Anodal transcranial direct current stimulation does not enhance the effects of motor imagery training of a sequential finger-tapping task in young adults.

When applied over the primary motor cortex (M1), anodal transcranial direct current stimulation (a-tDCS) could enhance the effects of a single motor imagery training (MIt) session on the learning of a sequential finger-tapping task (SFTT). This study aimed to investigate the effect of a-tDCS on the learning of an SFTT during multiple MIt sessions. Two groups of 16 healthy young adults participated in three consecutive MIt sessions over 3 days, followed by a retention test 1 week later. They received active or sham a-tDCS during a MIt session in which they mentally rehearsed an eight-item complex finger sequence with their left hand. Before and after each session, and during the retention test, they physically repeated the sequence as quickly and accurately as possible. Both groups (i) improved their performance during the first two sessions, showing online learning; (ii) stabilised the level they reached during all training sessions, reflecting offline consolidation; and (iii) maintained their performance level one week later, showing retention. However, no significant difference was found between the groups, regardless of the MSL stage. These results emphasise the importance of performing several MIt sessions to maximise performance gains, but they do not support the additional effects of a-tDCS.

Empowering general practitioners in dementia care: The ANTISTIGMA education intervention in Europe.

BACKGROUND: There is a well-documented lack or delay of diagnosis of dementia in all countries, including in Europe. Most general practitioners (GPs) have acquired adequate academic and scientific information about dementia but avoid using it in practice because of stigma. OBJECTIVES: To persuade GPs of their role in dementia detection, an Antistigma education intervention was designed, with teaching objectives focusing on "Why" and "How" to diagnosis and manage dementia, based on ethical and practical content, as opposed to classical training centered on teaching "What", with mainly academic content. METHODS: During the European Joint Action "ACT ON DEMENTIA", the Antistigma education intervention was implemented in four Universities: Lyon and Limoges (France), Sofia (Bulgaria) and Lublin (Poland). General data, including information about training and experience in dementia, was collected. Specific scales measured Dementia Negative Stereotypes DNS and Dementia Clinical Confidence D-CO before and after training. RESULTS: 134 GPs and 58 residents R completed the training. The participants were mainly women (74%), and the mean age was 42.8 ± 13.2. Before training, participants expressed difficulties in defining GPs role and worries about inflicting Stigma, Risks of diagnosis, Lack of benefit and Communication difficulties. Participants' D-CO was significantly higher for Diagnosis process (64%) than for other clinical situations. After training, total NS was reduced from 34.2% to 29.9% (p < 0.001), and stereotypes were improved: GPs' role (40.1% reduced to 35.9%; p < 0.001), Stigma (38.7% reduced to 35.5%; p < 0.001), Risks of diagnosis (39.0% reduced to 33.3%; p < 0.001), Lack of Benefit (29.3% reduced to 24.6%; p < 0.001) and Communication difficulties (19.9% reduced to 16.9%; p < 0.001). After training, D-CO was significantly increased in all the clinical situations (p < 0.001), but stayed highest for Diagnosis Process. There was no significant difference between the universities. Participants who benefited best from the Antistigma education intervention were those without training in Geriatrics and those working in nursing homes (who reduced the most D-NS), as well younger participants and those who managed less than five people living with dementia per week (who increased the most D-CO). CONCLUSION: The Antistigma program is based on the idea that most often GPs and R have acquired adequate academic and scientific information about dementia but avoid using it in practice because of stigma. These results outline the importance of addressing ethical issues and practical management situations in dementia education, to empower GPs in dementia care.

White matter hyperintensities in Alzheimer's disease: Beyond vascular contribution.

White matter hyperintensities (WMH), frequently seen in older adults, are usually considered vascular lesions, and participate in the vascular contribution to cognitive impairment and dementia. However, emerging evidence highlights the heterogeneity of WMH pathophysiology, suggesting that non-vascular mechanisms could also be involved, notably in Alzheimer's disease (AD). This led to the alternative hypothesis that in AD, part of WMH may be secondary to AD-related processes. The current perspective brings together the arguments from different fields of research, including neuropathology, neuroimaging and fluid biomarkers, and genetics, in favor of this alternative hypothesis. Possible underlying mechanisms leading to AD-related WMH, such as AD-related neurodegeneration or neuroinflammation, are discussed, as well as implications for diagnostic criteria and management of AD. We finally discuss ways to test this hypothesis and remaining challenges. Acknowledging the heterogeneity of WMH and the existence of AD-related WMH may improve personalized diagnosis and care of patients.

Global estimates on the number of persons across the Alzheimer's disease continuum.

INTRODUCTION: Global estimates on numbers of persons in early stages of Alzheimer's disease (AD), including prodromal and preclinical, are lacking, yet are needed to inform policy decisions on preventive measures and planning for future therapies targeting AD pathology. METHODS: We synthesized the literature on prevalence across the AD continuum and derived a model estimating the number of persons, stratified by 5-year age groups, sex, and disease stage (AD dementia, prodromal AD, and preclinical AD). RESULTS: The global number of persons with AD dementia, prodromal AD, and preclinical AD were estimated at 32, 69, and 315 million, respectively. Together they constituted 416 million across the AD continuum, or 22% of all persons aged 50 and above. DISCUSSION: Considering predementia stages, the number of persons with AD is much larger than conveyed in available literature. Our estimates are uncertain, especially for predementia stages in low- and middle-income regions where biomarker studies are missing.

Effect of reduction in brain amyloid levels on change in cognitive and functional decline in randomized clinical trials: An instrumental variable meta-analysis.

INTRODUCTION: Whether the reduction in brain amyloid beta (Aß) plaque alone may substantially slow cognitive and functional decline in patients with dementia or mild cognitive impairment due to Alzheimer's disease (AD) remains debated. METHODS: An instrumental variable meta-analysis was performed to infer the effect of change in positron emission tomography (PET)-measured Aß standardized uptake value ratio (SUVR) on cognitive and functional decline. RESULTS: Pooling data from 16 randomized trials demonstrates that each 0.1-unit decrease in PET Aß SUVR is associated with a reduction (95% confidence interval) by 0.09 (0.034-0.15), 0.33 (0.12-0.55), and 0.13 (0.017-0.24) point in the average change of the Clinical Dementia Rating-Sum of Boxes, the Alzheimer's Disease Assessment Scale-Cognitive Subscale, and the Mini-Mental State Examination, respectively. DISCUSSION: This meta-analysis provides statistically significant evidence of a likely causal relationship between a reduction in Aß plaque and a reduction in cognitive and functional decline in patients with AD. HIGHLIGHTS: A widely cited meta-analysis article concluded amyloid beta reduction does not substantially improve cognition. We identified data inconsistencies in the initial publication and found new trial data. We repeated the meta-analysis after correcting data inconsistencies and adding new trial data. Updated results suggested statistically significant clinical benefit of amyloid beta reduction. Amyloid beta is a viable biological target for the treatment and prevention of AD.

Associations among hypertension, dementia biomarkers, and cognition: The MEMENTO cohort.

INTRODUCTION: Approximately 40% of dementia cases could be delayed or prevented acting on modifiable risk factors including hypertension. However, the mechanisms underlying the hypertension-dementia association are still poorly understood. METHODS: We conducted a cross-sectional analysis in 2048 patients from the MEMENTO cohort, a French multicenter clinic-based study of outpatients with either isolated cognitive complaints or mild cognitive impairment. Exposure to hypertension was defined as a combination of high blood pressure (BP) status and antihypertensive treatment intake. Pathway associations were examined through structural equation modeling integrating extensive collection of neuroimaging biomarkers and clinical data. RESULTS: Participants treated with high BP had significantly lower cognition compared to the others. This association was mediated by higher neurodegeneration and higher white matter hyperintensities load but not by Alzheimer's disease (AD) biomarkers. DISCUSSION: These results highlight the importance of controlling hypertension for prevention of cognitive decline and offer new insights on mechanisms underlying the hypertension-dementia association. HIGHLIGHTS: Paths of hypertension-cognition association were assessed by structural equation models. The hypertension-cognition association is not mediated by Alzheimer's disease biomarkers. The hypertension-cognition association is mediated by neurodegeneration and leukoaraiosis. Lower cognition was limited to participants treated with uncontrolled blood pressure. Blood pressure control could contribute to promote healthier brain aging.

Validation of an automatic tool for the rapid measurement of brain atrophy and white matter hyperintensity: QyScore®.

OBJECTIVES: QyScore® is an imaging analysis tool certified in Europe (CE marked) and the US (FDA cleared) for the automatic volumetry of grey and white matter (GM and WM respectively), hippocampus (HP), amygdala (AM), and white matter hyperintensity (WMH). Here we compare QyScore® performances with the consensus of expert neuroradiologists. METHODS: Dice similarity coefficient (DSC) and the relative volume difference (RVD) for GM, WM volumes were calculated on 50 3DT1 images. DSC and the F1 metrics were calculated for WMH on 130 3DT1 and FLAIR images. For each index, we identified thresholds of reliability based on current literature review results. We hypothesized that DSC/F1 scores obtained using QyScore® markers would be higher than the threshold. In contrast, RVD scores would be lower. Regression analysis and Bland-Altman plots were obtained to evaluate QyScore® performance in comparison to the consensus of three expert neuroradiologists. RESULTS: The lower bound of the DSC/F1 confidence intervals was higher than the threshold for the GM, WM, HP, AM, and WMH, and the higher bounds of the RVD confidence interval were below the threshold for the WM, GM, HP, and AM. QyScore®, compared with the consensus of three expert neuroradiologists, provides reliable performance for the automatic segmentation of the GM and WM volumes, and HP and AM volumes, as well as WMH volumes. CONCLUSIONS: QyScore® represents a reliable medical device in comparison with the consensus of expert neuroradiologists. Therefore, QyScore® could be implemented in clinical trials and clinical routine to support the diagnosis and longitudinal monitoring of neurological diseases. KEY POINTS: • QyScore® provides reliable automatic segmentation of brain structures in comparison with the consensus of three expert neuroradiologists. • QyScore® automatic segmentation could be performed on MRI images using different vendors and protocols of acquisition. In addition, the fast segmentation process saves time over manual and semi-automatic methods. • QyScore® could be implemented in clinical trials and clinical routine to support the diagnosis and longitudinal monitoring of neurological diseases.

White matter hyperintensity topography in Alzheimer's disease and links to cognition.

INTRODUCTION: White matter hyperintensities (WMH) are often described in Alzheimer's disease (AD), but their topography and specific relationships with cognition remain unclear. METHODS: Regional WMH were estimated in 54 cognitively impaired amyloid beta-positive AD (Aßpos-AD), compared to 40 cognitively unimpaired amyloid beta-negative older controls (Aßneg-controls) matched for vascular risk factors. The cross-sectional association between regional WMH volume and cognition was assessed within each group, controlling for cerebral amyloid burden, global cortical atrophy, and hippocampal atrophy. RESULTS: WMH volume was larger in Aßpos-AD compared to Aßneg-controls in all regions, with the greatest changes in the splenium of the corpus callosum (S-CC). In Aßpos-AD patients, larger total and regional WMH volume, especially in the S-CC, was strongly associated with decreased cognition. DISCUSSION: WMH specifically contribute to lower cognition in AD, independently from amyloid deposition and atrophy. This study emphasizes the clinical relevance of WMH in AD, especially posterior WMH, and most notably S-CC WMH.

Effects of a Mindfulness-Based Intervention versus Health Self-Management on Subclinical Anxiety in Older Adults with Subjective Cognitive Decline: The SCD-Well Randomized Superiority Trial.

INTRODUCTION: Older adults experiencing subjective cognitive decline (SCD) have a heightened risk of developing dementia and frequently experience subclinical anxiety, which is itself associated with dementia risk. OBJECTIVE: To understand whether subclinical anxiety symptoms in SCD can be reduced through behavioral interventions. METHODS: SCD-Well is a randomized controlled trial designed to determine whether an 8-week mindfulness-based intervention (caring mindfulness-based approach for seniors; CMBAS) is superior to a structurally matched health self-management program (HSMP) in reducing subclinical anxiety. Participants were recruited from memory clinics at 4 European sites. The primary outcome was change in anxiety symptoms (trait subscale of the State-Trait Anxiety Inventory; trait-STAI) from pre- to postintervention. Secondary outcomes included a change in state anxiety and depression symptoms postintervention and 6 months postrandomization (follow-up). RESULTS: One hundred forty-seven participants (mean [SD] age: 72.7 [6.9] years; 64.6% women; CMBAS, n = 73; HSMP, n = 74) were included in the intention-to-treat analysis. There was no difference in trait-STAI between groups postintervention (adjusted change difference: -1.25 points; 95% CI -4.76 to 2.25) or at follow-up (adjusted change difference: -0.43 points; 95% CI -2.92 to 2.07). Trait-STAI decreased postintervention in both groups (CMBAS: -3.43 points; 95% CI -5.27 to -1.59; HSMP: -2.29 points; 95% CI -4.14 to -0.44) and reductions were maintained at follow-up. No between-group differences were observed for change in state anxiety or depression symptoms. CONCLUSIONS: A time-limited mindfulness intervention is not superior to health self-management in reducing subclinical anxiety symptoms in SCD. The sustained reduction observed across both groups suggests that subclinical anxiety symptoms in SCD are modifiable. ClinicalTrials.gov identifier: NCT03005652.

Proposition of a corrected measure of the Lawton instrumental activities of daily living score.

BACKGROUND: We aimed to propose a correction of the Lawton instrumental activity of daily living (IADL) score to take into account the possibility to have never done some activities, and measured its agreement and reliability with the usual IADL score. METHODS: A cross-sectional study was conducted in outpatients attending French memory clinics between 2014 and 2017. Lawton IADL, cognitive performance, diagnosis, neuropsychiatric symptoms, and sociodemographics characteristics were collected. A corrected IADL was calculated and its agreement with the usual IADL was assessed. RESULTS: The study included of 2391 patients (79.9 years old, 61.7% female). Based on the usual IADL, 36.9% of patients had never carried out at least one of the activities. This proportion reached 68.8% for men and 17.7% for women. Women had a mean IADL higher than men: 4.72 vs 3.49, this difference decreased when considering the corrected IADL: 4.82 vs 4.26 respectively. Based on Bland-Altman method, 93.5% of observations lied within the limits agreement. The ICC between the 2 scores was 0.98. The relationships between patients' characteristics and the IADL scores were similar, regardless the usual or corrected version. CONCLUSIONS: This corrected IADL score had an excellent degree of agreement with the usual version based the ICC. This simple correction could benefit both for the clinical practice by providing a more accurate description of the real clinical state of the patients allowing to manage them more precisely, and for research involving the evaluation of the functional abilities of patients.

Investigating the association between cancer and the risk of dementia: Results from the Memento cohort.

INTRODUCTION: Studies on the association of cancer and risk of dementia are inconclusive due to result heterogeneity and concerns of survivor bias and unmeasured confounding. METHODS: This study uses data from the Memento cohort, a French multicenter cohort following persons with either mild or isolated cognitive complaints for a median of 5 years. Illness-death models (IDMs) were used to estimate transition-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for incident cancer in relation to dementia from time since study entry. RESULTS: The analytical sample (N = 2258) excluded 65 individuals without follow-up information. At the end of follow-up, 286 individuals were diagnosed with dementia, 166 with incident cancer, and 95 died. Incident cancer was associated with a reduced risk of dementia (HR = 0.58, 95% CI = 0.35-0.97), with a corresponding E-value of 2.84 (lower CI = 1.21). DISCUSSION: This study supports a protective relationship between incident cancer and dementia, encouraging further investigations to understand potential underlying mechanisms.

Clinical relevance of brain atrophy subtypes categorization in memory clinics.

INTRODUCTION: The clinical relevance of brain atrophy subtypes categorization in non-demented persons without a priori knowledge regarding their amyloid status or clinical presentation is unknown. METHODS: A total of 2083 outpatients with either subjective cognitive complaint or mild cognitive impairment at study entry were followed during 4 years (MEMENTO cohort). Atrophy subtypes were defined using baseline magnetic resonance imaging (MRI) and previously described algorithms. RESULTS: Typical/diffuse atrophy was associated with faster cognitive decline and the highest risk of developing dementia and Alzheimer's disease (AD) over time, both in the whole analytic sample and in amyloid-positive participants. Hippocampal-sparing and limbic-predominant atrophy were also associated with incident dementia, with faster cognitive decline in the limbic predominant atrophy group. Lewy body dementia was more frequent in the hippocampal-sparing and minimal/no atrophy groups. DISCUSSION: Atrophy subtypes categorization predicted different subsequent patterns of cognitive decline and rates of conversion to distinct etiologies of dementia in persons attending memory clinics.

Multimorbidity in Elderly Persons According to the Year of Diagnosis of Human Immunodeficiency Virus Infection: A Cross-sectional Dat'AIDS Cohort Study.

BACKGROUND: We assessed prevalence of multimorbidity (MM) according to year of human immunodeficiency virus (HIV) diagnosis in elderly people living with HIV (PLWH). METHODS: This was a cross-sectional study of MM in PLWH aged ≥70 years from the Dat'AIDS French multicenter cohort. MM was defined as at least 3 coexistent morbidities of high blood pressure, diabetes mellitus, osteoporosis, non-AIDS cancer, chronic renal failure, cardiovascular and cerebrovascular disease, obesity, undernutrition, or hypercholesterolemia. Logistic regression models evaluated the association between MM and calendar periods of HIV diagnosis (1983-1996, 1997-2006, and 2007-2018). The secondary analysis evaluated MM as a continuous outcome, and a sensitivity analysis excluded PLWH with nadir CD4 count <200 cells/µL. RESULTS: Between January 2017 and September 2018, 2476 PLWH were included. Median age was 73 years, 75% were men, median CD4 count was 578 cells/µL, and 94% had controlled viremia. MM prevalence was 71%. HBP and hypercholesterolemia were the most prevalent comorbidities. After adjustment for age, gender, smoking status, hepatitis C and hepatitis B virus coinfection, group of exposure, nadir CD4 count, CD4:CD8 ratio, and last CD4 level, calendar period of diagnosis was not associated with MM (P = .169). MM was associated with older age, CD4/CD8 ratio <0.8, and nadir CD4 count <200 cells/µL. Similar results were found with secondary and sensitivity analyses. CONCLUSIONS: MM prevalence was high and increased with age, low CD4/CD8 ratio, and nadir CD4 count <200 cells/µL but was not associated with calendar periods of HIV diagnosis. Known duration of HIV diagnosis does not seem to be a criterion for selecting elderly PLWH at risk of MM.

Association between executive function and the evolution of behavioral disorders in Alzheimer's disease.

OBJECTIVE: This study was aimed at evaluating the association between cognitive functioning and the occurrence of behavioral and psychological symptoms of dementia (BPSD) in patients with Alzheimer's disease (AD). METHODS/DESIGN: The population is derived from the PACO cohort, including 237 patients with prodromal or mild AD. A neuropsychological tests battery exploring verbal and visual memory, language, attention, and executive functions was performed at baseline. BPSD were assessed at 6-, 12-, and 18-month follow-up with neuropsychiatric inventory (NPI). RESULTS: Lower baseline performance on Stroop test interference score was associated with higher subsequent overall NPI scores (P = .006), subscores of anxiety/depression (P = .03), and apathy inventory (P = .01). Conversely, other executive functions, verbal or visual memory, and language performances were not associated with a higher risk of BPSD. CONCLUSION: Our results suggest that poorer inhibition performance would be associated with a higher risk of 18-month BPSD occurrence, including anxiety, depression, and apathy. A better knowledge of the predictive factors of the BPSDs would make it possible to better identify the patients at risk, to propose preventive strategies and an earlier adapted care. J Am Geriatr Soc 68:-, 2020.

Cerebral amyloid angiopathy with focal presentation-about 3 cases.

Cerebral amyloid angiopathy (CAA) is a common cerebrovascular disease involved in ischemic and hemorrhagic strokes, and its progression is correlated to cognitive decline. In vivo diagnosis of CAA is guided by the modified Boston criteria, with the presence of multiple intracerebral hemorrhage or cerebral microbleeds (CMB), or single hemorrhage and cortical superficial siderosis. The diagnosis of CAA is highly dependent on the quality of imaging and the advent of susceptibility-weighted imaging (SWI) sequences has improved sensitivity of MRI to detect hemosiderin deposition and CMB, hallmarks of CAA. We report here 3 clinical cases of patients with Alzheimer's disease and a focal form (i.e., not disseminated) of probable CAA, diagnosed with SWI sequences. Focal CAA may require closer attention and could offer keys in the understanding of both Alzheimer's disease and CAA pathogenesis.

Description of the Treatment Course by Pregabalin for Anxiety in Patients With a Major Neurocognitive Disorder.

BACKGROUND: Anxiety symptoms frequently experienced by patients with a major neurocognitive disorder (NCD) are often treated with long-term benzodiazepines despite known adverse effects. Pregabalin has shown efficacy in generalized anxiety disorders but has not been studied in patients with a major NCD. The objective of this study was to describe the use of pregabalin for anxiety in patient with a major NCD and the impact of its use on the pharmacological treatment change. METHODS: A retrospective study was conducted using data of hospitalized patients in a cognitive-behavioral specialized unit between January 2015 and December 2017. Patients with a major NCD treated by pregabalin were included in this study. Data about the use of pregabalin (initiation and effective dosage, titration duration) and the use of other psychotropics were collected from the patients' medical records. RESULTS: Thirty-three patients were included (mean age, 79.6 ± 11.7 years; 66.7% women). The mean duration of pregabalin titration was 18.6 ± 1.4 days, and the mean effective dosage was 200.0 ± 130.8 mg/d (range, 50-700 mg/d). At admission (before pregabalin use), 78.8% of patients were treated with a systematic prescription of benzodiazepine. At discharge (with pregabalin use), a significant decrease in patients with systematic prescription of benzodiazepine was observed (78.8% vs 33.3%, P = 0.001). During hospitalizations, no pregabalin treatment has been discontinued for lack of efficacy or for tolerance. CONCLUSIONS: Larger controlled studies are needed to confirm the efficacy and the safety of pregabalin to treat anxiety symptoms associated with neurocognitive disorders.

A multicenter cohort study to investigate the factors associated with functional autonomy change in patients with cognitive complaint or neurocognitive disorders: the MEMORA study protocol.

BACKGROUND: The identification of factors associated with functional impairment, in particular those which are potentially modifiable, may help to delay the advanced stages of functional dependence in patients with neurocognitive disorders such as Alzheimer's disease and related disorders. The objectives of the MEMORA cohort are to investigate the factors associated, first with functional autonomy change over time, and secondarily with the cognitive performance and behavioral disorders changes over time. METHODS: The MEMORA study is a multicenter prospective cohort study carried out throughout the patient's care pathway, in Memory centers of Lyon (France). The study will include 6780 patients at all stages of memory disorders in 6 years. The follow-up for each patient is planned for 3 years. The main outcome is the functional autonomy level change as assessed by the instrumental abilities of daily living (IADL) score. Patient characteristics include sociodemographic and clinical features, neuropsychological performance, pharmaceutical and non-pharmaceutical therapy. DISCUSSION: This study conducted in a context of routine care may help to identify the factors associated with functional impairment related to progressive neurocognitive disorders. Subsequently, interventions on potentially modifiable factors could be proposed to the patients to improve their management and delay functional dependence. TRIAL REGISTRATION: NCT02302482 , registered 27 November 2014.

Study protocol on Alzheimer's disease and related disorders: focus on clinical and imaging predictive markers in co-existing lesions.

BACKGROUND: One of the crucial challenges for the future of therapeutic approaches to Alzheimer's disease (AD) is to target the main pathological processes responsible for disability and dependency. However, a progressive cognitive impairment occurring after the age of 70, the main population affected by dementia, is often related to mixed lesions of neurodegenerative and vascular origins. Whereas young patients are mostly affected by pure lesions, ageing favours the occurrence of co-lesions of AD, cerebrovascular disease (CVD) and Lewy body dementia (LBD). Most of clinical studies report on functional and clinical disabilities in patients with presumed pure pathologies. But, the weight of co-morbid processes involved in the transition from an independent functional status to disability in the elderly with co-lesions still remains to be elucidated. Neuropathological examination often performed at late stages cannot answer this question at mild or moderate stages of cognitive disorders. Brain MRI, Single Photon Emission Computed Tomography (SPECT) with DaTscan®, amyloid Positron Emission Tomography (PET) and CerebroSpinal Fluid (CSF) AD biomarkers routinely help in performing the diagnosis of underlying lesions. The combination of these measures seems to be of incremental value for the diagnosis of mixed profiles of AD, CVD and LBD. The aim is to determine the clinical, neuropsychological, neuroradiological and biological features the most predictive of cognitive, behavioral and functional impairment at 2 years in patients with co-existing lesions. METHODS: A multicentre and prospective cohort study with clinical, neuro-imaging and biological markers assessment will recruit 214 patients over 70 years old with a cognitive disorder of AD, cerebrovascular and Lewy body type or with coexisting lesions of two or three of these pathologies and fulfilling the diagnostic criteria for dementia at a mild to moderate stage. Patients will be followed every 6 months (clinical, neuropsychological and imaging examination and collection of cognitive, behavioural and functional impairment) for 24 months. DISCUSSION: This study aims at identifying the best combination of markers (clinical, neuropsychological, MRI, SPECT-DaTscan®, PET and CSF) to predict disability progression in elderly patients presenting coexisting patterns. TRIAL REGISTRATION: NCT02052947 .

Neurocognitive disorders: what are the prioritized caregiver needs? A consensus obtained by the Delphi method.

BACKGROUND: The symptoms related to neurocognitive disorders (NCD) may lead to caregiver burden increase. Involving caregivers in research may be an effective way of improving the practicalities and relevance of interventions. The aim of this study was to gather opinion and gain consensus on the caregivers 'priorities, using a Delphi method and including aspects of needs in pharmaceutical dimension. METHODS: Observational study using a modified Delphi method. This study was conducted in the Clinical and Research Memory Center of the University Hospital of Lyon (France), between September 2015 and January 2016. The expert panel was composed of 68 informal caregivers of people with subjective cognitive decline or NCD living at home. RESULTS: Caregivers assigned a very high importance to the dimension "information needs about their relative's disease", i.e. information on the disease, the treatment and the research; and to "coping skills", i.e. skills related to emotional support, communication, relationship evolution with the relative and skills to cope with behavioural crisis, behavioural and cognitive disorders. The aspect "coping with behavioural disorders" received a high selection rate (83%). CONCLUSIONS: The main needs selected can be used to design relevant interventions and give guidance to policy to support caregivers. To meet caregiver's needs, interventions should focus on information about disease and treatment and psychoeducational interventions.

Added value of 18F-florbetaben amyloid PET in the diagnostic workup of most complex patients with dementia in France: A naturalistic study.

INTRODUCTION: Although some studies have previously addressed the clinical impact of amyloid positron emission tomography (PET), none has specifically addressed its selective and hierarchical implementation in relation to cerebrospinal fluid analysis in a naturalistic setting. METHODS: This multicenter study was performed at French tertiary memory clinics in patients presenting with most complex clinical situations (i.e., early-onset, atypical clinical profiles, suspected mixed etiological conditions, unexpected rate of progression), for whom cerebrospinal fluid analysis was indicated but either not feasible or considered as noncontributory (ClinicalTrials.gov: NCT02681172). RESULTS: Two hundred five patients were enrolled with evaluable florbetaben PET scans; 64.4% of scans were amyloid positive. PET results led to changed diagnosis and improved confidence in 66.8% and 81.5% of patients, respectively, and altered management in 80.0% of cases. DISCUSSION: High-level improvement of diagnostic certainty and management is provided by selective and hierarchical implementation of florbetaben PET into current standard practices for the most complex dementia cases.