Disease-Modifying Treatments and Their Future in Alzheimer's Disease Management.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by memory impairment, a loss of cholinergic neurons, and cognitive decline that insidiously progresses to dementia. The pathoetiology of AD is complex, as genetic predisposition, age, inflammation, oxidative stress, and dysregulated proteostasis all contribute to its development and progression. The histological hallmarks of AD are the formation and accumulation of amyloid-ß plaques and interfibrillar tau tangles within the central nervous system. These histological hallmarks trigger neuroinflammation and disrupt the physiological structure and functioning of neurons, leading to cognitive dysfunction. Most treatments currently available for AD focus only on symptomatic relief. Disease-modifying treatments (DMTs) that target the biology of the disease in hopes of slowing or reversing disease progression are desperately needed. This narrative review investigates novel DMTs and their therapeutic targets that are either in phase three of development or have been recently approved by the U.S. Food and Drug Administration (FDA). The target areas of some of these novel DMTs consist of combatting amyloid or tau accumulation, oxidative stress, neuroinflammation, and dysregulated proteostasis, metabolism, or circadian rhythm. Neuroprotection and neuroplasticity promotion were also key target areas. DMT therapeutic target diversity may permit improved therapeutic responses in certain subpopulations of AD, particularly if the therapeutic target of the DMT being administered aligns with the subpopulation's most prominent pathological findings. Clinicians should be cognizant of how these novel drugs differ in therapeutic targets, as this knowledge may potentially enhance the level of care they can provide to AD patients in the future.

Impact of Mental Health Treatment on Outcomes in Patients With Heart Failure and Ischemic Heart Disease.

BACKGROUND: There is conflicting evidence as to the impact of mental health treatment on outcomes in patients with heart disease. The aim of this study was to examine whether individuals who received mental health treatment for anxiety or depression after being hospitalized for ischemic disorders or heart failure had a reduced frequency of rehospitalizations, emergency department visits, or mortality compared with those who did not receive treatment. METHODS AND RESULTS: A population-based, retrospective, cohort design was used to examine the association between psychotherapy or antidepressant medication prescription and health service utilization and mortality in patients with coronary artery disease or heart failure and comorbid anxiety or depression. Those receiving versus not receiving mental health treatment were compared based on the frequency of rehospitalization, emergency department visits, and mortality. The study sample included 1563 patients who had a mean age of 50.1 years. Individuals who received both forms of mental health treatment for anxiety or depression were 75% less likely to be rehospitalized, 74% less likely to have an emergency department visit, and 66% less likely to die from any cause. CONCLUSIONS: Mental health treatment for anxiety or depression has a significant impact on outcomes in patients with cardiovascular disease consisting of reduced hospitalizations, emergency department visits, and in some conditions improved survival.

Patient activation and medication adherence in adults.

BACKGROUND: Patients' level of medication adherence provides conflicting results in its relationship to patient activation. Multiple factors may be contributing to these mixed results. OBJECTIVES: The primary purpose was to assess the association of patient activation to medication adherence in adults with chronic health conditions and low health literacy (HL). Secondary objectives were to determine whether age, education, gender, and race were associated with activation. METHODS: Participants completed self-report questionnaires regarding chronic disease self-management. Patient activation was measured using Hibbard's Patient Activation Measure (PAM). Self-report of medication adherence was determined using the Gonzalez-Lu adherence questionnaire. Block regressions first assessed the relation of demographic variables and education to adherence and then the added relation of patient activation in a second model. RESULTS: The analyses included 301 participants (mean age 58 years; 53% female; mean chronic conditions of 6.6). Some of the most common chronic conditions included hypertension (60%), arthritis (51%), depression (49%), and hyperlipidemia (43%). The relation of older age to greater medication adherence was significant (P < 0.05) in both models. The addition of PAM was significantly related to better adherence (P < 0.001) and also increased the R squared value from 0.04 to 0.09. This change resulted in a moderate effect size (d = 0.50). CONCLUSION: Evaluating patient activation at baseline may predict those more likely to be medication adherent in patients with low HL.

An Online Shared Decision-making Intervention for Dementia Prevention: A Parallel-group Randomized Pilot Study.

OBJECTIVES: Evaluate the acceptability and efficacy of an online dementia prevention intervention based on a cognitive behavioral shared decision-making model. MATERIALS AND METHODS: This was an unblinded pilot study in which participants were randomly assigned to one of two treatment groups. This study was carried out remotely via telephone, video conferencing, and online data collection. Eighteen English-speaking persons 40 years of age and older interested in developing more brain-healthy lifestyles. Both groups received 12 weekly sessions on lifestyle factors related to cognitive decline. The treatment-as-usual (TAU) group received the information and was encouraged to make lifestyle changes. The cognitive behavioral shared decision- making model (CBSDM) group received structured weekly sessions with support for evidence- informed personal goal choices and behavior change strategies. Primary outcome measures were the Alzheimer's Disease Risk Inventory and the Memory Self-Efficacy and Dementia Knowledge Assessment Scales. Participants reported brain health activities during the first, sixth, and 12th weeks of the study. RESULTS: No significant between-group changes were seen in the three primary outcome measures. The intervention was viewed positively by participants, who all said they would participate in it again. Participants in the CBSDM group showed increases in knowledge of dementia risk factors and exercise. Other outcomes were consistent with moderate to large effect sizes for both groups. CONCLUSION: An online intervention providing psychoeducation and behavior change support was viewed positively by older adults. Results provide preliminary support for the CBSDM intervention's efficacy in promoting brain health in older adults. CLINICAL TRIAL REGISTRATION NUMBER: NCT04822129.

e-Health Literacy Scale, Patient Attitudes, Medication Adherence, and Internal Locus of Control.

BACKGROUND: Health literacy is related to a variety of health outcomes, including disease control, health-related quality of life, and risk for death. Few studies have investigated the relation of electronic health literacy (e-health literacy) to outcomes or the mechanism by which they may be related. METHODS: Secondary data were drawn from participants in a larger study on chronic disease self-management who were age 40 years and older, had at least one chronic health condition and a health literacy score of 8th grade or below on the validated short form of the Rapid Estimate of Adult Literacy in Medicine. Participants completed the e-Health Literacy Scale (eHEALS), the Multidimensional Health Locus of Control scale, a modified version of the Attitudes Toward Health Care Providers Scale (ATHCPS), the Wake Forest Physician Trust Scale (WFPTS), and the Gonzalez-Lu adherence questionnaire. Hypothesized relations were evaluated in a bootstrapped path analytic model using the Mplus statistical software. KEY RESULTS: Participants included 334 individuals (mean age: 57.5 years; 173 women and 161 men) with Black, Indigenous, and People of Color accounting for 83.3% of the participants and White individuals making up 16.7% of the participants. Model results showed that after controlling for age, education, gender, and race, the eHEALS score was significantly related to the ATHCPS and WFPTS but not to the Gonzalez-Lu adherence questionnaire (p < .05). The eHEALS score was significantly related to the Multidimensional Health Locus of Control scale. Analysis of indirect effects showed that a portion of the relation between e-health literacy and patient attitude and adherence was mediated by internal locus of control (all p < .05). CONCLUSIONS: In this study, e-health literacy was related to important patient attitude and behavior variables via locus of control. This finding has implications for the importance of improving patients' ability to use the internet to access and effectively use health information. [HLRP: Health Literacy Research and Practice. 2023;7(2):e80-e88.].

Cognitive function and impact on driving after SARS-COV-2 infection in a man with long-standing HIV infection: a case report.

A substantial number of individuals who experience COVID-19 infection experience prolonged physical and mental symptoms after resolution of their initial infection, and among them, many individuals experience cognitive difficulties including memory lapses and executive function difficulties, often referred to as "brain fog." The possible impact of COVID-19 infection on cognition in persons with HIV-related cognitive disorders is unknown. In this report, we describe post-COVID-19 cognitive and driving function in a 62-year-old man with HIV infection since the early 1990s.

Cogstim: A Shared Decision-making Model to Support Older Adults' Brain Health.

The lack of effective treatments for cognitive decline in older adults has led to an interest in the possibility that lifestyle interventions can help to prevent changes in mental functioning and reduce the risk for dementia. Multiple lifestyle factors have been related to risk for decline, and multicomponent intervention studies suggest that changing older adults' behaviors can have a positive impact on their cognition. How to translate these findings into a practical model for clinical use with older adults, however, is not clear. In this Commentary, we propose a shared decision-making model to support clinicians' efforts to promote brain health in older persons. The model organizes risk and protective factors into three broad groups based on their mechanism of action and provides older persons with basic information to allow them to make evidence- and preference-based choices in choosing goals for effective brain health programs. A final component includes basic instruction in behavior change strategies such as goal setting, self-monitoring, and problem-solving. The implementation of the model will support older persons' efforts to develop a personally relevant and effective brainhealthy lifestyle that may help to reduce their risk for cognitive decline.

A mobile app for chronic disease self-management for individuals with low health literacy: A multisite randomized controlled clinical trial.

Objective: The purpose of this study was to evaluate the effects of a mobile app designed to improve chronic disease self-management in older adult patients with low health literacy and who had at least one chronic health condition, and to assess the impact of delivering information at different levels of reading difficulty. Methods: A randomized controlled trial was completed at two sites. Individuals 40 years of age and older screened for low health literacy who had at least one chronic health condition were randomly assigned to a tailored information multimedia app with text at one of three grade levels. Four primary outcomes were assessed: patient activation, chronic disease self-efficacy, health-related quality of life, and medication adherence. Results: All groups showed overall increases in activation, self-efficacy, and health-related quality of life, but no change in medication adherence. No between-group differences were observed. Conclusions: The mobile app was effective in increasing participants' levels of several psychosocial variables, but reading difficulty level was not significantly related to outcomes.Registered at clinicaltrials.gov NCT02922439.

Chronic Disease Self-Management of Post-Acute Sequelae of COVID-19 Among Older Adults: A Mixed-Methods Analysis.

Introduction: Approximately 20-30% of individuals who contract acute coronavirus disease (COVID-19) infection develop longer term complications of their initial infection, referred to as Post-Acute Sequelae of SARS-CoV-2 infection (PASC). PASC is characterized by chronic, varying symptomatology. Methods: Using a mixed methods study design, we aimed to gain insight into individuals' experience with PASC, including cognitive issues, fatigue, and sleep disturbances. We explored whether our previously developed application (app), aimed at improving self-management skills among individuals with chronic diseases, is relevant for individuals with PASC and gained information to adapt the app for individuals with PASC. The study included 19 individuals, aged 40 years and older, recruited from our research participant database, Nova Southeastern University clinics, and community locations. We included this age range because older adults are more likely to have comorbid conditions, allowing us to better understand the impact of COVID-19 infection in these individuals. Participants completed seven standardized self-report questionnaires online, and an individual semi-structured interview via videoconferencing. Quantitative data were assessed using descriptive statistics and calculating individuals' scores in relation to norms. Qualitative data were analyzed using a thematic analysis approach. Triangulation of the data was accomplished by calculating correlations between participants' responses on self-report scales and themes found in semi-structured interviews. Results: Themes included disruption of everyday life, diverse physical symptoms, and cognitive problems including brain fog, fatigue, coping, and emotional upset. Quantitative analysis demonstrated that participants experienced high levels of fatigue, negative mood, cognitive problems, and overall reduction in health-related quality of life (HRQOL). Correlation analyses revealed that individual interview responses were related to participants' self-report of symptoms on standard questionnaires. Discussion: Findings indicate that self-report questionnaires may reflect the experience of individuals with PASC and its impact. Additionally, further efforts to expand our prior mobile app are warranted among individuals with PASC.

Durable viral suppression among persons with HIV in the deep south: an observational study.

This study assessed predictors of stable HIV viral suppression in a racially diverse sample of persons living with HIV (PWH) in the southern US. A total of 700 PWH were recruited from one of four HIV clinics in Metro Atlanta, GA. Data were collected from September 2012 to July 2017, and HIV viral loads were retrieved from EMR for 18 months. The baseline visits and EMR data were used for current analyses. Durable viral suppression was categorized as 1. Remain suppressed, 2. Remain unsuppressed, and 3. Unstable suppression. The number of antiretroviral medications and age were significantly associated with durable viral suppression. Older age, fewer ART medications and availability of social support were positively associated with durable viral suppression over the 18-month observation period. Findings suggest that regimen complexity is potentially a better predictor of viral suppression than self-reported medication adherence. The need for consensus on the definition of durable viral suppression is also urged.

Creating a Tailored Info App to Promote Self-Management Skills in Persons with Chronic Health Conditions: Development Strategies and User Experience.

Persons with chronic health conditions, such as heart disease, diabetes, hypertension, and others, often experience self-management problems that are not disease specific. These include disrupted sleep, pain, memory issues, and challenges in working with healthcare providers. These patients may benefit from information and skill development for these problems, but simply providing them information in brief sessions during clinical appointments or in handouts or pamphlets may not have a substantial impact on their behavior. Providing information tailored to persons' needs and individual characteristics has a greater impact on patients' behavior and may increase these persons' abilities to manage their health. Creating tailored information for each person, however, is labor intensive, making it difficult to use in everyday clinical practice. Computer-based tailoring is an alternative, allowing automated tailoring of information presented to patients based on their interactions with a computer app. The purpose of this article is to describe our process in developing a series of modules for chronic disease self-management for persons 40 years of age or older with one or more chronic health conditions.

Development of a computerized intervention to improve health literacy in older Hispanics with type 2 diabetes using a pharmacist supervised comprehensive medication management.

OBJECTIVE: The primary objective was to develop a computerized culturally adapted health literacy intervention for older Hispanics with type 2 diabetes (T2D). Secondary objectives were to assess the usability and acceptability of the intervention by older Hispanics with T2D and clinical pharmacists providing comprehensive medication management (CMM). MATERIALS AND METHODS: The study occurred in three phases. During phase I, an integration approach (i.e., quantitative assessments, qualitative interviews) was used to develop the intervention and ensure cultural suitability. In phase II, the intervention was translated to Spanish and modified based on data obtained in phase I. During phase III, the intervention was tested for usability/acceptability. RESULTS: Thirty participants (25 older Hispanics with T2D, 5 clinical pharmacists) were included in the study. Five major themes emerged from qualitative interviews and were included in the intervention: 1) financial considerations, 2) polypharmacy, 3) social/family support, 4) access to medication/information, and 5) loneliness/sadness. Participants felt the computerized intervention developed was easy to use, culturally appropriate, and relevant to their needs. Pharmacists agreed the computerized intervention streamlined patient counseling, offered a tailored approach when conducting CMM, and could save them time. CONCLUSION: The ability to offer individualized patient counseling based on information gathered from the computerized intervention allows for precision counseling. Future studies are needed to determine the effectiveness of the developed computerized intervention on adherence and health outcomes.

Computer-Delivered Cognitive Training and Transcranial Direct Current Stimulation in Patients With HIV-Associated Neurocognitive Disorder: A Randomized Trial.

Objective: HIV infection is associated with impaired cognition, and as individuals grow older, they may also experience age-related changes in mental abilities. Previous studies have shown that computer-based cognitive training (CCT) and transcranial direct current stimulation (tDCS) may be useful in improving cognition in older persons. This study evaluated the acceptability of CCT and tDCS to older adults with HIV-associated neurocognitive disorder, and assessed their impact on reaction time, attention, and psychomotor speed. Methods: In a single-blind randomized study, 46 individuals with HIV-associated mild neurocognitive disorder completed neuropsychological assessments and six 20-min training sessions to which they had been randomly assigned to one of the following conditions: (1) CCT with active tDCS; (2) CCT with sham tDCS, or (3) watching educational videos with sham tDCS. Immediately after training and again 1 month later, participants completed follow-up assessments. Outcomes were evaluated via repeated measures mixed effects models. Results: Participant ratings of the intervention were positive. Effects on reaction time were not significant, but measures of attention and psychomotor speed suggested positive effects of the intervention. Conclusion: Both CCT and tDCS were highly acceptable to older persons with HIV infection. CCT and tDCS may improve cognitive in affected individuals. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT03440840].

Enhancing the Impact of Mobile Health Literacy Interventions to Reduce Health Disparities.

Health literacy is a key factor in health outcomes that should be considered when creating mobile health promotion apps. In this paper, we detail our work over the past 10 years in developing the theory and practice of targeting the content of mobile apps at a level appropriate for the intended audience. We include a review of our theory of health literacy as expertise, the ASK model, and integrate it with the Theory of Planned Behavior. We then provide data that support both the model and its use. More recently, we have developed a predictive analytic model that uses demographic information and patient performance on a 10-item screening measure to determine patient level of health literacy at a high level of accuracy. The predictive model will enable apps to automatically provide content to users at an appropriate level of health literacy. This strategy, along with other aspects of tailoring, will allow apps to be more personally relevant to users, enhancing their effects in promoting health behavior change.

A mixed analysis approach to elucidate the multiple chronic condition experience of English- and Spanish-speaking older adults.

BACKGROUND: Having multiple chronic conditions (MCCs) is the most common health condition in older adults. The management of each condition presents many challenges. A key factor in patients' ability to manage their own health care is their level of health literacy. PURPOSE: The purpose of this mixed analysis study was to elucidate the experience of older adults living with MCCs and identify associations among the experiences to determine targets for future mobile health (mHealth) interventions focused on MCCs and health literacy. PARTICIPANTS AND METHODS: Using the Abilities, Skills, and Knowledge Model as a framework, semi-structured interviews were completed with 25 older adults in English and Spanish. Interviews were analyzed using inductive thematic analysis and hierarchical cluster analysis. RESULTS: The main themes from these results included 1) Reflections of chronic disease; 2) Emotional aspects of chronic disease; 3) Physical barriers to well-being; 4) Quality-of-care factors; and 5) Cognitive strategies for self-management. Qualitative results highlighted the importance of a multi-targeted approach to chronic disease self-management (CDSM). Cluster analysis identified associations within the qualitative data, revealing the importance of the subthemes related to coping with pain and the impact of the patient-provider relationship on treatment adherence. CONCLUSION: Results support the utility of mHealth interventions to improve health literacy and promote CDSM.

Association Between Cognitive Tests and Antiretroviral Medication Adherence in Older Adults With HIV.

BACKGROUND: One of the fastest growing populations living with HIV is older adults especially those 65 years of age or older. Current antiretroviral therapy (ART) has prolonged life expectancy of persons with HIV. However, for therapy to be effective, patients need to be adherent. Over time, older persons with HIV may experience HIV-associated neurocognitive disorders or other factors that could affect ART adherence. The use of expedient cognitive tests that help measure medication adherence may be useful for the optimal care of these patients. OBJECTIVE: To investigate the association between cognitive tests and ART adherence. METHODS: This was a prospective study evaluating patients 65 years of age or older with HIV. Cognitive tests used included the Executive Clock-Drawing Task (CLOX) 1 and 2, Trail Making Test parts A and B, and Grooved Pegboard Test (GPB). The medication event monitoring system cap over 1 month was used as the primary measure for adherence. RESULTS: CLOX 1 and GPB were significantly related to adherence ( P < 0.05). Comparison of the magnitude of each measure's relation to adherence suggests that the GPB is a better indicator of ability to adhere ( R = 0.514 vs R = 0.381). Conclusion and Relevance: CLOX 1 and GPB demonstrated an association with adherence in patients 65 years of age or older with HIV. Although the use of these tests to measure adherence in older persons with HIV seems promising, more research is needed to ascertain their ultimate utility.

HIV-1 Infection, Injecting Drug Use, and Neuroendocrine Response to Psychological Stress.

BACKGROUND: Previous studies have suggested that HIV-1 infection is associated with neuroendocrine abnormalities including alterations in autonomic nervous system (ANS) activity. The norepinephrine (NE) response to cold pressor stress, an α-adrenergic challenge, is blunted in HIV-1 infection. Given the relation of ANS activity to the function of the hypothalamic-pituitary-adrenal (HPA) axis and its role in cognitive functioning, changes in response to stress may be a factor in HIV-related cognitive dysfunction. OBJECTIVE: In this study, we evaluated the NE and cortisol response of persons in three groups. DESIGN/PARTICIPANTS: We studied stress response in three groups: (1) those with HIV-1 infection and a history of injecting drug use (IDU), those with HIV-1 infection but no IDU, and a control group of uninfected individuals without a history of IDU. Stress was induced by administering a neuropsychological test known to induce an immediate increase in NE, the Stroop Color-Word Test. Blood samples were obtained immediately before and after participants completed the Stroop and then at two intervals over the next 20 minutes. Data were analyzed using mixed-effects repeated measures models. MAIN MEASURES: Serum norepinephrine, epinephrine, and cortisol. RESULTS: Analyses showed that those with both HIV-1 infection and history of IDU had a significantly greater NE response to stress that did not return to baseline over 20 minutes compared to those without infection or IDU history. Epinephrine and cortisol responses followed similar patterns, but between-group differences were not statistically significant. CONCLUSIONS: The combination of history of IDU and HIV infection may produce an exaggerated neuroendocrine response that does not quickly return to baseline levels. Given the potential impact of these on cognitive and physical function in affected these individuals, implementing stress management techniques with them may be important.

Predicting medication adherence in older Hispanic patients with type 2 diabetes.

PURPOSE: Potential cognitive and demographic correlates of medication nonadherence in older Hispanic adults with type 2 diabetes were investigated. METHODS: Forty community-dwelling participants 65 years of age or older were recruited. Executive control function (ECF) was assessed using the executive clock drawing task (CLOX 1) test and the 25-item Executive Interview. Self-reported medication adherence was measured on a visual analog scale (VAS); measures of glycemic control included glycosylated hemoglobin (HbA1c) concentration. The primary objective was to determine if ECF performance correlated with medication adherence or glycemic control. RESULTS: Participants' mean ± S.D. age was 74.95 ± 7.07 years, and 73% (n = 29) were female. Lower VAS scores correlated with worse CLOX 1 performance (r = 0.38, p = 0.02) and worse HbA1c status (r = -0.42, p = 0.007). Linear regression modeling indicated significant associations between VAS scores and both CLOX 1 results (beta coefficient [ß] = 0.41, p = 0.01) and educational level (ß = 0.345, p = 0.03). Receiver operating characteristic analysis of CLOX 1 scores (scoring range, 0-15; lower scores indicate greater impairment) showed that a highly sensitive cutoff score for predicting adherence of <90% would be 7, but a cutoff of 10 would provide more specificity. CONCLUSION: Results of an evaluation of a small sample of Hispanic older adults with type 2 diabetes demonstrated a relationship between ECF, as measured by the CLOX 1 instrument, and self-reported medication adherence.

Racial Disparities in HIV Antiretroviral Medication Management are Mediated by Health Literacy.

BACKGROUND: Despite the availability of antiretroviral (ARV) therapy in the United States, only 30% of people living with HIV/AIDS (PLWH) in the US are virally suppressed. Nonadherence to ARVs remains the strongest correlate of viral suppression. African Americans (AA) living with HIV/AIDS remain disproportionately affected by this disease, and studies report a greater proportion of infections and deaths among this group. OBJECTIVE: Earlier studies by this team and others have shown that health literacy (HL) may negatively influence disparities in health behaviors, including management of ARV prescriptions, between AA and non-AA PLWH. This current study expands these findings and tests whether HL may explain disparities in medication management among AA and non-AA PLWH and includes important covariates and measures of participants' actual medication regimens. METHODS: PLWH were recruited from HIV care clinics in the greater metropolitan area of Atlanta, GA, and completed a face-to-face study visit. A total of 699 PLWH, 65% of whom were AA, completed this study visit. Assessment of knowledge and management of participants' actual medication regimens showed highly skewed responses, demonstrating accurate verbal descriptions of ARV prescription instructions. A measure of problem-solving (how to manage a mock ARV regimen) showed significantly different performance by race and that HL measures (both reading comprehension and numeracy) mediated this relationship. KEY RESULTS: Findings suggest that although PLWH may be able to verbally explain how they are supposed to take their ARV medication, challenges may arise with management issues (eg, determining need for a refill, counting pills to determine if a dose was missed) and that PLWH with low HL (who are disproportionately AA) may be at greater risk for mistakes. Other characteristics, such as cognitive impairment, were also shown to influence medication management. CONCLUSION: Attention to PLWH's potential for mismanagement of ARV and other medications is important to identify for educational interventions. [Health Literacy Research and Practice. 2018;2(4):e205-e213.]. PLAIN LANGUAGE SUMMARY: This study tested if problems with taking medicine to treat HIV may be caused by poor reading and math skills. Even though most people were able to correctly say how they should take their HIV pills, knowing if they had missed a pill or counting out a week's number of pills was harder for those with lower reading and math skills.