemented elderly persons. The average age of the sample participants was 74.5 years (range = 65-91); 87.8% were females., Results: Congruence between self-report and pharmacy data was generally high. Self-reports omitted drug classes in the pharmacy records less often than the pharmacy records did not include self-reported drug classes. The percentage of individuals with perfect agreement between self-reports and pharmacy records varied from 49% for major drug classes to 81% for specific cardiovascular and central nervous system drugs. Within a drug class, agreement tended to be higher for individuals without a prescription in that class. Poorer health was consistently related to poorer self-report of medications., Implications: Self-reported medications are most likely to be congruent with pharmacy records for drugs prescribed for more serious conditions, for more specific classes of drugs, and for healthier individuals.

A drug eluting coronary stent was developed for use in preclinical and clinical trial evaluation. The stent was coated with a phosphorylcholine (PC)-based polymer coating containing the cell migration inhibitor batimastat. A pharmacokinetic study was conducted in a rabbit iliac model using (14)C-radiolabeled version of the drug; this showed the drug release to be first order with 94% of it being released within 28 days. Unloaded and drug-loaded stents were implanted in a porcine coronary artery model; a number were explanted at 5 days and scanning electron microscopy was used to show that the presence of the drug did not affect the rate of stent endothelialization. The remainder of the stents were removed after 6 months and the stents carefully removed from the arterial tissue. Fourier-transform infrared (FT-IR) spectroscopy (both attenuated total reflectance and microscopic imaging) was used to show the presence of the PC coating on control unloaded, drug-loaded and explanted stents, providing evidence that the coating was still present. This was further confirmed by use of atomic force microscopy (AFM) amplitude-phase, distance (a-p,d) curves which generated the characteristic traces of the PC coating. Further AFM depth-profiling techniques found that the thicknesses of the PC coatings on an control unloaded stent was 252+/-19 nm, on an control batimastat-loaded stent 906+/-224 nm and on an explanted stent 405+/-224 nm. The increase in thickness after the drug-loading process was a consequence of drug incorporation in the film, and the return to the unloaded dimensions for the explanted sample indicative of elution of the drug from the coating. The drug delivery PC coating was therefore found to be stable following elution of the drug and after 6 months implantation in vivo.

Context: Cognitive function in older adults is related to independent living and need for care. However, few studies have addressed whether improving cognitive functions might have short- or long-term effects on activities related to living independently., Objective: To evaluate whether 3 cognitive training interventions improve mental abilities and daily functioning in older, independent-living adults., Design: Randomized, controlled, single-blind trial with recruitment conducted from March 1998 to October 1999 and 2-year follow-up through December 2001., Setting and Participants: Volunteer sample of 2832 persons aged 65 to 94 years recruited from senior housing, community centers, and hospital/clinics in 6 metropolitan areas in the United States., Interventions: Participants were randomly assigned to 1 of 4 groups: 10-session group training for memory (verbal episodic memory; n = 711), or reasoning (ability to solve problems that follow a serial pattern; n = 705), or speed of processing (visual search and identification; n = 712); or a no-contact control group (n = 704). For the 3 treatment groups, 4-session booster training was offered to a 60% random sample 11 months later., Main Outcome Measures: Cognitive function and cognitively demanding everyday functioning., Results: Thirty participants were incorrectly randomized and were excluded from the analysis. Each intervention improved the targeted cognitive ability compared with baseline, durable to 2 years (P<.001 for all). Eighty-seven percent of speed-, 74% of reasoning-, and 26% of memory-trained participants demonstrated reliable cognitive improvement immediately after the intervention period. Booster training enhanced training gains in speed (P<.001) and reasoning (P<.001) interventions (speed booster, 92%; no booster, 68%; reasoning booster, 72%; no booster, 49%), which were maintained at 2-year follow-up (P<.001 for both). No training effects on everyday functioning were detected at 2 years., Conclusions: Results support the effectiveness and durability of the cognitive training interventions in improving targeted cognitive abilities. Training effects were of a magnitude equivalent to the amount of decline expected in elderly persons without dementia over 7- to 14-year intervals. Because of minimal functional decline across all groups, longer follow-up is likely required to observe training effects on everyday function.

This prospective, non-randomized clinical trial was designed to determine the clinical outcome of patients who underwent Intradiscal Electrotherapy (IDET) for the treatment of chronic discogenic low back pain. Twenty-seven consecutive patients undergoing IDET were prospectively evaluated. All patients, as determined by provocative discography and/or MRI, had discogenic disease with chronic low back pain and were non-responsive to conservative treatment for at least 6 months. The mean pre-operative duration of symptoms was 38 months. The American Association of Neurological Surgeons/Congress of Neurological Surgeons Joint Section Lumbar Disc Herniation Study Questionnaire, which includes the Oswestry Low Back Pain Disability Questionnaire and the Short Form (SF) -36 Health Status Questionnaire, was used. The follow-up endpoint for all patients was one year. Seventy-five percent of patients improved based upon the Oswestry Low Back Pain Disability Questionnaire while only 48% of patients were found to improve on the SF-36 Survey. The SF-36 Bodily Pain Subscale did improve relative to other subscales in 52% of patients. There was no relationship found between outcome and duration of symptoms (p= .32), number of levels treated (p= .20), or worker's compensation (p= .38). There were no complications that resulted from the IDET treatment. IDET was found to be effective in 75% of patients in improving their chronic low back pain. This did not translate into a significant improvement in the SF-36 survey scores. The risks are negligible, and recovery time is minimal. The procedure may be useful in selected patients who would otherwise undergo an interbody fusion procedure.

The Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) trial is a randomized, controlled, single-masked trial designed to determine whether cognitive training interventions (memory, reasoning, and speed of information processing), which have previously been found to be successful at improving mental abilities under laboratory or small-scale field conditions, can affect cognitively based measures of daily functioning. Enrollment began during 1998; 2-year follow-up will be completed by January 2002. Primary outcomes focus on measures of cognitively demanding everyday functioning, including financial management, food preparation, medication use, and driving. Secondary outcomes include health-related quality of life, mobility, and health-service utilization. Trial participants (n = 2832) are aged 65 and over, and at entry into the trial, did not have significant cognitive, physical, or functional decline. Because of its size and the carefully developed rigor, ACTIVE may serve as a guide for future behavioral medicine trials of this nature.

Middle-aged (N = 252, M = 39.91), young-old (N = 486, M = 60.77), and old-old (N = 137, M = 74.42) participants in the Seattle Longitudinal Study were tested on two occasions on their recall of a 20-item word list. Proportions of participants in each group correctly recalling each word-unit served as the dependent measure. Word-unit scores obtained in 1991 were regressed on those from 1984, yielding linear functions that varied by age group. Each set of word-unit scores (three groups on two occasions) was then regressed on word familiarity, imageability, primacy, and recency. The relative influence of each of these variables on memorability was then compared, both between and within cohorts. Primacy and familiarity were consistently strong predictors. Imageability and recency were predictive of memorability in the middle-aged group, but less so in the young-old, and not at all in the old-old group. Results and possible implications are discussed.

Loss of functioning on complex tasks of daily living is an early indicator of dementia. The performance of 65 older adults with mild to moderate levels of Alzheimer's disease was examined on the Everyday Problems Test for the Cognitively Challenged Elderly (EPCCE), self-report inventories of functional performance, and a broad battery of clinical and neuropsychological measures. The EPCCE was designed to assess older adults on a set of complex tasks of daily living that involved not only global cognitive processes, but also higher-order executive functions. Participants solved an average of 45% of EPCCE tasks with significant differences in scores by disease severity. Performance was significantly related to global cognitive functioning and disease severity, and in particular to executive functions. Significant additional variance was accounted for by these executive functions beyond the variance accounted for by global cognitive measures.

The hypothesis that psychometric ability tests retain equivalent factor structures across a 7-year interval was examined in a sample of 984 persons (disaggregated into 6 cohort groups: M ages at first test = 32, 46, 53, 60, 67, and 76), assessed in 1984 and 1991 as part of the Seattle Longitudinal Study. A best fitting measurement model was estimated for 20 psychometric tests marking the 6 primary abilities of Inductive Reasoning, Spatial Orientation, Perceptual Speed, Numeric Facility, Verbal Ability, and Verbal Recall. Gender was partialed out at the variable level by including a gender factor. Weak factorial invariance over time was demonstrated for all cohorts. Configural invariance could be demonstrated across all cohort groups. However, weak factorial invariance across groups could be accepted for all but the youngest and oldest groups. Latent means were modeled for the accepted solutions across time and cohort groups.

Objective: To analyze cases of false diagnoses from a large series to help increase the accuracy of fine needle aspiration of palpable breast lesions., Study Design: The results of FNA of 835 palpable breast lesions were analyzed to determine the reasons for false positive, false negative and false suspicious diagnoses., Results: Of the 835 aspirates, 174 were reported as positive, 549 as negative and 66 as suspicious or atypical but not diagnostic of malignancy. Forty-six cases were considered unsatisfactory. Tissue was available for comparison in 286 cases. The cytologic diagnoses in these cases were reported as follows: positive, 125 (43.7%); suspicious, 33 (11.5%); atypical, 18 (6.2%); negative, 92 (32%); and unsatisfactory, 18 (6.2%). There was one false positive diagnosis, yielding a false positive rate of 0.8%. This lesion was a case of fibrocystic change with hyperplasia, focal fat necrosis and reparative atypia. There were 14 false negative cases, resulting in a false negative rate of 13.2%. Nearly all these cases were sampling errors and included infiltrating ductal carcinomas (9), ductal carcinomas in situ (2), infiltrating lobular carcinomas (2) and tubular carcinoma (1). Most of the suspicious and atypical lesions proved to be carcinomas (35/50). The remainder were fibroadenomas (6), fibrocystic change (4), gynecomastia (2), adenosis (2) and granulomatous mastitis (1)., Conclusion: A positive diagnosis of malignancy by FNA is reliable in establishing the diagnosis and planning the treatment of breast cancer. The false-positive rate is very low, with only a single case reported in 835 aspirates. Most false negatives are due to sampling and not to interpretive difficulties. The category "suspicious but not diagnostic of malignancy" serves a useful purpose in management of patients with breast lumps.