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.

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 70

These findings suggest that there is benefit for the individuals who chose to engage in feedback sessions. Feedback sessions can be utilized to assist with integral decision-making processes and assisting in treatment planning among other areas. It also allows time for patients and family members to discuss their concerns regarding important test findings and recommendations. Given the current climate of value-based services and clinical outcomes, the findings from this study lend support to the utility of neuropsychological assessments and, in particular, the role of feedback within neuropsychological evaluations.

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.

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.