Lipoproteins and Health Outcomes: Cognitive and Physical Function in Older Adults

Cardiovascular health is a major determinant of quality of life and mortality, especially in older adulthood. With the world’s oldest population increasing at expedited rates, challenges from cardiovascular conditions and its implications are spawning. Although it is well known that dyslipidemia may lead to cardiac events, less is known about the effects on cognitive and physical function in older adults. Epidemiological studies show that optimizing current preventive strategies even at older ages may reduce the incidence of cardiovascular comorbidity (e.g. hypertension, stroke) and increase quality of life. Determining the association between lipoproteins and cognitive and functional performance in older adults may help develop interdisciplinary interventions designed to maintain independence longer and improve the overall quality of life. The current dissertation contains two studies examining serum lipoproteins, specifically total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) in older adults in relation to cognitive and functional outcomes. The first study examined the association between lipoproteins and cognitive performance in a cognitively normal older adult population. Results showed an association between low levels of TG and higher composite cognitive scores (CCS), but this association disappeared when apolipoprotein ε4 allele (APOE ε4 allele) was adjusted for in the model. High levels of HDL-C were also associated with the CCS and this association remained significant even after adjusting for APOE ε4 allele. Furthermore, these associations were only significant among women. High HDL-C remained linked with visuospatial function and attention and working memory even after adjusting for APOE ε4 allele. Further moderation analysis indicated that the association between TGs, HDL-C and cognitive performance was moderated by the APOE ε4 allele. Stratification by carriers and non-carriers of the ε 4 allele indicated that the previous association was only significant for non-carriers. The second study of this dissertation is a longitudinal analysis, which explored the association between TC, LDL-C, TG and HDL-C and physical function. Random effects analysis was used to assess whether lipoprotein levels affect subsequent change in physical function. All models were adjusted for baseline age, sex, education, and perceived current economic situation, cardiovascular risk factors and comorbidity inclusive of cognitive disability. Results showed that lower levels of TC and HDL-C had cross-sectional associations with more ADL disability but not longitudinally, and higher levels of TG were related to better grip function. Moderation analysis of the previous significant association indicated that only cognitive disability moderated the cross-sectional association between TC and for ADLs. Further stratification showed that the association was only pertinent for participants with cognitive disability. Independent of cardiovascular risk factors and an extensive list of comorbidities, older adults living in the community with higher levels of TC, TG and HDL-C were associated with better physical function outcomes. Lipid patterns in older adults may be indicative of physical function and may serve clinicians as a tool to compress morbidity in older adults and help them maintain independence and a high quality of life for as long as possible. In conclusion, lipid levels in older adults play an important role in maintaining cognitive and physical function into older ages, thus maintaining a good quality of life. Higher HDL-C seemed to be the lipid associated with maintaining cognitive function, while TC dominated the association with physical function

Does Patient Dementia Limit the Use of Cardiac Catheterization in ST-Elevated Myocardial Infarction?

Regardless of age or mental capacity, percutaneous coronary intervention (PCI) is the first line of treatment for ST-elevated myocardial infarction (STEMI). This study evaluates the disparities in the use of diagnostic cardiac catheterization and PCI in STEMI patients with dementia. A retrospective analysis was performed of Florida‟s comprehensive inpatient surveillance system for the years 2006-2007 with admission diagnosis of STEMI. Logistic regression analysis was used to identify disparities in the use of intervention among all STEMI patients. A total of 8,331 STEMI patients met the inclusion criteria. Of these, 77% were catheterized and of these 67% received PCI. A total of 605 (7.3%) were demented. Patients with dementia were less likely to be catheterized (RR 0.4, 95% CI 0.3-0.5) and less likely to receive PCI within 24 hours (RR 0.5, 95% CI 0.4-0.6). This study concludes that STEMI patients with dementia were much less likely to receive cardiovascular interventions

Traumatic brain injury and dementia risk in male veteran older twins-Controlling for genetic and early life non-genetic factors.

INTRODUCTION: This study leveraged the twin study design, which controls for shared genetic and early life exposures, to investigate the association between traumatic brain injury (TBI) and dementia. METHODS: Members of the National Academy of Sciences-National Research Councils Twins Registry of World War II male veterans were assigned a cognitive outcome based on a multi-step assessment protocol. History of TBI was obtained via interviews. RESULTS: Among 8302 individuals, risk of non-Alzheimers disease (non-AD) dementia was higher in those with TBI (hazard ratio [HR] = 2.00, 95% confidence interval [CI], 0.97-4.12), than for AD (HR = 1.23, 95% CI, 0.76-2.00). To add more control of genetic and shared environmental factors, we analyzed 100 twin pairs discordant for both TBI and dementia onset, and found TBI-associated risk for non-AD dementia increased further (McNemar odds ratio = 2.70; 95% CI, 1.27-6.25). DISCUSSION: These findings suggest that non-AD mechanisms may underlie the association between TBI and dementia, potentially providing insight into inconsistent results from prior studies

The Association Between Lipoproteins, Disability, and Physical Function Among Older Costa Rican Adults

Objective: To examine the relationship between total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) with disability and physical performance. Method: Wave 1 data were from Costa Rican Longevity and Healthy Aging Study (n = 2,827). Lipoprotein profiles were measured using blood samples. Disability and physical functioning were measured with activities of daily living/instrumental activities of daily living (ADLs/IADLs) and objective assessment of physical performance. Results: Lower HDL-C was associated with greater ADL disability, and lower TC with longer time to pick-a-pencil and Time-Up-Go (TUG) test. Age interacted between (a) TG and lung function, chair stands, and pick-a-pencil, and (b) HDL-C and TUG. Stratification showed lower TG and longer time picking up a pencil only for those above 84 years. Based on significant interactions with sex, lower TC was associated with slower chair stand time in women and higher HDL-C with slower chair stand time in men. Discussion: Lower levels of lipoproteins may suggest worse physical function, but the association may differ by sex

The NAS-NRC Twin Registry and Duke Twins Study of Memory in Aging: An Update

The National Academy of Sciences-National Research Council (NAS-NRC) Twin Registry is one of the oldest, national population-based twin registries in the USA. It comprises 15,924 White male twin pairs born in the years 1917-1927 (N = 31.848), both of whom served in the armed forces, chiefly during World War II. This article updates activities in this registry since the most recent report in Twin Research and Human Genetics (Page, 2006). Records-based data include information from enlistment charts and Veterans Administration data linkages. There have been three major epidemiologic questionnaires and an education and earnings survey. Separate data collection efforts with the NAS-NRC registry include the National Heart, Lung, and Blood Institute (NHLBI) subsample, the Duke Twins Study of Memory in Aging and a clinically based study of Parkinson's disease. Progress has been made on consolidating the various data holdings of the NAS-NRC Twin Registry. Data that had been available through the National Academy of Sciences are now freely available through National Archive of Computerized Data on Aging (NACDA)

The Impact of Multiple Dimensions of Socioeconomic Status on Physical Functioning Across the Life Course

Objective: We used the Physical Performance Across the LifeSpan Study to investigate the relationships of multiple indicators of socioeconomic status (SES), both in early life and late life, with physical function. Method: We examined associations between multiple early and late life SES indicators with physical function measured by aerobic endurance, gait speed, and lower body strength. Results: Higher participant education and household income were associated with increased physical function. In our age-stratified analysis, we observed widening SES disparities with increasing age among those in the two younger strata with lower SES associated with worse physical function. Finally, we observed an association between socioeconomic trend and gait speed, aerobic endurance, and lower body strength. There was also an association between lower aerobic endurance and being in a downward socioeconomic trend. Discussion: These findings highlight the significance of considering multiple dimensions of the social environment as important correlates of physical functioning across the life course

The Preventing Alzheimer\u27s with Cognitive Training (PACT) randomized clinical trial

BACKGROUND: To address the rising prevalence of Alzheimer\u27s disease and related dementias, effective interventions that can be widely disseminated are warranted. The Preventing Alzheimer\u27s with Cognitive Training study (PACT) investigates a commercially available computerized cognitive training program targeting improved Useful Field of View Training (UFOVT) performance. The primary goal is to test the effectiveness of UFOVT to reduce incidence of clinically defined mild cognitive impairment (MCI) or dementia with a secondary objective to examine if effects are moderated by plasma β-amyloid level or apolipoprotein E e4 (APOE e4) allele status. METHODS/DESIGN: This multisite study utilizes a randomized, controlled experimental design with blinded assessors and investigators. Individuals who are 65 years of age and older are recruited from the community. Eligible participants who demonstrate intact cognitive status (Montreal Cognitive Assessment score \u3e 25) are randomized and asked to complete 45 sessions of either a commercially available computerized-cognitive training program (UFOVT) or computerized games across 2.5 years. After three years, participants are screened for cognitive decline. For those demonstrating decline or who are part of a random subsample, a comprehensive neuropsychological assessment is completed. Those who perform below a pre-specified level are asked to complete a clinical evaluation, including an MRI, to ascertain clinical diagnosis of normal cognition, MCI, or dementia. Participants are asked to provide blood samples for analyses of Alzheimer\u27s disease related biomarkers. DISCUSSION: The PACT study addresses the rapidly increasing prevalence of dementia. Computerized cognitive training may provide a non-pharmaceutical option for reducing incidence of MCI or dementia to improve public health. REGISTRATION: The PACT study is registered at http://Clinicaltrials.govNCT03848312