Enhancing Cognitive Performance Prediction through White Matter Hyperintensity Connectivity Assessment: A Multicenter Lesion Network Mapping Analysis of 3,485 Memory Clinic Patients.

Introduction: White matter hyperintensities of presumed vascular origin (WMH) are associated with cognitive impairment and are a key imaging marker in evaluating cognitive health. However, WMH volume alone does not fully account for the extent of cognitive deficits and the mechanisms linking WMH to these deficits remain unclear. We propose that lesion network mapping (LNM), enables to infer if brain networks are connected to lesions, and could be a promising technique for enhancing our understanding of the role of WMH in cognitive disorders. Our study employed this approach to test the following hypotheses: (1) LNM-informed markers surpass WMH volumes in predicting cognitive performance, and (2) WMH contributing to cognitive impairment map to specific brain networks. Methods & results: We analyzed cross-sectional data of 3,485 patients from 10 memory clinic cohorts within the Meta VCI Map Consortium, using harmonized test results in 4 cognitive domains and WMH segmentations. WMH segmentations were registered to a standard space and mapped onto existing normative structural and functional brain connectome data. We employed LNM to quantify WMH connectivity across 480 atlas-based gray and white matter regions of interest (ROI), resulting in ROI-level structural and functional LNM scores. The capacity of total and regional WMH volumes and LNM scores in predicting cognitive function was compared using ridge regression models in a nested cross-validation. LNM scores predicted performance in three cognitive domains (attention and executive function, information processing speed, and verbal memory) significantly better than WMH volumes. LNM scores did not improve prediction for language functions. ROI-level analysis revealed that higher LNM scores, representing greater disruptive effects of WMH on regional connectivity, in gray and white matter regions of the dorsal and ventral attention networks were associated with lower cognitive performance. Conclusion: Measures of WMH-related brain network connectivity significantly improve the prediction of current cognitive performance in memory clinic patients compared to WMH volume as a traditional imaging marker of cerebrovascular disease. This highlights the crucial role of network effects, particularly in attentionrelated brain regions, improving our understanding of vascular contributions to cognitive impairment. Moving forward, refining WMH information with connectivity data could contribute to patient-tailored therapeutic interventions and facilitate the identification of subgroups at risk of cognitive disorders.

Neuropsychological assessment in the multicultural memory clinic: Development and feasibility of the TULIPA battery.

Neuropsychological assessment of culturally diverse populations is hindered by barriers in language, culture, education, and a lack of suitable tests. Furthermore, individuals from diverse backgrounds are often unfamiliar with being cognitively tested. The aim of this study was to develop a new neuropsychological test battery and study its feasibility in multicultural memory clinics.Composition of the TULIPA battery (Towards a Universal Language: Intervention and Psychodiagnostic Assessment) entailed a literature review and consultation with experts and individuals from diverse backgrounds. Feasibility was investigated by examining administration and completion rates and the frequency of factors complicating neuropsychological assessment in 345 patients from 37 countries visiting four multicultural memory clinics in the Netherlands.The test battery included existing tests such as the Cross-Cultural Dementia screening (CCD), Rowland Universal Dementia Assessment Scale (RUDAS), tests from the European Cross-Cultural Neuropsychological Test Battery, and newly developed tests. Completion rates for the test battery were generally high (82%-100%), except for CCD Dots subtest B (58%). Although tests of the "core" TULIPA battery were administered often (median: 6 of 7, IQR: 5-7), supplementary tests were administered less frequently (median: 1 of 9; IQR: 0-3). The number of administered tests correlated with disease severity (RUDAS, ρ=.33, adjusted p < .001), but not with other patient characteristics. Complicating factors were observed frequently, e.g. suboptimal effort (29%-50%), fatigue (29%), depression (37%-57%).The TULIPA test battery is a promising new battery to assess culturally diverse populations in a feasible way, provided that complicating factors are taken into account.Supplemental data for this article is available online at https://doi.org/10.1080/13854046.2022.2043447 .

Cross-cultural neuropsychological assessment in Europe: Position statement of the European Consortium on Cross-Cultural Neuropsychology (ECCroN).

Over the past decades European societies have become increasingly diverse. This diversity in culture, education, and language significantly impacts neuropsychological assessment. Although several initiatives are under way to overcome these barriers - e.g. newly developed and validated test batteries - there is a need for more collaboration in the development and implementation of neuropsychological tests, such as in the domains of social cognition and language.To address these gaps in cross-cultural neuropsychological assessment in Europe, the European Consortium on Cross-Cultural Neuropsychology (ECCroN) was established in 2019.ECCroN recommends taking a broad range of variables into account, such as linguistic factors, literacy, education, migration history, acculturation and other cultural factors. We advocate against race-based norms as a solution to the challenging interpretation of group differences on neuropsychological tests, and instead support the development, validation, and standardization of more widely applicable/cross-culturally applicable tests that take into account interindividual variability. Last, ECCroN advocates for an improvement in the clinical training of neuropsychologists in culturally sensitive neuropsychological assessment, and the development and implementation of guidelines for interpreter-mediated neuropsychological assessment in diverse populations in Europe.ECCroN may impact research and clinical practice by contributing to existing theoretical frameworks and by improving the assessment of diverse individuals across Europe through collaborations on test development, collection of normative data, cross-cultural clinical training, and interpreter-mediated assessment.

Caregiver Burden in a Culturally Diverse Memory Clinic Population: The Caregiver Strain Index-Expanded.

INTRODUCTION: Although qualitative studies have highlighted substantial barriers to dementia diagnosis and care in culturally diverse populations in Europe, quantitative studies examining the level of caregiver burden in these populations have been lacking thus far and are urgently needed. METHODS: We compared the caregiver burden levels on the Caregiver Strain Index (CSI)-Expanded of 63 culturally diverse patient-caregiver dyads from a multicultural memory clinic with 30 native Dutch patient-caregiver dyads and examined the association between caregiver burden and determinants of burden. RESULTS: Informal caregivers in the multicultural memory clinic cohort experienced a high level of caregiver burden (mean CSI-score multicultural cohort: 6.1 [SD: 3.3]; mean CSI-score native Dutch cohort: 4.8 [SD: 3.2]). Burden was significantly associated with impairment on proxy-rated and objective measures of cognitive functioning, such as the Informant Questionnaire on Cognitive Decline and the Rowland Universal Dementia Assessment Scale, and with instrumental activities of daily living. Burden was the highest in spousal caregivers. The positive subscale of the CSI-Expanded provided limited additional information. CONCLUSION: Caregivers of culturally diverse patients experience a high level of caregiver burden, in particular at more advanced disease stages. This study highlights the need to screen culturally diverse caregivers in European memory clinics on caregiver burden to identify those in need of caregiver support.

Cross-cultural neuropsychological assessment in the European Union: a Delphi expert study.

OBJECTIVE: The increasing ethnic diversity in the European Union (EU) calls for adaptations to neuropsychological assessment practices. The aims of this study were to examine the current state of cross-cultural neuropsychological assessment in EU-15 countries and to provide recommendations for researchers and policy makers. METHOD: Twelve experts from nine EU-15 countries participated in a Delphi consensus study involving two sequential rounds of web-based questionnaires and an in-person consensus meeting. The experts individually rated Delphi topics on the basis of importance (scale 1-10). The degree of consensus was determined by assessing first and third quartiles (Q1 and Q3) and medians. RESULTS: Consensus outcomes showed the following priorities: (a) the development of tests (median importance rating 10, Q1-Q3: 9-10), (b) the collection of normative data (median importance rating 9, Q1-Q3: 8-10), and (c) more training, awareness, and knowledge regarding cross-cultural assessment among neuropsychologists in the EU (median importance rating 9, Q1-Q3: 8-10). Whereas memory tests were often available, tests measuring social cognition (median 9, Q1-Q3: 8-10) and language (median 9, Q1-Q3: 7-10) are particularly lacking. Recommendations were made regarding essential skills and knowledge necessary for cross-cultural neuropsychological assessment. CONCLUSIONS: This study in a small group of experts suggests that the development and availability of cross-cultural tests and normative data should be prioritized, as well as the development and implementation of training initiatives. Furthermore, EU guidelines could be established for working with interpreters during neuropsychological assessment. Before implementing these recommendations, follow-up studies are recommended that include more minority neuropsychologists and community stakeholders.

A Systematic Review of Neuropsychological Tests for the Assessment of Dementia in Non-Western, Low-Educated or Illiterate Populations.

OBJECTIVE: Neuropsychological tests are important instruments to determine a cognitive profile, giving insight into the etiology of dementia; however, these tests cannot readily be used in culturally diverse, low-educated populations, due to their dependence upon (Western) culture, education, and literacy. In this review we aim to give an overview of studies investigating domain-specific cognitive tests used to assess dementia in non-Western, low-educated populations. The second aim was to examine the quality of these studies and of the adaptations for culturally, linguistically, and educationally diverse populations. METHOD: A systematic review was performed using six databases, without restrictions on the year or language of publication. RESULTS: Forty-four studies were included, stemming mainly from Brazil, Hong Kong, Korea, and considering Hispanics/Latinos residing in the USA. Most studies focused on Alzheimer's disease (n = 17) or unspecified dementia (n = 16). Memory (n = 18) was studied most often, using 14 different tests. The traditional Western tests in the domains of attention (n = 8) and construction (n = 15), were unsuitable for low-educated patients. There was little variety in instruments measuring executive functioning (two tests, n = 13), and language (n = 12, of which 10 were naming tests). Many studies did not report a thorough adaptation procedure (n = 39) or blinding procedures (n = 29). CONCLUSIONS: Various formats of memory tests seem suitable for low-educated, non-Western populations. Promising tasks in other cognitive domains are the Stick Design Test, Five Digit Test, and verbal fluency test. Further research is needed regarding cross-cultural instruments measuring executive functioning and language in low-educated people.

Normative brain volumetry derived from different reference populations: impact on single-subject diagnostic assessment in dementia.

Brain imaging data are increasingly made publicly accessible, and volumetric imaging measures derived from population-based cohorts may serve as normative data for individual patient diagnostic assessment. Yet, these normative cohorts are usually not a perfect reflection of a patient's base population, nor are imaging parameters such as field strength or scanner type similar. In this proof of principle study, we assessed differences between reference curves of subcortical structure volumes of normal controls derived from two population-based studies and a case-control study. We assessed the impact of any differences on individual assessment of brain structure volumes. Percentile curves were fitted on the three healthy cohorts. Next, percentile values for these subcortical structures for individual patients from these three cohorts, 91 mild cognitive impairment and 95 Alzheimer's disease cases and patients from the Alzheimer Center, were calculated, based on the distributions of each of the three cohorts. Overall, we found that the subcortical volume normative data from these cohorts are highly interchangeable, suggesting more flexibility in clinical implementation.

Assessment of Visual Association Memory in Low-Educated, Non-Western Immigrants with the Modified Visual Association Test.

BACKGROUND: Neuropsychological tests are influenced by culture, language, level of education, and literacy, but there are few cognitive tests of which the applicability in ethnic minority populations has been studied. OBJECTIVES: The aim of this study was to assess the reliability and validity of the Visual Association Test (VAT), a test of visual association memory, in a non-Western, low-educated memory clinic population. Additionally, a modified version of the VAT using colored photographs instead of line drawings was studied (mVAT). METHOD: Both the original VAT and the mVAT were administered to non-Western immigrants (n = 73) from 2 multicultural memory clinics in Rotterdam, The Netherlands, and a control sample of non-demented Turkish elderly (n = 14) with low education levels (32 and 29% illiterate, respectively). RESULTS: Both the VAT and the mVAT were able to discriminate persons with and without dementia (area under the curve: VAT, 0.77-0.88; mVAT, 0.85-0.95). The mVAT had more homogeneous item difficulty levels than the VAT. Administration of parallel versions of the VAT and the mVAT within the same person revealed higher scores on the mVAT (Z = -3.35, p = 0.001). CONCLUSIONS: The mVAT is a reliable and valid measure of memory in non-Western immigrants. Clinicians and researchers should be aware that the memory performance of immigrants may be systematically underestimated when using tests with black-and-white line drawings, such as the original VAT.

Early recognition and treatment of neuropsychiatric symptoms to improve quality of life in early Alzheimer's disease: protocol of the BEAT-IT study.

BACKGROUND: Neuropsychiatric symptoms (NPS) are very common in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia and are associated with various disadvantageous clinical outcomes including a negative impact on quality of life, caregiver burden, and accelerated disease progression. Despite growing evidence of the efficacy of (non)pharmacological interventions to reduce these symptoms, NPS remain underrecognized and undertreated in memory clinics. The BEhavioural symptoms in Alzheimer's disease Towards early Identification and Treatment (BEAT-IT) study is developed to (1) investigate the neurobiological etiology of NPS in AD and (2) study the effectiveness of the Describe, Investigate, Create, Evaluate (DICE) approach to structure and standardize the current care of NPS in AD. By means of the DICE method, we aim to improve the quality of life of AD patients with NPS and their caregivers who visit the memory clinic. This paper describes the protocol for the intervention study that incorporates the latter aim. METHODS: We aim to enroll a total of 150 community-dwelling patients with MCI or AD and their caregivers in two waves. First, we will recruit a control group who will receive care as usual. Next, the second wave of participants will undergo the DICE method. This approach consists of the following steps: (1) describe the context in which NPS occur, (2) investigate the possible causes, (3) create and implement a treatment plan, and (4) evaluate whether these interventions are effective. Primary outcomes are the quality of life of patients and their caregivers. Secondary outcomes include NPS change, caregiver burden, caregivers' confidence managing NPS, psychotropic medication use, the experiences of patients and caregivers who underwent the DICE method, and the cost-effectiveness of the intervention. CONCLUSIONS: This paper describes the protocol of an intervention study that is part of the BEAT-IT study and aims to improve current recognition and treatment of NPS in AD by structuring and standardizing the detection and treatment of NPS in AD using the DICE approach. TRIAL REGISTRATION: The trial was registered on the Netherlands Trial Registry ( NTR7459 ); registered 6 September 2018.

Qualitative Assessment of Verbal Fluency Performance in Frontotemporal Dementia.

BACKGROUND/AIMS: Verbal fluency is impaired in patients with frontotemporal dementia (FTD) and primary progressive aphasia (PPA). This study explored qualitative differences in verbal fluency (clustering of words, switching between strategies) between FTD and PPA variants. METHODS: Twenty-nine patients with behavioral variant FTD (bvFTD) and 50 with PPA (13 nonfluent/agrammatic, 14 semantic, and 23 logopenic) performed a semantic and letter fluency task. Clustering (number of multiword strings) and switching (number of transitions between clustered and nonclustered words) were recorded by two independent raters. Between-group differences, associations with memory, language, and executive functioning, and longitudinal change (subsample) in clustering and switching were examined. RESULTS: Interrater reliability was high (median 0.98). PPA patients generated (a) smaller (number of) clusters on semantic and letter fluency than bvFTD patients (p < 0.05). Semantic variant patients used more switches than nonfluent/agrammatic or logopenic variant patients (p < 0.05). Clustering in semantic fluency was significantly associated with memory and language (range standardized regression coefficients 0.24-0.38). Switching in letter fluency was associated with executive functioning (0.32-0.35). CONCLUSION: Clustering and switching in verbal fluency differed between patients with subtypes of FTD and PPA. Qualitative aspects of verbal fluency provide additional information on verbal ability and executive control which can be used for clinically diagnostic purposes.