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.

Does education moderate gender disparities in later-life memory function? A cross-national comparison of harmonized cognitive assessment protocols in the United States and India.

INTRODUCTION: We compared gender disparities in later-life memory, overall and by education, in India and the United States (US). METHODS: Data (N = 7443) were from harmonized cognitive assessment protocols (HCAPs) in the Longitudinal Aging Study of India-Diagnostic Assessment of Dementia (LASI-DAD; N = 4096; 2017-19) and US Health and Retirement Study HCAP (HRS-HCAP; N = 3347; 2016-17). We derived harmonized memory factors from each study using confirmatory factor analysis. We used multivariable-adjusted linear regression to compare gender disparities in memory function between countries, overall and by education. RESULTS: In the United States, older women had better memory than older men (0.28 SD-unit difference; 95% CI: 0.22, 0.35). In India, older women had worse memory than older men (-0.15 SD-unit difference; 95% CI: -0.20, -0.10), which attenuated with increasing education and literacy. CONCLUSION: We observed gender disparities in memory in India that were not present in the United States, and which dissipated with education and literacy.

Longitudinal decline in semantic versus letter fluency, but not their ratio, marks incident Alzheimer's disease in Latinx Spanish-speaking older individuals.

OBJECTIVE: To compare longitudinal verbal fluency performance among Latinx Spanish speakers who develop Alzheimer's disease to those who do not develop dementia in absolute number of words produced on each task and their ratio to combine both scores. METHOD: Participants included 833 Latinx Spanish-speaking older adults from a community-based prospective cohort in Manhattan. We performed growth curve modeling to investigate the trajectories of letter and semantic fluency, and their ratio (i.e., 'semantic index'), between individuals who developed Alzheimer's disease and those who did not (i.e., controls). The semantic index quantifies the proportion of words generated for semantic fluency in relation to the total verbal fluency performance. RESULTS: Letter fluency performance did not decline in controls; we observed a linear decline in those who developed Alzheimer's disease. Semantic fluency declined in both groups and showed an increased rate of change over time in the incident Alzheimer's disease group; in comparison, the control group had a linear and slower decline. There were no group differences in the longitudinal trajectory (intercept and slope) of the semantic index. CONCLUSION: A decline in letter fluency and a more rapid and accelerating decline over time in semantic fluency distinguished people who developed Alzheimer's disease from controls. Using the semantic index was not a superior marker of incident Alzheimer's disease compared to examining the two fluency scores individually. Results suggest the differential decline in verbal fluency tasks, when evaluated appropriately, may be useful for early identification of Alzheimer's disease in Latinx Spanish speakers, a historically understudied population.

Midlife Vascular Factors and Prevalence of Mild Cognitive Impairment in Late-Life in Mexico.

OBJECTIVE: To estimate the prevalence of mild cognitive impairment (MCI) and its subtypes and investigate the impact of midlife cardiovascular risk factors on late-life MCI among the aging Mexican population. METHOD: Analyses included a sample of non-demented adults over the age of 55 living in both urban and rural areas of Mexico (N = 1807). MCI diagnosis was assigned based on a comprehensive cognitive assessment assessing the domains of memory, executive functioning, language, and visuospatial ability. The normative sample was selected by means of the robust norms approach. Cognitive impairment was defined by a 1.5-SD cut-off per cognitive domain using normative corrections for age, years of education, and sex. Risk factors included age, education, sex, rurality, depression, insurance status, workforce status, hypertension, diabetes, stroke, and heart disease. RESULTS: The prevalence of amnestic MCI was 5.9%. Other MCI subtypes ranged from 4.2% to 7.7%. MCI with and without memory impairment was associated with older age (OR = 1.01 [1.01, 1.05]; OR = 1.03 [1.01, 1.04], respectively) and residing in rural areas (OR = 1.49 [1.08, 2.06]; OR = 1.35 [1.03, 1.77], respectively). Depression (OR = 1.07 [1.02, 1.12]), diabetes (OR = 1.37 [1.03, 1.82]), and years of education (OR = 0.94 [0.91, 0.97]) were associated with MCI without memory impairment. Midlife CVD increased the odds of MCI in late-life (OR = 1.76 [1.19, 2.59], which was driven by both midlife hypertension and diabetes (OR = 1.70 [1.18, 2.44]; OR = 1.88 [1.19, 2.97], respectively). CONCLUSIONS: Older age, depression, low education, rurality, and midlife hypertension and diabetes were associated with higher risk of late-life MCI among older adults in Mexico. Our findings suggest that the causes of cognitive impairment are multifactorial and vary by MCI subtype.

Consideration of sex and gender in Alzheimer's disease and related disorders from a global perspective.

Sex or gender differences in the risk of Alzheimer's disease and related dementias (ADRD) differ by world region, suggesting that there are potentially modifiable risk factors for intervention. However, few epidemiological or clinical ADRD studies examine sex differences; even fewer evaluate gender in the context of ADRD risk. The goals of this perspective are to: (1) provide definitions of gender, biologic sex, and sexual orientation. and the limitations of examining these as binary variables; (2) provide an overview of what is known with regard to sex and gender differences in the risk, prevention, and diagnosis of ADRD; and (3) discuss these sex and gender differences from a global, worldwide perspective. Identifying drivers of sex and gender differences in ADRD throughout the world is a first step in developing interventions unique to each geographical and sociocultural area to reduce these inequities and to ultimately reduce global ADRD risk. HIGHLIGHTS: The burden of dementia is unevenly distributed geographically and by sex and gender. Scientific advances in genetics and biomarkers challenge beliefs that sex is binary. Discrimination against women and sex and gender minority (SGM) populations contributes to cognitive decline. Sociocultural factors lead to gender inequities in Alzheimer's disease and related dementias (ADRD) worldwide.

Dementia risk in the general population: large-scale external validation of prediction models in the AGES-Reykjavik study.

We aimed to evaluate the external performance of prediction models for all-cause dementia or AD in the general population, which can aid selection of high-risk individuals for clinical trials and prevention. We identified 17 out of 36 eligible published prognostic models for external validation in the population-based AGES-Reykjavik Study. Predictive performance was assessed with c statistics and calibration plots. All five models with a c statistic > .75 (.76-.81) contained cognitive testing as a predictor, while all models with lower c statistics (.67-.75) did not. Calibration ranged from good to poor across all models, including systematic risk overestimation or overestimation for particularly the highest risk group. Models that overestimate risk may be acceptable for exclusion purposes, but lack the ability to accurately identify individuals at higher dementia risk. Both updating existing models or developing new models aimed at identifying high-risk individuals, as well as more external validation studies of dementia prediction models are warranted.

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.

Letter and Category Fluency Performance Correlates with Distinct Patterns of Cortical Thickness in Older Adults.

Verbal fluency tasks are generally thought to be mediated by frontal brain regions for letter fluency and temporal regions for category fluency. This idea, however, is primarily based on lesion studies and adapted versions of the fluency tasks in functional neuroimaging, without fundamental evidence from structural neuroimaging in healthy individuals. We investigated the cortical structural correlates of letter and category fluency, including overlapping and different regions, in 505 individuals who participated in a community-based study of healthy aging. The correlation between cortical thickness and verbal fluency in whole-brain analyses revealed distinct cortical signatures for letter fluency, primarily in frontal regions, and category fluency, in frontal and temporal-parietal regions. There was a dissociation in the left inferior frontal gyrus between letter and category fluency, with increased thickness in the posterior-dorsal versus anterior-ventral parts, respectively. These results distinguish the detailed anatomical correlates for verbal fluency within the coarse frontal-temporal distinction inferred from lesion studies and among the mixture of regions identified in functional neuroimaging. The evidence for the anatomical substrates of letter and category fluency, each recruiting slightly different language and cognitive processes, can serve both clinical applications as well as a deeper theoretical understanding of the organization of the cerebral cortex.

Semantic and lexical features of words dissimilarly affected by non-fluent, logopenic, and semantic primary progressive aphasia.

OBJECTIVE: To determine the effect of three psycholinguistic variables-lexical frequency, age of acquisition (AoA), and neighborhood density (ND)-on lexical-semantic processing in individuals with non-fluent (nfvPPA), logopenic (lvPPA), and semantic primary progressive aphasia (svPPA). Identifying the scope and independence of these features can provide valuable information about the organization of words in our mind and brain. METHOD: We administered a lexical decision task-with words carefully selected to permit distinguishing lexical frequency, AoA, and orthographic ND effects-to 41 individuals with PPA (13 nfvPPA, 14 lvPPA, 14 svPPA) and 25 controls. RESULTS: Of the psycholinguistic variables studied, lexical frequency had the largest influence on lexical-semantic processing, but AoA and ND also played an independent role. The results reflect a brain-language relationship with different proportional effects of frequency, AoA, and ND in the PPA variants, in a pattern that is consistent with the organization of the mental lexicon. Individuals with nfvPPA and lvPPA experienced an ND effect consistent with the role of inferior frontal and temporoparietal regions in lexical analysis and word form processing. By contrast, individuals with svPPA experienced an AoA effect consistent with the role of the anterior temporal lobe in semantic processing. CONCLUSIONS: The findings are in line with a hierarchical mental lexicon structure with a conceptual (semantic) and a lexeme (word-form) level, such that a selective deficit at one of these levels of the mental lexicon manifests differently in lexical-semantic processing performance, consistent with the affected language-specific brain region in each PPA variant.

Secular trends in cognitive trajectories of diverse older adults.

INTRODUCTION: This study aimed to determine if later birth year influences trajectory of age-related cognitive decline across racial/ethnic groups and to test whether years of school, childhood socioeconomic status, and cardiovascular disease burden explain such secular trends. METHODS: We compared cognitive trajectories of global cognition and subdomains in two successive racially/ethnically and educationally diverse birth cohorts of a prospective cohort study. RESULTS: Later birth year was associated with higher initial cognitive levels for Whites and Blacks, but not Hispanics. Later birth year was also associated with less rapid rate of decline in all three racial/ethnic groups. More years of education, higher childhood socioeconomic status, and, to a smaller extent, greater cardiovascular disease burden accounted for higher intercepts in the later-born cohort, but did not account for attenuated slope of cognitive decline. DISCUSSION: Later birth year is related to a slower rate of age-related decline in some cognitive domains in some racial/ethnic groups. Our analyses suggest that racial/ethnic and social inequalities are part of the mechanisms driving secular trends in cognitive aging and dementia.

Sex/gender differences in cognitive trajectories vary as a function of race/ethnicity.

INTRODUCTION: The present study sought to determine whether cognitive trajectories differ between men and women across and within racial/ethnic groups. METHODS: Participants were 5258 non-Hispanic White (NHW), Black, and Hispanic men and women in the Washington/Hamilton Heights-Inwood Columbia Aging Project who were administered neuropsychological tests of memory, language, and visuospatial abilities at 18- to 24-month intervals for up to 25 years. Multiple-group latent growth curve modeling examined trajectories across sex/gender by race/ethnicity. RESULTS: After adjusting for age and education, the largest baseline differences were between NHW men and Hispanic women on visuospatial and language, and between NHW women and Black men on memory. Memory and visuospatial decline was steeper for Black women compared with Hispanic men and NHW women, respectively. DISCUSSION: This study takes an important first step in understanding interactions between race/ethnicity and sex/gender on cognitive trajectories by demonstrating variability in sex/gender differences across race/ethnicity.

Levels of Abstractness in Semantic Noun and Verb Processing: The Role of Sensory-Perceptual and Sensory-Motor Information.

Effects of concreteness and grammatical class on lexical-semantic processing are well-documented, but the role of sensory-perceptual and sensory-motor features of concepts in underlying mechanisms producing these effects is relatively unknown. We hypothesized that processing dissimilarities in accuracy and response time performance in nouns versus verbs, concrete versus abstract words, and their interaction can be explained by differences in semantic weight-the combined amount of sensory-perceptual and sensory-motor information to conceptual representations-across those grammatical and semantic categories. We assessed performance on concrete and abstract subcategories of nouns and verbs with a semantic similarity judgment task. Results showed that when main effects of concreteness and grammatical class were analyzed in more detail, the grammatical-class effect, in which nouns are processed more accurately and quicker than verbs, was only present for concrete words, not for their abstract counterparts. Moreover, the concreteness effect, measured at different levels of abstract words, was present for both nouns and verbs, but it was less pronounced for verbs. The results do not support the grammatical-class hypothesis, in which nouns and verbs are separately organized, and instead provide evidence in favor of a unitary semantic space, in which lexical-semantic processing is influenced by the beneficial effect of sensory-perceptual and sensory-motor information of concepts.

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.

What Drives Task Performance in Animal Fluency in Individuals Without Dementia? The SMART-MR Study.

PURPOSE: In this study, we aim to understand whether and how performance in animal fluency (i.e., total correct word count) relates to linguistic levels and/or executive functions by looking at sequence information and item-level metrics (i.e., clusters, switches, and word properties). METHOD: Seven hundred thirty-one Dutch-speaking individuals without dementia from the Second Manifestations of ARTerial disease-Magnetic Resonance study responded to an animal fluency task (120 s). We obtained cluster size and number of switches for the task, and eight different word properties for each correct word produced. We detected variables that determine total word count with random forests, and used conditional inference trees to assess points along the scales of such variables, at which total word count changes significantly. RESULTS: Number of switches, average cluster size, lexical decision response times, word frequency, and concreteness determined total correct word count in animal fluency. People who produced more correct words produced more switches and bigger clusters. People who produced fewer words produced fewer switches and more frequent words. CONCLUSIONS: Concurrent with existing literature, individuals without dementia rely on language and executive functioning to produce words in animal fluency. The novelty of our work is that such results were shown based on a data-driven approach using sequence information and item-level metrics. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.23713269.

The cross-sectional association between amyloid burden and white matter hyperintensities in older adults without cognitive impairment: A systematic review and meta-analysis.

Alzheimer's disease (AD) is the most common cause of dementia, characterized by the aggregation of amyloid-beta (Aß) proteins into plaques. Individuals with AD frequently show mixed pathologies, often caused by cerebral small vessel disease (CSVD), resulting in lesions such as white matter hyperintensities (WMH). The current systematic review and meta-analysis investigated the cross-sectional relationship between amyloid burden and WMH in older adults without objective cognitive impairment. A systematic search performed in PubMed, Embase, and PsycINFO yielded 13 eligible studies. Aß was assessed using PET, CSF, or plasma measurements. Two meta-analyses were performed: one on Cohen's d metrics and one on correlation coefficients. The meta-analyses revealed an overall weighted small-to-medium Cohen's d of 0.55 (95% CI: 0.31-0.78) in CSF, an overall correlation of 0.31 (0.09-0.50) in CSF, and a large Cohen's d of 0.96 (95% CI: 0.66-1.27) in PET. Only two studies assessed this relationship in plasma, with an effect size of - 0.20 (95% CI: -0.75 to 0.34). These findings indicate a relationship between both amyloid and vascular pathologies in cognitively normal adults in PET and CSF. Future studies should assess the possible relationship of blood amyloid-beta and WMH for broader identification of at risk individuals showing mixed pathology in preclinical stages.

Bear in mind: the role of personal background in semantic animal fluency - The SMART-MR study.

Objectives: Semantic fluency is a prominent neuropsychological task, typically administered within the category 'animals'. With the increasing development of novel item-level metrics of semantic fluency, a concern around the validity of item-level analyses could be that personal background factors (e.g., hobbies like birdwatching or fishing) may disproportionally influence performance. We analyzed animal fluency performance at the item level and investigated the prevalence of individuals with abundant knowledge in specific classes of animals (e.g., birds, fish, insects) and the relationship of such knowledge with personal background factors and other cognitive tasks (episodic memory and executive functioning). Method: Participants included 736 Dutch middle-aged to older adults from the SMART-MR cohort (mean age 58 ± 9.4 years, 18% women). Individuals were asked to name as many animals as possible for 2 min. Number of people with abundant animal class knowledge was calculated for the ability to recall a series of minimum ≥5 and up to ≥15 animals within a specific class with at most one interruption by an animal from another class. Subsequent analyses to investigate relationships of abundant class knowledge with sociodemographic characteristics (t-tests and chi-square tests) and cognitive performance (linear regressions) were performed for a cut-off of ≥10 animals within a specific class (90th percentile), with a sensitivity analysis for ≥7 animals (67th percentile). Results: A total of 416 (56.2%) participants recalled a series of ≥5 animals from a specific class, 245 (33.3%) participants recalled ≥7, 78 (10.6%) participants recalled ≥10, and 8 (1.1%) participants recalled ≥15. Those who recalled a series of at least 10 animals within a class were older, more often men, and more often retired than those who did not. Moreover, they had a higher total score on animal fluency, letter fluency (i.e., executive functioning), and episodic memory tasks compared to those who did not. Discussion: Our results suggest that the benefit of abundant animal class knowledge gained by personal background does not disproportionally influence animal fluency performance as individuals with such knowledge also performed better on other cognitive tasks unrelated to abundant knowledge of animal classes.

Semantic item-level metrics relate to future memory decline beyond existing cognitive tests in older adults without dementia.

In normal aging, the cognitive domain of semantic memory remains preserved, while the domain of episodic memory declines to some extent. In Alzheimer's disease dementia, both semantic and episodic memory become impaired early in the disease process. Given the need to develop sensitive and accessible cognitive markers for early detection of dementia, we investigated among older adults without dementia whether item-level metrics of semantic fluency related to episodic memory decline above and beyond existing neuropsychological measures and total fluency score. Participants were drawn from the community-based Washington Heights-Inwood Columbia Aging Project cohort (N = 583 English speakers, Mage = 76.3 ± 6.8) followed up to five visits across up to 11 years. We examined the association of semantic fluency metrics with subsequent declines in memory performance using latent growth curve models covaried for age and recruitment wave. Results showed that item-level metrics (e.g., lexical frequency, age of acquisition, and semantic neighborhood density) were associated with a decline in episodic memory-even when covarying for other cognitive tests-while the standard total score was not. Moderation analyses showed that the relationship of semantic fluency metrics with memory decline did not differ across race, sex/gender, or education. In conclusion, item-level data hold a wealth of information with potential to reveal subtle semantic memory impairment, which tracks with episodic memory impairment, among older adults without dementia beyond existing neuropsychological measures. Implementation of psycholinguistic metrics may point to cognitive tools that have better prognostic value or are more sensitive to cognitive change in the context of clinical trials or observational studies. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Longitudinal changes in qualitative aspects of semantic fluency in presymptomatic and prodromal genetic frontotemporal dementia.

BACKGROUND: The semantic fluency test is one of the most widely used neuropsychological tests in dementia diagnosis. Research utilizing the qualitative, psycholinguistic information embedded in its output is currently underexplored in presymptomatic and prodromal genetic FTD. METHODS: Presymptomatic MAPT (n = 20) and GRN (n = 43) mutation carriers, and controls (n = 55) underwent up to 6 years of neuropsychological assessment, including the semantic fluency test. Ten mutation carriers became symptomatic (phenoconverters). Total score and five qualitative fluency measures (lexical frequency, age of acquisition, number of clusters, cluster size, number of switches) were calculated. We used multilevel linear regression modeling to investigate longitudinal decline. We assessed the co-correlation of the qualitative measures at each time point with principal component analysis. We explored associations with cognitive decline and grey matter atrophy using partial correlations, and investigated classification abilities using binary logistic regression. RESULTS: The interrater reliability of the qualitative measures was good (ICC = 0.75-0.90). There was strong co-correlation between lexical frequency and age of acquisition, and between clustering and switching. At least 4 years pre-phenoconversion, GRN phenoconverters had fewer but larger clusters (p < 0.001), and fewer switches (p = 0.004), correlating with lower executive function (r = 0.87-0.98). Fewer switches was predictive of phenoconversion, correctly classifying 90.3%. Starting at least 4 years pre-phenoconversion, MAPT phenoconverters demonstrated an increase in lexical frequency (p = 0.009) and a decline in age of acquisition (p = 0.034), correlating with lower semantic processing (r = 0.90). Smaller cluster size was predictive of phenoconversion, correctly classifying 89.3%. Increase in lexical frequency and decline in age of acquisition were associated with grey matter volume loss of predominantly temporal areas, while decline in the number of clusters, cluster size, and switches correlated with grey matter volume loss of predominantly frontal areas. CONCLUSIONS: Qualitative aspects of semantic fluency could give insight into the underlying mechanisms as to why the "traditional" total score declines in the different FTD mutations. However, the qualitative measures currently demonstrate more fluctuation than the total score, the measure that seems to most reliably deteriorate with time. Replication in a larger sample of FTD phenoconverters is warranted to identify if qualitative measures could be sensitive cognitive biomarkers to identify and track mutation carriers converting to the symptomatic stage of FTD.

Memory and language cognitive data harmonization across the United States and Mexico.

INTRODUCTION: We used cultural neuropsychology-informed procedures to derive and validate harmonized scores representing memory and language across population-based studies in the United States and Mexico. METHODS: Data were from the Health and Retirement Study Harmonized Cognitive Assessment Protocol (HRS-HCAP) and the Mexican Health and Aging Study (MHAS) Ancillary Study on Cognitive Aging (Mex-Cog). We statistically co-calibrated memory and language domains and performed differential item functioning (DIF) analysis using a cultural neuropsychological approach. We examined relationships among harmonized scores, age, and education. RESULTS: We included 3170 participants from the HRS-HCAP (Mage = 76.6 [standard deviation (SD): 7.5], 60% female) and 2042 participants from the Mex-Cog (Mage = 68.1 [SD: 9.0], 59% female). Five of seven memory items and one of twelve language items demonstrated DIF by study. Harmonized memory and language scores showed expected associations with age and education. DISCUSSION: A cultural neuropsychological approach to harmonization facilitates the generation of harmonized measures of memory and language function in cross-national studies. HIGHLIGHTS: We harmonized memory and language scores across studies in the United States and Mexico.A cultural neuropsychological approach to data harmonization was used.Harmonized scores showed minimal measurement differences between cohorts.Future work can use these harmonized scores for cross-national studies of Alzheimer's disease and related dementias.