Patients carrying the mutation p.R406W in MAPT present with non-conforming phenotypic spectrum.

The missense mutation p.R406W in microtubule-associated protein tau leads to frontotemporal lobar degeneration with an amnestic, Alzheimer's disease-like phenotype with an autosomal dominant pattern of inheritance. In 2003, we described the pedigree of a Belgian family, labelled ADG, with 28 p.R406W patients. Over 18 years follow-up, we extended the family with 10 p.R406W carriers and provided an in-depth clinical description of the patients. Additionally, genetic screening was used to identify p.R406W carriers in Belgian cohorts of frontotemporal dementia and Alzheimer's disease patients and to calculate p.R406W frequency. In the frontotemporal dementia cohort, we found four p.R406W carriers (n = 647, 0.62%) and three in the Alzheimer's disease cohort (n = 1134, 0.26%). Haplotype sharing analysis showed evidence of a shared haplotype suggesting that they are descendants of a common ancestor. Of the p.R406W patients, we describe characteristics of neuropsychological, imaging and fluid biomarkers as well as neuropathologic examination. Intriguingly, the phenotypic spectrum among the p.R406W patients ranged from typical behavioural variant frontotemporal dementia to clinical Alzheimer's disease, based on CSF biomarker analysis and amyloid PET scan. Heterogeneous overlap syndromes existed in between, with highly common neuropsychiatric symptoms like disinhibition and aggressiveness, which occurred in 100% of frontotemporal dementia and 58% of clinical Alzheimer's disease patients. This was also the case for memory problems, 89% in frontotemporal dementia and 100% in clinical Alzheimer's disease patients. Median age at death was significantly lower in patients with frontotemporal dementia (68 years) compared to clinical Alzheimer's disease patients (79 years), although the sizes of the sub-cohorts are limited and do not allow prognostic predictions. Post-mortem brain analysis of one p.R406W patient with behavioural variant frontotemporal dementia revealed frontotemporal lobar degeneration with tau pathology. Notably, neuropathological investigation showed only 3R tau isoforms in the absence of 4R tau reactivity, an unusual finding in microtubule-associated protein tau-related frontotemporal lobar degeneration. No traces of amyloid pathology were present. Prevalence of the p.R406W mutation was relatively high in both frontotemporal dementia and Alzheimer's disease Belgian patient cohorts. These findings grant new insights into genotype-phenotype correlations of p.R406W carriers. They may help in further unravelling of the pathophysiology of this tauopathy and in facilitating the identification of patients with p.R406W-related frontotemporal lobar degeneration, both in clinical diagnostic and research settings.

Difficultés et besoins non satisfaits des aidants de personnes âgées démentes : une analyse phénoménologique interprétative avant et après un groupe de psycho-éducation.

Résumé Une analyse phénoménologique interprétative longitudinale des difficultés et des besoins non satisfaits rencontrés par les aidants de patients atteints de maladies neuro-dégénératives a été effectuée sur un groupe de 14 conjoints avant (T1) et après (T2) avoir participé à un groupe de psychoéducation de 6 mois. Lors du premier temps (T1), les aidants décrivent principalement une perte des échanges avec le patient, la solitude et la détresse qu'elle entraîne. Ils verbalisent également les difficultés de gérer la relation d'aide, en particulier leurs besoins non satisfaits de temps libre. Lors du second temps (T2) et sous les effets de la progression de la pathologie, ce sont nouvelles difficultés qui apparaissent, avec l'augmentation de la difficulté à gérer les pertes fonctionnelles et les troubles psychocomportementaux. Nos résultats suggèrent que la psychoéducation a aidé les soignants à faire face aux difficultés liées au fardeau objectif (besoin de temps personnel). Les interventions psychoéducatives devraient à l'avenir aborder davantage la relation dyadique et le besoin de soutien affectif de l'aidant, car il s'agit d'un besoin fort, non satisfait, des aidants. Des interventions de psychoéducation systématiques et répétées peuvent ainsi permettre de mieux identifier les difficultés et les besoins des aidants et de leur fournir une aide adaptée, tout particulièrement en ce qui concerne la relation de couple et l'état émotionnel des aidants. Abstract Psycho-education provides information, tools and support to caregivers, and a strong consensus favors the importance of tailoring psycho-education interventions to caregiver needs. Most studies assess needs cross-sectionally, neglecting the evolving nature of needs and challenges inherent to dementia and caregiving, failing to report on how psycho-educative interventions address or incorporate caregiver needs. The purpose of this study was to provide a qualitative and longitudinal assessment of the difficulties and unmet needs of spousal caregivers before and after participating in a psycho-education group. To investigate the difficulties and needs related to caregiving, before and after psycho-education participation, we used a longitudinal Interpretative Phenomenological Analysis (LIPA). LIPA is a prospective person-centered method that explores the lived experience of phenomena without formulating a priori hypotheses. The psycho-educational program was available to any informal caregiver of a person living with dementia (PLWD) in the Brussels region. The multimodal program contains: educational and practical information on dementia sessions with a neuropsychologist specialized in dementia, group sharing and support; home visits by a nurse for personalized assistance to caregivers, art therapy group: available for PLWD that could not be left unsupervised in conjunction with psycho-education sessions. Our study yielded three key findings: (1) caregivers described a loss of relational reciprocity with the person living with dementia at T1 and T2, and reported feeling distressed; (2) at T1, caregivers verbalised difficulties related to their role, the majority of them only identified the lack of personal time as an unmet need; (3) at T2, most caregivers had actively addressed their unmet need for personal time and used respite services to obtain personal time. Our findings would suggest that psycho-education helped caregivers to address difficulties related to objective burden (need for personal time). Psycho-education interventions should systematically and repeatedly assess caregiver difficulties and assist them in identifying their needs in order to provide adequate and tailored strategies and support.

Impact on quitting smoking of cognitive impairment in stroke patients.

INTRODUCTION: Smoking is a well-established risk factor for strokes, leading to a high incidence of cognitive deficits. Since the impact of cognitive impairment on the effectiveness of interventions for smoking cessation is not yet known, we considered important to assess it. METHODS: We compared, from April 2012 to November 2015, the success rate of quitting smoking in two groups of acutely hospitalised adult smokers. The first group consisted of stroke patients (SP, n = 54) with lesions confirmed by cerebral imaging. The second used as a control group (NSP, n = 38), included patients hospitalised for any reason other than stroke and characterised by normal global cognition. All participants were assessed twice, in acute phase (T0) and 3 months later (T1), using exhaled carbon monoxide (CO) and several questionnaires. RESULTS: At T1, we observed in SP group an inverse correlation between the Montreal Cognitive Assessment (MoCA) and CO (r = -0.33, p = 0.015). Amongst patients who continued smoking, a higher increase in CO between T0 and T1 was observed in SP group (average 20 ± 15, p < 0.001) than NSP (average 9 ± 13, p = 0.002). CONCLUSIONS: The inverse correlation between CO and cognitive parameters at T1 in SP group suggests an increased susceptibility to tobacco dependency in case of residual cognitive impairment. The global cognitive assessment should thus be taken into consideration when providing assistance with quitting smoking, especially in case of stroke patients.

Unraveling the Cognitive-Motor Interaction in Individuals With Amnestic Mild Cognitive Impairment.

PURPOSE: This study aimed to determine whether increasing the contribution of executive functions worsens dual-task performance in individuals with amnestic mild cognitive impairment (aMCI). METHODS: Fourteen individuals with aMCI (mean [SD]: 74 [4] years) and 19 control adults (71 [5] years) recalled a list of letters in the order of presentation (SPAN-O) or in alphabetic order (SPAN-A) while ascending or descending a 3-step staircase. Dual-task cost (DTC) represented the average decrement of motor and cognitive performances during dual tasks, with greater DTC indicating worse performance. RESULTS: SPAN-A (P < 0.001) and stair descent (P = 0.023) increased the DTC in both groups compared with SPAN-O and stair ascent. Furthermore, individuals with aMCI had a greater DTC (93.4 [41.2]%) than the control group (48.3 [27.9]%) for SPAN-A (P < 0.001). Dual-task cost was also greater in descent (76.6 [42.1]%) than ascent (64.0 [34.5]%) in individuals with aMCI (P = 0.024) but not in the control group (P = 0.99). Significant negative partial correlations (ß < -0.39; P < 0.05) were found between Montreal Cognitive Assessment score and DTC, while controlling for age and physical function. DISCUSSION AND CONCLUSIONS: A greater DTC in individuals with aMCI when the cognitive task requires working memory (SPAN-A) or during complex locomotor task (descent) suggests that aMCI impedes the capacity to perform 2 tasks simultaneously when higher-order cognitive processes are challenged. Furthermore, a greater DTC in our dual-task situations appears to reflect cognitive decline, as assessed by the Montreal Cognitive Assessment score. Overall, this study indicates that increasing the contribution of executive functions worsens the cognitive-motor interaction in individuals with aMCI.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1 available at: http://links.lww.com/JNPT/A375).

Decreased Alpha Peak Frequency Is Linked to Episodic Memory Impairment in Pathological Aging.

The Free and Cued Selective Reminding Test (FCSRT) is a largely validated neuropsychological test for the identification of amnestic syndrome from the early stage of Alzheimer's disease (AD). Previous electrophysiological data suggested a slowing down of the alpha rhythm in the AD-continuum as well as a key role of this rhythmic brain activity for episodic memory processes. This study therefore investigates the link between alpha brain activity and alterations in episodic memory as assessed by the FCSRT. For that purpose, 37 patients with altered FCSRT performance underwent a comprehensive neuropsychological assessment, supplemented by 18F-fluorodeoxyglucose positron emission tomography/structural magnetic resonance imaging (18FDG-PET/MR), and 10 min of resting-state magnetoencephalography (MEG). The individual alpha peak frequency (APF) in MEG resting-state data was positively correlated with patients' encoding efficiency as well as with the efficacy of semantic cues in facilitating patients' retrieval of previous stored word. The APF also correlated positively with patients' hippocampal volume and their regional glucose consumption in the posterior cingulate cortex. Overall, this study demonstrates that alterations in the ability to learn and store new information for a relatively short-term period are related to a slowing down of alpha rhythmic activity, possibly due to altered interactions in the extended mnemonic system. As such, a decreased APF may be considered as an electrophysiological correlate of short-term episodic memory dysfunction accompanying pathological aging.

Diagnostic Performance of Automated MRI Volumetry by icobrain dm for Alzheimer's Disease in a Clinical Setting: A REMEMBER Study.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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%). CONCLUSION: 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.

Frontotemporal dementia patients exhibit deficits in predictive saccades.

Prediction and time estimation are all but required for motor function in everyday life. In the context of eye movements, for instance, they allow predictive saccades and eye re-acceleration in anticipation of a target re-appearance. While the neural pathways involved are not fully understood, it is known that the frontal lobe plays an important role. As such, neurological disorders that affect it, such as frontotemporal (FTD) dementia, are likely to induce deficits in such movements. In this work, we study the performances of frontotemporal dementia patients in an oculomotor task designed to elicit predictive saccades at different rates, and compare them to young and older adults. Clear deficits in the production of predictive saccades were found in patients, in particular when the time between saccades was short (~500 ms). Furthermore, one asymptomatic C9ORF72 mutation bearer showed patterns of oculomotor behavior similar to FTD patients. He exhibited FTD symptoms within 3 years post-measure, suggesting that an impairment of oculomotor function could be an early clinical sign. Taken together, these results argue in favor of a role of the frontal lobe in predictive movements timing over short timescales, and suggest that predictive saccades in FTD patients warrant further investigation to fully assess their potential as a diagnostic aid.

Gesturing helps memory encoding in aMCI.

Encoding in episodic memory is a step often impaired in patients with amnestic Mild Cognitive Impairment (aMCI). However, procedural memory processes are still relatively preserved. In line with previous research on the enactment effect, we investigated the potential benefit of encoding words combined with imitative gestures on episodic memory. Based on the Grober and Buschke's free/cued recall procedure, we developed the Symbiosis test in which 13 patients with aMCI and 16 healthy elderly participants learned 32 words belonging to 16 different semantic categories either in a verbal encoding (A) or a bimodal (B; verbal and motor imitation) condition, using a blocked ABBA/BAAB procedure. Overall, memory retrieval was better in healthy participants than in patients with aMCI, and better for cued retrieval in the bimodal encoding (gesture cues) than the verbal encoding (category cues) condition, but there was no interaction effect between group and encoding conditions. These results show that performing concomitant gestures can enhance cued episodic memory retrieval in patients with aMCI and in healthy elderly controls. The Symbiosis test broadens the scope of the enactment effect, from action phrases to isolated words learning in patients with aMCI. Future work should investigate how bimodal encoding provides novel perspectives for memory rehabilitation in patients with aMCI.

Evolution of lived experience of dementia caregivers after a psycho-educational group: an interpretative phenomenological analysis.

The 'Help and Support for Caregivers and Patients' psycho-education group aims to educate and support dementia caregivers. Fourteen spousal caregivers were interviewed before (T1) and after (T2) psycho-education participation. Intrapersonal processes and the potential evolution of lived experience were explored using longitudinal interpretative phenomenological analysis. Three trajectory groups were identified at T1: proactive help-seekers, passive but hopeful caregivers and ambivalent caregivers. T2 interviews revealed that caregivers experienced growth in their role, benefitted from peer interactions, feelings of guilt were addressed and they were using out-of-home dementia-specific services. Identifying beliefs or attitudes that might prevent caregivers from getting help or support is important. Caregiver well-being remains a public health priority and furthering our knowledge about their complex and changing needs is paramount to provide well-designed and tailored resources.

Effects of a Psychoeducational Program on Caregivers of Patients with Dementia.

BACKGROUND: The number of demented patients has increased significantly in recent years. The many challenges that dementia causes increase the stress of their caregivers and lead to shortening the time to institutionalization compared to the general population. A psychoeducational program for these accompanying persons was set up in Brussels. This type of program resulted in a 557-day delay in institutionalization in New York City. The objective of our study was to check whether our program also has such an impact, but also to see its potential effect on the psychobehavioral disorders of patients and the burden of caregivers. METHODS: We recruited two groups without randomization: psychoeducated caregivers and caregivers interested in the program and contacted regularly (every 6 months) without having participated. They were all contacted by telephone and responded to the NCPI and Zarit Burden Scale (ZBS) questionnaires. RESULTS: We could not demonstrate any significant impact, either on the institutionalization delay (p = 0.960), on the frequency of psychobehavioral disorders in demented patients (p > 0.05), or on the burden of caregivers (p = 0.403). However, the survival rate among the demented patients with psychoeducated caregivers was significantly higher than that among the demented patients with nonpsychoeducated caregivers (p < 0.001). CONCLUSIONS: Our small-sample, nonrandomized study did not reveal any differences in institutionalization delay, caregiver burden, or perception of psychobehavioral disorders related to our psychoeducational program. A new study should be carried out on the impact of psychoeducation on the survival of demented patients, in view of our preliminary analyses.

Practices and opinions about disclosure of the diagnosis of Alzheimer's disease to patients with MCI or dementia: a survey among Belgian medical experts in the field of dementia.

Previous surveys revealed that only a minority of clinicians routinely disclosed the diagnosis of Alzheimer's disease (AD) to their patients. Many health professionals fear that the disclosure could be harmful to the patient. Recent advances in the development of biomarkers and new diagnostic criteria allow for an earlier diagnosis of AD at the mild cognitive impairment (MCI) stage. The Belgian Dementia Council, a group of Belgian experts in the field of dementia, performed a survey among its 44 members about their opinions and practices regarding disclosure of the diagnosis of AD, including MCI due to AD, and its consequences. Twenty-six respondents declared that they often or always disclose the diagnosis of AD to patients with dementia and to patients with MCI when AD CSF biomarkers are abnormal. The majority observed that the disclosure of AD is rarely or never harmful to the patients. Their patients and their caregivers rarely or never demonstrated animosity towards the clinicians following disclosure of the diagnosis of AD. These results should reassure clinicians about the safety of AD diagnosis disclosure in most cases whether the patient is at the MCI or the dementia stage.

Age-Associated Capacity to Progress When Playing Cognitive Mobile Games: Ecological Retrospective Observational Study.

BACKGROUND: The decline of cognitive function is an important issue related to aging. Over the last few years, numerous mobile apps have been developed to challenge the brain with cognitive exercises; however, little is currently known about how age influences capacity for performance improvement when playing cognitive mobile games. OBJECTIVE: The objective of this study was to analyze the score data of cognitive mobile games over a period of 100 gaming sessions to determine age-related learning ability for new cognitive tasks by measuring the level of score improvement achieved by participants of different ages. METHODS: Scores from 9000 individuals of different ages for 7 cognitive mobile games over 100 gaming sessions were analyzed. Scores from the first session were compared between age groups using one-way analysis of variance. Mixed models were subsequently used to investigate the progression of scores over 100 sessions. RESULTS: Statistically significant differences were found between age groups for the initial scores of 6 of the 7 games (linear trend, P<.001). Cognitive mobile game scores increased for all participants (P<.001) suggesting that all participants were able to improve their performance. The rate of improvement was, however, strongly influenced by the age of the participant with slower progression for older participants (P<.001). CONCLUSIONS: This study provides evidence to support two interesting insights-cognitive mobile game scores appear to be sensitive to the changes in cognitive ability that occur with advancing age; therefore, these games could be a convenient way to monitor cognitive function over long-term follow-up, and users who train with the cognitive mobile games improve regardless of age.

[Dementia caregiver journey and motivation to participate in a psycho-educational group: an interpretative phenomenological analysis]. / Cheminement de l'aidant proche et motivation à la participation à un groupe de psychoéducation : une analyse phénoménologique interprétative.

The "Help and support for caregivers and patients program, (ASAPP) is a multidisciplinary project to better the interactions between unformal caregivers and patients living with a neurodegenerative disorder, by improving the disease understanding. OBJECTIVE: The aim of our study was to understand the trajectory, expectations and motivation of the caregivers to participate in the program. METHODS: 7 spousal caregivers participated in a semi-structural interview, whose results were analysed by means of a qualitative technique of phenomenological analysis. RESULTS: Three main themes emerged 1) loneliness, social isolation and emotional impact of the illness, 2) lack of time for themselves, and feelings of solitude, 3) expectations of improvement by the psychoeducational program. CONCLUSION: These results highlight the importance to understand the expectations of the caregivers to tailor the intervention program according to their main needs.

Dementia, End of Life, and Euthanasia: A Survey Among Dementia Specialists Organized by the Belgian Dementia Council.

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.

Hemispatial neglect and serial order in verbal working memory.

Working memory refers to our ability to actively maintain and process a limited amount of information during a brief period of time. Often, not only the information itself but also its serial order is crucial for good task performance. It was recently proposed that serial order is grounded in spatial cognition. Here, we compared performance of a group of right hemisphere-damaged patients with hemispatial neglect to healthy controls in verbal working memory tasks. Participants memorized sequences of consonants at span level and had to judge whether a target consonant belonged to the memorized sequence (item task) or whether a pair of consonants were presented in the same order as in the memorized sequence (order task). In line with this idea that serial order is grounded in spatial cognition, we found that neglect patients made significantly more errors in the order task than in the item task compared to healthy controls. Furthermore, this deficit seemed functionally related to neglect severity and was more frequently observed following right posterior brain damage. Interestingly, this specific impairment for serial order in verbal working memory was not lateralized. We advance the hypotheses of a potential contribution to the deficit of serial order in neglect patients of either or both (1) reduced spatial working memory capacity that enables to keep track of the spatial codes that provide memorized items with a positional context, (2) a spatial compression of these codes in the intact representational space.

The Use of Mobile Games to Assess Cognitive Function of Elderly with and without Cognitive Impairment.

BACKGROUND: In the past few years numerous mobile games have been developed to train the brain. There is a lack of information about the relation between the scores obtained in these games and the cognitive abilities of the patients. OBJECTIVE: The aim of this study was to determine whether or not mobile games can be used to assess cognitive abilities of elderly. METHODS: Twenty healthy young adults, 29 old patients with cognitive impairments (Mini-Mental State Exam (MMSE) [20- 24]) and 27-aged controls participated in this study. Scores obtained in 7 mobile games were correlated with MMSE and the Addenbrooke's Cognitive Evaluation revised (ACE-R). RESULTS: Statistically significant differences were found for all games between patients with cognitive impairments and the aged controls. Correlations between the average scores of the games and the MMSE and ACE-R are significant (R = 0.72 [p < 0.001] and R = 0.81 [p < 0.001], respectively). CONCLUSION: Scores of cognitive mobile games could be used as an alternative to MMSE and ACE-R to evaluate cognitive function of aged people with and without cognitive impairment at least when MMSE is higher than 20/30.

A Retrospective Belgian Multi-Center MRI Biomarker Study in Alzheimer's Disease (REMEMBER).

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.

Alzheimer's disease and driving: review of the literature and consensus guideline from Belgian dementia experts and the Belgian road safety institute endorsed by the Belgian Medical Association.

Alzheimer's disease (AD) is a highly prevalent condition and its prevalence is expected to further increase due to the aging of the general population. It is obvious that the diagnosis of AD has implications for driving. Finally, driving discussions are also emotionally charged because driving is associated with independence and personal identity. However, it is not clear how to implement this in clinical practice and the Belgian law on driving is rather vague in its referral to neurodegenerative brain diseases in general nor does it provide clear-cut instructions for dementia or AD compared to for example driving for patients with epilepsy and as such does not prove to be very helpful. The present article reviews what is known from both literature and existing guidelines and proposes a consensus recommendation tailored to the Belgian situation agreed by both AD experts and the Belgian Road Safety Institute endorsed by the Belgian Medical Association. It is concluded that the decision about driving fitness should be considered as a dynamic process where the driving fitness is assessed and discussed early after diagnosis and closely monitored by the treating physician. The diagnosis of AD on itself definitely does not imply the immediate and full revocation of a driving license nor does it implicate a necessary referral for a formal on-road driving assessment. There is no evidence to recommend a reduced exposure or a mandatory co-pilot. A MMSE-based framework to trichotomise AD patients as safe, indeterminate or unsafe is presented. The final decision on driving fitness can only be made after careful history taking and clinical examination, neuropsychological, functional and behavioral evaluation and, only for selected cases, a formal assessment of driving performance.