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Objectives: This study aimed to evaluate the potential clinical value of a new brain age prediction model as a single interpretable variable representing the condition of our brain. Among many clinical use cases, brain age could be a novel outcome measure to assess the preventive effect of life-style interventions. Methods: The REMEMBER study population (N = 742) consisted of cognitively healthy (HC,N = 91), subjective cognitive decline (SCD,N = 65), mild cognitive impairment (MCI,N = 319) and AD dementia (ADD,N = 267) subjects. Automated brain volumetry of global, cortical, and subcortical brain structures computed by the CE-labeled and FDA-cleared software icobrain dm (dementia) was retrospectively extracted from T1-weighted MRI sequences that were acquired during clinical routine at participating memory clinics from the Belgian Dementia Council. The volumetric features, along with sex, were combined into a weighted sum using a linear model, and were used to predict ‘brain age’ and ‘brain predicted age difference’ (BPAD = brain age–chronological age) for every subject. Results: MCI and ADD patients showed an increased brain age compared to their chronological age. Overall, brain age outperformed BPAD and chronological age in terms of classification accuracy across the AD spectrum. There was a weak-to-moderate correlation between total MMSE score and both brain age (r = -0.38,p <.001) and BPAD (r = -0.26,p <.001). Noticeable trends, but no significant correlations, were found between BPAD and incidence of conversion from MCI to ADD, nor between BPAD and conversion time from MCI to ADD. BPAD was increased in heavy alcohol drinkers compared to non-/sporadic (p =.014) and moderate (p =.040) drinkers. Conclusions: Brain age and associated BPAD have the potential to serve as indicators for, and to evaluate the impact of lifestyle modifications or interventions on, brain health., SCOPUS: ar.j, info:eu-repo/semantics/published

Magnetic resonance imaging (MRI) has become important in the diagnostic work-up of neurodegenerative diseases. icobrain dm, a CE-labeled and FDA-cleared automated brain volumetry software, has shown potential in differentiating cognitively healthy controls (HC) from Alzheimer's disease (AD) dementia (ADD) patients in selected research cohorts. This study examines the diagnostic value of icobrain dm for AD in routine clinical practice, including a comparison to the widely used FreeSurfer software, and investigates if combined brain volumes contribute to establish an AD diagnosis. The study population included HC (n = 90), subjective cognitive decline (SCD, n = 93), mild cognitive impairment (MCI, n = 357), and ADD (n = 280) patients. Through automated volumetric analyses of global, cortical, and subcortical brain structures on clinical brain MRI T1w (n = 820) images from a retrospective, multi-center study (REMEMBER), icobrain dm's (v.4.4.0) ability to differentiate disease stages via ROC analysis was compared to FreeSurfer (v.6.0). Stepwise backward regression models were constructed to investigate if combined brain volumes can differentiate between AD stages. icobrain dm outperformed FreeSurfer in processing time (15-30 min versus 9-32 h), robustness (0 versus 67 failures), and diagnostic performance for whole brain, hippocampal volumes, and lateral ventricles between HC and ADD patients. Stepwise backward regression showed improved diagnostic accuracy for pairwise group differentiations, with highest performance obtained for distinguishing HC from ADD (AUC = 0.914; Specificity 83.0%; Sensitivity 86.3%). Automated volumetry has a diagnostic value for ADD diagnosis in routine clinical practice. Our findings indicate that combined brain volumes improve diagnostic accuracy, using real-world imaging data from a clinical setting.

BACKGROUND: Palliative care and Advance Care Planning (ACP) are increasingly recommended for an optimal management of late-stage dementia. In Belgium, euthanasia has been decriminalized in 2002 for patients who are "mentally competent" (interpreted as non-demented). It has been suggested that advance directives for euthanasia (ADE) should be made possible for dementia patients. OBJECTIVE: This study presents the results of an internet survey among Belgian dementia specialists. METHODS: In 2013, the Belgian Dementia Council (BeDeCo) organized a debate on end of life decisions in dementia. Participants were medical doctors who are specialists in the dementia field. After the debate, an anonymous internet survey was organized. The participation rate was 55%. The sample was representative of the BeDeCo members. RESULTS: The results showed consensus in favor of palliative care and ACP, although ACP is not systematically addressed in practice. Few patients with dementia have requested euthanasia, but for those who did the participants had agreed to implement it for some patients. A majority of participants (94%) believe that most patients and their families are poorly informed about euthanasia. Although most participants (77%) said they approved the Law on euthanasia, 65% said they were against an extension of the Law to allow ADE for dementia. CONCLUSION: Palliative care and ACP are clearly accepted by professionals, although a gap between recommendation and practice remain. Euthanasia is a much more debated issue, even if a majority of professionals are, in principle, in favor of the current Law and seem to disapprove with a Law change allowing ADE for dementia. A better education for both health professionals and the lay public will be a key element in the future.

BACKGROUND: The aims of this study were to present the psychometric properties of a newly designed cognitive screening instrument, the Multicultural Cognitive Examination (MCE), and to compare it with the Rowland Universal Dementia Assessment Scale (RUDAS) in a multicultural population.METHODS: The study was a Western European cross-sectional multicenter study. The MCE consists of four components evaluating separate cognitive functions and was constructed by adding measures of memory, verbal fluency, and visuospatial function to the RUDAS to create a scale with 0 to 100 points.RESULTS: A total of 66 patients with dementia and 123 cognitively intact participants were included across six memory clinics; 96 had minority ethnic background, and 93 had majority ethnic background. Moderate to large differences were present between patients with dementia and control participants on all MCE components. The MCE significantly improved diagnostic accuracy compared with using the RUDAS alone, with area under the curves of .918, .984, and .991 for the RUDAS, MCE composite, and demographically corrected composite scores, respectively. Diagnostic accuracy of the MCE did not significantly differ between minority and majority ethnic groups. Across MCE subcomponents, patients with Alzheimer's disease (AD) dementia performed significantly poorer on the memory component compared with those with non-AD dementia.CONCLUSIONS: The MCE is a brief cross-cultural cognitive screening instrument that expands evaluation of the cognitive functions covered by the RUDAS, does not require any specialized training, and may be useful for classification of mild dementia or dementia subtypes.

BACKGROUND: The aims of this study were to establish the diagnostic accuracy of the European Cross-Cultural Neuropsychological Test Battery (CNTB) for dementia in different ethnic populations in Western Europe, to examine its ability to differentiate cognitive impairment profiles for dementia subtypes, and to assess the impact of demographic variables on diagnostic properties.METHODS: The study was a Western European cross-sectional multi-center study. A total of 66 patients with dementia and 118 cognitively intact participants were included across six memory clinics; 93 had ethnic minority background and 91 had ethnic majority background. Tests in the CNTB cover global cognitive function, memory, language, executive functions, and visuospatial functions.RESULTS: Significant differences with moderate to large effect sizes were present between patients with dementia and control participants on all CNTB measures. Area under the curves (AUC) ranged from .62 to .99 with a mean AUC across all measures of .83. Comparison of ethnic minority and majority groups generally revealed higher sensitivity in the minority group but no significant difference in the mean AUC's across all measures (.84 vs78, P = .42). Comparison of impairment profiles for patients with Alzheimer's disease (AD) and non-AD dementia revealed that AD patients were significantly more impaired on the memory domain, whereas patients with non-AD dementia were more impaired on the executive functions domain.CONCLUSIONS: The CNTB was found to have promising cross-cultural diagnostic properties for evaluation of dementia in the targeted minority and majority populations and could represent a valid cross-cultural alternative to other well-established neuropsychological test batteries when assessing patients from these populations.

ABSTRACTBackground:With increasing cultural diversity and growing elderly immigrant populations in Western European countries, the availability of brief cognitive screening instruments adequate for assessment of dementia in people from diverse backgrounds becomes increasingly important. The aim of the present study was to investigate diagnostic accuracy of the Rowland Universal Dementia Assessment Scale (RUDAS) in a multicultural sample and to calculate normative data as a basis for demographic adjustment of RUDAS scores.METHODS: The study was a prospective international cross-sectional multi-center study. Receiver operating characteristic curve analysis was used to examine diagnostic accuracy. Regression analysis was used to assess the impact of demographic variables.RESULTS: Data was collected from 341 cognitively intact participants and 80 people with dementia with a wide age- and educational range. Of the 421 included participants, 239 (57%) had immigrant background. The RUDAS had high diagnostic accuracy with an area under the curve (AUC) of 0.93. The optimal cut-off score was <25 (sensitivity 0.80, specificity 0.90). Regression analysis revealed that RUDAS scores were mainly affected by education and were unrelated to data collection site and immigrant status. Education-adjusted normative data was calculated as a basis for education adjustment of RUDAS scores. Applying education-adjusted RUDAS scores slightly but significantly improved diagnostic accuracy with an AUC of 0.95.CONCLUSION: We found the RUDAS to have excellent diagnostic properties in our multicultural sample. However, we suggest that RUDAS scores should be adjusted for education to increase diagnostic accuracy and that the choice of cut-off score should be considered based on the clinical context and expected base rate of dementia.

BACKGROUND: Magnetic resonance imaging (MRI) acquisition/processing techniques assess brain volumes to explore neurodegeneration in Alzheimer's disease (AD). OBJECTIVE: We examined the clinical utility of MSmetrix and investigated if automated MRI volumes could discriminate between groups covering the AD continuum and could be used as a predictor for clinical progression. METHODS: The Belgian Dementia Council initiated a retrospective, multi-center study and analyzed whole brain (WB), grey matter (GM), white matter (WM), cerebrospinal fluid (CSF), cortical GM (CGM) volumes, and WM hyperintensities (WMH) using MSmetrix in the AD continuum. Baseline (n = 887) and follow-up (FU, n = 95) T1-weighted brain MRIs and time-linked neuropsychological data were available. RESULTS: The cohort consisted of cognitively healthy controls (HC, n = 93), subjective cognitive decline (n = 102), mild cognitive impairment (MCI, n = 379), and AD dementia (n = 313). Baseline WB and GM volumes could accurately discriminate between clinical diagnostic groups and were significantly decreased with increasing cognitive impairment. MCI patients had a significantly larger change in WB, GM, and CGM volumes based on two MRIs (n = 95) compared to HC (FU>24months, p = 0.020). Linear regression models showed that baseline atrophy of WB, GM, CGM, and increased CSF volumes predicted cognitive impairment. CONCLUSION: WB and GM volumes extracted by MSmetrix could be used to define the clinical spectrum of AD accurately and along with CGM, they are able to predict cognitive impairment based on (decline in) MMSE scores. Therefore, MSmetrix can support clinicians in their diagnostic decisions, is able to detect clinical disease progression, and is of help to stratify populations for clinical trials.

OBJECTIVE: The aim of this study was to examine test performance on a cross-cultural neuropsychological test battery for assessment of middle-aged and elderly ethnic minority and majority populations in western Europe, and to present preliminary normative data.METHOD: The study was a cross-sectional multi-center study. Tests in the European Cross-Cultural Neuropsychological Test Battery (CNTB) cover several cognitive domains, including global cognitive function, memory, executive functions, and visuospatial functions.RESULTS: A total of 330 participants were included: 14 Moroccan, 45 Pakistani/Indian Punjabi, 41 Polish, 66 Turkish, and 19 former Yugoslavian minority participants, and 145 western European majority participants. Significant differences between ethnic groups were found on most CNTB measures. However, ethnic groups differed greatly in demographic characteristics and differences in test scores were mainly related to educational differences, explaining an average of 15% of the variance. Preliminary multicultural CNTB normative data dichotomized by education and age were constructed using overlapping cells. Applying this normative data across the whole sample resulted in an acceptable number of participants scoring in the impaired range across all ethnic groups. Factor analyses found the CNTB to have a stable and clinically meaningful factor structure.CONCLUSIONS: The CNTB represents the first European joint effort to establish neuropsychological measures appropriate for ethnic minority populations in western Europe. The CNTB can be applied in approximately 60 min, covers several cognitive domains, and appears appropriate for assessment of the targeted populations. However, due to the small sample size in some ethnic groups further studies are needed replicate and support this.

Over-medicalization is a broad concept, which also concerns the elderly patient. It encompasses both over-diagnosis and over-treatment. An increasing awareness of this issue has emerged since 2013, with the first " Preventing Overdiagnosis " conference. Currently, Evidence-Based Medicine does not prevent over-diagnosis. Indeed, the presence of geriatric characteristics such as multiple comorbidities, polypharmacy and frailty can lead to misdiagnosis and to potentially deleterious treatment. Subclinical hypothyroidism and Alzheimer's disease are two examples of pitfalls in the interpretation of biological and para-clinical data that may lead to the administration of useless treatment. Different issues are discussed to identify the causes of over-medicalization and to better prevent it., SCOPUS: ar.j, info:eu-repo/semantics/published

Background: Magnetic resonance imaging (MRI) acquisition/processing techniques assess brain volumes to explore neurodegeneration in Alzheimer's disease (AD). Objective: We examined the clinical utility of MSmetrix and investigated if automated MRI volumes could discriminate between groups covering the AD continuum and could be used as a predictor for clinical progression. Methods: The Belgian Dementia Council initiated a retrospective, multi-center study and analyzed whole brain (WB), grey matter (GM), white matter (WM), cerebrospinal fluid (CSF), cortical GM (CGM) volumes, and WM hyperintensities (WMH) using MSmetrix in the AD continuum. Baseline (n=887) and follow-up (FU, n=95) T1-weighted brain MRIs and time-linked neuropsychological data were available. Results: The cohort consisted of cognitively healthy controls (HC, n=93), subjective cognitive decline (n=102), mild cognitive impairment (MCI, n=379), and AD dementia (n=313). Baseline WB and GM volumes could accurately discriminate between clinical diagnostic groups and were significantly decreased with increasing cognitive impairment. MCI patients had a significantly larger change in WB, GM, and CGM volumes based on two MRIs (n=95) compared to HC (FU>24months, p=0.020). Linear regression models showed that baseline atrophy of WB, GM, CGM, and increased CSF volumes predicted cognitive impairment. Conclusion: WB and GM volumes extracted by MSmetrix could be used to define the clinical spectrum of AD accurately and along with CGM, they are able to predict cognitive impairment based on (decline in) MMSE scores. Therefore, MSmetrix can support clinicians in their diagnostic decisions, is able to detect clinical disease progression, and is of help to stratify populations for clinical trials., SCOPUS: ar.j, info:eu-repo/semantics/published

Introduction: In recent years knowledge about Alzheimer's disease (AD) presented a major change since the availability of new diagnostic criteria incorporating biomarkers within the known cl inical criteria. Such criteria were elaborated by NIA-AA (National Institute on Aging - Alzheimer's Association) for clinical use and IWG (International Working Group) for research purpose. The aim of this study is to investigate the use of complementary examinations included in the NIA-AA and IWG criteria in a memory clinic characterized by a heterogenous population of patients. Methods: We retrospectively reviewed patient's characteristics of cases consulting between 01/01/2010 and 31/12/2013 based on the implementation of three additional tests: neuropsychological testing, measurement of cerebrospinal fluid (CSF) biomarkers and brain MRI. Patients were compared according to their origins. Results: 919 patients' medical records were included in the study, 20 % of which were from immigrant background. Non-European Union migrants underwent less neuropsychological testing and more lumbar punctures in comparison with the local population. Conclusion: CSF biomarkers allow defining an objective diagnostic component of AD by suppressing the variability due to language, culture, education and the clinical presentation of the disease. Despite the known use in the research domain but not yet validated for clinical use, the IWG criteria are applied in heterogeneous populations with a high percentage of migrants, especially when the results of the neuropsychological testing are poorly contributive. We expect recommendations for clinical use of the CSF biomarkers or better cognitive assessment methods for these populations in the future., SCOPUS: ar.j, info:eu-repo/semantics/published

We conducted a survey regarding the medical care of patients with dementia in expert settings in Belgium. Open, unrestricted and motivated answers were centralized, blindly interpreted and structured into categories. The report of the results was then submitted to the participants in subsequent plenary meetings and through email. Fourteen experts responded to the questionnaire, confirming that recent propositions to modify Alzheimer's disease (AD) diagnostic criteria and options have stirred up debate among well-informed and dedicated experts in the field. The opinions were not unanimous and illustrate how difficult it is to find a standardized method of diagnosing this disease. The responses to the survey suggest that application of a step-by-step pragmatic method is used in practice. Only when the combination of clinical findings and classical structural neuro-imaging is insufficient for a diagnosis or suggests an atypical presentation, additional biomarkers are considered. Interestingly, few differences, if any, were observed between the use of biomarkers in MCI and in AD. In conclusion, the Belgian experts consulted in this survey were generally in agreement with the new diagnostic criteria for AD, although some concern was expressed about them being too "amyloidocentric". Although the clinical examination, including a full neuropsychological evaluation, is still considered as the basis for diagnosis, most experts also stated that they use biomarkers to help with diagnosis.