Dementia is increasing recognized as a major problem to public health worldwide. Prevention and treatment strategies are in critical need. Nowadays, research for dementia usually featured as complex longitudinal studies, which provide extensive information and also propose challenge to statistical methodology. The purpose of this dissertation research was to apply statistical methodology in the field of dementia to strengthen the understanding of dementia from three perspectives: 1) Application of statistical methodology to investigate the association between potential risk factors and incident dementia. 2) Application of statistical methodology to analyze changes over time, or trajectory, in cognitive tests and symptoms. 3) Application of statistical learning methods to predict development of dementia in the future. Prevention of Alzheimer’s disease with Vitamin E and Selenium (PREADViSE) (7547 subjects included) and Alzheimer’s disease Neuroimaging Initiative (ADNI) (591 participants included) were used in this dissertation. The first study, “Self-reported sleep apnea and dementia risk: Findings from the PREADViSE Alzheimer’s disease prevention trial ”, shows that self-reported baseline history of sleep apnea was borderline significantly associated with risk of dementia after adjustment for confounding. Stratified analysis by APOE ε4 carrier status showed that baseline history of sleep apnea was associated with significantly increased risk of dementia in APOE ε4 non-carriers. The second study, “comparison of trajectories of episodic memory for over 10 years between baseline normal and MCI ADNI subjects,” shows that estimated 30% normal subjects at baseline assigned to group 3 and 6 stay stable for over 9 years, and normal subjects at baseline assigned to Group 1 (18.18%) and Group 5 (16.67%) were more likely to develop into dementia. In contrast to groups identified for normal subjects, all trajectory groups for MCI subjects at baseline showed the tendency to decline. The third study, “comparison between neural network and logistic regression in PREADViSE trial,” demonstrates that neural network has slightly better predictive performance than logistic regression, and also it can reveal complex relationships among covariates. In third study, the effect of years of education on response variable depends on years of age, status of APOE ɛ4 allele and memory change.

Title: Borderline personality disorder: examining trajectories of development among adolescents Background: Borderline personality disorder (BPD) tends to be highly comorbid with other disorders. In adolescence, information about the classification and development of BPD is in its early stages. There is limited empirical research available that investigates predictors of clinically significant symptom trajectories of the disorder using data collected in childhood. Given the enormous personal and societal costs associated with BPD, early detection and prevention is important. Clinical implications of this research include an improved understanding of risk factors and possible mechanisms for development of BPD symptomatology. Objectives: To identify trajectories of BPD symptomatology in a Canadian sample of adolescents (N = 703) assessed at ages 13, 14, 15 and 16, while examining predictors of trajectory group membership assessed at age 12. Methods: Data from the McMaster Teen Study was used to examine trajectories of BPD symptoms using group-based trajectory modeling. The influence of gender, depression, ADHD, family functioning and various sociodemographic variables as predictors of an individual’s group membership was tested. Chi-square, analysis of variance and multinomial logistic regression was used to analyze the data. Results: A four-group trajectory model was most robust at describing BPD symptomatology in this age group. Univariate analyses supported female gender, depression and ADHD at baseline, parental age, marital status, education, and income as significant predictors of group membership. Female gender, depression and ADHD severity at baseline were significant predictors of group membership when adopting a multivariate approach. There is a greater prevalence of girls with higher depression and ADHD scores in the high-increasing features and BPD group. Conclusion: Findings demonstrate four various developmental trajectories of BPD features. Results further the understanding of the factors associated with development of the disorder across time. / Thesis / Master of Science (MSc) / Information about the classification and development of borderline personality disorder (BPD) in adolescence is in its early stages. While evidence for similar construct validity to the adult disorder exists for adolescents, major gaps in knowledge regarding the stability in course of BPD symptoms and predictors of clinically significant symptom trajectories in this age group remain. As most clinicians will assess youth already having significant features of the disorder, early detection requires knowledge of the indicators that precede an unfavourable trajectory. This dissertation will help address these gaps by modeling trajectories of BPD symptoms in youth across ages 13-16, whilst examining factors influencing trajectory group membership.

Thesis advisor: Barbara E. Wolfe / Despite the chronicity and less than optimal outcomes of inpatient treatment (IPT) for anorexia nervosa (AN), treatment guidelines continue to reflect the common notion of one-size-fits-all and the process of weight restoration continues to be poorly understood. Weight restoration, a primary goal of IPT for AN, does not occur in isolation but rather reflects an adaptation process within internal and external environments. It is unknown whether or not there are unique patterns of change in body weight that are associated with factors identified in the existing literature as being predictors of weight gain. The purpose of this study was to explore the extent to which patterns of change in body weight existed among individuals during IPT for AN, and the relationship with factors identified in the existing literature as being predictors of weight gain (i.e., age at time of admission, admission caloric intake, percent of ideal body weight [IBW] at time of admission, body weight at time of discharge, body mass index [BMI] at time of discharge). Individuals who were diagnosed with AN and admitted to the inpatient unit of an eating disorder treatment facility in the Northeast between January 1, 2012 to December 31, 2015 were included in this retrospective, exploratory study (N = 500). Group-based trajectory modeling (GBTM) was used to identify distinct trajectories of change in body weight, and to determine the risk of being in a particular trajectory. Four distinct trajectories were identified: weight gain (n = 197), weight loss (n = 177), weight plateau (n = 82), and weight fluctuate (n = 44) groups. Significant predictors of trajectories were age, history of prior IPT for AN, admission caloric intake, body weight at time of admission and discharge, and length of stay. Results from this study suggest that a further understanding of patterns of change in body weight among individuals with AN, will help guide assessment and treatment interventions and consequently influence outcomes. Additionally, there is an opportunity to update treatment guidelines and recommendations for AN. / Thesis (PhD) — Boston College, 2016. / Submitted to: Boston College. Connell School of Nursing. / Discipline: Nursing.

Background For the 1.2 million older adults residing in U.S. nursing homes, little is known about their experience with physical frailty and cognitive impairment, two critical interrelated aging conditions. Methods Minimum Data Set 3.0 was used. Physical frailty was measured by FRAIL-NH and cognitive impairment by Brief Interview for Mental Status and Cognitive Performance Scale. Demographic and clinical characteristics were adjusted accordingly. Aim 1 described the prevalence of physical frailty and cognitive impairment and longitudinally examined the association between two conditions with the non-proportional odds model. Aim 2 used latent class analysis to identify physical frailty subgroups and estimated their association with cognitive impairment using multinomial logistic regression. Aim 3 fitted group-based trajectory models to identify physical frailty trajectories and cognitive impairment trajectories and quantified the association between the two sets of trajectories. Main Results Around 60% of older residents were physically frail and 68% had moderate/severe cognitive impairment, with improvement and worsening observed in both conditions, particularly in the first three months. Older residents with moderate/severe cognitive impairment were consistently and increasingly more likely to be frail. Three physical frailty subgroups were identified at admission. Greater cognitive impairment was associated with higher odds to belong to “severe physical frailty”. Five physical frailty trajectories and three cognitive impairment trajectories were identified over the first six months. One in five older residents were “Consistently Frail” and “Consistently Severe Cognitive Impairment”. Conclusion Findings emphasized the need for care management tailored to the heterogeneous presentations and progression trajectories of physical frailty and cognitive impairment.

From 2001-2007, students from India have consistently comprised the largest ethnic group of international students on college campuses across the United States (Open Doors: Report on International Educational Exchange, 2007). Despite a number of studies that have researched the mental health of international students in the U.S., none have done so primarily with Indian graduate students. Theoretical and empirical literature regarding the psychological changes and acculturation patterns that international students undergo after their transition do not explore the possibility of multiple pathways of change. The current study identified four separate mental health trajectories for Indian international graduate students during their first year in the U.S. It also found three distinct patterns of acculturation for the Indian culture and four acculturation trajectories for the European American culture. The size of one's adjustment, feelings about transition, gender role attitudes, and availability of out-group support were all significant contributors to the variability among empirically derived mental health trajectories.

Background: Childhood excess weight and family food insecurity are food-system related public health problems that exist in Canada. Since both relate to issues of food accessibility and availability, which have elements of “place”, they may share common risk factors in the local environment that are amenable to intervention. In this area of research, the literature derives mostly from a US context, and there is a dearth of high quality evidence, specifically from longitudinal studies. Objectives: The main objectives of this thesis were to examine the adjusted associations between the place factors: material deprivation, social deprivation, social cohesion, disorder, and living location, with change in child BMI Z-score and with change in family food insecurity status in a Canadian cohort of children. Methods: The Québec Longitudinal Study of Child Development was used to meet the main objectives of this thesis. Response data from six collection cycles (4 – 10 years of age) were used in three main analyses. The first analysis examined change in child BMI Z-score as a function of the place factors using mixed models regression. The second analysis examined change in child BMI Z-score as a function of place factors using group-based trajectory modeling. The third and final analysis examined change in family food insecurity status as a function of the place factors using generalized estimating equations. Results: Social deprivation, social cohesion and disorder were strongly and positively associated with family food insecurity, increasing the odds by 45-76%. These place factors, on the other hand, were not consistently associated with child weight status. Material deprivation was not important for either outcome, except for a slight positive association in the mixed models analysis of child weight status. Living location was not important in explaining family food insecurity. On the other hand, it was associated with child weight status in both analyses, but the nature of the relationship is still unclear. Conclusions: Results do not suggest that addressing similar place factors may alleviate both child excess weight and family food insecurity. More high quality longitudinal and experimental studies are needed to clarify relationships between the local environment and child weight status and family food insecurity.

Ovarian cancer (OC) is the fifth most common cancer among women and has the highest mortality of any cancer of the female reproductive system. The majority (61%) of OC cases are diagnosed at a distant stage. Because diagnoses occur most commonly at a late-stage and prognosis for advanced disease is poor, research focusing on the development of effective OC screening methods to facilitate early detection in high-risk, asymptomatic women is fundamental in reducing OC-specific mortality. Presently, there is no screening modality proven efficacious in reducing OC-mortality. However, transvaginal ultrasonography (TVS) has shown value in early detection of OC. TVS presents with the possibility of false positive results which occur when a women receives an abnormal TVS screening test result that is deemed benign following repeat testing (about 7% of the time). The purpose of this dissertation was to evaluate the impact of false positive TVS screening test results on a variety of psychological and behavioral outcomes using mixed and trajectory statistical modeling. The three specific aims of this dissertation were to 1) compare psychological and behavioral outcomes between women receiving normal and false positive results, 2) identify characteristics of women receiving false positive results associated with increased OC-specific distress and 3) characterize distress trajectories following receipt of false positive results. Analyses included a subset of women participating in an experimental study conducted through the University of Kentucky Ovarian Cancer Screening Program. 750 women completed longitudinal assessments: 375 false positive and 375 normal results. Mixed and group-based trajectory modeling were used to evaluate the specific aims. Results suggest women receiving false positive TVS result experience increased OC-specific distress compared to women receiving normal results. Among those receiving false positives, less education, no history of an abnormal screening test result, less optimism and more social constraint were associated with increased OC-specific distress. Family history was associated with increased distress among women with monitoring informational coping styles. Three distinct trajectories characterize the trajectory of distress over a four-month study period. Although decreasing over time, a notable proportion of women experience sustained high levels of OC-specific distress.

Background: Childhood excess weight and family food insecurity are food-system related public health problems that exist in Canada. Since both relate to issues of food accessibility and availability, which have elements of “place”, they may share common risk factors in the local environment that are amenable to intervention. In this area of research, the literature derives mostly from a US context, and there is a dearth of high quality evidence, specifically from longitudinal studies. Objectives: The main objectives of this thesis were to examine the adjusted associations between the place factors: material deprivation, social deprivation, social cohesion, disorder, and living location, with change in child BMI Z-score and with change in family food insecurity status in a Canadian cohort of children. Methods: The Québec Longitudinal Study of Child Development was used to meet the main objectives of this thesis. Response data from six collection cycles (4 – 10 years of age) were used in three main analyses. The first analysis examined change in child BMI Z-score as a function of the place factors using mixed models regression. The second analysis examined change in child BMI Z-score as a function of place factors using group-based trajectory modeling. The third and final analysis examined change in family food insecurity status as a function of the place factors using generalized estimating equations. Results: Social deprivation, social cohesion and disorder were strongly and positively associated with family food insecurity, increasing the odds by 45-76%. These place factors, on the other hand, were not consistently associated with child weight status. Material deprivation was not important for either outcome, except for a slight positive association in the mixed models analysis of child weight status. Living location was not important in explaining family food insecurity. On the other hand, it was associated with child weight status in both analyses, but the nature of the relationship is still unclear. Conclusions: Results do not suggest that addressing similar place factors may alleviate both child excess weight and family food insecurity. More high quality longitudinal and experimental studies are needed to clarify relationships between the local environment and child weight status and family food insecurity.

Background: Childhood excess weight and family food insecurity are food-system related public health problems that exist in Canada. Since both relate to issues of food accessibility and availability, which have elements of “place”, they may share common risk factors in the local environment that are amenable to intervention. In this area of research, the literature derives mostly from a US context, and there is a dearth of high quality evidence, specifically from longitudinal studies. Objectives: The main objectives of this thesis were to examine the adjusted associations between the place factors: material deprivation, social deprivation, social cohesion, disorder, and living location, with change in child BMI Z-score and with change in family food insecurity status in a Canadian cohort of children. Methods: The Québec Longitudinal Study of Child Development was used to meet the main objectives of this thesis. Response data from six collection cycles (4 – 10 years of age) were used in three main analyses. The first analysis examined change in child BMI Z-score as a function of the place factors using mixed models regression. The second analysis examined change in child BMI Z-score as a function of place factors using group-based trajectory modeling. The third and final analysis examined change in family food insecurity status as a function of the place factors using generalized estimating equations. Results: Social deprivation, social cohesion and disorder were strongly and positively associated with family food insecurity, increasing the odds by 45-76%. These place factors, on the other hand, were not consistently associated with child weight status. Material deprivation was not important for either outcome, except for a slight positive association in the mixed models analysis of child weight status. Living location was not important in explaining family food insecurity. On the other hand, it was associated with child weight status in both analyses, but the nature of the relationship is still unclear. Conclusions: Results do not suggest that addressing similar place factors may alleviate both child excess weight and family food insecurity. More high quality longitudinal and experimental studies are needed to clarify relationships between the local environment and child weight status and family food insecurity.

Ce travail est principalement axé sur la modélisation par approche de groupe de trajectoires développementales de la consommation d'alcool des adolescents au Quebec. / Contexte: L’impulsion à cette étude est le fait que la consommation d'alcool chez les adolescents a augmenté au cours des dernières années et que la consommation excessive d'alcool épisodique est de plus en plus fréquente chez les jeunes adultes. La prévention des problèmes de la consommation d’alcool chez les jeunes doit commencer par l'identification appropriée des sous-groupes d'adolescents à risque élevé. Objectifs: Cette étude avait trois objectifs: (i) identifier les trajectoires de développement de la consommation d'alcool chez les adolescents; (ii) d'examiner l'influence du sexe sur les trajectoires et (iii) d'examiner la relation entre les trajectoires de consommation d'alcool à l'adolescence et la consommation d'alcool excessive épisodique à l'âge jeune adulte. Méthode: Nous avons utilisé des données de l'étude longitudinale (n = 1294, 1999 - 2012) des adolescents âgés de 12 à 13 ans au début de l'étude de NDIT (Dépendance de la nicotine chez les adolescents). Les 1245 participants qui ont complété au moins trois des 22 cycles de NDIT ont été stratifiés selon leur statut alcoolique. C’est à dire ceux qui avaient consommé de l'alcool au début de l’étude, les buveurs (n = 497) et ceux qui n'avaient jamais consommé d'alcool au début de l’étude, les abstinents (n=748). Nous avons identifié les trajectoires de développement de la fréquence de la consommation d'alcool sur la base de 19 vagues de collecte de données après le début de l’étude de la 7e année (de 12 à 13 ans) à la 11e année (17-18 ans) en utilisant la modélisation semi-paramétrique basée sur l’approche des trajectoires par groupe (GBTM). Nous avons conduit des séries de régression logistique afin d'étudier l'association entre les trajectoires de développement de la consommation d'alcool et la consommation excessive épisodique à l'âge jeune adulte chez les buveurs d’alcool au début de l’étude et les abstinents au début de l’étude. Résultats: Pour l’ensemble de l’échantillon global (abstinents et buveurs) cinq groupes de trajectoires ont été identifiés. Ensuite, quatre groupes de trajectoires ont été identifiés parmi les abstinents au début de l’étude (‘faible’ consommateurs (28.3%, n=215), consommateurs tardifs croissants (21.5%, n=161), consommateurs modérés (29.9%, n=224) et consommateurs réguliers (20.3%, n=152). Parmi les consommateurs d’alcool (buveurs) au début de l’étude, les groupes de trajectoires comprenaient des consommateurs d’alcool peu fréquents (rares) (15.4%, n=76), des consommateurs en hausse (34.1%, n=170), des consommateurs réguliers (41.7%, n=207) et des consommateurs en baisse (8.8%, n=44). Les adolescents des groupes de trajectoires de fréquence de consommation d’alcool les plus élevées étaient plus susceptibles de pratiquer la consommation d’alcool excessive épisodique à l’âge jeune adulte. Conclusion: Cette étude montre la variabilité des trajectoires de développement de la consommation d'alcool des adolescents. Les données suggèrent que des approches multiples peuvent être nécessaires pour prévenir la consommation problématique d'alcool chez les adolescents et que ces approches devraient être nécessairement adaptées au sexe. / Background: The impetus for this study is that alcohol use among adolescents has increased in recent years and that heavy episodic or binge drinking is increasingly common in young adults. Prevention of problem drinking must begin with appropriate identification of sub-groups of adolescents at higher risk. Objective: This study had three objectives: (i) to identify the developmental trajectories of alcohol consumption among teens; (ii) to examine the influence of sex on trajectories and (iii) to examine the relationship between alcohol consumption trajectories in adolescence and binge drinking in young adulthood. Method: We used data from the NDIT (Nicotine Dependence In Teens) longitudinal study (n=1294; 1999 – 2012) of adolescents ages 12-13 years at inception. The 1245 participants who completed at least three of 22 NDIT cycles were stratified into those who had consumed alcohol at baseline, baseline drinkers (n=497) and those who had never consumed alcohol, baseline nondrinkers (n=748). We identified the developmental trajectories of the frequency of alcohol consumption based on 19 data collection waves after baseline from grade 7 (age 12-13) to grade 11 (age 17-18), using semi-parametric group-based trajectory modeling. Logistic regression was conducted to investigate the association between the alcohol consumption developmental trajectories and binge drinking in young adulthood among baseline drinkers and baseline nondrinkers. Results: Five trajectory were identified for the whole sample (baseline nondrinkers and baseline drinkers, n=1245). Then, four trajectory groups were identified among baseline nondrinkers (low consumers (28.3%, n=211), increasing late consumers (21.5%, n=161), moderate drinkers (29.9%, n=224), and regular users (20.3%, n=152). Among baseline drinkers, trajectory groups included experimenters (15.4%, n=76), increasing (34.1%, n=170), regular (41.7%, n=207) and decreasing consumers (8.8%, n=44). Participants in the higher trajectory groups were more likely to binge drink in young adulthood. Conclusion: This study shows variability among adolescents in alcohol consumption developmental trajectories. The data suggest that multiple approaches may be necessary to prevent problem alcohol consumption among adolescents and that these approaches may need to be sex-sensitive.