Biostatistics Commons^™

Age-Related Losses In Cardiac Autonomic Activity During A Daytime Nap, Pin-Chun Chen, Negin Sattari, Lauren N. Whitehurst, Sara C. Mednick

Psychology Faculty Publications

In healthy, young individuals, a reduction in cardiovascular output and a shift from sympathetic to parasympathetic (vagal) dominance is observed from wake into stages of nocturnal and daytime sleep. This cardiac autonomic profile, measured by heart rate variability (HRV), has been associated with significant benefits for cardiovascular health. Aging is associated with decreased nighttime sleep quality and lower parasympathetic activity during both sleep and resting. However, it is not known whether age-related dampening of HRV extends to daytime sleep, diminishing the cardiovascular benefits of naps in the elderly. Here, we investigated this question by comparing the autonomic activity profile between …

Brain Structure Changes Over Time In Normal And Mildly Impaired Aged Persons, Charles D. Smith, Linda J. Van Eldik, Gregory A. Jicha, Frederick A. Schmitt, Peter T. Nelson, Erin L. Abner, Richard J. Kryscio, Richard R. Murphy, Anders H. Andersen

Neurology Faculty Publications

Structural brain changes in aging are known to occur even in the absence of dementia, but the magnitudes and regions involved vary between studies. To further characterize these changes, we analyzed paired MRI images acquired with identical protocols and scanner over a median 5.8-year interval. The normal study group comprised 78 elders (25M 53F, baseline age range 70-78 years) who underwent an annual standardized expert assessment of cognition and health and who maintained normal cognition for the duration of the study. We found a longitudinal grey matter (GM) loss rate of 2.56 ± 0.07 ml/year (0.20 ± 0.04%/year) and a …

Post-Acquisition Processing Confounds In Brain Volumetric Quantification Of White Matter Hyperintensities, Ahmed A. Bahrani, Omar M. Al-Janabi, Erin L. Abner, Shoshana H. Bardach, Richard J. Kryscio, Donna M. Wilcock, Charles D. Smith, Gregory A. Jicha

Neurology Faculty Publications

BACKGROUND: Disparate research sites using identical or near-identical magnetic resonance imaging (MRI) acquisition techniques often produce results that demonstrate significant variability regarding volumetric quantification of white matter hyperintensities (WMH) in the aging population. The sources of such variability have not previously been fully explored.

NEW METHOD: 3D FLAIR sequences from a group of randomly selected aged subjects were analyzed to identify sources-of-variability in post-acquisition processing that can be problematic when comparing WMH volumetric data across disparate sites. The methods developed focused on standardizing post-acquisition protocol processing methods to develop a protocol with less than 0.5% inter-rater variance.

RESULTS: A series …

Metformin Blunts Muscle Hypertrophy In Response To Progressive Resistance Exercise Training In Older Adults: A Randomized, Double‐Blind, Placebo‐Controlled, Multicenter Trial: The Masters Trial, R. Grace Walton, Cory M. Dungan, Douglas E. Long, S. Craig Tuggle, Kate Kosmac, Bailey D. Peck, Heather M. Bush, Alejandro G. Villasante Tezanos, Gerald Mcgwin, Samuel T. Windham, Fernando Ovalle, Marcas M. Bamman, Philip A. Kern, Charlotte A. Peterson

Center for Muscle Biology Faculty Publications

Progressive resistance exercise training (PRT) is the most effective known intervention for combating aging skeletal muscle atrophy. However, the hypertrophic response to PRT is variable, and this may be due to muscle inflammation susceptibility. Metformin reduces inflammation, so we hypothesized that metformin would augment the muscle response to PRT in healthy women and men aged 65 and older. In a randomized, double-blind trial, participants received 1,700 mg/day metformin (N = 46) or placebo (N = 48) throughout the study, and all subjects performed 14 weeks of supervised PRT. Although responses to PRT varied, placebo gained more lean body …

Mechanics Of Phenotypic Aging Trajectories In C. Elegans And Humans, William Zhang

Arts & Sciences Electronic Theses and Dissertations

Overall, my dissertation integrates longitudinal measurements of physiology to investigate the aging process. In the first half, I examine the surprising and largely unexplained degree of variation in lifespan within even homogeneous populations. I sought to understand how physiological aging differs between long- and short-lived individuals within a population of genetically identical C. elegans reared in a homogeneous environment. Using a novel culture apparatus, I longitudinally monitored aspects of aging physiology across a large population of isolated individuals. Aggregating several measures into an overall estimate of senescence, I find that long- and short-lived individuals start adulthood on an equal physiological …

Tdp-43 Proteinopathy In Aging: Associations With Risk-Associated Gene Variants And With Brain Parenchymal Thyroid Hormone Levels, Peter T. Nelson, Zsombor Gal, Wang-Xia Wang, Dana M. Niedowicz, Sergey C. Artiushin, Samuel Wycoff, Angela Wei, Gregory A. Jicha, David W. Fardo

Pathology and Laboratory Medicine Faculty Publications

TDP-43 proteinopathy is very prevalent among the elderly (affecting at least 25% of individuals over 85 years of age) and is associated with substantial cognitive impairment. Risk factors implicated in age-related TDP-43 proteinopathy include commonly inherited gene variants, comorbid Alzheimer's disease pathology, and thyroid hormone dysfunction. To test parameters that are associated with aging-related TDP-43 pathology, we performed exploratory analyses of pathologic, genetic, and biochemical data derived from research volunteers in the University of Kentucky Alzheimer's Disease Center autopsy cohort (n = 136 subjects). Digital pathologic methods were used to discriminate and quantify both neuritic and intracytoplasmic TDP-43 pathology …

Serum Nutrient Levels And Aging Effects On Periodontitis, Jeffrey L Ebersole, Joshua Lambert, Heather Bush, Pinar Emecen Huja, Arpita Basu

Biostatistics Faculty Publications

Periodontal disease damages tissues as a result of dysregulated host responses against the chronic bacterial biofilm insult and approximately 50% of US adults > 30 years old exhibit periodontitis. The association of five blood nutrients and periodontitis were evaluated due to our previous findings regarding a potential protective effect for these nutrients in periodontal disease derived from the US population sampled as part of the National Health and Nutrition Examination Survey (1999–2004). Data from over 15,000 subjects was analyzed for blood levels of cis-β-carotene, β-cryptoxanthin, folate, vitamin D, and vitamin E, linked with analysis of the presence and severity of periodontitis. …

Associations Of Smoking Status And Serious Psychological Distress With Chronic Obstructive Pulmonary Disease, Ke-Sheng Wang, Liang Wang, Shimin Zheng, Long-Yang Wu

Shimin Zheng

Background: Chronic obstructive pulmonary disease (COPD) has been a major public health problem due to its high prevalence, morbidity, and mortality. Smoking is a major risk factor for COPD, while serious psychological distress (SPD) is prevalent among COPD patients. However, no study focusing on the effect of SPD on COPD has been so far conducted, while few studies have focused on the associations of SPD and behavioral factors with COPD by smoking status. Objectives: This study aimed to examine the associations of SPD and behavioral factors (such as smoking and physical activity) with COPD. Materials and Methods: Weighted logistic regression …

Genomics And Csf Analyses Implicate Thyroid Hormone In Hippocampal Sclerosis Of Aging, Peter T. Nelson, Yuriko Katsumata, Kwangsik Nho, Sergey C. Artiushin, Gregory A. Jicha, Wang-Xia Wang, Erin L. Abner, Andrew J. Saykin, Walter A. Kukull, Alzheimer’S Disease Neuroimaging Initiative (Adni), David W. Fardo

Sanders-Brown Center on Aging Faculty Publications

We report evidence of a novel pathogenetic mechanism in which thyroid hormone dysregulation contributes to dementia in elderly persons. Two single nucleotide polymorphisms (SNPs) on chromosome 12p12 were the initial foci of our study: rs704180 and rs73069071. These SNPs were identified by separate research groups as risk alleles for non-Alzheimer’s neurodegeneration. We found that the rs73069071 risk genotype was associated with hippocampal sclerosis (HS) pathology among people with the rs704180 risk genotype (National Alzheimer’s Coordinating Center/Alzheimer’s Disease Genetic Consortium data; n = 2113, including 241 autopsy-confirmed HS cases). Furthermore, both rs704180 and rs73069071 risk genotypes were associated with widespread brain …

Apoe Ε4 Allele Modifies The Association Of Lead Exposure With Age-Related Cognitive Decline In Older Individuals, Diddier Prada, Elena Colicino, Melinda C. Power, Marc G Weisskopf, Jia Zhong, Lifang Hou, Avron Spiro, Pantel Vokonas, Plus 4 Others...

Epidemiology Faculty Publications

BACKGROUND: Continuing chronic and sporadic high-level of lead exposure in some regions in the U.S. has directed public attention to the effects of lead on human health. Long-term lead exposure has been associated with faster cognitive decline in older individuals; however, genetic susceptibility to lead-related cognitive decline during aging has been poorly studied.

METHODS: We determined the interaction of APOE-epsilon variants and environmental lead exposure in relation to age-related cognitive decline. We measured tibia bone lead by K-shell-x-ray fluorescence, APOE-epsilon variants by multiplex PCR and global cognitive z-scores in 489 men from the VA-Normative Aging Study. To determine global cognitive …

Abcc9/Sur2 In The Brain: Implications For Hippocampal Sclerosis Of Aging And A Potential Therapeutic Target, Peter T. Nelson, Gregory A. Jicha, Wang-Xia Wang, Eseosa T. Ighodaro, Sergey C. Artiushin, Colin G. Nichols, David W. Fardo

Sanders-Brown Center on Aging Faculty Publications

The ABCC9 gene and its polypeptide product, SUR2, are increasingly implicated in human neurologic disease, including prevalent diseases of the aged brain. SUR2 proteins are a component of the ATP-sensitive potassium (“K _ATP ”) channel, a metabolic sensor for stress and/or hypoxia that has been shown to change in aging. The K _ATP channel also helps regulate the neurovascular unit. Most brain cell types express SUR2, including neurons, astrocytes, oligodendrocytes, microglia, vascular smooth muscle, pericytes, and endothelial cells. Thus it is not surprising that ABCC9 gene variants are associated with risk for human brain diseases. For example, Cantu syndrome is …

Novel Human Abcc9/Sur2 Brain-Expressed Transcripts And An Eqtl Relevant To Hippocampal Sclerosis Of Aging, Peter T. Nelson, Wang-Xia Wang, Bernard R. Wilfred, Angela Wei, James Dimayuga, Qingwei Huang, Eseosa T. Ighodaro, Sergey C. Artiushin, David W. Fardo

Sanders-Brown Center on Aging Faculty Publications

ABCC9 genetic polymorphisms are associated with increased risk for various human diseases including hippocampal sclerosis of aging. The main goals of this study were 1 > to detect the ABCC9 variants and define the specific 3′ untranslated region (3′UTR) for each variant in human brain, and 2 > to determine whether a polymorphism (rs704180) associated with risk for hippocampal sclerosis of aging pathology is also associated with variation in ABCC9 transcript expression and/or splicing. Rapid amplification of ABCC9 cDNA ends (3′RACE) provided evidence of novel 3′ UTR portions of ABCC9 in human brain. In silico and experimental studies were performed focusing on …

Reassessment Of Risk Genotypes (Grn, Tmem106b, And Abcc9 Variants) Associated With Hippocampal Sclerosis Of Aging Pathology, Peter T. Nelson, Wang-Xia Wang, Amanda B. Partch, Sarah E. Monsell, Otto Valladares, Sally R. Ellingson, Bernard R. Wilfred, Adam C. Naj, Li-San Wang, Walter A. Kukull, David W. Fardo

Pathology and Laboratory Medicine Faculty Publications

Hippocampal sclerosis of aging (HS-Aging) is a common high-morbidity neurodegenerative condition in elderly persons. To understand the risk factors for HS-Aging, we analyzed data from the Alzheimer’s Disease Genetics Consortium and correlated the data with clinical and pathologic information from the National Alzheimer’s Coordinating Center database. Overall, 268 research volunteers with HS-Aging and 2,957 controls were included; detailed neuropathologic data were available for all. The study focused on single-nucleotide polymorphisms previously associated with HS-Aging risk: rs5848 ( GRN ), rs1990622 ( TMEM106B ), and rs704180 ( ABCC9 ). Analyses of a subsample that was not previously evaluated (51 HS-Aging cases …

Associations Of Smoking Status And Serious Psychological Distress With Chronic Obstructive Pulmonary Disease, Ke-Sheng Wang, Liang Wang, Shimin Zheng, Long-Yang Wu

ETSU Faculty Works

Background: Chronic obstructive pulmonary disease (COPD) has been a major public health problem due to its high prevalence, morbidity, and mortality. Smoking is a major risk factor for COPD, while serious psychological distress (SPD) is prevalent among COPD patients. However, no study focusing on the effect of SPD on COPD has been so far conducted, while few studies have focused on the associations of SPD and behavioral factors with COPD by smoking status.

Objectives: This study aimed to examine the associations of SPD and behavioral factors (such as smoking and physical activity) with COPD.

Materials and Methods: Weighted logistic regression …

Lifetime Musical Activities And Cognitive Function Of The Elderly, Alicia Nevriana, Pandu Riono, Tri Budi W. Rahardjo, Adji Kusumadjati

Kesmas

Penurunan fungsi kognitif merupakan salah satu masalah umum pada lanjut usia yang mampu memengaruhi kualitas hidup mereka. Musik merupakan sebuah elemen yang dipercaya mampu berkontribusi terhadap kualitas hidup mereka. Meski demikian, hubungan antara aktivitas musikal yang dilakukan sepanjang hidup dan fungsi kognitif lansia belum diketahui secara pasti. Pada penelitian ini, hubungan antara aktivitas musikal sepanjang hidup dan fungsi kognitif dievaluasi. Lima puluh tiga lansia penghuni panti tresna werdha di Jakarta Timur dipilih dan diwawancarai terkait karakteristik dan aktivitas musikal sepanjang hidup mereka. Fungsi kognitif juga diukur menggunakan MMSE. Hasil penelitian ini menunjukkan adanya kemungkinan asosiasi antara aktivitas musikal sepanjang hidup …

Decline In Health For Older Adults: 5-Year Change In 13 Key Measures Of Standardized Health, Paula H. Diehr, Stephen M. Thielke, Anne B. Newman, Calvin H. Hirsch, Russell Tracy

UW Biostatistics Working Paper Series

Introduction

The health of older adults declines over time, but there are many ways of measuring health. We examined whether all measures declined at the same rate, or whether some aspects of health were less sensitive to aging than others.

Methods

We compared the decline in 13 measures of physical, mental, and functional health from the Cardiovascular Health Study: hospitalization, bed days, cognition, extremity strength, feelings about life as a whole, satisfaction with the purpose of life, self-rated health, depression, digit symbol substitution test, grip strength, ADLs, IADLs, and gait speed. Each measure was standardized against self-rated health. We compared …

National Estimates Of The Prevalence Of Alzheimer's Disease In The United States, Ron Brookmeyer, Denis Evans, Liesi Hebert, Langa Kenneth, Heeringa Steven, Plassman Brenda, Kukull Kenneth

Ron Brookmeyer

Several methods of estimating prevalence of dementia are presented in this article. For both Brookmeyer and the Chicago Health and Aging project (CHAP), the estimates of prevalence are derived statistically, forward calculating from incidence and survival figures. The choice of incidence rates on which to build the estimates may be critical. Brookmeyer used incidence rates from several published studies, whereas the CHAP investigators applied the incidence rates observed in their own cohort. The Aging, Demographics, and Memory Study (ADAMS) and the East Boston Senior Health Project (EBSHP) were sample surveys designed to ascertain the prevalence of Alzheimer’s disease and dementia. …

Age-Specific Differences In The Use Of Thrombolytic Therapy And Hospital Outcomes In Patients With Acute Myocardial Infarction: A Community-Wide Perspective, Omar Ali, Immad Sadiq, Robert Goldberg, Jorge Yarzebski, Darleen Lessard, Jerry Gurwitz, Joel Gore

Jorge L. Yarzebski

BACKGROUND: Relatively limited information is available about recent, and trends over time, use of thrombolytic therapy in patients of different ages hospitalized with acute myocardial infarction and the association between use of thrombolytic therapy and hospital outcomes. METHODS: We conducted an observational study of 5601 residents of the Worcester, Massachusetts, metropolitan area (1990 census = 437,000) with confirmed acute myocardial infarction in all local hospitals during 6 one-year periods between 1990 and 1999. RESULTS: Despite relatively stable use of thrombolytic therapy between 1990 and 1995, decreases in the use of thrombolytic therapy in all patients with acute myocardial infarction were …

Prevalence, Incidence, And Persistence Of Major Depressive Symptoms In The Cardiovascular Health Study, Stephen M. Thielke Md, Ms, Paula Diehr Phd

Paula Diehr

PURPOSE: To explore the association of major depressive symptoms with advancing age, sex, and self-rated health among older adults. DESIGN AND METHODS: We analyzed 10 years of annual assessments in a longitudinal cohort of 5888 Medicare recipients in the Cardiovascular Health Study. Self-rated health was assessed with a single question, and subjects categorized as healthy or sick. Major depressive symptoms were assessed using the Center for Epidemiologic Studies Short Depression Scale, with subjects categorized as nondepressed (score < 10) or depressed (> or =10). Age-, sex-, and health-specific prevalence of depression and the probabilities of transition between depressed and nondepressed states were estimated. RESULTS: The …

Worldwide Variation In The Doubling Time Of Alzheimer's Disease Incidence Rates, Kathryn Ziegler-Graham, Ron Brookmeyer, Elizabeth Johnson, H. Michael Arrighi

Ron Brookmeyer

Background The doubling time is the number of chronological years for the age-specific incidence rate to double in magnitude. Doubling times describe the rate of increase of the risk of Alzheimer's disease (AD) with advancing age. Estimates of doubling times of AD assist in understanding disease etiology and forecasting future disease prevalence. The objective of this study was to investigate regional and gender differences in the doubling of AD age-specific incidence rates.

Methods We identified all studies in the peer review literature that reported age-specific incidence rates for AD. We modeled the logarithm of the incidence rate as a linear …

The Number Of Sick Persons In A Cohort, Paula Diehr

Paula Diehr

To see if the number of sick persons in a cohort was approximately constant over time, we calculated the number of sick persons in a “research” cohort of older adults followed for up to 14 years, and also in a synthetic birth cohort. Methods: In the research cohort, we calculated the actual number of persons in each health state over time, using eight different definitions of “sick”. For the birth cohort, we estimated the number of sick persons each year after birth. Results: The number of sick persons in the research cohort was approximately constant for 14 years, for all …

Software To Forecast The Global Burden Of Alzheimer's Disease, Ron Brookmeyer, Elizabeth Johnson, Kathryn Ziegler-Graham, H. Michael Arrighi

Ron Brookmeyer

Software was developed to forecast the global burden of Alzheimer’s disease and evaluate the potential impact of interventions that delay disease onset and progression. The output includes 50 year projections of Alzheimer's disease prevalence by stage of disease and region of the world. The methods are based on a stochastic multi-state model The software incorporates U.N. worldwide population forecasts and data from epidemiological studies on risks of Alzheimer’s disease. The user can also supply their own population projections, and modify input parameters for the model including the disease incidence rates, effects of interventions on disease onset and progression, and stages …

Modeling The Effect Of Alzheimer's Disease On Mortality, Elizabeth Johnson, Ron Brookmeyer, Kathryn Ziegler-Graham

Ron Brookmeyer

Mortality rate ratios and the associated proportional hazards models have been used to summarize the effect of Alzheimer's disease on longevity. However, the mortality rate ratios vary by age and therefore do not provide a simple parsimonious summary of the effect of the disease on lifespan. Instead, we propose a new parameter that is defined by an additive multistate model. The proposed multistate model accounts for different stages of disease progression. The underlying assumption of the model is that the effect of disease on mortality is to add a constant amount to death rates once the disease progresses from an …

Aging And The Public Health Impact Of Dementia, Ron Brookmeyer, Claudia Kawas

Ron Brookmeyer

No abstract provided.

Projections Of Alzheimer's Disease In The United States And The Public Health Impact Of Delaying Disease Onset., Ron Brookmeyer, Sarah Gray, Claudia Kawas

Ron Brookmeyer

OBJECTIVES: The goal of this study was to project the future prevalence and incidence of Alzheimer's disease in the United States and the potential impact of interventions to delay disease onset.

METHODS: The numbers of individuals in the United States with Alzheimer's disease and the numbers of newly diagnosed cases that can be expected over the next 50 years were estimated from a model that used age-specific incidence rates summarized from several epidemiological studies, US mortality rates, and US Bureau of the Census projections.

RESULTS: in 1997, the prevalence of Alzheimer's disease in the United States was 2.32 million (range: …