Cerebral Small Vessel Disease Burden: An Independent Biomarker for Anomia Treatment Responsiveness in Chronic Stroke Patients With Aphasia.

OBJECTIVE: To determine whether MRI-based cerebral small vessel disease (cSVD) burden predicts treatment-induced aphasia recovery in chronic stroke patients above and beyond initial aphasia severity and stroke-lesion volume. DESIGN: Retrospective. Four cSVD neuroimaging markers were rated using validated visual scales: white matter hyperintensities, enlarged perivascular spaces, lacunes, and global cortical atrophy. We also calculated a cSVD total score. We employed linear regression models to model treatment response as a function of cSVD burden. We also ran correlation analyses to determine the association among cSVD burden and pre-treatment linguistic and non-linguistic cognition. SETTING: Research clinic. PARTICIPANTS: The study includes data from 30 chronic stroke patients with aphasia who received treatment for word finding difficulties and completed additional pre-treatment neuroimaging and behavioral assessments (N=30). INTERVENTIONS: 120-minute sessions of anomia treatment 2 times per week for up to 12 weeks. MAIN OUTCOME MEASURES: Change in accuracy on the treatment probes measured as a percentage (ie, change in accuracy percentage score=post-treatment accuracy percentage minus pre-treatment accuracy percentage). RESULTS: Baseline cSVD burden predicted response to anomia treatment independently from demographic and stroke-related factors. Patients with lower cSVD burden exhibited enhanced rehabilitation response compared with those with higher cSVD burden (ß=-6.816e-02, P=.019). cSVD burden was highly associated with nonverbal executive function at baseline (r=-0.49, P=.005): patients with lower cSVD burden exhibited higher performance on nonverbal executive function tasks compared with participants with higher cSVD burden. No association was observed among cSVD burden and performance on language tasks at the baseline. CONCLUSIONS: cSVD, a marker of brain reserve and a robust risk factor for post-stroke dementia, may be used as a biomarker for distinguishing patients who are more likely to respond to anomia therapy from those who are less likely to do so and for individualizing treatment parameters (eg, targeting both linguistic and nonlinguistic cognition in severe cSVD).

Addressing the disparities in dementia risk, early detection and care in Latino populations: Highlights from the second Latinos & Alzheimer's Symposium.

The Alzheimer's Association hosted the second Latinos & Alzheimer's Symposium in May 2021. Due to the COVID-19 pandemic, the meeting was held online over 2 days, with virtual presentations, discussions, mentoring sessions, and posters. The Latino population in the United States is projected to have the steepest increase in Alzheimer's disease (AD) in the next 40 years, compared to other ethnic groups. Latinos have increased risk for AD and other dementias, limited access to quality care, and are severely underrepresented in AD and dementia research and clinical trials. The symposium highlighted developments in AD research with Latino populations, including advances in AD biomarkers, and novel cognitive assessments for Spanish-speaking populations, as well as the need to effectively recruit and retain Latinos in clinical research, and how best to deliver health-care services and to aid caregivers of Latinos living with AD.

Strength of Temporal White Matter Pathways Predicts Semantic Learning.

Learning the associations between words and meanings is a fundamental human ability. Although the language network is cortically well defined, the role of the white matter pathways supporting novel word-to-meaning mappings remains unclear. Here, by using contextual and cross-situational word learning, we tested whether learning the meaning of a new word is related to the integrity of the language-related white matter pathways in 40 adults (18 women). The arcuate, uncinate, inferior-fronto-occipital and inferior-longitudinal fasciculi were virtually dissected using manual and automatic deterministic fiber tracking. Critically, the automatic method allowed assessing the white matter microstructure along the tract. Results demonstrate that the microstructural properties of the left inferior-longitudinal fasciculus predict contextual learning, whereas the left uncinate was associated with cross-situational learning. In addition, we identified regions of special importance within these pathways: the posterior middle temporal gyrus, thought to serve as a lexical interface and specifically related to contextual learning; the anterior temporal lobe, known to be an amodal hub for semantic processing and related to cross-situational learning; and the white matter near the hippocampus, a structure fundamental for the initial stages of new-word learning and, remarkably, related to both types of word learning. No significant associations were found for the inferior-fronto-occipital fasciculus or the arcuate. While previous results suggest that learning new phonological word forms is mediated by the arcuate fasciculus, these findings show that the temporal pathways are the crucial neural substrate supporting one of the most striking human abilities: our capacity to identify correct associations between words and meanings under referential indeterminacy.SIGNIFICANCE STATEMENT The language-processing network is cortically (i.e., gray matter) well defined. However, the role of the white matter pathways that support novel word learning within this network remains unclear. In this work, we dissected language-related (arcuate, uncinate, inferior-fronto-occipital, and inferior-longitudinal) fasciculi using manual and automatic tracking. We found the left inferior-longitudinal fasciculus to be predictive of word-learning success in two word-to-meaning tasks: contextual and cross-situational learning paradigms. The left uncinate was predictive of cross-situational word learning. No significant correlations were found for the arcuate or the inferior-fronto-occipital fasciculus. While previous results showed that learning new phonological word forms is supported by the arcuate fasciculus, these findings demonstrate that learning new word-to-meaning associations is mainly dependent on temporal white matter pathways.

Reducing bias in survival under nonrandom temporary emigration.

Despite intensive monitoring, temporary emigration from the sampling area can induce bias severe enough for managers to discard survival parameter estimates toward the terminus of the times series (terminal bias). Under random temporary emigration, unbiased parameters can be estimated with CJS models. However, unmodeled Markovian temporary emigration causes bias in parameter estimates, and an unobservable state is required to model this type of emigration. The robust design is most flexible when modeling temporary emigration, and partial solutions to mitigate bias have been identified; nonetheless, there are conditions were terminal bias prevails. Long-lived species with high adult survival and highly variable nonrandom temporary emigration present terminal bias in survival estimates, despite being modeled with the robust design and suggested constraints. Because this bias is due to uncertainty about the fate of individuals that are undetected toward the end of the time series, solutions should involve using additional information on survival status or location of these individuals at that time. Using simulation, we evaluated the performance of models that jointly analyze robust design data and an additional source of ancillary data (predictive covariate on temporary emigration, telemetry, dead recovery, or auxiliary resightings) in reducing terminal bias in survival estimates. The auxiliary resighting and predictive covariate models reduced terminal bias the most. Additional telemetry data were effective at reducing terminal bias only when individuals were tracked for a minimum of two years. High adult survival of long-lived species made the joint model with recovery data ineffective at reducing terminal bias because of small-sample bias. The naive constraint model (last and penultimate temporary emigration parameters made equal), was the least efficient, although still able to reduce terminal bias when compared to an unconstrained model. Joint analysis of several sources of data improved parameter estimates and reduced terminal bias. Efforts to incorporate or acquire such data should be considered by researchers and wildlife managers, especially in the years leading up to status assessments of species of interest. Simulation modeling is a very cost-effective method to explore the potential impacts of using different sources of data to produce high-quality demographic data to inform management.

Multilevel factors predict treatment response following semantic feature-based intervention in bilingual aphasia.

Semantic feature-based treatments (SFTs) are effective rehabilitation strategies for word retrieval deficits in bilinguals with aphasia (BWA). However, few studies have prospectively evaluated the effects of key parameters of these interventions on treatment outcomes. This study examined the influence of intervention-level (i.e., treatment language and treatment sessions), individual-level (baseline naming severity and age), and stimulus-level (i.e., lexical frequency, phonological length, and phonological neighborhood density) factors on naming improvement in a treated and untreated language for 34 Spanish-English BWA who completed 40 hours of SFT. Results revealed significant improvement over time in both languages. In the treated language, individuals who received therapy in their L1 improved more. Additionally, higher pre-treatment naming scores predicted greater response to treatment. Finally, a frequency effect on baseline naming accuracy and phonological effects on accuracy over time were associated with differential treatment gains. These findings indicate that multilevel factors are influential predictors of bilingual treatment outcomes.

The cognate facilitation effect on lexical access in bilingual aphasia: Evidence from the Boston Naming Test.

Most cognate research suggests facilitation effects in picture naming, but how these effects manifest in bilinguals after brain damage remains unclear. Additionally, whether this effect is captured in clinical measures is largely unknown. Using data from the Boston Naming Test, we examined the naming of cognates and noncognates, the extent of cognate facilitation produced, and the individual differences in bilingual language experience associated with naming outcomes in forty Spanish-English bilingual persons with aphasia (BPWA) relative to thirty-one Spanish-English healthy bilinguals (HB). Results suggest that naming performance in L1 and L2 in both groups is modulated by lexical frequency, bilingual language experience, and by language impairment in BPWA. Although the two groups showed similarities, they deviated in benefit drawn from the extent of phoneme/grapheme overlap in cognate items. HB showed an association between cognate facilitation and bilingual language experience, while cognate facilitation in BPWA was only associated with L2 language impairment.

The right uncinate fasciculus supports verbal short-term memory in aphasia.

Verbal short-term memory (STM) deficits are associated with language processing impairments in people with aphasia. Importantly, the integrity of STM can predict word learning ability and anomia therapy gains in aphasia. While the recruitment of perilesional and contralesional homologous brain regions has been proposed as a possible mechanism for aphasia recovery, little is known about the white-matter pathways that support verbal STM in post-stroke aphasia. Here, we investigated the relationships between the language-related white matter tracts and verbal STM ability in aphasia. Nineteen participants with post-stroke chronic aphasia completed a subset of verbal STM subtests of the TALSA battery including nonword repetition (phonological STM), pointing span (lexical-semantic STM without language output) and repetition span tasks (lexical-semantic STM with language output). Using a manual deterministic tractography approach, we investigated the micro- and macrostructural properties of the structural language network. Next, we assessed the relationships between individually extracted tract values and verbal STM scores. We found significant correlations between volume measures of the right Uncinate Fasciculus and all three verbal STM scores, with the association between the right UF volume and nonword repetition being the strongest one. These findings suggest that the integrity of the right UF is associated with phonological and lexical-semantic verbal STM ability in aphasia and highlight the potential compensatory role of right-sided ventral white matter language tracts in supporting verbal STM after aphasia-inducing left hemisphere insult.

Expressive recall and recognition as complementary measures to assess novel word learning ability in aphasia.

Novel word learning ability has been associated with language treatment outcomes in people with aphasia (PWA), and its assessment could inform prognosis and rehabilitation. We used a brief experimental task to examine novel word learning in PWA, determine the value of phonological cueing in assessing learning outcomes, and identify factors that modulate learning ability. Twelve PWA and nineteen healthy controls completed the task, and recall and recognition tests of learning ability. Most PWA showed comparable learning outcomes to those of the healthy controls. Learning assessed via expressive recall was more clearly evidenced with phonological cues. Better single word processing abilities and phonological short-term memory and higher integrity of the left inferior frontal gyrus were related to better learning performance. Brief learning tasks like this one are clinically feasible and hold promise as screening tools of verbal learning in PWA once validated and evaluated for their capacity to predict treatment outcomes.

Clinical perspectives and strategies for confronting disparities in social determinants of health for Hispanic bilinguals with aphasia.

Disparities in social determinants of health (SDOH) such as socioeconomic status and access to quality healthcare present serious barriers to enrollment in clinical rehabilitation programs for individuals who have experienced a stroke, especially for those who identify with a racial-ethnic minority group. Hispanic bilinguals with aphasia (HBWA) are one marginalized group who face even greater enrollment challenges since post-stroke language impairment and limited English proficiency make it difficult to advocate for one's needs and identify appropriate rehabilitation programs. Given the increasing representation of Hispanic individuals in the U.S. (projected to be 30% of the population in 2050), it is imperative that clinicians counter disparities in stroke care by facilitating access to clinical services for HBWA. However, the Hispanic population remains largely understudied in the stroke and aphasia literature, due in part to reduced opportunities to enroll in large-scale clinical research studies. In this paper we highlight how our team at Boston University has designed and implemented a variety of recruitment practices, assessment modifications, and treatment accommodations to circumvent the known barriers to participation in clinical research experienced by HBWA. Furthermore, we discuss the importance of cultural responsiveness and demonstrate how including principles of sensitivity and humility in clinical trial protocols improves participant enrollment and retention. Although clinical adjustments in this study were developed for use with HBWA, the effectiveness of the procedures suggests they may be useful blueprints for expanding access to research opportunities for various marginalized groups.

Language learning in aphasia: A narrative review and critical analysis of the literature with implications for language therapy.

People with aphasia (PWA) present with language deficits including word retrieval difficulties after brain damage. Language learning is an essential life-long human capacity that may support treatment-induced language recovery after brain insult. This prospect has motivated a growing interest in the study of language learning in PWA during the last few decades. Here, we critically review the current literature on language learning ability in aphasia. The existing studies in this area indicate that (i) language learning can remain functional in some PWA, (ii) inter-individual variability in learning performance is large in PWA, (iii) language processing, short-term memory and lesion site are associated with learning ability, (iv) preliminary evidence suggests a relationship between learning ability and treatment outcomes in this population. Based on the reviewed evidence, we propose a potential account for the interplay between language and memory/learning systems to explain spared/impaired language learning and its relationship to language therapy in PWA. Finally, we indicate potential avenues for future research that may promote more cross-talk between cognitive neuroscience and aphasia rehabilitation.

Clustering and Switching in Verbal Fluency Across Varying Degrees of Cognitive Control Demands: Evidence From Healthy Bilinguals and Bilingual Patients With Aphasia.

Different linguistic contexts place varying amounts of cognitive control on lexical retrieval in bilingual speakers, an issue that is complicated in bilingual patients with aphasia (BPWA) due to subsequent language and cognitive deficits. Verbal fluency tasks may offer insight into the interaction between executive and language control in healthy bilinguals and BPWA, by examining conditions with varying cognitive control demands. The present study examined switching and clustering in verbal fluency tasks in BPWA and healthy bilinguals across single- and dual-language conditions. We also examined the influence of language processing and language proficiency on switching and clustering performance across the dual-language conditions. Thirty-five Spanish-English BPWA and twenty-two Spanish-English healthy bilinguals completed a language use questionnaire, tests of language processing, and two verbal fluency tasks. The semantic category generation task included four conditions: two single-language conditions (No-Switch L1 and No-Switch L2) that required word production in each language separately; one dual-language condition that allowed switching between languages as desired (Self-Switch); and one dual-language condition that required switching between languages after each response (Forced-Switch). The letter fluency task required word production in single-language contexts. Overall, healthy bilinguals outperformed BPWA across all measures. Results indicate that switching is more sensitive to increased control demands than clustering, with this effect being more pronounced in BPWA, underscoring the interaction between semantic executive processes and language control in this group. Additionally, for BPWA switching performance relies on a combination of language abilities and language experience metrics.

Predicting language treatment response in bilingual aphasia using neural network-based patient models.

Predicting language therapy outcomes in bilinguals with aphasia (BWA) remains challenging due to the multiple pre- and poststroke factors that determine the deficits and recovery of their two languages. Computational models that simulate language impairment and treatment outcomes in BWA can help predict therapy response and identify the optimal language for treatment. Here we used the BiLex computational model to simulate the behavioral profile of language deficits and treatment response of a retrospective sample of 13 Spanish-English BWA who received therapy in one of their languages. Specifically, we simulated their prestroke naming ability and poststroke naming impairment in each language, and their treatment response in the treated and the untreated language. BiLex predicted treatment effects accurately and robustly in the treated language and captured different degrees of cross-language generalization in the untreated language in BWA. Our cross-validation approach further demonstrated that BiLex generalizes to predict treatment response for patients whose data were not used in model training. These findings support the potential of BiLex to predict therapy outcomes for BWA and suggest that computational modeling may be helpful to guide individually tailored rehabilitation plans for this population.

Telerehabilitation for Word Retrieval Deficits in Bilinguals With Aphasia: Effectiveness and Reliability as Compared to In-person Language Therapy.

Background: Bilinguals with post-stroke aphasia (BWA) require treatment options that are sensitive to their particular bilingual background and deficits across languages. However, they may experience limited access to bilingual clinical resources due to reduced availability of bilingual practitioners, geographical constraints, and other difficulties. Telerehabilitation can improve access to bilingual clinical services for BWA and facilitate the delivery of specific language treatments at distance, but more evidence on its effectiveness and reliability is needed. This study aimed to determine the equivalence of effectiveness and reliability of a semantic treatment for word retrieval deficits in BWA delivered via telerehabilitation relative to in-person therapy. Methods: We examined the retrospective data of 16 BWA who received 20 sessions of therapy based on semantic feature analysis for word retrieval deficits in person (n = 8) or via telerehabilitation (n = 8). The two groups were comparable on age, years of education, time of post-stroke onset, aphasia severity, and naming ability in both languages. Treatment effectiveness (i.e., effect sizes in the treated and the untreated language, and change on secondary outcome measures) and reliability (i.e., clinician adherence to treatment protocol) were computed for each delivery modality and compared across groups. Results: Significant improvements were observed in most patients, with no significant differences in treatment effect sizes or secondary outcomes in the treated and the untreated language between the teletherapy group and the in-person therapy group. Also, the average percentage of correctly delivered treatment steps by clinicians was high for both therapy delivery methods with no significant differences between the telerehabilitation vs. the in-person modality. Discussion: This study provides evidence of the equivalence of treatment gains between teletherapy and in-person therapy in BWA and the high reliability with which treatment for word retrieval deficits can be delivered via telerehabilitation, suggesting that the essential treatment components of the intervention can be conducted in a comparable manner in both delivery modalities. We further discuss the benefits and potential challenges of the implementation of telerehabilitation for BWA. In the future, telerehabilitation may increase access to therapy for BWA with varying linguistic and cultural backgrounds, thus, offering a more inclusive treatment approach to this population.

Presence, involvement and efficacy of a virtual reality intervention on pain.

We explored the impact of an interactive VR environment on pain cognitions (in vivo catastrophizing and pain self-efficacy) and pain-related measures: pain threshold, pain tolerance, Pain Sensitivity Range (PSR), pain intensity and time estimation in a sample of healthy students. Sense of presence is essential to conduct a psychological treatment; if patients are not able to involve themselves in a virtual world they cannot experience relevant emotions, and the desired processes that are necessary for most psychological treatments will not occur. However, some authors argue that presence must be distinguished from the degree of engagement, involvement in the portrayed environment. The results obtained in our study are consistent with this view, since the Involvement scale of the IPQ did not correlate with any of the measures related with the treatment's efficacy.

Verbal fluency as a measure of lexical access and cognitive control in bilingual persons with aphasia.

BACKGROUND: Lexical access in bilinguals can be influenced by the demands that different interactional contexts pose on cognitive control processes (Green & Abutalebi, 2013: Adaptive Control Hypothesis; Green, 1998: Inhibitory Control Model). However, how varying cognitive control demands impact lexical access in bilingual persons with aphasia (BPWA) remains unclear. Verbal fluency tasks may provide valuable insights into the interplay between cognitive control and lexical access in BPWA by addressing word generation abilities in language contexts that exert varying degrees of cognitive control effort. AIMS: The present study aimed to examine the performance of BPWA on a semantic category generation task that required word retrieval in single and dual-language contexts under varying cognitive control demands and a traditional letter fluency task conducted in single-language contexts. We also examined the associations between verbal fluency performance and (i) bilingual language history, and (ii) performance on standardized language assessments in both BPWA and healthy bilinguals. METHODS AND PROCEDURES: Thirteen Spanish-English BPWA and twenty-two Spanish-English healthy bilinguals completed a language use questionnaire, verbal fluency testing and standardized language assessments in each language. The semantic category generation task included four conditions: two conditions examined word retrieval in the first-acquired (L1) and second-acquired language (L2) in single language contexts (No Switch-L1 and No Switch-L2) and two conditions elicited word retrieval in dual-language contexts (Self-Switch and Forced-Switch) with low and high cognitive control demands by allowing or restricting switching across languages. The letter fluency task was administered in single language contexts only (F, A, S for English and P, M, R for Spanish). Verbal fluency performance was compared across conditions and groups using multivariate analyses. Further, correlational analyses were used to examine associations between verbal fluency tasks and bilingual language history, language assessments, and cognitive function. OUTCOMES AND RESULTS: Overall, the healthy bilinguals produced a higher proportion of accurate words in both verbal fluency tasks relative to the BPWA. Results indicate that BPWA were more sensitive to the effects of increased cognitive control on lexical access relative to healthy bilinguals. BPWA and healthy bilinguals' performance on both verbal fluency tasks was associated with metrics of bilingual language history and standardized language assessments. Additionally, for BPWA, L2 letter fluency performance was associated with cognitive function. CONCLUSIONS: Our findings suggest that verbal fluency tasks can help characterize the impact of cognitive control on lexical access in BPWA in single and mixed language contexts with important clinical implications.

The influence of prestroke proficiency on poststroke lexical-semantic performance in bilingual aphasia.

BACKGROUND: Bilingual persons with aphasia (BWA) may present different degrees and patterns of impairment in their two languages. Previous research suggests that prestroke proficiency may be amongst the factors determining poststroke language impairment in BWA, however this relationship is not well understood. AIMS: The purpose of this study was to examine the relationship between prestroke proficiency and poststroke lexical-semantic performance in BWA and to identify common patterns of language impairment in this population. METHODS AND PROCEDURES: Twenty-seven Spanish-English BWA (14 female, age range = 29-88 years) were administered a language use questionnaire (LUQ) to measure several aspects of their bilingual language history that contribute to their prestroke proficiency in both languages. They also underwent standardized language assessments tapping lexical-semantic performance in each language. A principal component analysis was first conducted on the LUQ metrics to determine the factors that contributed to prestroke proficiency in each language. Next, regression analyses allowed assessing the relationships between prestroke proficiency and poststroke lexical-semantic performance in both languages. Differences in proficiency and language performance across languages were contrasted prior and after stroke to identify profiles of impairment. OUTCOMES AND RESULTS: Prestroke proficiency in the native language was determined by daily use, educational history, lifetime exposure, and language ability rating. Prestroke proficiency in the second language was determined by age of acquisition, daily use, educational history, lifetime exposure, lifetime confidence, family proficiency, and language ability rating. Prestroke proficiency significantly predicted poststroke lexical-semantic performance in BWA in both languages. Twenty-two participants presented parallel impairment while only three presented differential impairment. CONCLUSIONS: Our results confirm that prestroke language proficiency is a key predictor of poststroke language impairment in BWA. These findings have important implications for the assessment and diagnosis of aphasia in bilingual individuals.

White Matter Hyperintensities Predict Response to Language Treatment in Poststroke Aphasia.

BACKGROUND: White matter hyperintensities (WMH) are a radiological marker of brain health that has been associated with language status in poststroke aphasia; however, its association with language treatment outcomes remains unknown. OBJECTIVE: To determine whether WMH in the right hemisphere (RH) predict response to language therapy independently from demographics and stroke lesion-related factors in poststroke aphasia. METHODS: We used the Fazekas scale to rate WMH in the RH in 30 patients with poststroke aphasia who received language treatment. We developed ordinal regression models to examine language treatment effects as a function of WMH severity after controlling for aphasia severity, stroke lesion volume, time post onset, age, and education level. We also evaluated associations between WMH severity and both pre-treatment naming ability and executive function. RESULTS: The severity of WMH in the RH predicted treatment response independently from demographic and stroke-related factors such that patients with less severe WMH exhibited better treatment outcome. WMH scores were not significantly correlated with pretreatment language scores, but they were significantly correlated with pretreatment scores of executive function. CONCLUSION: We suggest that the severity of WMH in the RH is a clinically relevant predictor of treatment response in this population.

Predicting treatment outcomes for bilinguals with aphasia using computational modeling: Study protocol for the PROCoM randomised controlled trial.

INTRODUCTION: Bilinguals with aphasia (BWA) present varying degrees of lexical access impairment and recovery across their two languages. Because both languages may benefit from therapy, identifying the optimal target language for treatment is a current challenge for research and clinical practice. Prior research has demonstrated that the BiLex computational model can accurately simulate lexical access in healthy bilinguals, and language impairment and treatment response in bilingual aphasia. Here, we aim to determine whether BiLex can predict treatment outcomes in BWA in the treated and the untreated language and compare these outcome predictions to determine the optimal language for rehabilitation. METHODS AND ANALYSIS: The study involves a prospective parallel-group, double-blind, randomised controlled trial. Forty-eight Spanish-English BWA will receive 20 sessions of semantic treatment for lexical retrieval deficits in one of their languages and will complete assessments in both languages prior and after treatment. Participants will be randomly assigned to an experimental group receiving treatment in the optimal language determined by the model or a control group receiving treatment in the language opposite to the model's recommendation. Primary treatment outcomes include naming probes while secondary treatment outcomes include tests tapping additional language domains. Treatment outcomes will be compared across the two groups using 2×2 mixed effect models for repeated measures Analysis of variance (ANOVA) on metrics of treatment effects commonly employed in rehabilitation studies (ie, effect size and percentage change). ETHICS AND DISSEMINATION: All procedures included in this protocol (protocol number 29, issue date: 19 March 2019) were approved by the Boston University Charles River Campus Institutional Review Board at Boston, Massachusetts (reference number: 4492E). The results of this study will be published in peer-reviewed scientific journals and will be presented at national and international conferences. TRIAL REGISTRATION NUMBER: NCT02916524.

BiLex: A computational approach to the effects of age of acquisition and language exposure on bilingual lexical access.

Lexical access in bilinguals can be modulated by multiple factors in their individual language learning history. We developed the BiLex computational model to examine the effects of L2 age of acquisition, language use and exposure on lexical retrieval in bilingual speakers. Twenty-eight Spanish-English bilinguals and five monolinguals recruited to test and validate the model were evaluated in their picture naming skills in each language and filled out a language use questionnaire. We examined whether BiLex can (i) simulate their naming performance in each language while taking into account their L2 age of acquisition, use and exposure to each language, and (ii) predict naming performance in other participants not used in model training. Our findings showed that BiLex could accurately simulate naming performance in bilinguals, suggesting that differences in L2 age of acquisition, language use and exposure can account for individual differences in bilingual lexical access.

Tau Protein is Associated with Longitudinal Memory Decline in Cognitively Healthy Subjects with Normal Alzheimer's Disease Cerebrospinal Fluid Biomarker Levels.

BACKGROUND: We investigated a sample of cognitively healthy subjects with normal Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarker levels to identify the earliest variables related to longitudinal memory changes. OBJECTIVE: Employing a new highly demanding learning and memory test (the Ancient Farming Equipment Test; AFE-T), we aimed to investigate whether a biomarker related to neurodegeneration (i.e., CSF tau) was associated with longitudinal memory decline. METHODS: Thirty-two cognitively and biologically normal (CBN) subjects underwent MRI, neuropsychological assessment, and the AFE-T at baseline and 18 months later. To explore the relationship between cognitive performance and relevant factors, a linear model was set up. For a secondary analysis that further explore the effect of tau, the subjects were divided into CBN-Tau↓ (tau < 228.64 pg/ml; n = 16) and CBN-Tau↑ (tau > 228.64 pg/ml; n = 16). We also performed voxel-based morphometry (VBM) to identify regions of grey matter volume that would predict both baseline and longitudinal cognitive performance. RESULTS: Our main finding was an association between CSF tau and longitudinal memory decline measured with AFE-T (B = -0.17, p < 0.05; r = -0.414; p < 0.01), and further analyses showed different evolvement between subgroups, with an accelerated decline in individuals with higher tau (F(1,31) = 8.37; p < 0.01). VBM results suggested that AFE-T performance is related to grey matter volume in a medial temporal, middle frontal, and posterior cerebellar network at baseline, and that there are strategic brain areas driving the longitudinal cognitive changes. CONCLUSIONS: The present findings provide evidence for structural and biological markers linked to cognitive aging by highlighting the role of tau, a marker of neurodegeneration, which can be related with the earliest memory changes in healthy subjects.