Reference Data for Attentional, Executive, Linguistic, and Visual Processing Tests Obtained from Cognitively Healthy Individuals with Normal Alzheimer's Disease Cerebrospinal Fluid Biomarker Levels.

BACKGROUND: Conventional neuropsychological norms likely include cognitively unimpaired (CU) individuals with preclinical Alzheimer's disease (AD) pathology (amyloid-ß, tau, and neurodegeneration) since they are based on cohorts without AD biomarkers data. Due to this limitation, population-based norms would lack sensitivity for detecting subtle cognitive decline due to AD, the transitional stage between healthy cognition and mild cognitive impairment. We have recently published norms for memory tests in individuals with normal cerebrospinal fluid (CSF) AD biomarker levels. OBJECTIVE: The aim of the present study was to provide further AD biomarker-based cognitive references covering attentional, executive function, linguistic, and visual processing tests. METHODS: We analyzed 248 CU individuals aged between 50-70 years old with normal CSF Aß, p-tau, and neurodegeneration (t-tau) biomarker levels. The tests included were the Trail Making Test (TMT), Semantic Fluency Test, Digit and Symbol Span, Coding, Matrix Reasoning, Judgement of Line Orientation and Visual Puzzles. Normative data were developed based on regression models adjusted for age, education, and sex when needed. We present equations to calculate z-scores, the corresponding normative percentile tables, and online calculators. RESULTS: Age, education, and sex were associated with performance in all tests, except education for the TMT-A, and sex for the TMT-B, Coding, and Semantic Fluency. Cut-offs derived from the current biomarker-based reference data were higher and more sensitive than standard norms. CONCLUSION: We developed reference data obtained from individuals with evidence of non-pathologic AD biomarker levels that may improve the objective characterization of subtle cognitive decline in preclinical AD.

Enhancing the Sensitivity of Memory Tests: Reference Data for the Free and Cued Selective Reminding Test and the Logical Memory Task from Cognitively Healthy Subjects with Normal Alzheimer's Disease Cerebrospinal Fluid Biomarker Levels.

BACKGROUND: Cognitive performance of a given individual should be interpreted in the context of reference standards obtained in cognitively healthy populations. Recent evidence has shown that removing asymptomatic individuals with biomarker evidence of Alzheimer's disease pathology from normative samples increases the sensitivity of norms to detect memory impairments. These kind of norms may be useful for defining subtle cognitive decline, the transitional cognitive decline between normal cognition and mild cognitive impairment. OBJECTIVE: The present study aims to provide norms for the Free and Cued Selective Reminding Test (FCSRT) and the Logical Memory subtest of the Wechsler Memory Scale-IV in a sample of individuals aged 50-70 years with normal levels of amyloid-ß and tau cerebrospinal fluid (CSF) biomarkers. METHODS: The sample was composed of 248 individuals from the ALFA+ study with negative amyloid-ß and tau CSF biomarker levels. Regression-based norms were developed, including adjustments for age, education, and sex when applicable. RESULTS: We found that education was associated with the performance in all the variables of both tests while age had a marginal effect only in the delayed free recall of the FCSRT. Sex was also related to the performance in the FCSRT, with women outperforming men. Equations to calculate z-scores and normative percentile tables were created. As compared with previously published norms the reference data presented were more sensitive but less specific, as expected. CONCLUSION: The use of the norms provided in this work, in combination with the already published conventional norms, may contribute to detecting subtle memory impairment.

The role of executive control in bilingual language production: A study with Parkinson's disease individuals.

The basal ganglia are critically involved in language control (LC) processes, allowing a bilingual to utter correctly in one language without interference from the non-requested language. It has been hypothesized that the neural mechanism of LC closely resembles domain-general executive control (EC). The purpose of the present study is to investigate the integrity of bilingual LC and its overlap with domain-general EC in a clinical population such as individuals with Parkinson's disease (PD), notoriously associated with structural damage in the basal ganglia. We approach these issues in two ways. First, we employed a language switching task to investigate the integrity of LC in a group of Catalan-Spanish bilingual individuals with PD, as compared to a group of matched healthy controls. Second, to test the relationship between domain-general EC and LC we compared the performances of individuals with PD and healthy controls also in a non-linguistic switching task. We highlight that, compared to controls, individuals with PD report decreased processing speed, less accuracy and larger switching costs in terms of RT and errors in the language switching task, whereas in the non-linguistic switching task PD patients showed only increased switching cost in terms of errors. However, we report a positive correlation between the magnitudes of linguistic and non-linguistic mixing costs in individuals with PD. Taken together, these results support the notion of a critical role of the basal ganglia and connected structures in LC, and suggest a possible link between LC and domain-general EC.

Losing control of your languages: a case study.

Bilingual speakers are usually quite good at restricting their lexicalization output to the desired language while preventing all sorts of language intrusions from the language not in use. However, brain damage can affect these abilities of language control, leading to striking and flagrant linguistic behaviours, such as pathological language mixing (pLM) and pathological switching (pLS). In this paper we report the performance of a Catalan-Spanish bilingual individual (R.R.T.) who, due to a neuroinflammatory disease and subcortical lesions, shows pLS. We tested R.R.T. in several tasks of language production and control, such as picture naming (objects and actions), word translation, blocked naming, and language switching task. R.R.T. was also tested in executive control (EC) tasks, such as task switching and a flanker task. We found several interesting results. First, cross-language intrusions were present much more frequently when R.R.T. was asked to speak in her first (and dominant) language (Catalan) than when she was asked to do so in the nondominant language (Spanish). Second, the results provide evidence suggesting that damage to certain subcortical structures may lead to problems in controlling the language output during verbalization in bilingual speakers. Third, we observed that R.R.T. seemed to show more difficulties in language control with verbs. Fourth, R.R.T. showed impaired performance compared to controls in both task switching and a flanker task. The results are discussed in relation to other findings of pLM and pLS in published single-case reports and in relation to EC deficits.

On the parallel deterioration of lexico-semantic processes in the bilinguals' two languages: evidence from Alzheimer's disease.

In this article we aimed to assess how Alzheimer's disease (AD), which is neurodegenerative, affects the linguistic performance of early, high-proficient bilinguals in their two languages. To this end, we compared the Picture Naming and Word Translation performances of two groups of AD patients varying in disease progression (Mild and Moderate) with that of bilingual individuals diagnosed with mild cognitive impairment (MCI). The results revealed that the linguistic deterioration caused by AD affected the two languages similarly. We also found that cognate status and word frequency were two major determinants of language performance in all three groups of participants. These results are consistent with the notion of a common neural substrate recruited to represent and process the two languages of high-proficient bilinguals.