Rates of Undiagnosed Cognitive Impairment and Performance on the Montreal Cognitive Assessment Among Older Adults in Primary Care.

BACKGROUND: The number of adults in the USA with cognitive impairment is increasing; however, few studies report prevalence rates of undiagnosed cognitive impairment among older adults in primary care. OBJECTIVE: To determine the prevalence of undiagnosed cognitive impairment among adults ages 55 years and older in primary care settings and provide normative data for the Montreal Cognitive Assessment in this context. DESIGN: Single interview, observational study. PARTICIPANTS: English-speaking adults ages 55 years and older without diagnoses of cognitive impairment recruited from primary care practices in New York City, NY, and Chicago, IL (n = 872). MAIN MEASURES: Montreal Cognitive Assessment (MoCA). Undiagnosed cognitive impairment was defined by age and education adjusted z-scores more than 1.0 and 1.5 standard deviations below published norms, corresponding to mild or moderate to severe cognitive impairment, respectively. KEY RESULTS: The mean age was 66.8 (8.0) years, 44.7% were male, 32.9% were Black or African-American, and 29.1% were Latinx. Undiagnosed cognitive impairment was identified in 20.8% of subjects (mild impairment, 10.5%; moderate-severe impairment, 10.3%). Impairment at any level of severity was associated in bivariate analyses with several patient characteristics, most notably for race and ethnicity (White, non-Latinx, 6.9% vs. Black, non-Latinx, 26.8%, Latinx, 28.2%, other race, 21.9%; p < 0.0001), place of birth (US 17.5% vs. non-US 30.7%, p < 0.0001), depression (33.1% vs. no depression, 18.1%; p < 0.0001), and impairment in activities of daily living (≥ 1 ADL impairment, 34.0% vs. no ADL impairment, 18.2%; p < 0.0001). CONCLUSIONS: Undiagnosed cognitive impairment is common among urban dwelling older adults attending primary care practices, and was associated with several patient characteristics, including non-White race and ethnicity and depression. Normative data for the MoCA from this study may serve as a useful resource for studies of similar patient populations.

Improving generalizability and study design of Alzheimer's disease cohort studies in the United States by including under-represented populations.

The poor generalizability of clinical research data due to the enrollment of highly educated, non-Latinx White participants hampers the development of therapies for Alzheimer's disease (AD). Black and Latinx older adults have a greater risk for dementia, yet it is unclear how health-care disparities and sociocultural factors influence potential AD therapies and prognosis. Low enrollment of under-represented populations may be attributable to several factors including greater exclusion due to higher rates of comorbidities, lower access to AD clinics, and the legacy of unethical treatment in medical research. This perspective outlines solutions tested in the Brain Health Registry (BHR) and the Alzheimer's Disease Neuroimaging Initiative (ADNI), including culturally-informed digital research methods, community-engaged research strategies, leadership from under-represented communities, and the reduction of exclusion criteria based on comorbidities. Our successes demonstrate that it is possible to increase the inclusion and engagement of under-represented populations into US-based clinical studies, thereby increasing the generalizability of their results.

Screening and enrollment of underrepresented ethnocultural and educational populations in the Alzheimer's Disease Neuroimaging Initiative (ADNI).

INTRODUCTION: An analysis of the ethnocultural and socioeconomic composition of Alzheimer's Disease Neuroimaging Initiative (ADNI) participants is needed to assess the generalizability of ADNI data to diverse populations. METHODS: ADNI data collected between October 2004 and November 2020 were used to determine ethnocultural and educational composition of the sample and differences in the following metrics: screening, screen fails, enrollment, biomarkers. RESULTS: Of 3739 screened individuals, 11% identified as being from ethnoculturally underrepresented populations (e.g., Black, Latinx) and 16% had <12 years of education. Of 2286 enrolled participants, 11% identified as ethnoculturally underrepresented individuals and 15% had <12 years of education. This participation is considerably lower than US Census data for adults 60+ (ethnoculturally underrepresented populations: 25%; <12 years of education: 4%). Individuals with <12 years of education failed screening at a higher rate. DISCUSSION: Our findings suggest that ADNI results may not be entirely generalizable to ethnoculturally diverse and low education populations.

The neurocognitive effects of a past cannabis use disorder in a diverse sample of people living with HIV.

People living with HIV (PLWH) report higher rates of cannabis use than the general population, a trend likely to continue in light of recent policy changes and the reported therapeutic benefits of cannabis for PLWH. Therefore, it is important to better understand cannabis-associated effects on neurocognition, especially as PLWH are at heightened risk for neurocognitive impairment. This study aimed to elucidate the effects of a past cannabis use disorder on current neurocognition in a diverse sample of PLWH. This cross-sectional study included 138 PLWH (age M(SD) = 47.28(8.06); education M(SD) = 12.64(2.73); 73% Male; 71% Latinx) who underwent neuropsychological, DSM-diagnostic, and urine toxicology evaluations. One-way ANCOVAs were conducted to examine effects of a past cannabis use disorder (CUD+) on tests of attention/working memory, processing speed, executive functioning, verbal fluency, learning, memory, and motor ability. Compared to the past CUD- group, the past CUD+ group performed significantly better on tests of processing speed, visual learning and memory, and motor ability (p's < .05). Findings suggest PLWH with past cannabis use have similar or better neurocognition across domains compared to PLWH without past use.

Verbal learning deficits in posttraumatic stress disorder and depression.

Verbal learning and memory deficits are frequently reported in posttraumatic stress disorder (PTSD), but may be a product of its psychiatric comorbidities, especially major depressive disorder (MDD). To evaluate this hypothesis, 25 medication-free patients with PTSD and comorbid MDD were compared to 148 medication-free patients with equally severe MDD alone and to 96 nonpatients on a measure of verbal learning and memory. Additional measures of attention, working memory, and executive function were administered to evaluate their contribution to verbal memory impairment. Patients with comorbid PTSD and MDD demonstrated the greatest deficit in verbal learning compared to both MDD patients and nonpatients (omnibus effect sizes ranged d = 0.41 to 0.50), one that was not accounted for by other cognitive deficits. Findings suggest that a current diagnosis of PTSD makes a contribution to verbal learning deficits beyond the effect of depression alone.

Aging and HIV/AIDS: neurocognitive implications for older HIV-positive Latina/o adults.

In recent years, HIV/AIDS populations have become older and increasingly more ethnically diverse. Concurrently, the prevalence of HIV-related neurocognitive (NC) impairment remains high. This study examined the effects of age and ethnicity on NC function in HIV-positive adults. The sample (N = 126; 84 Latina/o and 42 Non-Hispanic White) completed a comprehensive NC battery. Global NC and domain average demographically-corrected t-scores were generated. There were no significant differences between Younger (<50 years) Latina/os and non-Hispanic Whites on Global NC function or NC domains (all p's >.10), with generally small effect sizes. Older Latina/os (≥50 years) were significantly more impaired than Older Non-Hispanic Whites on processing speed and learning, with trends in Global NC function and memory. Further, effect sizes fell within the medium to large range (Cohen's d's = .49-1.15). This study suggests that older Latina/os are at potentially greater risk for NC impairment, particularly in processing speed and learning, when compared to similarly-aged non-Hispanic whites.

Participant completion of longitudinal assessments in an online cognitive aging registry: The role of medical conditions.

INTRODUCTION: This study aimed to understand whether older adults' longitudinal completion of assessments in an online Alzheimer's disease and related dementias (ADRD)-related registry is influenced by self-reported medical conditions. METHODS: Brain Health Registry (BHR) is an online cognitive aging and ADRD-related research registry that includes longitudinal health and cognitive assessments. Using logistic regressions, we examined associations between longitudinal registry completion outcomes and self-reported (1) number of medical conditions and (2) eight defined medical condition groups (cardiovascular, metabolic, immune system, ADRD, current psychiatric, substance use/abuse, acquired, other specified conditions) in adults aged 55+ (N = 23,888). Longitudinal registry completion outcomes were assessed by the completion of the BHR initial questionnaire (first questionnaire participants see at each visit) at least twice and completion of a cognitive assessment (Cogstate Brief Battery) at least twice. Models included ethnocultural identity, education, age, and subjective memory concern as covariates. RESULTS: We found that the likelihood of longitudinally completing the initial questionnaire was negatively associated with reporting a diagnosis of ADRD and current psychiatric conditions but was positively associated with reporting substance use/abuse and acquired medical conditions. The likelihood of longitudinally completing the cognitive assessment task was negatively associated with number of reported medical conditions, as well as with reporting cardiovascular conditions, ADRD, and current psychiatric conditions. Previously identified associations between ethnocultural identity and longitudinal assessment completion in BHR remained after accounting for the presence of medical conditions. DISCUSSION: This post hoc analysis provides novel, initial evidence that older adults' completion of longitudinal assessments in an online registry is associated with the number and types of participant-reported medical conditions. Our findings can inform future efforts to make online studies with longitudinal health and cognitive assessments more usable for older adults with medical conditions. The results need to be interpreted with caution due to selection biases, and the under-inclusion of minoritized communities.

Isolating cognitive and neurologic HIV effects in substance-dependent, confounded cohorts: a pilot study.

Controversy exists as to whether effects of HIV infection can be detected in the cognitive profiles of substance users, with methodological differences in degree of control for confounding factors a major contributor to empirical discrepancies. To address this shortcoming, we conducted a small but well-controlled study aimed at isolating HIV neurocognitive (NC) effects in a group of chronic substance users. Thirty HIV-negative substance users were individually matched to 30 HIV-positive substance users on relevant medical and demographic factors, including reading level and methadone therapy status. Results revealed that reading level, methadone maintenance therapy, and positive urine toxicology each exerted significant influence on NC function, and that HIV status was a significant predictor of learning and speeded processing after these control factors were considered. The HIV-positive group also displayed significantly more neurologically assessed motor impairment (p < .05), which was specifically related to impaired cognition in this group and independent of degree of immunocompromise. These data demonstrate the need for increased attention to clinical/demographic characteristics of groups under study. They also show that with applied methodological rigor, the deleterious effects of HIV on cognition can be parsed from substance use, even in small samples with chronic and active use histories.

Effects of stereotype threat, perceived discrimination, and examiner race on neuropsychological performance: simple as black and white?

The purpose of the current study was to examine the predictive roles of stereotype threat and perceived discrimination and the mediating role of examiner-examinee racial discordance on neuropsychological performance in a non-clinical sample of African American and Caucasian individuals. Ninety-two African American (n = 45) and Caucasian (n = 47) adults were randomly assigned to either a stereotype threat or non-threat condition. Within each condition, participants were randomly assigned to either a same race or different race examiner. All participants underwent neuropsychological testing and completed a measure of perceived discrimination. African Americans in the stereotype threat condition performed significantly worse on global NP (Mz = -.30, 95% confidence interval [CI] [-0.07, -0.67] than African Americans in the non-threat condition (Mz = 0.09, CI [0.15, 0.33]. African Americans who reported high levels of perceived discrimination performed significantly worse on memory tests when tested by an examiner of a different race, Mz = -1.19, 95% CI [-1.78, -.54], than African Americans who were tested by an examiner of the same race, Mz = 0.24, 95% CI [-0.24, 0.72]. The current study underscores the importance of considering the role of contextual variables in neuropsychological performance, as these variables may obscure the validity of results among certain racial/ethnic groups.

Distal sensory polyneuropathy is associated with neuropsychological test performance among persons with HIV.

While distal sensory polyneuropathy (DSP) is the most common neurological condition associated with HIV, causing nerve damage in upper and lower extremities, its impact on neuropsychological test performance is unclear. In this study, we analyzed baseline data for 278 HIV-infected participants with comprehensive neurological and neurocognitive evaluations to examine the contribution of DSP and anatomic distribution of neuropathic signs (upper extremity or lower extremity) on standardized domain scores. We found that participants with DSP performed significantly worse in multiple domains containing timed psychomotor tests (i.e., motor, information processing speed and executive functioning). With regard to executive functioning, differences were limited to a test with a motor component (Trail Making Test, Part B). The group with clinically detectable neuropathic signs in the upper extremities and the group with signs limited to the lower extremities both performed worse in the motor domain than the group without DSP. Participants with DSP demonstrated a unique pattern of impairment limited to neuropsychological domains with timed psychomotor tests. These results suggest that caution should be used in interpretation of neuropsychological tests in patients with DSP, as some abnormalities may be exacerbated by peripheral nervous system pathology. (JINS, 2012, 19, 1-10).

Emotion processing bias and age of seizure onset among epilepsy patients with depressive symptoms.

The current study examined whether mood-congruent biases in emotion processing extend to epilepsy patients with depressive symptoms and the potentially moderating effects of age of seizure onset on these biases. In addition, we examined associations between depression (Beck Depression Inventory - 2nd Edition; BDI-II) and quality of life (Quality of Life in Epilepsy - 10-item questionnaire; QOLIE-10). Data from 101 epilepsy patients were analyzed, including 61 females and 40 males. Measures included the Comprehensive Affect Testing System - Abbreviated (CATS-A), from which indices of mood-congruent bias were derived. A significant interaction between BDI-II raw scores and age of seizure onset was found for mood-congruent bias scores in the facial affect modality (ß=-0.24, p<.03). Beck Depression Inventory - 2nd Edition raw scores were significantly and positively correlated with quality of life (QOLIE-10; r=.69, p<.01). Results of the current study show that epilepsy patients with an early age of seizure onset may be most at risk for mood-congruent biases when experiencing depressive symptoms and that such symptoms have real-world implications for quality of life for persons living with epilepsy.

Assessing Cognitive Decline in High-Functioning Spanish-Speaking Patients: High Score Base Rates on the Spanish-Language NIH Toolbox Cognition Battery.

OBJECTIVE: Prior research has focused on the normal frequency of obtaining low scores on a neuropsychological test battery, but few studies have examined the normal frequency of obtaining high scores. This study involved the preparation of high score multivariate base rates for the Spanish-language National Institutes of Health (NIH) Toolbox Cognition Battery (NIHTB-CB). METHOD: Participants included 250 healthy Latinx adults (age range: 19-80) from the Spanish-language NIHTB-CB normative sample who completed the full battery (two crystallized and four fluid cognition tests). Multivariate base rates, stratified by education, crystallized ability, and sociocultural characteristics, quantified the frequency at which participants obtained one or more "high" fluid test scores (i.e., ≥50th, ≥63rd, ≥75th, ≥84th, ≥91st, ≥95th, and ≥ 98th percentile). RESULTS: It was common for participants to obtain one or more high scores (i.e., 50.8% obtained one or more scores ≥84th percentile) and uncommon for participants to obtain "no" high scores, especially when using non-conventional thresholds for defining a high score (i.e., 10.8% obtained no scores ≥50th percentile). High scores were more commonly obtained by participants with greater education and higher crystallized ability, who were bilingual, born and educated within the United States, and from higher income households. CONCLUSIONS: This study demonstrated that participants administered multiple neuropsychological tests commonly obtain high scores, and that the frequency of high scores varies by education, crystallized ability, and sociocultural characteristics. The absence of high scores may be indicative of cognitive impairment among examinees who are higher functioning, have greater education, and have specific sociocultural characteristics (e.g., bilingualism, higher socioeconomic status).

A Multivariate Interpretation of the Spanish-Language NIH Toolbox Cognition Battery: The Normal Frequency of Low Scores.

OBJECTIVE: The current study involved the preparation of multivariate base rates for the Spanish-language NIH Toolbox Cognition Battery (NIHTB-CB) based on the U.S. normative sample, quantifying the normal frequency of low scores among healthy adults. METHOD: Participants included 250 healthy Latinx adults (M = 38.8 ± 13.7 years old, range: 19-80; 72.0% women; education: M = 11.5 ± 3.9 years) who completed the full Spanish-language NIHTB-CB, including two tests of crystallized cognition and five tests of fluid cognition. Multivariate base rates quantified the frequency at which participants obtained 1 or more fluid scores ≤25th, ≤16th, ≤9th, ≤5th, and ≤2nd percentile, per age-adjusted or demographically adjusted (age, gender, education) normed scores. RESULTS: A substantial minority of participants had 1 or more low scores (e.g., 40.4% had 1 or more age-adjusted score ≤16th percentile). The frequencies of low scores increased with fewer years of education and lower crystallized cognitive ability. Higher frequencies of low scores were observed among participants who were born and educated abroad, versus within the USA; monolingual Spanish speakers, versus bilingual Spanish/English speakers; and from households below the national median income, versus households above the national median. CONCLUSION: Low scores were common and related to crystallized ability, education, and sociocultural variables. Although using demographically adjusted scores reduced group differences related to sociocultural variables, group differences were not eliminated, indicating that age, gender, and education score adjustments do not fully explain the associations between sociocultural variables and test performances. These stratified base rates may be useful when working with Spanish-speaking patients with diverse sociocultural characteristics.

Underrepresentation of diverse populations and clinical characterization in opioid agonist treatment research: A systematic review of the neurocognitive effects of buprenorphine and methadone treatment.

INTRODUCTION: The relative neurocognitive effects of the two most common opioid agonist treatments (OAT; buprenorphine and methadone) for opioid use disorder (OUD) are poorly understood. The aim of this systematic review is to examine the neurocognitive effects of OAT (buprenorphine and methadone) and the clinical and sociodemographic characteristics of study samples. METHODS: The research team queried PubMed, PsycINFO and Cochrane Reviews for articles (01/1980-01/2020) with terms related to neurocognitive testing in adults (age ≥ 18) prescribed OAT. The team extracted neurocognitive data and grouped them by domain (e.g., executive functioning, learning/memory), and assessed study quality. RESULTS: The search retrieved 2341 abstracts, the team reviewed 278 full articles, and 32 met inclusion criteria. Of these, 31 were observational designs and one was an experimental design. Healthy controls performed better across neurocognitive domains than OAT-treated persons (buprenorphine or methadone). Compared to those with active OUD, OAT-treated persons had better neurocognition in various domains. However, in seven studies comparing buprenorphine- and methadone-treated persons, buprenorphine was associated with better neurocognition than was methadone, with moderate to large effect sizes in executive functioning, attention/working memory, and learning/memory. Additionally, OAT research underreports clinical characteristics and underrepresents Black and Latinx adults, as well as women. CONCLUSIONS: Findings suggest that compared to active opioid use, both buprenorphine and methadone treatment are associated with better neurocognitive functioning, but buprenorphine is associated with better executive functioning, attention/working memory, and learning/memory. These findings should be interpreted with caution given widespread methodological heterogeneity, and limited representation of ethnoracially diverse adults and women. Rigorous longitudinal comparisons with more diverse, better characterized samples will help to inform treatment and policy recommendations for persons with OUD.

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.

Demographically adjusted norms for the Trail Making Test in native Spanish speakers: Results from the neuropsychological norms for the US-Mexico border region in Spanish (NP-NUMBRS) project.

OBJECTIVE: Despite the wide use of the Trail Making Test (TMT), there is a lack of normative data for Spanish speakers living in the USA. Here we describe the development of regional norms for the TMT for native Spanish speakers residing in the Southwest Mexico-Border Region of the USA. METHOD: Participants were 252 healthy native Spanish speakers, 58% women, from ages 19 to 60, and ranging in education from 0 to 20 years, recruited in San Diego, CA and Tucson, AZ. All completed the TMT in Spanish along with a comprehensive neuropsychological test battery as part of their participation in the Neuropsychological Norms for the US-Mexico Border Region in Spanish (NP-NUMBRS) project. Univariable and interactive effects of demographics on test performance were examined. T-scores were calculated using fractional polynomial equations to account for linear and any non-linear effects of age, education, and sex. RESULTS: Older age and lower education were associated with worse scores on both TMT A and B. No sex differences were found. The newly derived T-scores showed no association with demographic variables and displayed the expected 16% rates of impairment using a -1 SD cut point based on a normal distribution. By comparison, published norms for English-speaking non-Hispanic Whites applied to the current data yielded significantly higher impairment for both TMT A and B with more comparable rates using non-Hispanic African Americans norms. CONCLUSIONS: Population-specific, demographically adjusted regional norms improve the utility and diagnostic accuracy of the TMT for use with native Spanish speakers in the US-Mexico Border region.

Cognitive functioning during highly active antiretroviral therapy interruption in human immunodeficiency virus type 1 infection.

Although no longer considered therapeutically beneficial, antiretroviral treatment interruptions (TIs) still occur frequently among patients with human immunodeficiency virus (HIV) infection for a variety of reasons. TIs typically result in viral rebound and worsening immunosuppression, which in turn are risk factors for neurocognitive decline and dementia. We sought to determine the extent of neurocognitive risk with TIs and subsequent reintroduction of highly active antiretroviral therapy (HAART) by using a comprehensive, sensitive neuropsychological assessment and by concurrently determining changes in plasma and cerebrospinal fluid (CSF) viral load and CD4 counts. Prospective, serial, clinical evaluations including neuropsychological (NP) testing and measurement of plasma HIV RNA and CD4 count and mood state were performed on HIV-1-infected individuals (N=11) at three time points: (1) prior to a TI, while on HAART; (2) after TIs averaging 6 months; and (3) after reinitiating HAART therapy. During TI, plasma HIV RNA increased and CD4 counts declined significantly, but NP performance did not change. Following reinitiation of HAART, viral loads fell below pre-TI levels, and CD4 counts rose. Improved viral suppression and immune restoration with reinitiation of HAART resulted in significant improvement in neurocognitive performance. No changes on comprehensive questionnaires of mood state were observed in relation to TI.NP performance and mood state remained stable during TIs despite worsened viral loads and CD4 counts. Because "practice effects" are generally greatest between the first and second NP testing sessions, improvement at the third, post-TI time point was unlikely to be accounted for by practice. TIs of up to 6 months appear to be neurocognitively and psychiatrically safe for most patients.

Characterization and sociocultural predictors of neuropsychological test performance in HIV+ Hispanic individuals.

Hispanic individuals in the U.S. have been disproportionately impacted by HIV/AIDS, yet little is known regarding the neuropsychological sequelae of HIV within the Hispanic population. This study characterized neuropsychological (NP) test performance of HIV+ English-speaking Hispanic participants (n = 51) and investigated the combined roles of sociocultural factors (e.g., ethnicity, socioeconomic status [SES] proxy, and reading level) on NP test performance among our HIV+ Hispanic and non-Hispanic White participants (n = 49). Results revealed that the pattern of NP impairment in HIV+ Hispanic participants is consistent with the frontal-striatal pattern observed in HIV-associated CNS sequelae, and the overall prevalence of global NP impairment was high compared to previous reports with more ethnically homogeneous, non-Hispanic White cohorts. Multivariate prediction models that considered both sociocultural factors and CD4 count revealed that reading level was the only unique predictor of global NP functioning, learning, and attention/working memory. In contrast, ethnicity was the only unique predictor of abstraction/executive functioning. This study provides support for the use of neuropsychological evaluation in detecting HIV-associated NP impairment among HIV+ Hispanic participants and adds to the growing literature regarding the importance of considering sociocultural factors in the interpretation of NP test performance.