Diversity in Alzheimer\u27s Disease Drug Trials: The Importance of Eligibility Criteria

INTRODUCTION: To generalize safety and efficacy findings, it is essential that diverse populations are well represented in Alzheimer\u27s disease (AD) drug trials. In this review, we aimed to investigate participant diversity in disease-modifying AD trials over time, and the frequencies of participant eligibility criteria. METHODS: A systematic review was performed using Medline, Embase, the Cochrane Library, and Clinicaltrials.gov, identifying 2247 records. RESULTS: In the 101 included AD trials, participants were predominantly White (median percentage: 94.7%, interquartile range: 81.0-96.7%); and this percentage showed no significant increase or decrease over time (2001-2019). Eligibility criteria such as exclusion of persons with psychiatric illness (78.2%), cardiovascular disease (71.3%) and cerebrovascular disease (68.3%), obligated caregiver attendance (80.2%), and specific Mini-Mental State Examination scores (90.1%; no significant increase/decrease over time) may have led to a disproportionate exclusion of ethnoracially diverse individuals. DISCUSSION: Ethnoracially diverse participants continue to be underrepresented in AD clinical trials. Several recommendations are provided to broaden eligibility criteria

A Protocol for the Inclusion of Minoritized Persons in Alzheimer Disease Research From the ADNI3 Diversity Taskforce

Importance: Black or African American (hereinafter, Black) and Hispanic or Latino/a/x (hereinafter, Latinx) adults are disproportionally affected by Alzheimer disease, but most research studies do not enroll adequate numbers of both of these populations. The Alzheimer’s Disease Neuroimaging Initiative-3 (ADNI3) launched a diversity taskforce to pilot a multipronged effort to increase the study inclusion of Black and Latinx older adults. Objective: To describe and evaluate the culturally informed and community-engaged inclusion efforts to increase the screening and enrollment of Black and Latinx older adults in ADNI3. Design, Setting, and Participants: This cross-sectional study used baseline data from a longitudinal, multisite, observational study conducted from January 15, 2021, to July 12, 2022, with no follow-up. The study was conducted at 13 ADNI3 sites in the US. Participants included individuals aged 55 to 90 years without cognitive impairment and those with mild cognitive impairment or Alzheimer disease. Exposures: Efforts included (1) launch of an external advisory board, (2) changes to the study protocol, (3) updates to the digital prescreener, (4) selection and deployment of 13 community-engaged research study sites, (5) development and deployment of local and centralized outreach efforts, and (6) development of a community-science partnership board. Main Outcomes and Measures: Screening and enrollment numbers from centralized and local outreach efforts, digital advertisement metrics, and digital prescreener completion. Results: A total of 91 participants enrolled in the trial via centralized and local outreach efforts, of which 22 (24.2%) identified as Latinx and 55 (60.4%) identified as Black (median [IQR] age, 65.6 [IQR, 61.5-72.5] years; 62 women [68.1%]). This represented a 267.6% increase in the monthly rate of enrollment (before: 1.11 per month; during: 4.08 per month) of underrepresented populations. For the centralized effort, social media advertisements were run between June 1, 2021, and July 31, 2022, which resulted in 2079 completed digital prescreeners, of which 1289 met criteria for subsequent site-level screening. Local efforts were run between June 1, 2021, to July 31, 2022. A total of 151 participants underwent site-level screening (100 from local efforts, 41 from centralized efforts, 10 from other sources). Conclusions and Relevance: In this cross-sectional study of pilot inclusion efforts, a culturally informed, community-engaged approach increased the inclusion of Black and Latinx participants in an Alzheimer disease cohort study.</p

HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors

Combination antiretroviral therapy (CART) has greatly reduced medical morbidity and mortality with HIV infection, but high rates of HIV-associated neurocognitive disorders (HAND) continue to be reported. Because large HIV-infected (HIV+) and uninfected (HIV−) groups have not been studied with similar methods in the pre-CART and CART eras, it is unclear whether CART has changed the prevalence, nature, and clinical correlates of HAND. We used comparable methods of subject screening and assessments to classify neurocognitive impairment (NCI) in large groups of HIV + and HIV − participants from the pre-CART era (1988–1995; N = 857) and CART era (2000–2007; N = 937). Impairment rate increased with successive disease stages (CDC stages A, B, and C) in both eras: 25%, 42%, and 52% in pre-CART era and 36%, 40%, and 45% in CART era. In the medically asymptomatic stage (CDC-A), NCI was significantly more common in the CART era. Low nadir CD4 predicted NCI in both eras, whereas degree of current immunosuppression, estimated duration of infection, and viral suppression in CSF (on treatment) were related to impairment only pre-CART. Pattern of NCI also differed: pre-CART had more impairment in motor skills, cognitive speed, and verbal fluency, whereas CART era involved more memory (learning) and executive function impairment. High rates of mild NCI persist at all stages of HIV infection, despite improved viral suppression and immune reconstitution with CART. The consistent association of NCI with nadir CD4 across eras suggests that earlier treatment to prevent severe immunosuppression may also help prevent HAND. Clinical trials targeting HAND prevention should specifically examine timing of ART initiation

Structural and Interpersonal Benefits and Risks of Participation in HIV Research: Perspectives of Female Sex Workers in Guatemala

This study explored perceived benefits and risks of participation in HIV research among 33 female sex workers in Tecun Uman, Guatemala. Stigma associated with sex work and HIV was a critical barrier to research participation. Key benefits of participation included access to HIV/STI prevention and testing, as well as positive and trusting relationships between sex workers and research teams. Control exerted by managers had mixed influences on perceived research risks and benefits. Results underscore the critical need for HIV investigators to develop population-tailored procedures to reduce stigma, engage managers, and reinforce trusting, reciprocal relationships between sex work communities and researchers

Enhancing the Ethical Conduct of HIV Research with Migrant Sex Workers: Human Rights, Policy, and Social Contextual Influences.

BACKGROUND:Migrant sex workers are often highly marginalized and disproportionately experience health and social inequities, including high prevalence of HIV, sexually transmitted infections, and human rights violations. In recent years, research involving migrant sex workers has increased, yet many knowledge gaps remain regarding how best to protect research participant rights and welfare. Our objective was to identify key challenges and opportunities related to the responsible conduct of HIV research with migrant sex workers. METHODS:Focus groups and interviews conducted with 33 female sex workers ≥18 years old at the Guatemala-Mexico border from June 2013-February 2014 were analyzed. Participants were recruited through community outreach by a local HIV prevention organization to sex work establishments such as bars, hotels, street corners, and truck stops. RESULTS:Key themes influencing research engagement for migrant sex workers included researcher mistrust and fear related to research participation, rooted in the social isolation frequently faced by recent migrants; intersecting concerns related to immigration status, fear of criminalization, and compliance with sex work regulations; and perceived benefits and risks of HIV/STI testing for migrants (e.g., immigration implications, stigma) represent potential barriers and opportunities for the responsible conduct of research involving migrant sex workers. CONCLUSIONS:Results highlight the intersection between the human rights vulnerabilities of migrant sex workers and barriers to research participation, including social isolation of migrants and policy/legal barriers related to immigration and sex work. Findings illustrate the need for researchers to develop population-tailored procedures to address fears related to immigration and criminalization, and to reinforce positive and non-stigmatizing relationships with migrant sex workers. Community-led efforts to reduce stigma and foster community organization and supports for migrant sex workers are recommended, as are broader policy shifts that move away from punitive legal approaches towards approaches that safeguard and prioritize the human rights of migrant sex workers

Tackling a Major Deficiency of Diversity in Alzheimer's Disease Therapeutic Trials: An CTAD Task Force Report.

As the last opportunity to assess treatment effect modification in a controlled setting prior to formal approval, clinical trials are a critical tool for understanding the safety and efficacy of new treatments in diverse populations. Recruitment of diverse participants in Alzheimer's Disease (AD) clinical trials are therefore essential to increase the generalizability of study results, with diversity broadly described to be representative and inclusive. This representation of study participants is equally critical in longitudinal cohort (observational) studies, which will be key to understanding disease disparities and are often used to design adequately powered AD clinical trials. New and innovative recruitment initiatives and enhanced infrastructure facilitate increased participant diversity in AD clinical studies

Demographically-Corrected Norms for the Grooved Pegboard Test and Finger Tapping Test in monolingual Spanish speakers from the US-Mexico Border Region

Abstract Objective We developed demographically-corrected norms for US-dwelling, Spanish-speaking Hispanics on two widely used tests of motor skills - the Grooved Pegboard Test (Pegs) and Finger Tapping Test (Tapping). We then examined the effects of applying established norms for non-Hispanic Caucasians (NH Whites) and non-Hispanic African Americans (NH Blacks) on motor test results from our Hispanic population. Participants and Method 254 participants living in the US-Mexico border region of San Diego, CA and Tucson, AZ completed Pegs, and a subset (n = 183) completed Tapping. Age ranged from 19-60 and education from 0-20 years, with 59% women. Raw test scores were converted to demographically-corrected T-scores with a fractional polynomial procedure and compared to a fitted curve for the original data. Results Findings included significant main effects of education on both tests (p &lt; .001), and of age for Pegs (p &lt; .001). There was a significant interaction of sex and age on Tapping, such that older age was associated with lower scores in men only (p = .02). The resulting normative T-scores were confirmed to be free from demographic influences. Using a T &lt; 40 cut point, rates of impairment in the Spanish speaking normative sample for dominant (D) and nondominant (ND) hands, respectively, were 17% and 14% for Pegs, and 12% and 10% for Tapping. Applying existing norms for NH Whites and NH Blacks to the raw scores of Spanish speakers generally yielded lower impairment rates on all measures, with one exception, Pegs ND, for which NH White norms overestimated impairment (23%). Conclusions Normative standards from other groups are not a good fit for interpreting motor test performance in this Hispanic population, which in the current instance would have generally underdiagnosed fine motor impairment. These findings underscore the importance of appropriate, population-specific normative data- even for tests of motor ability

The functional impact of HIV-associated neuropsychological impairment in Spanish-speaking adults: A pilot study

Among English-speaking adults, HIV-associated neuropsychological (NP) impairments have been associated with problems in everyday functioning, including ability to function at work and drive an automobile. Latinos account for a disproportionate number of HIV/AIDS cases nationwide, and a significant segment of this population is primarily Spanish speaking. We have previously developed an assessment that evaluates English-speakers on a variety of instrumental activities of daily living. In this pilot study, we used Spanish-language translations of our functional battery to investigate the cultural relevance of such measures, and to explore relationships between NP status and ability to perform important everyday tasks in HIV-infected Spanish-speakers. Sixteen HIV-infected monolingual Spanish-speaking adults received comprehensive, Spanish language NP testing and functional assessments included the following domains: Medication Management, Cooking, Finances, Shopping, and Restaurant Scenario. Results revealed that most of the functional tasks appeared culturally relevant and appropriate with minor modifications. NP-impaired participants were significantly more functionally impaired compared to NP-normals (88% vs. 13%, p \u3c .01). Performances on the functional assessment and the NP battery were also related to indicators of real world functioning, including employment status and quality of life. These results, though preliminary, suggest that Spanish language functional assessments are potentially valid tools for detecting everyday functioning deficits associated with NP impairments in HIV-infected Spanish-speakers

The state of neuropsychological test norms for Spanish-speaking adults in the United States.

Objective: The present review paper aimed to identify published neuropsychological test norms developed for Spanish-speakers living in the United States (U.S.). Methods: We conducted a systematic review of the literature via an electronic search on PubMed using keywords "Normative data," "Neuropsychological test," "norms", "Hispanic/Latinos," "Spanish Speakers," and "United States." We added other studies and published manuals as identified by citations in papers from the original search. Results Eighteen sources of normative data for Spanish-speakers in the U.S. were identified. Of the 18 citations identified, only four provide normative data on comprehensive batteries of tests for Spanish-Speakers. Two of these are based on persons living in the southwest of the U.S., who tend to be of Mexican origin. Overall, a number of the studies are focused on older persons and although the majority include participants with wide ranges of education, participants in the ends of the education distribution tend to be underrepresented. Conclusion: Here we provide a detailed description of the neuropsychological normative data currently available for Spanish-speakers living in the U.S. While there has been increased attention towards developing norms for neuropsychological batteries in Spanish-speaking countries (e.g., Latin America and Spain), there is still an urgent need to standardize neuropsychological tests among diverse groups of Spanish-speaking adults living in the U.S. The present review presents a list of norms for U.S.-dwelling Spanish-speakers, thus providing an important tool for clinicians and researchers