Dosimetric comparison of four-dimensional computed tomography based internal target volume against variations in respiratory motion during treatment between volumetric modulated arc therapy and three-dimensional conformal radiotherapy in lung stereotactic body radiotherapy.

This study focused on the dosimetric impact of variations in respiratory motion during lung stereotactic body radiotherapy (SBRT). Dosimetric comparisons between volumetric modulated arc therapy (VMAT) and three-dimensional conformal radiotherapy (3DCRT) were performed using four-dimensional computed tomography (4DCT)-based internal target volumes (ITV). We created retrospective plans for ten patients with lung cancer who underwent SBRT using 3DCRT and VMAT techniques. A Delta4 Phantom + (ScandiDos, Uppsala, Sweden) was used to evaluate the dosimetric robustness of 4DCT-based ITV against variations in respiratory motion during treatment. We analyzed respiratory motion during treatment. Dose-volume histogram parameters were evaluated for the 95% dose (D95%) to the planning target volume (PTV) contoured on CT images obtained under free breathing. The correlations between patient respiratory parameters and dosimetric errors were also evaluated. In the phantom study, the average PTV D95% dose differences for all fractions were - 2.9 ± 4.4% (- 16.0 - 1.2%) and - 2.0 ± 2.8% (- 11.2 - 0.7%) for 3DCRT and VMAT, respectively. The average dose difference was < 3% for both 3DCRT and VMAT; however, in 5 out of 42 fractions in 3DCRT, the difference in PTV D95% was > 10%. Dosimetric errors were correlated with respiratory amplitude and velocity, and differences in respiratory amplitude between 4DCT and treatment days were the main factors causing dosimetric errors. The overall average dose error of the PTV D95% was small; however, both 3DCRT and VMAT cases exceeding 10% error were observed. Larger errors occurred with amplitude variation or baseline drift, indicating limited robustness of 4DCT-based ITV.

A comparison of computer adaptive tests (CATs) and short forms in terms of accuracy and number of items administrated using PROMIS profile.

PURPOSE: In the Patient-Reported Outcomes Measurement Information System (PROMIS), seven domains (Physical Function, Anxiety, Depression, Fatigue, Sleep Disturbance, Social Function, and Pain Interference) are packaged together as profiles. Each of these domains can also be assessed using computer adaptive tests (CATs) or short forms (SFs) of varying length (e.g., 4, 6, and 8 items). We compared the accuracy and number of items administrated of CAT versus each SF. METHODS: PROMIS instruments are scored using item response theory (IRT) with graded response model and reported as T scores (mean = 50, SD = 10). We simulated 10,000 subjects from the normal distribution with mean 60 for symptom scales and 40 for function scales, and standard deviation 10 in each domain. We considered a subject's score to be accurate when the standard error (SE) was less than 3.0. We recorded range of accurate scores (accurate range) and the number of items administrated. RESULTS: The average number of items administrated in CAT was 4.7 across all domains. The accurate range was wider for CAT compared to all SFs in each domain. CAT was notably better at extending the accurate range into very poor health for Fatigue, Physical Function, and Pain Interference. Most SFs provided reasonably wide accurate range. CONCLUSIONS: Relative to SFs, CATs provided the widest accurate range, with slightly more items than SF4 and less than SF6 and SF8. Most SFs, especially longer ones, provided reasonably wide accurate range.

Randomized controlled trial of a positive affect intervention for people newly diagnosed with HIV.

OBJECTIVE: We conducted a randomized controlled trial to determine whether IRISS (Intervention for those Recently Informed of their Seropositive Status), a positive affect skills intervention, improved positive emotion, psychological health, physical health, and health behaviors in people newly diagnosed with HIV. METHOD: One-hundred and fifty-nine participants who had received an HIV diagnosis in the past 3 months were randomized to a 5-session, in-person, individually delivered positive affect skills intervention or an attention-matched control condition. RESULTS: For the primary outcome of past-day positive affect, the group difference in change from baseline over time did not reach statistical significance (p = .12, d = .30). Planned secondary analyses within assessment point showed that the intervention led to higher levels of past-day positive affect at 5, 10, and 15 months postdiagnosis compared with an attention control. For antidepressant use, the between group difference in change from baseline was statistically significant (p = .006, d = -.78 baseline to 15 months) and the difference in change over time for intrusive and avoidant thoughts related to HIV was also statistically significant (p = .048, d = .29). Contrary to findings for most health behavior interventions in which effects wane over the follow up period, effect sizes in IRISS seemed to increase over time for most outcomes. CONCLUSIONS: This comparatively brief positive affect skills intervention achieved modest improvements in psychological health, and may have the potential to support adjustment to a new HIV diagnosis. (PsycINFO Database Record

Associations between body mass index and sexual functioning in midlife women: the Study of Women's Health Across the Nation.

OBJECTIVE: This study aims to examine baseline and longitudinal associations between body mass index (BMI) and sexual functioning in midlife women. METHODS: Midlife women (N = 2,528) from the Study of Women's Health Across the Nation reported on sexual functioning and underwent measurements of BMI annually beginning in 1995-1997, with follow-up spanning 13.8 years. Associations between baseline levels and longitudinal changes in BMI and sexual desire, arousal, intercourse frequency, and ability to climax were assessed with generalized linear mixed-effects models. Models were adjusted for demographic variables, depressive symptoms, hormone therapy use, alcohol intake, menopause status, smoking status, and health status. RESULTS: Mean BMI increased from 27.7 to 29.1 kg/m2, whereas all sexual functioning variables declined across time (P values ≤ 0.001). Higher baseline BMI was associated with less frequent intercourse (P = 0.003; 95% CI, -0.059 to -0.012). Although overall change in BMI was not associated with changes in sexual functioning, years of greater-than-expected BMI increases relative to women's overall BMI change trajectory were characterized by less frequent intercourse (P < 0.001; 95% CI, -0.106 to -0.029) and reduced sexual desire (P = 0.020; 95% CI, -0.078 to -0.007). CONCLUSIONS: Although women's overall BMI change across 13.8 years of follow-up was not associated with overall changes in sexual functioning, sexual desire and intercourse frequency diminished with years of greater-than-expected weight gain. Results suggest that adiposity and sexual functioning change concurrently from year to year. Further research should explore the impact of weight management interventions as a strategy for preserving sexual functioning in midlife women.

Conscientiousness, dementia related pathology, and trajectories of cognitive aging.

The study aim was to determine the contribution of dementia related pathologies to the association of conscientiousness with late-life cognitive health. At enrollment in 2 longitudinal clinical-pathologic cohort studies, 309 older individuals without cognitive impairment completed a standard conscientiousness measure. Annually thereafter, they completed a battery of 17 cognitive tests. On death, they underwent a uniform neuropathologic examination from which measures of neurofibrillary tangles, Lewy bodies, chronic gross cerebral infarction, and hippocampal sclerosis were derived. The relation of conscientiousness and the neuropathologic markers to cognitive decline was assessed in mixed-effects change point models to accommodate nonlinear cognitive decline. During a mean of 10.7 years of follow-up, annual decline on a composite measure of global cognition (baseline M = 0.082, SD = 0.499) was gradual (estimated M = -0.036, 95% CI [-0.046, -0.025]) until a mean of 3.2 years before death (95% CI [-3.6, -2.8]) when it accelerated to a mean annual loss of 0.369 unit (95% CI [-0.426, -0.317]), a tenfold increase. Higher conscientiousness (baseline M = 33.6, SD = 5.1) was associated with slower terminal decline (estimate = 0.064, 95% CI [0.024, 0.103]) but not preterminal decline (estimate = 0.005, 95% CI [-0.003, 0.013]). After adjustment for neuropathologic burden, conscientiousness was still related to terminal decline (estimate = 0.057, 95% CI [0.019, 0.094]) and accounted for 4% of the variance in terminal slopes. In addition, the association of neocortical Lewy bodies with terminal cognitive decline was attenuated in those with higher conscientiousness. The results suggest that higher conscientiousness is protective of late-life cognitive health.

Residual decline in cognition after adjustment for common neuropathologic conditions.

OBJECTIVE: Neurodegenerative and cerebrovascular conditions are common in old age and are associated with cognitive decline. However, considerable heterogeneity remains in residual decline (i.e., person-specific trajectories of cognitive decline adjusted for these common neuropathologic conditions). The present study aimed to characterize profiles of residual decline in late life cognition. METHOD: Up to 19 waves of longitudinal cognitive data were collected from 876 autopsied participants from 2 ongoing clinical-pathologic cohort studies of aging. Uniform neuropathologic examinations quantified measures of Alzheimer's disease, cerebral infarcts, Lewy body disease, and hippocampal sclerosis. Random effects mixture models characterized latent profiles of residual decline in global cognition. RESULTS: We identified 4 latent groups, and each group demonstrated distinct residual decline profiles. On average, 44% of the participants had little or no decline, 35% showed moderate decline, 13% showed severe decline and the rest (8%) had substantial within-subject fluctuation of longitudinal cognitive measures. These latent groups differed in psychological, experiential and neurobiologic factors that have been previously shown to be associated with cognitive decline. Specifically, compared with nondecliners, decliners had more depressive symptoms, were more socially isolated; were less engaged in cognitive or physical activities; and had lower density of noradrenergic neurons in locus ceruleus. CONCLUSIONS: After controlling for common dementia related pathologies, considerable residual variability remains in cognitive aging trajectories and this variability is not random but rather is related to markers of cognitive and neural reserve. The mixture modeling approach provides a powerful tool to identify latent groups with distinct cognitive trajectories.

Meal preparation and cleanup time and cardiometabolic risk over 14 years in the Study of Women's Health Across the Nation (SWAN).

OBJECTIVE: To determine whether baseline levels and longitudinal changes in meal preparation and cleanup time are associated with changes in cardiometabolic risk factors in midlife women. METHODS: Subjects were 2755 midlife women enrolled in the Study of Women's Health Across the Nation, a multi-ethnic, longitudinal cohort study in the United States. The five diagnostic components of the metabolic syndrome and meal preparation/cleanup time were assessed repeatedly across 14 years of follow-up (spanning 1996-2011) at seven U.S. sites. Mixed-effects logistic and ordered logistic models tested associations between meal preparation/cleanup time and odds of meeting criteria for metabolic syndrome and its individual diagnostic components. RESULTS: Women who spent more time preparing and cleaning up meals at baseline, or demonstrated greater increases in this activity, had greater increases over time in their odds of having metabolic syndrome and in the number of metabolic syndrome components for which they met criteria. Adjusted associations were observed between meal preparation/cleanup time and hypertension, impaired fasting glucose, hypertriglyceridemia, and low high-density lipoprotein cholesterol, but not abdominal obesity. CONCLUSIONS: In midlife women, greater meal preparation/cleanup time is associated with the development of an adverse cardiometabolic risk profile. Public health interventions should place greater emphasis on cooking healthfully, not just cooking frequently.

Association between physical activity and depressive symptoms: midlife women in SWAN.

INTRODUCTION: The relation of physical activity (PA) and positive mood has been the focus of considerable research, which were primarily cross-sectional. This study was done to evaluate the relation between PA and high depressive symptoms across time and to examine whether being physically active attenuates the risk of depressive symptoms in midlife women. METHODS: The present study is a longitudinal observational study on the menopausal transition in a multiethnic population. Ten years of data on 2891 women were analyzed. The participants were women from seven geographic areas nationwide, age 42-52 yr at baseline, still menstruating, and not using exogenous reproductive hormones. PA was measured with the Kaiser Permanente Physical Activity Scale. The main outcome measure, depressive symptoms, was assessed with the Center for Epidemiological Studies Depression Scale (CES-D), with primary outcome of CES-D score of 16 or higher. RESULTS: In mixed effect logistic regression models adjusted for covariates, compared with inactivity, PA meeting PA guidelines (approximating public health guidelines) and PA below PA guidelines were each associated with lower risk of high depressive symptoms (CES-D score of 16 or higher) (odds ratio, 0.52; 95% confidence interval, 0.40-0.70; and odds ratio, 0.81; 95% confidence interval, 0.67-0.98, respectively] across 10 yr. Being married, Japanese and Hispanic ethnicity, current smoking, reporting very upsetting life events, using antidepressive medications, having hot flashes, and high body mass index were all positively associated with high depressive symptoms, whereas high social support was negatively associated. CONCLUSIONS: Higher PA was associated with lower levels of depressive symptoms persistently over 10 yr, independent of potential confounders. Our findings suggest that reaching moderate-intensity PA levels during midlife may be protective against depressive symptoms.

Employment status, depressive symptoms, and waist circumference change in midlife women: the Study of Women's Health Across the Nation (SWAN).

PURPOSE: Changes in employment status have shown inconsistent associations with adiposity. This study tested whether the presence of elevated depressive symptoms explains variability in the time-varying association between employment status and central adiposity. METHOD: Employment status, depressive symptoms, and waist circumference (WC) were assessed annually over 10 years in a multiethnic sample of 3220 midlife women enrolled in the Study of Women's Health Across the Nation. Linear mixed-effects models tested time-varying associations of employment status, depressive symptoms, and their interaction with WC. RESULTS: WC increases were greatest during the years of combined nonemployment and elevated depressive symptoms (1.00 cm/y) and lowest in the years of full-time employment and elevated depressive symptoms (0.25 cm/y), compared with the years of full-time employment and nonelevated depressive symptoms (0.51 cm/y). Employment status was unrelated to WC in years without elevated depressive symptoms. The pattern of results was unchanged when analyses were restricted to preretirement observations and did not vary according to WC at baseline or ethnicity/race. CONCLUSIONS: Identifying and managing depressive symptoms in midlife women who are not working may help prevent increases in central adiposity.

Cognitive decline impairs financial and health literacy among community-based older persons without dementia.

Literacy is an important determinant of health and well-being across the life span but is critical in aging, when many influential health and financial decisions are made. Prior studies suggest that older persons exhibit lower literacy than younger persons, particularly in the domains of financial and health literacy, but the reasons why remain unknown. The objectives of this study were to: (a) examine pathways linking diverse resources (i.e., education, word knowledge, cognitive function, and decision making style) to health and financial literacy among older persons and determine the extent to which the relation of age with literacy represents a direct effect versus an indirect effect due to decrements in specific cognitive functions (i.e., executive functions and episodic memory); and (b) test the hypothesis that declines in executive function and episodic memory are associated with lower literacy among older persons without dementia. Six-hundred and forty-five community-based older persons without dementia underwent detailed assessments of diverse resources, including education, word knowledge, cognitive function (i.e., executive function, episodic memory) and decision making style (i.e., risk aversion), and completed a measure of literacy that included items similar to those used in the Health and Retirement Study, such as numeracy, financial concepts such as compound inflation and knowledge of stocks and bonds, and important health concepts such as understanding of drug risk and Medicare Part D. Path analysis revealed a strong effect of age on literacy, with about half of the effect of age on literacy due to decrements in executive functions and episodic memory. In addition, executive function had an indirect effect on literacy via decision making style (i.e., risk aversion), and education and word knowledge had independent effects on literacy. Finally, among (n = 447) persons with repeated cognitive assessments available for up to 14 years, regression analysis supported the association of multiple resources with literacy; moreover, more rapid declines in executive function and episodic memory over an average of 6.4 years prior to the literacy assessment predicted lower literacy scores (ps < 0.02), but rate of decline in word knowledge did not. These findings suggest that diverse individual resources contribute to financial and health literacy and lower literacy in old age is partially due to declines in executive function and episodic memory.

APOE ε4, Alzheimer's disease pathology, cerebrovascular disease, and cognitive change over the years prior to death.

The goal of this study was to examine the association of the APOE ε4 allele with the late-life cognitive trajectory and test the hypothesis that the association of ε4 with cognitive decline is explained by Alzheimer's disease (AD) neuropathology. Participants (N = 581) came from 2 longitudinal clinical-pathologic studies of aging and dementia, the Religious Orders Study (ROS) and the Memory and Aging Project (MAP). Longitudinal measures of cognition were derived from detailed annual neuropsychological testing. Uniform neuropathologic evaluations provided quantitative measures of AD pathology, chronic cerebral infarctions, and Lewy bodies. Participants with 1 or more copies of the ε4 allele (ε2/4 excluded) were considered ε4 carriers. Random change point models were applied to examine the association of the ε4 allele with onset of terminal decline as well as preterminal and terminal slopes. On average, the onset of terminal decline occurred around 3 years before death, and the rate of terminal decline was eightfold faster than the preterminal decline. The presence of the ε4 allele was associated with an earlier onset of terminal decline and faster rates of decline before and after its onset. After adjusting for AD pathology, the ε4 allele was no longer associated with onset of terminal decline or preterminal slope, and the association with terminal slope became marginal. The APOE ε4 allele is an important determinant of late-life change in cognition, including terminal decline, and works primarily through AD pathology.

The influence of cognitive decline on well-being in old age.

This study addressed the hypothesis that late life cognitive decline leads to loss of well-being. Participants are older persons from the Rush Memory and Aging Project. Beginning in 2001, they underwent annual clinical evaluations that included detailed cognitive performance testing and a 10-item self-report measure of purpose in life, an aspect of well-being. Initial analyses involved 1,049 individuals who were without dementia at baseline and followed a mean of 5.0 years. The intercepts and slopes of global cognition and purpose were positively correlated, and level of cognition at a given evaluation predicted level of purpose at the subsequent evaluation, consistent with the study hypothesis. Purpose also predicted subsequent cognition. These findings persisted in analyses that excluded mild cognitive impairment or controlled for time varying levels of depressive symptoms or disability. To see whether cognitive decline's correlation with purpose differed from its correlation with other aspects of well-being, we conducted additional analyses on a subgroup of 560 persons without dementia who completed a multidimensional measure of well-being once between 2008 and 2011. More rapid cognitive decline in the period preceding well-being assessment (M = 5.5 years, SD = 2.8) was associated with lower level of nearly all aspects of well-being (5 of 6 measures), but the extent of the association varied across well-being dimensions and was stronger for purpose than for self-acceptance and autonomy. The results support the hypothesis that cognitive aging leads to diminished well-being, particularly aspects such as purpose in life that involve behavioral regulation.

The natural history of cognitive decline in Alzheimer's disease.

The study aim was to describe the temporal course of cognitive decline in Alzheimer's disease (AD). We selected 226 persons from 2 longitudinal clinical-pathological studies who were cognitively healthy at baseline, followed at least 4 years (M = 10.2, SD = 3.5), and clinically diagnosed with AD at some point during follow-up. Each evaluation included a battery of 17 cognitive tests from which a previously established composite measure of global cognition was derived. In those who died, a uniform neuropathologic examination established the pathological diagnoses of Alzheimer's disease and other common conditions that impair cognition. Mixed-effects models with 2 change points were used to assess trajectories of cognitive decline. In the main analysis, there was no change in cognitive function until a mean of 7.5 years before dementia was diagnosed (95% confidence interval [CI]: -8.3, -6.7). The global cognitive measure declined a mean of 0.087-unit per year (95% CI: -0.099, -0.073) until a mean of 2.0 years before the diagnosis (95% CI: -2.2, -1.7) when it increased more than 4-fold to a mean loss of 0.370-unit per year (95% CI: -0.417, -0.334). Of 126 individuals who died and underwent autopsy, 101 (80%) met pathologic criteria for AD, of whom 67 had at least one other pathologic condition. Pathologic measures of AD and cerebral infarction were not strongly related to cognitive trajectories. The results indicate that cognitive decline in AD begins many years before dementia is diagnosed and accelerates during the course of the disease.

Association of cognition with temporal discounting in community based older persons.

BACKGROUND: The objective of this study was to test the hypothesis that cognitive function is negatively associated with temporal discounting in old age. METHODS: Participants were 388 community-dwelling older persons without dementia from the Rush Memory and Aging Project, an ongoing longitudinal epidemiologic study of aging in the Chicago metropolitan area. Temporal discounting was measured using standard questions in which participants were asked to choose between an immediate, smaller payment and a delayed, larger one. Cognition was measured using a detailed battery including 19 tests. The association between cognition and temporal discounting was examined via mixed models adjusted for age, sex, education, income, and the number of chronic medical conditions. RESULTS: Descriptive data revealed a consistent pattern whereby older persons with lower cognitive function were more likely to discount greater but delayed rewards compared to those with higher cognitive function. Further, in a mixed effect model adjusted for age, sex, education, income, and chronic medical conditions, global cognitive function was negatively associated with temporal discounting (estimate = -0.45, SE = 0.18, p = 0.015), such that a person with lower cognition exhibited greater discounting. Finally, in subsequent models examining domain specific associations, perceptual speed and visuospatial abilities were associated with temporal discounting, but episodic memory, semantic memory and working memory were not. CONCLUSION: Among older persons without dementia, a lower level of cognitive function is associated with greater temporal discounting. These findings have implications regarding the ability of older persons to make decisions that involve delayed rewards but maximize well-being.

A random change point model for cognitive decline in Alzheimer's disease and mild cognitive impairment.

BACKGROUND: We present a random change point model to characterize decline in cognition among community-based elderly who developed Alzheimer's disease (AD) or amnestic mild cognitive impairment (MCI), and to examine how decline varies with age, sex, education, and APOE status. METHODS: Using longitudinal cohort data on cognitive function, we fit a piecewise linear trajectory with a random change point that allows different rates of cognitive decline before and after the change point. We estimated the change point that signals the onset of cognitive impairment, and examined the association of risk factors with the location of the change point as well as the rates of decline before and after the change point. RESULTS: Among participants who were dementia free at enrollment and developed incident AD, the change point occurred on average 5.7 years after enrollment and the rate of cognitive decline after the change point nearly quadrupled. Age, education, and APOE status play important but different roles in the timing of the onset of cognitive impairment and in the rates of decline before and after its onset. Results were similar among participants who were cognitively unimpaired at enrollment but later developed amnestic MCI or AD. CONCLUSIONS: The random change point model provides a more comprehensive understanding of the relation of risk factors with the onset of cognitive impairment and rates of decline before and after its onset.

Association between cognitive activity and cognitive function in older Hispanics.

There is limited research on the association between participation in cognitively stimulating activity and cognitive function in older Hispanics. The main purpose of the present study was to explore whether frequency of cognitive activity and its association with cognitive function in Hispanics is comparable to that of non-Hispanics. In a multiethnic cohort of 1571 non-demented older adults, we assessed past and current cognitive activity, availability of cognitive resources in the home in childhood and middle age, and five domains of cognitive function. The measures of cognitive activity and cognitive resources had adequate reliability and validity in our subset of Hispanic participants (n = 81). Hispanics reported lower levels of education, lower frequency of cognitive activity and less cognitive resources than non-Hispanic White (n = 1102) and non-Hispanic Black (n = 388) participants. Despite these differences the strength of the association between cognitive activity and cognitive function was comparable across ethnic groups. Because Hispanics have lower frequency of cognitive activity, the benefit of cognitive activity to late life cognitive function may be potentially larger in this segment of the population. Thus, interventions aimed at increasing frequency of participation in cognitively stimulating activity may offer a potential target to reduce cognitive impairment in Hispanics.

Terminal decline in motor function.

The study aim was to test the hypothesis that motor function undergoes accelerated decline proximate to death. As part of a longitudinal clinical-pathologic study, 124 older Roman Catholic nuns, priests, and monks completed at least 7 annual clinical evaluations, died, and underwent brain autopsy and uniform neuropathologic examination. Each evaluation included administration of 11 motor tests and 19 cognitive tests from which global measures of motor and cognitive function were derived. The global motor measure (baseline M = 0.82, SD = 0.21) declined a mean 0.024 unit per year (95% confidence interval [CI]: -0.032, -0.016) until a mean of 2.46 years (95% CI: -2.870, -2.108) before death when rate of decline increased nearly fivefold to -0.117 unit per year (95% CI: -0.140, -0.097). The global cognitive measure (baseline M = 0.07, SD = 0.45) declined a mean of 0.027-unit per year (95% CI: -0.041, -0.014) until a mean of 2.76 years (95% CI: -3.157, -2.372) before death when rate of decline increased more than 13-fold to -0.371 unit per year (95% CI: -0.443, -0.306). Onset of terminal motor decline was highly correlated with onset of terminal cognitive decline (r = .94, 95% CI: 0.81, 0.99), but rates of motor and cognitive change were not strongly correlated (preterminal r = .20, 95% CI: -0.05, 0.38; terminal r = .34, 95% CI: 0.03, 0.62). Higher level of plaques and tangles was associated with earlier onset of terminal decline in motor function, but no pathologic measures were associated with rate of preterminal or terminal motor decline. The results demonstrate that motor and cognitive functions both undergo a period of accelerated decline in the last few years of life.

Influence of late-life cognitive activity on cognitive health.

OBJECTIVE: To test the hypothesis that late-life participation in mentally stimulating activities affects subsequent cognitive health. METHODS: Analyses are based on 1,076 older persons without dementia at study onset participating in a longitudinal cohort study. They completed annual clinical evaluations for a mean of 4.9 years. Each evaluation included administration of a self-report scale about participation in mentally stimulating activities and a battery of cognitive performance tests. Previously established measures of cognitively stimulating activity and cognitive function were derived. We assessed the temporal sequence of activity changes in relation to functional changes in a series of cross-lagged panel models adjusted for age, sex, and education. RESULTS: During the observation period, cognitive activity participation (estimate of mean annual change = -0.066, SE = 0.005, p < 0.001) and cognitive functioning (estimate = -0.077, SE = 0.005, p < 0.001) declined at rates that were moderately correlated (r = 0.44, p < 0.001). The level of cognitive activity in a given year predicted the level of global cognitive function in the following year, but the level of global cognition did not predict the subsequent level of cognitive activity participation. Cognitive activity showed the same pattern of unidirectional associations with measures of episodic and semantic memory, but its associations with working memory were bidirectional. CONCLUSIONS: The results suggest that more frequent mental stimulation in old age leads to better cognitive functioning.

Trajectories of smoking among freshmen college students with prior smoking history and risk for future smoking: data from the University Project Tobacco Etiology Research Network (UpTERN) study.

AIMS: Little is known about smoking during the transition to college. The current study examined trajectories of smoking among college freshmen, how trajectories predicted later smoking and the social context of smoking. DESIGN: Weekly assessments of daily smoking were collected via the web during the first year of college for a large cohort with a previous history of smoking. PARTICIPANTS AND SETTING: A total of 193 college freshmen from a large public university with a previous history of smoking who smoked frequently enough to be included in trajectory analysis. MEASUREMENTS: Measures included weekly reports of daily smoking, family smoking, perceived peer attitudes and smoking, social norms and social smoking environment. FINDINGS: Seven trajectories were identified: one of low-level sporadic smoking, one of low-level smoking with a small increase during the year, two classes with a substantial decrease during the year, two classes with relatively small decreases and one class with a substantial increase in smoking. Trajectories of smoking in the freshman year predicted levels of sophomore year smoking, and some social context variables tended to change as smoking increased or decreased for a given trajectory class. CONCLUSIONS: The transition into college is marked by changes in smoking, with smoking escalating for some students and continuing into the sophomore year. Shifts in social context that support smoking were associated with trajectories of smoking. Despite the focus of developmental models on smoking in early adolescence, the transition into college warrants further investigation as a dynamic period for smoking.

Mixed-effects Poisson regression analysis of adverse event reports: the relationship between antidepressants and suicide.

A new statistical methodology is developed for the analysis of spontaneous adverse event (AE) reports from post-marketing drug surveillance data. The method involves both empirical Bayes (EB) and fully Bayes estimation of rate multipliers for each drug within a class of drugs, for a particular AE, based on a mixed-effects Poisson regression model. Both parametric and semiparametric models for the random-effect distribution are examined. The method is applied to data from Food and Drug Administration (FDA)'s Adverse Event Reporting System (AERS) on the relationship between antidepressants and suicide. We obtain point estimates and 95 per cent confidence (posterior) intervals for the rate multiplier for each drug (e.g. antidepressants), which can be used to determine whether a particular drug has an increased risk of association with a particular AE (e.g. suicide). Confidence (posterior) intervals that do not include 1.0 provide evidence for either significant protective or harmful associations of the drug and the adverse effect. We also examine EB, parametric Bayes, and semiparametric Bayes estimators of the rate multipliers and associated confidence (posterior) intervals. Results of our analysis of the FDA AERS data revealed that newer antidepressants are associated with lower rates of suicide adverse event reports compared with older antidepressants. We recommend improvements to the existing AERS system, which are likely to improve its public health value as an early warning system.