Brain-phenotype models fail for individuals who defy sample stereotypes.

Individual differences in brain functional organization track a range of traits, symptoms and behaviours1-12. So far, work modelling linear brain-phenotype relationships has assumed that a single such relationship generalizes across all individuals, but models do not work equally well in all participants13,14. A better understanding of in whom models fail and why is crucial to revealing robust, useful and unbiased brain-phenotype relationships. To this end, here we related brain activity to phenotype using predictive models-trained and tested on independent data to ensure generalizability15-and examined model failure. We applied this data-driven approach to a range of neurocognitive measures in a new, clinically and demographically heterogeneous dataset, with the results replicated in two independent, publicly available datasets16,17. Across all three datasets, we find that models reflect not unitary cognitive constructs, but rather neurocognitive scores intertwined with sociodemographic and clinical covariates; that is, models reflect stereotypical profiles, and fail when applied to individuals who defy them. Model failure is reliable, phenotype specific and generalizable across datasets. Together, these results highlight the pitfalls of a one-size-fits-all modelling approach and the effect of biased phenotypic measures18-20 on the interpretation and utility of resulting brain-phenotype models. We present a framework to address these issues so that such models may reveal the neural circuits that underlie specific phenotypes and ultimately identify individualized neural targets for clinical intervention.

Assessment of disparities in timely diagnosis and comprehensive workup of cognitive impairment between English and Spanish speakers.

BACKGROUND: Previous studies have examined disparities in dementia care that affect the U.S. Hispanic/Latino population, including clinician bias, lack of cultural responsiveness, and less access to health care. However, there is limited research that specifically investigates the impact of language barriers to health disparities in dementia diagnosis. METHODS: In this retrospective cross-sectional study, 12,080 English- or Spanish- speaking patients who received an initial diagnosis of mild cognitive impairment (MCI) or dementia between July 2017 and June 2019 were identified in the Yale New Haven Health (YNHH) electronic medical record. To evaluate the timeliness of diagnosis, an initial diagnosis of MCI was classified as "timely", while an initial diagnosis of dementia was considered "delayed." Comprehensiveness of diagnosis was assessed by measuring the presence of laboratory studies, neuroimaging, specialist evaluation, and advanced diagnostics six months before or after diagnosis. Binomial logistic regressions were calculated with and without adjustment for age, legal sex, ethnicity, neighborhood disadvantage, and medical comorbidities. RESULTS: Spanish speakers were less likely to receive a timely diagnosis when compared with English speakers both before (unadjusted OR, 0.65; 95% CI, 0.53-0.80, p <0.0001) and after adjusting for covariates (adjusted OR, 0.55; 95% CI, 0.40-0.75, p = 0.0001). Diagnostic services were provided equally between groups, except for referrals to geriatrics, which were more frequent among Spanish-speaking patients. A subgroup analysis revealed that Spanish-speaking Hispanic/Latino patients were less likely to receive a timely diagnosis compared to English-speaking Hispanic/Latino patients (adjusted OR, 0.53; 95% CI, 0.38-0.73, p = 0.0001). CONCLUSIONS: Non-English language preference is likely to be a contributing factor to timely diagnosis of cognitive impairment. In this study, Spanish language preference rather than Hispanic/Latino ethnicity was a significant predictor of a less timely diagnosis of cognitive impairment. Policy changes are needed to reduce barriers in cognitive disorders care for Spanish-speaking patients.

Education differentially contributes to cognitive reserve across racial/ethnic groups.

INTRODUCTION: We examined whether educational attainment differentially contributes to cognitive reserve (CR) across race/ethnicity. METHODS: A total of 1553 non-Hispanic Whites (Whites), non-Hispanic Blacks (Blacks), and Hispanics in the Washington Heights-Inwood Columbia Aging Project (WHICAP) completed structural magnetic resonance imaging. Mixture growth curve modeling was used to examine whether the effect of brain integrity indicators (hippocampal volume, cortical thickness, and white matter hyperintensity [WMH] volumes) on memory and language trajectories was modified by education across racial/ethnic groups. RESULTS: Higher educational attainment attenuated the negative impact of WMH burden on memory (ß = -0.03; 99% CI: -0.071, -0.002) and language decline (ß = -0.024; 99% CI:- 0.044, -0.004), as well as the impact of cortical thinning on level of language performance for Whites, but not for Blacks or Hispanics. DISCUSSION: Educational attainment does not contribute to CR similarly across racial/ethnic groups.

A preliminary examination of the TOMM2 in a sample of Spanish speakers in the United States.

BACKGROUND: The Test of Memory Malingering (TOMM) is a widely used performance validity measure that is available in both English and Spanish. The Spanish version, however, has historically lacked normative data from samples that are representative of the U.S. Hispanic/Spanish speaking population. OBJECTIVE: The aim of the current study was to collect normative data on the update TOMM 2 for Hispanic individuals residing in the U.S. METHODS: Normative data on the TOMM 2 was collected across 9 sites from different regions of the U.S. The total sample consisted of n = 188 cognitively healthy adults aged 18 and over with no current or prior history of neurological or psychiatric disorder. Descriptive analyses were performed on total raw scores. RESULTS: Participants obtained a mean score of 48.15 (SD = 2.81) on trial 1 of the TOMM 2, 49.86 (SD = 0.487) on trial 2, and 49.84 (SD = 0.509) on the recognition trial. Scores are provided for traditional cutoff scores as well as some popular cutoffs reported in the literature. Item level analyses were conducted as well as evaluation of performance based on a variety of demographics. CONCLUSION: When compared to the English-speaking normative sample used for the original TOMM, this sample demonstrated better performance on the TOMM 2 indicating better cultural appropriateness of the items. This is the first study conducted that provides culturally appropriate descriptive norms for use with Spanish speakers living in the U.S.

Normative data for tests of visuo-spatial, visuo-constructional skills, and visual memory for Spanish-speaking adults in the United States.

BACKGROUND: The Rey-Osterrieth Complex Figure Test (ROCFT) and the Clock Drawing Test (CDT) are commonly used in clinical practice. The ROCFT measures constructional praxis, visual perception, and visuospatial learning and memory, and the CDT assesses for visuospatial, constructional, and executive difficulties. Several neurological disorders are associated with visuospatial and visuo-constructional impairments, yet reliable normative data accounting for sociodemographic and acculturative variables are scarce for Hispanics living in the U.S. OBJECTIVE: To generate normative data for the ROCFT and CDT in a Spanish-speaking adult population living in the U.S. METHODS: The sample consisted of 245 cognitively healthy normal adults recruited from several states in the U.S. Each participant was administered the ROCFT and CDT as part of a larger cognitive battery. The ROCFT and CDT were normed using a Bayesian approach. Age, age2, education, sex, acculturation, and language proficiency were included as predictors in the analyses. RESULTS: ROCFT performance was associated with education and age, particularly as they interacted with Spanish language proficiency and time spent in the U.S. Education was significantly associated with recall abilities and a lower memory recall on the ROCFT. Age was found to vary depending on a person's bilingual abilities. Sex did not emerge as a predictor of performance, and it did not interact significantly with other variables. CONCLUSION: This is the first study to include acculturation and language proficiency variables in the creation of norms for the assessment of visuo-constructional abilities. This study will have a large impact on the practice of neuropsychology in the U.S.

WHO-UCLA auditory verbal learning test: Normative data for Spanish-speaking adults in the United States.

BACKGROUND: Hispanics are a significant demographic in the U.S., with diverse cultures and languages. Assessing cognition in this group is complex as cultural and linguistic factors have been found to affect test performance. OBJECTIVE: To generate normative data on the World Health Organization-University of California Los Angeles Auditory Verbal Learning Test (WHO-UCLA AVLT) in a sample of Spanish-speaking Hispanics residing in the U.S. METHODS: The sample included 245 Spanish-speaking individuals aged 18-80 across the U.S. (California, Connecticut, Florida, Indiana, New Jersey, Oregon, Virginia, and Wisconsin). Participants were administered the WHO-UCLA AVLT as part of a comprehensive neuropsychological battery. A Bayesian regression approach was used to estimate normative data, including covariates found to be important for predicting performances on measures of learning and memory. RESULTS: Bayesian models showed a logarithmic link between education and all WHO-UCLA AVLT trials, except recognition. For delayed recall, increased Spanish proficiency benefited women's performance exclusively. Time in the U.S. was a significant predictor for total recall, indicating worse performance with longer residency. CONCLUSION: Recognizing cultural factors like language proficiency and duration of U.S. residence is essential for accurately evaluating cognitive function among Spanish-speaking Hispanics. This research emphasizes the importance of accounting for cultural nuances in developing norms for neuropsychological assessments, thereby improving their relevance and effectiveness in diverse communities.

Normative data for verbal fluency and naming tests in Spanish-speaking adults in the United States.

BACKGROUND: Linguistic deficits are common across neurological and neurodegenerative disorders. Currently there are limited neuropsychological norms available for Spanish-speaking adults residing in the U.S. OBJECTIVE: To generate norms for two verbal fluency tests and the Boston Naming Test (BNT) in a Spanish-speaking population in the U.S., with adjustments for demographic and cultural variables. METHODS: The sample consisted of 245 adults from the U.S. Participants completed phonological and semantic verbal fluency tests and the BNT. A standardized two-step statistical procedure was used. RESULTS: For the phoneme F, interactions between Spanish proficiency, age, and education arose. Better performance on phonemes A, S, and M was related to education. Spanish proficiency, acculturation, and time in the U.S. were associated with the phonemes S, A, P, M, and R. An age by education interaction was found for phonemes M and R. The FAS and PMR triads were related to age, sex, time in U.S., and Spanish proficiency. For the semantic verbal fluency tests, an interaction between education and Spanish proficiency arose. For the BNT, test scores were related to education, and significant interactions were also found based on education's interaction with Spanish proficiency and acculturation. CONCLUSION: This study highlights the importance of accounting for sociodemographic and acculturative factors when developing normative data for verbal fluency tests and the BNT for dominant Spanish-speaking adults in the U.S. These sociodemographically-adjusted norms will help improve accuracy of diagnosis and interpretation of linguistic test performance in Spanish speakers living in the U.S.

Executive function tests: Normative data for Spanish-speaking adults in the United States.

BACKGROUND: Normative data for Spanish-speaking populations, particularly Hispanics in the U.S., is notably scarce. OBJECTIVE: This study aims to establish normative data for executive function tests (Modified Wisconsin Card Sorting Test and Stroop Color and Word Test) among Spanish-speaking Hispanics in the U.S. METHODS: We assessed 245 individuals aged 18-80 from eight U.S. states (California, Connecticut, Florida, Indiana, New Jersey, Oregon, Virginia, and Wisconsin) and employed Bayesian regression to estimate norms, considering various sociodemographic factors influencing performance. RESULTS: The posterior distribution suggests a high probability that age impacts SCWT performance, with older adults likely to show greater declines, particularly among those with high proficiency in Spanish. The posterior distribution suggests a stronger effect of age on M-WCST performance among individuals with longer U.S. residency. Educational attainment demonstrates a robust positive impact on M-WCST outcomes, with lower levels of education associated with a higher probability of increased errors. An interaction between education and Spanish proficiency was observed, influencing SCWT scores differently across proficiency levels. Sex and acculturation levels interact to affect SCWT performance, with distinct patterns observed between men and women. This suggests that the impact of acculturation on cognitive test performance may vary by gender. CONCLUSION: Establishing culturally sensitive normative data can enhance accurate identification of executive dysfunction and reduce misdiagnosis risks. This study underscores the importance of considering sociocultural factors including acculturation and language proficiency in neuropsychological assessments to better serve diverse populations.

Associations between dementia staging, neuropsychiatric behavioral symptoms, and divorce or separation in late life: A case control study.

Dementia can be difficult for married couples for many reasons, including the introduction of caregiving burden, loss of intimacy, and financial strain. In this study, we investigated the impact of dementia staging and neuropsychiatric behavioral symptoms on the likelihood of divorce or separation for older adult married couples. For this case-control study, we used data from the National Alzheimer's Coordinating Center (NACC) Uniform dataset (UDS) versions 2 and 3. This dataset was from 2007 to 2021 and contains standardized clinical information submitted by NIA/NIH Alzheimer's Disease Research Centers (ADRCs) across the United States (US). This data was from 37 ADRCs. We selected participants who were married or living as married/domestic partners at their initial visit. Cases were defined by a first divorce/separation occurring during the follow-up period, resulting in 291 participants. We selected 5 controls for each married/living as married case and matched on age. Conditional logistic regression estimated the association between overall Neuro Psychiatric Inventory (NPI) score and severity of individual symptoms of the NPI with case/control status, adjusted for education, the CDR® Dementia Staging Instrument score, living situation, symptom informant, sex, and race. Separate analyses were conducted for each symptom. Multiple comparisons were accounted for with the Hochberg method. Later stage of dementia was negatively associated with divorce/separation with an adjusted odds ratio (AOR) = 0.68 (95%CI = 0.50 to 0.93). A higher overall NPI score was positively associated with divorce/separation AOR = 1.08 (95% CI = 1.03 to 1.12,). More severe ratings of agitation/aggression, depression/dysphoria, disinhibition, and elation/euphoria were associated with greater odds of divorce/separation. Among older adults in the US, a later stage of dementia is associated with a lower likelihood of divorce or separation, while having more severe neuropsychiatric behavioral symptoms of agitation/aggression, depression/dysphoria, disinhibition, and elation/euphoria are associated with a higher likelihood of divorce or separation.

Impact and Implications of Neurocognitive Dysfunction in the Management of Ischemic Heart Failure.

Neurocognitive dysfunction is common in heart failure (HF), with 30% to 80% of patients experiencing some degree of deficits in one or more cognitive domains, including memory, attention, learning ability, executive function, and psychomotor speed. Although the mechanism is not fully understood, reduced cardiac output, comorbidities, chronic cerebral hypoperfusion, and cardioembolic brain injury leading to cerebral hypoxia and brain damage seem to trigger the neurocognitive dysfunction in HF. Cognitive impairment is independently associated with worse outcomes including mortality, rehospitalization, and reduced quality of life. Patients with poorer cognitive function are at an increased risk of severe disease as they tend to have greater difficulty complying with treatment requirements. Coronary revascularization in patients with ischemic HF has the potential to improve cardiovascular outcomes but risks worsening neurocognitive dysfunction even further. Revascularization by coronary artery bypass grafting carries inherent risks for delirium, cognitive impairment, neurologic injury, and stroke, which are known to exacerbate the risk of neurocognitive dysfunction. Alternatively, percutaneous coronary intervention, as a less-invasive approach, has the potential to minimize the risk of cognitive impairment but has not yet been evaluated as an alternative to coronary artery bypass grafting in patients with ischemic HF. Therefore, it is paramount to raise awareness of the neurocognitive consequences in ischemic HF and devise strategies for recognition and prevention as an important target of patient management and personalized decision making that contributes to patient outcomes.

Functional reserve: The residual variance in instrumental activities of daily living not explained by brain structure, cognition, and demographics.

OBJECTIVE: Cognitive reserve is a concept that explains individual differences in resilience to brain pathology and susceptibility to poor late-life cognitive outcomes. We evaluate the analogous concept of "Functional Reserve," defined as the difference between observed functional abilities and those predicted by brain structure, cognitive performance, and demographics. This study aims to validate the construct of functional reserve by testing its utility in predicting clinical outcomes and exploring its predictors. METHOD: Longitudinal data collected annually for up to 7 years from 1,084 older adults (ndementia = 163; nMCI = 333; nCN = 523) were analyzed. Functional reserve was operationalized as the residual variance in the Lawton-Brody Instrumental Activities of Daily Living (IADL) Scale after accounting for demographics (sex/gender, race, ethnicity, education), neuropathology (gray matter, hippocampal, and white matter hyperintensity volumes), and cognition (executive function, verbal episodic memory, semantic memory, and spatial function). Structural equation models estimated (a) functional reserve's associations with 7-year changes in clinical diagnosis and disease severity and (b) predictors of functional reserve. RESULTS: Functional reserve was lower in dementia versus cognitively normal individuals. Higher baseline functional reserve was associated with lower concurrent dementia severity and slower clinical progression and attenuated the association of cognition with concurrent dementia severity. Physical function and apathy were the strongest predictors of functional reserve. CONCLUSIONS: Results provide preliminary validation of functional reserve for explaining individual differences in susceptibility to IADL dysfunction independent of neuropathology, cognition, and demographics. Physical functioning and apathy are promising modifiable intervention targets to enhance functional reserve in the context of brain atrophy and cognitive decline. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Teleneuropsychology for Monolingual and Bilingual Spanish-Speaking Adults in the Time of COVID-19: Rationale, Professional Considerations, and Resources.

OBJECTIVE: Neuropsychological assessments with monolingual Spanish and bilingual Spanish/English-speaking adults present unique challenges. Barriers include, but are not limited to, the paucity of test norms, uncertainty about the equivalence of translated neuropsychological tests, and limited proficiency in the provision of culturally competent services. Similar issues generalize to telephone- and video-based administration of neuropsychological tests or teleneuropsychology (TeleNP) with Hispanics/Latinos (as), and few studies have examined its feasibility and validity in this group. The sudden onset of the COVID-19 pandemic prompted neuropsychologists to identify alternative ways to provide equitable care. Clinicians providing TeleNP to this population during (and after) the pandemic must consider safety, professional factors, and systemic barriers to accessing and benefitting from virtual modalities. METHOD: This clinical process manuscript describes how cross-cultural neuropsychologists across five U.S. academic institutions serving Hispanics/Latinos (as) developed TeleNP models of care during the pandemic. RESULTS: Workflows, test batteries, and resources for TeleNP assessment with monolingual and bilingual Spanish-speaking patients are included. Factors guiding model development and informing decisions to incorporate virtual administration of neuropsychological tests into their practice are also discussed. CONCLUSIONS: Provision of TeleNP is a promising modality. Additional research in this area is warranted with focus on cultural and contextual factors that support or limit the use of TeleNP with this community.