Development and validation of a nonverbal consensus-based semantic memory paradigm in patients with epilepsy.

OBJECTIVE: Brain areas implicated in semantic memory can be damaged in patients with epilepsy (PWE). However, it is challenging to delineate semantic processing deficits from acoustic, linguistic, and other verbal aspects in current neuropsychological assessments. We developed a new Visual-based Semantic Association Task (ViSAT) to evaluate nonverbal semantic processing in PWE. METHOD: The ViSAT was adapted from similar predecessors (Pyramids & Palm Trees test, PPT; Camels & Cactus Test, CCT) comprised of 100 unique trials using real-life color pictures that avoid demographic, cultural, and other potential confounds. We obtained performance data from 23 PWE participants and 24 control participants (Control), along with crowdsourced normative data from 54 Amazon Mechanical Turk (Mturk) workers. RESULTS: ViSAT reached a consensus >90% in 91.3% of trials compared to 83.6% in PPT and 82.9% in CCT. A deep learning model demonstrated that visual features of the stimulus images (color, shape; i.e., non-semantic) did not influence top answer choices (p = 0.577). The PWE group had lower accuracy than the Control group (p = 0.019). PWE had longer response times than the Control group in general and this was augmented for the semantic processing (trial answer) stage (both p < 0.001). CONCLUSIONS: This study demonstrated performance impairments in PWE that may reflect dysfunction of nonverbal semantic memory circuits, such as seizure onset zones overlapping with key semantic regions (e.g., anterior temporal lobe). The ViSAT paradigm avoids confounds, is repeatable/longitudinal, captures behavioral data, and is open-source, thus we propose it as a strong alternative for clinical and research assessment of nonverbal semantic memory.

Depression, loneliness, and lower social activity as partial mediators of the association between visual impairment and cognitive decline.

OBJECTIVES: Sensory impairment is a hypothesized risk factor for cognitive decline; however, the psychosocial pathways are not well understood. We evaluated whether the association between visual impairment (VI) and cognitive decline was partially mediated via depressive symptoms, loneliness, or social activity. METHODS: We used data from 2601 older adults enrolled in the Memory and Aging Project in 1997 and the Minority Aging Research Study in 2004 with neuropsychological tests across five domains measured annually for up to 16 years. VI was assessed with the Rosenbaum Pocket Vision Screener. Depressive symptoms, loneliness, and social activity were self-reported using validated scales. We used structural equation models to estimate the associations of VI with baseline and change in cognitive function, directly and indirectly through each mediator (depressive symptoms, loneliness, and social activity). We evaluated mediation via "psychological distress" using a latent variable combining depressive symptoms and loneliness. RESULTS: The association between VI and global cognitive decline was mediated via lower social activity (indirect effect) [95% confidence interval (CI)] of linear slope: -0.025 (-0.048, -0.011), via loneliness (-0.011 [95% CI: -0.028, -0.002]), and via psychological distress (-0.017 [95% CI: -0.042, -0.003]). We did not find sufficient evidence for mediation via depressive symptoms alone. CONCLUSIONS: The harmful effect of VI on cognitive decline may be partially mediated through loneliness and lower social activity.

Sex and gender differences in cognitive resilience to aging and Alzheimer's disease.

Sex and gender-biological and social constructs-significantly impact the prevalence of protective and risk factors, influencing the burden of Alzheimer's disease (AD; amyloid beta and tau) and other pathologies (e.g., cerebrovascular disease) which ultimately shape cognitive trajectories. Understanding the interplay of these factors is central to understanding resilience and resistance mechanisms explaining maintained cognitive function and reduced pathology accumulation in aging and AD. In this narrative review, the ADDRESS! Special Interest Group (Alzheimer's Association) adopted a multidisciplinary approach to provide the foundations and recommendations for future research into sex- and gender-specific drivers of resilience, including a sex/gender-oriented review of risk factors, genetics, AD and non-AD pathologies, brain structure and function, and animal research. We urge the field to adopt a sex/gender-aware approach to resilience to advance our understanding of the intricate interplay of biological and social determinants and consider sex/gender-specific resilience throughout disease stages. HIGHLIGHTS: Sex differences in resilience to cognitive decline vary by age and cognitive status. Initial evidence supports sex-specific distinctions in brain pathology. Findings suggest sex differences in the impact of pathology on cognition. There is a sex-specific change in resilience in the transition to clinical stages. Gender and sex factors warrant study: modifiable, immune, inflammatory, and vascular.

A scoping review of neuropsychological assessment for Asian Indians in the United States - research and clinical recommendations.

Objective: There is an increasing focus on understanding health disparities among various cultural groups in the United States. The need for heterogeneity in norms and test stimuli across ethnically diverse individuals are being increasingly recognized. However, to date it remains unknown whether and to what extent differences in cognitive norms and tests exist in Asian Indians, a fast-growing population in the U.S. It is essential to understand these differences to improve diagnostic accuracy and provide timely and appropriate clinical care. Method: In this study, we conducted a scoping review of available cognitive tests that were normed, developed, or adapted for Asian Indians living in the U.S. Results: The results suggested a paucity of norms and tests specifically examining cognition in this community. Conclusions: Based on the findings, we provide suggestions for research directions focusing on the development of culturally sensitive neuropsychological tools, normative data representative of this demographic, and interventions addressing healthcare access barriers. Overall, this review provides readers with relevant clinical information to immediately enhance patient care as well as provide actionable items in research to improve the future utility of neuropsychology for Asian Indians in the United States.

Microvascular Dysfunction and Whole-Brain White Matter Connectivity: The Maastricht Study.

BACKGROUND: Microvascular dysfunction is involved in the development of various cerebral disorders. It may contribute to these disorders by disrupting white matter tracts and altering brain connectivity, but evidence is scarce. We investigated the association between multiple biomarkers of microvascular function and whole-brain white matter connectivity. METHODS AND RESULTS: Cross-sectional data from The Maastricht Study, a Dutch population-based cohort (n=4326; age, 59.4±8.6 years; 49.7% women). Measures of microvascular function included urinary albumin excretion, central retinal arteriolar and venular calibers, composite scores of flicker light-induced retinal arteriolar and venular dilation, and plasma biomarkers of endothelial dysfunction (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, and von Willebrand factor). White matter connectivity was calculated from 3T diffusion magnetic resonance imaging to quantify the number (average node degree) and organization (characteristic path length, global efficiency, clustering coefficient, and local efficiency) of white matter connections. A higher plasma biomarkers of endothelial dysfunction composite score was associated with a longer characteristic path length (ß per SD, 0.066 [95% CI, 0.017-0.114]) after adjustment for sociodemographic, lifestyle, and cardiovascular factors but not with any of the other white matter connectivity measures. After multiple comparison correction, this association was nonsignificant. None of the other microvascular function measures were associated with any of the connectivity measures. CONCLUSIONS: These findings suggest that microvascular dysfunction as measured by indirect markers is not associated with whole-brain white matter connectivity.