Matching Items (2)
Filtering by
- All Subjects: Cognition disorders--Endocrine aspects.
- All Subjects: missing completely at random
- Creators: Aiken, Leona S.
Description
This dissertation examines a planned missing data design in the context of mediational analysis. The study considered a scenario in which the high cost of an expensive mediator limited sample size, but in which less expensive mediators could be gathered on a larger sample size. Simulated multivariate normal data were generated from a latent variable mediation model with three observed indicator variables, M1, M2, and M3. Planned missingness was implemented on M1 under the missing completely at random mechanism. Five analysis methods were employed: latent variable mediation model with all three mediators as indicators of a latent construct (Method 1), auxiliary variable model with M1 as the mediator and M2 and M3 as auxiliary variables (Method 2), auxiliary variable model with M1 as the mediator and M2 as a single auxiliary variable (Method 3), maximum likelihood estimation including all available data but incorporating only mediator M1 (Method 4), and listwise deletion (Method 5).
The main outcome of interest was empirical power to detect the mediated effect. The main effects of mediation effect size, sample size, and missing data rate performed as expected with power increasing for increasing mediation effect sizes, increasing sample sizes, and decreasing missing data rates. Consistent with expectations, power was the greatest for analysis methods that included all three mediators, and power decreased with analysis methods that included less information. Across all design cells relative to the complete data condition, Method 1 with 20% missingness on M1 produced only 2.06% loss in power for the mediated effect; with 50% missingness, 6.02% loss; and 80% missingess, only 11.86% loss. Method 2 exhibited 20.72% power loss at 80% missingness, even though the total amount of data utilized was the same as Method 1. Methods 3 – 5 exhibited greater power loss. Compared to an average power loss of 11.55% across all levels of missingness for Method 1, average power losses for Methods 3, 4, and 5 were 23.87%, 29.35%, and 32.40%, respectively. In conclusion, planned missingness in a multiple mediator design may permit higher quality characterization of the mediator construct at feasible cost.
The main outcome of interest was empirical power to detect the mediated effect. The main effects of mediation effect size, sample size, and missing data rate performed as expected with power increasing for increasing mediation effect sizes, increasing sample sizes, and decreasing missing data rates. Consistent with expectations, power was the greatest for analysis methods that included all three mediators, and power decreased with analysis methods that included less information. Across all design cells relative to the complete data condition, Method 1 with 20% missingness on M1 produced only 2.06% loss in power for the mediated effect; with 50% missingness, 6.02% loss; and 80% missingess, only 11.86% loss. Method 2 exhibited 20.72% power loss at 80% missingness, even though the total amount of data utilized was the same as Method 1. Methods 3 – 5 exhibited greater power loss. Compared to an average power loss of 11.55% across all levels of missingness for Method 1, average power losses for Methods 3, 4, and 5 were 23.87%, 29.35%, and 32.40%, respectively. In conclusion, planned missingness in a multiple mediator design may permit higher quality characterization of the mediator construct at feasible cost.
ContributorsBaraldi, Amanda N (Author) / Enders, Craig K. (Thesis advisor) / Mackinnon, David P (Thesis advisor) / Aiken, Leona S. (Committee member) / Tein, Jenn-Yun (Committee member) / Arizona State University (Publisher)
Created2015
Description
Aging and the menopause transition are both intricately linked to cognitive changes
during mid-life and beyond. Clinical literature suggests the age at menopause onset can differentially impact cognitive status later in life. Yet, little is known about the relationship between behavioral and brain changes that occur during the transitional stage into the post-menopausal state. Much of the pre-clinical work evaluating an animal model of menopause involves ovariectomy in rodents; however, ovariectomy results in an abrupt loss of circulating hormones and ovarian tissue, limiting the ability to evaluate gradual follicular depletion. The 4-vinylcyclohexene diepoxide (VCD) model simulates transitional menopause in rodents by selectively depleting the immature ovarian follicle reserve and allowing animals to retain their follicle-deplete ovarian tissue, resulting in a profile similar to the majority of menopausal women. Here, Vehicle or VCD treatment was administered to ovary-intact adult and middle-aged Fischer-344 rats to assess the cognitive effects of transitional menopause via VCD-induced follicular depletion over time, as well as to understand potential interactions with age, with VCD treatment beginning at either six or twelve months of age. Results indicated that subjects that experience menopause onset at a younger age had impaired spatial working memory early in the transition to a follicle-deplete state. Moreover, in the mid- and post- menopause time points, VCD-induced follicular depletion amplified an age effect, whereby Middle-Aged VCD-treated animals had poorer spatial working and reference memory performance than Young VCD-treated animals. Correlations suggested that in middle age, animals with higher circulating estrogen levels tended to perform better on spatial memory tasks. Overall, these findings suggest that the age at menopause onset is a critical parameter to consider when evaluating learning and memory across the transition to reproductive senescence. From a translational perspective, this study informs the field with respect to how the age at menopause onset might impact cognition in menopausal women, as well as provides insight into time points to explore for the window of opportunity for hormone therapy during the menopause transition to attenuate age- and menopause- related cognitive decline, and produce healthy brain aging profiles in women who retain their ovaries throughout the lifespan.
during mid-life and beyond. Clinical literature suggests the age at menopause onset can differentially impact cognitive status later in life. Yet, little is known about the relationship between behavioral and brain changes that occur during the transitional stage into the post-menopausal state. Much of the pre-clinical work evaluating an animal model of menopause involves ovariectomy in rodents; however, ovariectomy results in an abrupt loss of circulating hormones and ovarian tissue, limiting the ability to evaluate gradual follicular depletion. The 4-vinylcyclohexene diepoxide (VCD) model simulates transitional menopause in rodents by selectively depleting the immature ovarian follicle reserve and allowing animals to retain their follicle-deplete ovarian tissue, resulting in a profile similar to the majority of menopausal women. Here, Vehicle or VCD treatment was administered to ovary-intact adult and middle-aged Fischer-344 rats to assess the cognitive effects of transitional menopause via VCD-induced follicular depletion over time, as well as to understand potential interactions with age, with VCD treatment beginning at either six or twelve months of age. Results indicated that subjects that experience menopause onset at a younger age had impaired spatial working memory early in the transition to a follicle-deplete state. Moreover, in the mid- and post- menopause time points, VCD-induced follicular depletion amplified an age effect, whereby Middle-Aged VCD-treated animals had poorer spatial working and reference memory performance than Young VCD-treated animals. Correlations suggested that in middle age, animals with higher circulating estrogen levels tended to perform better on spatial memory tasks. Overall, these findings suggest that the age at menopause onset is a critical parameter to consider when evaluating learning and memory across the transition to reproductive senescence. From a translational perspective, this study informs the field with respect to how the age at menopause onset might impact cognition in menopausal women, as well as provides insight into time points to explore for the window of opportunity for hormone therapy during the menopause transition to attenuate age- and menopause- related cognitive decline, and produce healthy brain aging profiles in women who retain their ovaries throughout the lifespan.
ContributorsKoebele, Stephanie Victoria (Author) / Bimonte-Nelson, Heather A. (Thesis advisor) / Aiken, Leona S. (Committee member) / Conrad, Cheryl D. (Committee member) / Wynne, Clive DL (Committee member) / Arizona State University (Publisher)
Created2015