Systolic Blood Pressure Is Associated with Increased Brain Amyloid Load in Mild Cognitively Impaired Participants: Alzheimer's Disease Neuroimaging Initiatives Study.

BACKGROUND: Cardiovascular disease (CVD), including elevated blood pressure (BP), is known to promote Alzheimer's disease (AD) risk. Although brain amyloid load is a recognized hallmark of pre-symptomatic AD, its relationship to increased BP is less known. The objective of this study was to examine the relationship of BP to brain estimates of amyloid-ß (Aß) and standard uptake ratio (SUVr). We hypothesized that increased BP is associated with increased SUVr. METHODS: Using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we stratified BP according to the Seventh Joint National Committee (JNC) on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure Classification (JNC VII). Florbetapir (AV-45) SUVr was derived from the averaged frontal, anterior cingulate, precuneus, and parietal cortex relative to the cerebellum. A linear mixed-effects model enabled the elucidation of amyloid SUVr relationships to BP. The model discounted the effects of demographics, biologics, and diagnosis at baseline within APOE genotype groups. The least squares means procedure was used to estimate the fixed-effect means. All analyses were performed using the Statistical Analysis System (SAS). RESULTS: In non-ɛ4 carrier MCI subjects, escalating JNC categories of BP was associated with increasing mean SUVr using JNC-4 as a reference point (low-normal (JNC1) p = 0.018; normal (JNC-1) p = 0.039; JNC-2 p = 0.018 and JNC-3 p = 0.04). A significantly higher brain SUVr was associated with increasing BP despite adjustment for demographics and biological variables in non-ɛ4 carriers but not in ɛ4-carriers. This observation supports the view that CVD risk may promote increased brain amyloid load, and potentially, amyloid-mediated cognitive decline. CONCLUSION: Increasing levels of JNC classification of BP is dynamically associated with significant changes in brain amyloid burden in non-ɛ4 carriers but not in ɛ4-carrier MCI subjects. Though not statistically significant, amyloid burden tended to decrease with increasing BP in ɛ4 homozygote, perhaps motivated by increased vascular resistance and the need for higher brain perfusion pressure.

The Role of Transportation in the Enrollment of Elderly African Americans into Exercise and Memory Study: GEMS Study.

BACKGROUND: Understanding the factors driving recruitment and enrollment of African Americans (AA)s in clinical translational research will assure that underrepresented populations benefit from scientific progress and new developments in the diagnosis and treatment of Alzheimer's disease and related disorders. While transportation is pivotal to volunteers' ability to participate in research, its contribution to enrollment in exercise studies on AD is yet to be elucidated. Thus, this research focuses on identifying factors that influence the recruitment and enrollment of African Americans in biomedical studies and determining whether the availability of transportation motivates participation in time-demanding exercise studies on AD. METHODS: We analyzed recruitment data collected from 567 volunteers ages 55 and older screened through various recruitment sources and considered for enrollment in our exercise and memory study. To determine whether transportation influenced the enrollment of African Americans (AA)s in biomedical studies, multiple logistic regression analysis was performed to identify significant factors that drive enrollment. Furthermore, the association of race and demographic factors on the availability of transportation was assessed. RESULTS: Demographic factors, age at screening, education, gender, and cognitive scores were not significantly different among those enrolled compared to control (not-enrolled). In the relationship of enrollment to transportation, enrolled participants were more likely to have access to transportation (79.12%) than not-enrolled participants who had less access to transportation (71.6%); however, the association was not statistically significant. However, race differentially influenced the likelihood of enrollment, with elderly AAs being significantly less likely to have transportation (p = 0.020) than the Whites but more likely than "others" to have transportation. CONCLUSION: Our findings suggest that access to transportation may be a key factor motivating enrollment in an exercise and memory study in a predominantly AA sample. Notably, AAs in our sample were less likely to have transportation than Whites. Other demographic factors and cognitive scores did not significantly influence enrollment in our sample. A larger sample and more detailed assessment of transportation are needed to further discern the role of transportation in clinical trials.

Exercise Training-Increased FBXO32 and FOXO1 in a Gender-Dependent Manner in Mild Cognitively Impaired African Americans: GEMS-1 Study.

The ubiquitin proteasome system (UPS) and FOXOs transcription factors play a pivotal role in cellular clearance and minimizing the accumulation of Aß in neurodegeneration (ND). In African Americans (AAs) with mild cognitive impairment (MCI), the role of components of UPS and FOXOs; and whether they are amenable to exercise effects is unknown. We hypothesized that exercise can enhance cellular clearance systems during aging and ND by increasing expressions of FBXO32 and FOXO1. To test this hypothesis, we used TaqMan gene expression analysis in peripheral blood (PB) to investigate the component of UPS and FOXOs; and provide mechanistic insight at baseline, during exercise, and in both genders. At baseline, levels of FBXO32 were higher in women than in men. In our attempt to discern gender-specific exercise-related changes, we observed that levels of FBXO32 increased in men but not in women. Similarly, levels of FOXO1 increased in men only. These data suggest that a graded dose of FBXO32 and FOXO1 may be beneficial when PB cells carrying FBXO32 and FOXO1 summon into the brain in response to Alzheimer's disease (AD) perturbation (docking station PB cells). Our observation is consistent with emerging studies that exercise allows the trafficking of blood factors. Given the significance of FBXO32 and FOXO1 to ND and associated muscle integrity, our findings may explain, at least in part, the benefits of exercise on memory, associated gait, and balance perturbation acknowledged to herald the emergence of MCI.

Aerobic Exercise Training-Induced Changes on DNA Methylation in Mild Cognitively Impaired Elderly African Americans: Gene, Exercise, and Memory Study - GEMS-I.

BACKGROUND: DNA methylation at CpG sites is a vital epigenetic modification of the human genome affecting gene expression, and potentially, health outcomes. However, evidence is just budding on the effects of aerobic exercise-induced adaptation on DNA methylation in older mild cognitively impaired (MCI) elderly African American (AAs). Therefore, we examined the effects of a 6-month aerobic exercise-intervention on genome-wide DNA methylation in elderly AA MCI volunteers. DESIGN: Elderly AA volunteers confirmed MCI assigned into a 6-month program of aerobic exercise (eleven participants) underwent a 40-min supervised-training 3-times/week and controls (eight participants) performed stretch training. Participants had maximal oxygen consumption (VO2max) test and Genome-wide methylation levels at CpG sites using the Infinium HumanMethylation450 BeadChip assay at baseline and after a 6-month exercise program. We computed false discovery rates (FDR) using Sidak to account for multiplicity of tests and performed quantitative real-time polymerase chain-reaction (qRT-PCR) to confirm the effects of DNA methylations on expression levels of the top 5 genes among the aerobic participants. CpG sites identified from aerobic-exercise participants were similarly analyzed by the stretch group to quantify the effects of exercise-induced methylation changes among the group of stretch participants. RESULTS: Eleven MCI participants (aerobic: 73% females; mean age 72.3 ± 6.6 years) and eight MCI participants (stretch: 75% female; mean age 70.6 ± 6.7 years) completed the training. Aerobic exercise-training was associated with increases in VO2max and with global hypo- and hypermethylation changes. The most notable finding was CpG hypomethylation within the body of the VPS52 gene (P = 5.4 × 10-26), a Golgi-associated protein, involved in intracellular protein trafficking including amyloid precursor protein. qRT-PCR confirmed a nearly twofold increased expression of VPS52. Other top findings with FDR q-value < 10-5, include hypomethylations of SCARB1 (8.8 × 10-25), ARTN (6.1 × 10-25), NR1H2 (2.1 × 10-18) and PPP2R5D (9.8 × 10-18). CONCLUSION: We conclude that genome-wide DNA methylation patterns is associated with exercise training-induced methylation changes. Identification of methylation changes around genes previously shown to interact with amyloid biology, intracellular protein trafficking, and lipoprotein regulations provide further support to the likely protective effect of exercise in MCI. Future studies in larger samples are needed to confirm our findings.

Exercise Training Induced Changes In Nuclear Magnetic Resonance-Measured Lipid Particles In Mild Cognitively Impaired Elderly African American Volunteers: A Pilot Study.

PURPOSE: Poor cardiorespiratory fitness (CRF) is linked to cognitive deterioration, but its effects on lipid heterogeneity and functional properties in older African American (AA) subjects with mild cognitive impairment (MCI) need elucidation. This study determined whether exercise training-induced changes in blood lipid particle sizes (LPS) were associated with CRF determined by VO2Max in elderly AAs with MCI. Given the pivotal role of brain-derived neurotrophic factor (BDNF) on glucose metabolism, and therefore, "diabetic dyslipidemia", we also determined whether changes in LPS were associated with the levels of serum BDNF. METHODS: This analysis included 17 of the 29 randomized elderly AAs with MCI who had NMR data at baseline and after a 6-month training. We used Generalized Linear Regression (GLM) models to examine cardiorespiratory fitness (VO2Max) effects on training-induced change in LPS in the stretch and aerobic groups. Additionally, we determined whether the level of BDNF influenced change in LPS. RESULTS: Collectively, mean VO2Max (23.81±6.17) did not differ significantly between aerobic and stretch groups (difference=3.17±3.56, P=0.495). Training-related changes in very low-density lipoprotein, chylomicrons, and total low-density lipoprotein (LDL) particle sizes correlated significantly with VO2Max, but not after adjustment for age and gender. However, increased VO2Max significantly associated with reduced total LDL particle size after similar adjustments (P = 0.046). While stretch exercise associated with increased protective large high-density lipoprotein particle size, the overall effect was not sustained following adjustments for gender and age. However, changes in serum BDNF were associated with changes in triglyceride and cholesterol transport particle sizes (P < 0.051). CONCLUSION: Promotion of stretch and aerobic exercise to increase CRF in elderly AA volunteers with MCI may also promote beneficial changes in lipoprotein particle profile. Because high BDNF concentration may reduce CVD risk, training-related improvements in BDNF levels are likely advantageous. Large randomized studies are needed to confirm our observations and to further elucidate the role for exercise therapy in reducing CVD risk in elderly AAs with MCI.

Associations of Pulse and Blood Pressure with Hippocampal Volume by APOE and Cognitive Phenotype: The Alzheimer's Disease Neuroimaging Initiative (ADNI).

BACKGROUND: It is increasingly evident that high blood pressure can promote reduction in global and regional brain volumes. While these effects may preferentially affect the hippocampus, reports are inconsistent. METHODS: Using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we examined the relationships of hippocampal volume to pulse pressure (PPR) and systolic (SBP) and diastolic (DBP) blood pressure according to apolipoprotein (APOE) ɛ4 positivity and cognitive status. The ADNI data included 1,308 participants: Alzheimer disease (AD = 237), late mild cognitive impairment (LMCI = 454), early mild cognitive impairment (EMCI = 254), and cognitively normal (CN = 365), with up to 24 months of follow-up. RESULTS: Higher quartiles of PPR were significantly associated with lower hippocampal volumes (Q1 vs. Q4, p = 0.034) in the CN and AD groups, but with increasing hippocampal volume (Q1, p = 0.008; Q2, p = 0.020; Q3, p = 0.017; Q4 = reference) in the MCI groups. In adjusted stratified analyses among non-APOE ɛ4 carriers, the effects in the CN (Q1 vs. Q4, p = 0.006) and EMCI groups (Q1, p = 0.002; Q2, p = 0.013; Q3, p = 0.002; Q4 = reference) remained statistically significant. Also, higher DBP was significantly associated with higher hippocampal volume (p = 0.002) while higher SBP was significantly associated with decreasing hippocampal volume in the EMCI group (p = 0.015). CONCLUSION: Changes in PPR, SBP, and DBP differentially influenced hippocampal volumes depending on the cognitive and APOE genotypic categories.

The lived experience of individuals in cardiac rehabilitation who have a positive outlook on their cardiac recovery: A phenomenological inquiry.

BACKGROUND: Cardiac rehabilitation is often under-utilized despite its well-known benefits. Individuals with cardiac disease who exhibit a positive outlook often experience improved health outcomes. This study tried to explore the question: "What are the lived experiences of cardiac recovery in cardiac rehabilitation individuals with a predominantly positive outlook in the context of an acute cardiac event?" AIMS: Our primary aim explored the experiences of cardiac recovery in cardiac rehabilitation participants with a predominantly positive outlook, within the context of an acute cardiac event, including exploring barriers and facilitators of cardiac recovery. Our secondary aim explored how a positive outlook impacted completion of phase two of the cardiac rehabilitation program. METHODS: Husserlian phenomenology guided this study. A purposive sample of 10 individuals who had experienced an acute cardiac event and had a predominantly positive outlook were interviewed. Data were analyzed using Colaizzi's method. RESULTS: Three themes emerged from the data. The first was "choosing life over death," where participants discussed how they made a decision to improve their health. The second theme was "learning to live a new self," where participants described the changes they had to make in order to improve their health. The third theme was "a life-transforming cardiac event" where participants shared how the cardiac event had changed their life. CONCLUSION: The participants' decisions to choose to live, led them to embrace their cardiac recovery. It is important for nurses to identify individuals in cardiac rehabilitation that need additional support. In addition, alternative models of cardiac rehabilitation programs need to be explored.

Supportive medical care in life-threatening illness: A pilot study.

OBJECTIVE: The goal of this pilot study was to identify the processes by which healing occurs in patients who experience a life-threatening illness. METHOD: Healing was examined by using two qualitative studies that employed a semistructured interview process (interviews lasted between 30 and 115 minutes). There were 10 cardiac event survivors and 9 cancer survivors. These participants came from a community hospital setting (cardiac), nonmedical holistic services organization (cancer), and a research hospital (cancer). Before participants could take part in the study, they were administered preliminary screening measurements, the first of which was an instrument similar to the Distress Thermometer. Participants then self-reported their positive life-transforming changes. If one to three changes were reported six months after onset of the illness, participants were deemed to have passed the screening. Finally, participants were tested for speaking volume and clarity. RESULTS: An overall theme that was prevalent throughout the interviews was medical support. Participants found that their positive, life-transforming changes were typically connected with supportive caregivers who helped to create a culture of care. They also indicated that an absence of this medical supportive care hindered development of such life-transforming changes. SIGNIFICANCE OF RESULTS: Our results indicate that a medical care team will be more effective if a positive culture of care is created. This can be implemented if the team provides comfort, which involves being more engaged in the treatment of patients as well as being more attentive to their psychosocial needs.

Spirituality in the context of life-threatening illness and life-transforming change.

OBJECTIVE: Individuals with life-threatening illness often engage in some form of spirituality to meet increased needs for meaning and purpose. This study aimed to identify the role of spirituality in persons who had reported positive, life-transforming change in relation to life-threatening cancer or cardiac events, and to connect these roles to palliative and supportive care. METHOD: A purposive sample of 10 cardiac survivors and 9 cancer survivors was recruited. Once the participants had given informed consent and passed screening in relation to life-transforming change and distress, they engaged in a semistructured one-hour qualitative interview on the theme of how their life-transforming change occurred in the context of their life-threatening illness. In the present article, our phenomenological analysis focuses on participants' references to purpose and meaning in their lives, with particular attention to the role and context of participants' spirituality. RESULTS: Participants mentioned spirituality, meaning, and purpose in many contexts, including connecting with family and friends, nature, art, music, and sometimes creating a relationship with God. Participants often accessed spirituality by enhancing connections in their own lives: with a higher power, people, their work, or themselves. These enhanced connections gave participants greater meaning and purpose in their lives, and substantially helped participants to adjust to their life-threatening illnesses. SIGNIFICANCE OF RESULTS: Understanding the roles and contexts of spirituality among patients with a life-threatening illness allows us to develop better palliative and supportive care plans. Spiritually oriented supportive care may include support groups, yoga, meditation, nature, music, prayer, or referral to spiritual or religious counselors. A quantitative scale is needed to help healthcare clinicians assess the spiritual and coping needs of individuals with life-threatening illness.

Psychosocial experiences in the context of life-threatening illness: the cardiac rehabilitation patient.

OBJECTIVE: One of the most prevalent life-threatening illnesses is heart disease. The initial trauma of being diagnosed with a life-threatening illness or having a cardiac event can begin a psychosocial chain reaction that results in a transformation of the lives of these patients. The goal of our study was to investigate the lived experiences of psychosocial healing in rehabilitation of cardiac patients using a qualitative written interview. METHOD: A purposive sample of 14 cardiac event survivors was recruited. Participants were interviewed after informed consent and screening. We used a qualitative analysis and model-revision approach similar to the procedure outlined by Charmaz (2006). RESULTS: Participants consistently mentioned that a heightened awareness of mortality was a motivating factor that led to participants focusing more on their family and relationships, having an enhanced outlook on life, and making healthy lifestyle changes. SIGNIFICANCE OF RESULTS: If clinicians are able to employ a measure to better understand the nature of a patient's progression from cardiac event to successful recovery, interventions such as cardiac rehabilitation can be implemented earlier and more effectively during the course of the illness and recovery phases of treatment. Theoretically, this early detection of a patient's progression could reduce the time spent recovering from a cardiac event, and it would allow treatments for these conditions to better alleviate the psychosocial concerns faced by patients.

Current status of spirituality in cardiac rehabilitation programs: a review of literature.

PURPOSE: Strong spiritual experiences in life are a protective, positive, prognostic factor in cardiovascular diseases. However, spirituality is often neglected in cardiac rehabilitation (CR) programs. The purpose of this article was to review studies that investigated spirituality in CR programs. METHODS: The electronic databases PubMed, CINHAL, PsycINFO, and Cochrane Library of Systematic Reviews were searched for studies that measured spirituality in a CR population. The search included studies with and without spiritual interventions in CR settings. RESULTS: Five quantitative studies and 1 qualitative study that enrolled a total of 1636 patients in phase 2 CR programs were reviewed. The spiritual interventions found were relaxation responses and spiritual classes. Two studies showed preliminary evidence that supports the further exploration of spiritual interventions in CR programs. CONCLUSIONS: Evidence supporting the use of spiritual interventions for medical and psychological outcomes in CR programs is very limited because of a lack of controlled clinical trials. However, the descriptive and observational studies provide some empirical support to further explore spiritual interventions in CR programs, with the goal of enhancing the psychosocial and emotional status of CR participants. Further rigorous research design and procedures are needed to establish the contribution of spirituality in CR programs for cardiac patients.