Digital Biomarkers for the Assessment of Non-Cognitive Symptoms in Patients with Dementia with Lewy Bodies: A Systematic Review.

Background: Portable digital health technologies (DHTs) could help evaluate non-cognitive symptoms, but evidence to support their use in patients with dementia with Lewy bodies (DLB) is uncertain. Objective: 1) To describe portable or wearable DHTs used to obtain digital biomarkers in patients with DLB, 2) to assess the digital biomarkers' ability to evaluate non-cognitive symptoms, and 3) to assess the feasibility of applying digital biomarkers in patients with DLB. Methods: We systematically searched databases MEDLINE, Embase, and Web of Science from inception through February 28, 2023. Studies assessing digital biomarkers obtained by portable or wearable DHTs and related to non-cognitive symptoms were eligible if including patients with DLB. The quality of studies was assessed using a modified check list based on the NIH Quality assessment tool for Observational Cohort and Cross-sectional Studies. A narrative synthesis of data was carried out. Results: We screened 4,295 records and included 20 studies. Seventeen different DHTs were identified for assessment of most non-cognitive symptoms related to DLB. No thorough validation of digital biomarkers for measurement of non-cognitive symptoms in DLB was reported. Studies did not report on aspects of feasibility in a systematic way. Conclusions: Knowledge about feasibility and validity of individual digital biomarkers remains extremely limited. Study heterogeneity is a barrier for establishing a broad evidence base for application of digital biomarkers in DLB. Researchers should conform to recommended standards for systematic evaluation of digital biomarkers.

Differential diagnosis of MCI with Lewy bodies and MCI due to Alzheimer's disease by visual assessment of occipital hypoperfusion on SPECT images.

PURPOSE: Predicting progression of mild cognitive impairment (MCI) to Alzheimer's disease (AD) or dementia with Lewy bodies (DLB) is important. We evaluated morphological and functional differences between MCI with Lewy bodies (MCI-LB) and MCI due to AD (MCI-AD), and a method for differentiating between these conditions using brain MRI and brain perfusion SPECT. METHODS: A continuous series of 101 subjects, who had visited our memory clinic and met the definition of MCI, were enrolled retrospectively. They were consisted of 60 MCI-LB and 41 MCI-AD subjects. Relative cerebral blood flow (rCBF) on SPECT images and relative brain atrophy on MRI images were evaluated. We performed voxel-based analysis and visually inspected brain perfusion SPECT images for regional brain atrophy, occipital hypoperfusion and the cingulate island sign (CIS), for differential diagnosis of MCI-LB and MCI-AD. RESULTS: MRI showed no significant differences in regional atrophy between the MCI-LB and MCI-AD groups. In MCI-LB subjects, occipital rCBF was significantly decreased compared with MCI-AD subjects (p < 0.01, family wise error [FWE]-corrected). Visual inspection of occipital hypoperfusion had sensitivity, specificity, and accuracy values of 100%, 73.2% and 89.1%, respectively, for differentiating MCI-LB and MCI-AD. Occipital hypoperfusion was offered higher diagnostic utility than the CIS. CONCLUSIONS: The occipital lobe was the region with significantly decreased rCBF in MCI-LB compared with MCI-AD subjects. Occipital hypoperfusion on brain perfusion SPECT may be a more useful imaging biomarker than the CIS for visually differentiating MCI-LB and MCI-AD.

Burden of Illness Among Patients with Psychosis due to Dementia with Lewy Bodies and Other Dementias.

Limited research is available on the real-world experiences of patients with dementia with Lewy bodies (DLB). This study evaluated clinical events, healthcare utilization, and healthcare costs of patients with DLB vs other dementia types with psychosis (ODP). Study patients included commercial and Medicare Advantage with Part D enrollees aged ≥40 years with evidence of DLB and ODP from 6/01/2015‒5/31/2019. Compared with patients with ODP, more patients with DLB had clinical events including anticholinergic effects, neurologic effects, and cognitive decline. Patients with DLB used more healthcare resources with greater dementia-related office and outpatient visits and psychosis-related inpatient stays and office, outpatient, and emergency visits compared with their ODP patient counterparts. Patients with DLB also incurred higher healthcare costs for all-cause and dementia-related office visits and pharmacy fills, and psychosis-related total costs. Understanding the clinical and economic impact of DLB and ODP is important to improve care for patients with dementia.

Costs During the Last Five Years of Life for Patients with Clinical and Pathological Confirmed Diagnosis of Lewy Body Dementia and Alzheimer's Disease.

BACKGROUND: Little is known regarding healthcare expenditures for patients with dementia with Lewy bodies (DLB) during the end of life. OBJECTIVE: This study estimated Medicare expenditures during the last 5 years of life in a decedent sample of patients who were clinically diagnosed with Alzheimer's disease (AD) or DLB and had autopsy confirmed diagnosis. METHODS: The study included 58 participants clinically diagnosed with mild dementia at study entry (AD: n = 44, DLB: n = 14) and also had autopsy-confirmed diagnoses of pure AD (n = 32), mixed AD+Lewy body (LB) (n = 5), or pure LB (n = 11). Total Medicare expenditures were compared by clinical and pathology confirmed diagnosis, adjusting for sex, age at death, and patient's cognition, function, comorbidities, and psychiatric and extrapyramidal symptoms. RESULTS: When pathology diagnoses were not considered, predicted annualized total Medicare expenditures during the last 5 years of life were similar between clinically diagnosed AD ($7,465±1,098) and DLB ($7,783±1,803). When clinical diagnoses were not considered, predicted expenditures were substantially higher in patients with pathology confirmed mixed AD+LB ($12,005±2,455) than either pure AD ($6,173±941) or pure LB ($4,629±1,968) cases. Considering clinical and pathology diagnosis together, expenditures for patients with clinical DLB and pathology mixed AD+LB ($23,592±3,679) dwarfed other groups. CONCLUSION: Medicare expenditures during the last 5 years of life were substantially higher in patients with mixed AD+LB pathology compared to those with pure-AD and pure-LB pathologies, particularly in those clinically diagnosed with DLB. Results highlight the importance of having both clinical and pathology diagnoses in examining healthcare costs.

Costs of dementia with lewy bodies: A Chinese multicenter cross-sectional study.

INTRODUCTION: Dementia with Lewy bodies (DLB) significantly increases the economic burden on caregivers and society, but few studies have focused on the costs. This study aims to evaluate the current economic costs of DLB and its related factors. METHODS: A total of 193 patients diagnosed with probable DLB were consecutively enrolled from 6 memory clinics between August 2017 to July 2021. Data were collected from August to December of 2021, patients' per capita annual economic costs related to DLB in the year preceding the interview were evaluated, and factors related to the costs were assessed using regression analysis. RESULTS: Patients with DLB led to per capita annual total costs of US $21,378.3 in 2021, with direct medical costs, direct non-medical costs and indirect costs of US $3471.4, US $3946.4 and US $13,960.5, respectively, accounting for 16.2%, 18.5% and 65.3%, of total costs. Factors related to the costs of DLB showed that impairments in activities of daily living (ADL) and caregivers' subjective burden had a greater impact on the total, direct medical and indirect costs. CONCLUSION: The economic burden of DLB in China is huge, and indirect costs account for the largest proportion, serious impairment of the ADL and the subjective burden of caregivers, which possibly has a greater effect on costs. The substantial contributions made by family members and other unpaid caregivers of DLB should be fully recognized in strategic policy discussions and in case-level planning and assessments.

Assessment of clinical features and coexisting geriatric syndromes in newly diagnosed dementia with Lewy bodies: a retrospective study in a tertiary geriatrics setting in Turkey.

PURPOSE: Identifying the associated clinical conditions in patients with newly diagnosed dementia with Lewy bodies (DLB) may contribute to the disease management. This study aimed to examine the clinical features and coexisting geriatric syndromes of patients with newly diagnosed DLB. METHOD: This cross-sectional study included newly diagnosed DLB participants who were admitted to a tertiary geriatric outpatient clinic. Of the 857 patients with dementia, 116 DLB diagnoses were eligible for analysis. The core and supportive clinical features of DLB were recorded. Geriatric syndromes including polypharmacy, depression, insomnia, dependency, a history of delirium, falls, malnutrition, urinary incontinence, functional impairment, and living alone, were assessed and recorded at baseline. RESULTS: The mean age was 79.0 ± 6.9 years, and 50.9% of the participants were female. The majority (63.8%) had mild dementia, 31.9% had moderate, and 4.3% had severe disease. Cognitive fluctuations (78.4%), visual hallucinations (77.6%), and Parkinsonism (73.3%) were the most common clinical features. Functional impairment (59.5%) and urinary incontinence (59.5%) were the leading geriatric syndromes, followed by polypharmacy (56.9%), depressive symptoms (54.7%), falls (52.6%), insomnia (49.1%), malnutrition (24.3%), and delirium (6.0%). Women had more functional impairment and depressive symptoms than men. CONCLUSION: Although most patients had mild dementia, three-quarters of the DLB cohort had hallucinations, and nearly two-thirds were functionally impaired. The proportion of other serious health conditions also increased, indicating a high comorbidity and geriatric syndrome burden. Comprehensive geriatric assessment is strongly recommended for DLB patients from the time of diagnosis until death to reduce disability and comorbidities. THE CLINICAL TRIAL REGISTRATION NUMBER: NCT05052450.

Family Caregiver Comorbidities in Lewy Body Dementia Versus Alzheimer Disease and Associated Disorders.

BACKGROUND: Family caregivers of people living with dementia have high caregiver strain and poor health consequences. Limited research exists on Lewy body dementia (LBD) caregivers and their specific comorbidities. This study aimed to (1) identify the prevalence of self-reported comorbidities among LBD caregivers and (2) contextualize these findings with historical data on caregivers of persons living with Alzheimer disease and associated disorders (ADADs). METHODS: In a national, online survey, LBD family caregivers completed the Self-Administered Comorbidity Questionnaire and we compared these findings with extant literature on ADAD caregiver comorbidities. RESULTS: Among 217 LBD caregivers, 84.3% were female, 39.1% were 64 years old or younger, and 66.8% had >2 years of caregiving experience. Caregivers self-identified as current (83.9%) or former (16.1%) caregivers. The most frequent comorbidities were hypertension (38.2%), depression (35.0%), back pain (34.1%), and arthritis (27.7%). LBD caregivers, particularly younger caregivers, had a higher prevalence of depression compared with ADAD caregivers and older adult populations, and back pain prevalence nearly equivalent to spinal cord injury caregivers. CONCLUSIONS: Our study is the first to illustrate and contextualize specific comorbidities among LBD caregivers. Understanding the causality and impact of these conditions will be critical in designing effective interventions to improve the lives of families affected by LBD.

Functional loss and worsening geriatric assessment parameters are more common in dementia with Lewy bodies than Alzheimer's disease.

BACKGROUND: The main aim of this study was to compare older patients with Alzheimer's disease (AD) to those with dementia with Lewy bodies (DLB) according to their dependency in daily living activities and comprehensive geriatric assessment parameters. METHOD: A total of 227 AD and 123 DLB patients underwent a geriatric assessment that included comorbidities, number of drugs used, falls, urinary incontinence, hand grip strength, Mini-Nutritional Assessment (MNA), Tinetti Performance Oriented Mobility Assessment Scale, Insomnia Severity Index (ISI), and Epworth Sleepiness Scale. Basic and instrumental activities of daily living were assessed by the Barthel Index and the Lawton scale, respectively. RESULTS: The mean age of the participants was 83.4 years, and 73% were female. There were no statistically significant differences between AD and DLB patients in age, gender, cognitive function, or comorbidities except for coronary artery disease (P < 0.05). The number of falls, drugs used, and ISI and Epworth scores were higher in patients with DLB than patients with AD (P < 0.05). DLB patients had lower MNA, Tinetti scale, and hand grip strength scores than AD patients. The ratio of patients highly dependent in basic daily activities as a whole was significantly greater in DLB than in AD (P < 0.05), but there was no significant difference in the overall levels of dependency in instrumental activities. CONCLUSION: DLB patients are more dependent on their caregivers than AD patients. Nutritional deterioration, sleep disorders, falls, balance and gait problems, decreased muscle strength, and multiple drug use are more common in those with DLB compared to those with AD. The management of older patients with DLB may be more difficult than older patients with AD.

Clinical outcomes and treatment patterns of older adults with dementia-related psychosis by dementia type in the United States.

BACKGROUND: Little is known about the incidence of clinical events and treatment patterns among older adults with dementia-related psychosis. Given that dementia-related psychosis comprises various dementia types, this study describes the incidence of clinical events and treatment patterns by dementia type after patients with dementia are diagnosed with psychosis. METHODS: Adults aged ≥ 65 years with dementia and newly diagnosed with psychosis were identified in US Medicare claims during 2013-2018. Baseline characteristics were evaluated at the time of the psychosis diagnosis. After the initial psychosis diagnosis, incidence rates (IRs) of clinical events (e.g., falls/fractures, infections, healthcare utilization), mortality, and patterns of antipsychotic treatment were described for each dementia type (Alzheimer's disease [AD], Parkinson's disease dementia [PDD], dementia with Lewy bodies [DLB], frontotemporal dementia [FTD], vascular dementia [VD], and unspecified dementia). Daily mean cumulative counts were estimated to describe the incidence of recurrent events over time. Mortality was described using Kaplan-Meier survival curves. RESULTS: We identified 484,520 patients with dementia-related psychosis: mean age, 84 years (standard deviation, 7.8); female, 66%. At the time of psychosis diagnosis, the most prevalent type of dementia was unspecified dementia (56%), followed by AD (31%), VD (12%), PDD (10%), DLB (3%), and FTD (< 1%), and most patients had scores indicating severe illness on the Charlson Comorbidity Index (71%) and frailty index (62%). Across all dementia types, IRs (per 100 person-years) were high for emergency department visits, oral anti-infective use, and urinary tract infections after the initial psychosis diagnosis. Patients with DLB had the highest incidence of most clinical outcomes. After 1 year of follow-up, the cumulative probability of death was about 30% for all dementia types, and after 5 years, was about 80% among patients with DLB, VD, AD, or PDD and about 60%-65% among patients with FTD or unspecified dementia. CONCLUSIONS: Patients with dementia-related psychosis had a high burden of comorbidities, frailty, emergency department visits, infections, and death. Specifically, after DRP diagnosis, patients with DLB and VD had the highest burden of clinical events of interest.

Can we really 'read' art to see the changing brain? A review and empirical assessment of clinical case reports and published artworks for systematic evidence of quality and style changes linked to damage or neurodegenerative disease.

The past three decades have seen multiple reports of people with neurodegenerative disorders, or other forms of changes in their brains, who also show putative changes in how they approach and produce visual art. Authors argue that these cases may provide a unique body of evidence, so-called 'artistic signatures' of neurodegenerative diseases, that might be used to understand disorders, provide diagnoses, be employed in treatment, create patterns of testable hypotheses for causative study, and also provide unique insight into the neurobiological linkages between the mind, brain, body, and the human penchant for art-making itself. However-before we can begin to meaningfully build from such emerging findings, much less formulate applications-not only is such evidence currently quite disparate and in need of systematic review, almost all case reports and artwork ratings are entirely subjective, based on authors' personal observations or a sparse collection of methods that may not best fit underlying research aims. This leads to the very real question of whether we might actually find patterns of systematic change if fit to a rigorous review-Can we really 'read' art to illuminate possible changes in the brain? How might we best approach this topic in future neuroscientific, clinical, and art-related research? This paper presents a review of this field and answer to these questions. We consider the current case reports for seven main disorders-Alzheimer's and Parkinson's disease, frontotemporal and Lewy body dementia, corticobasal degeneration, aphasia, as well as stroke-consolidating arguments for factors and changes related to art-making and critiquing past methods. Taking the published artworks from these papers, we then conduct our own assessment, employing computerized and human-rater-based approaches, which we argue represent best practice to identify stylistic or creativity/quality changes. We suggest, indeed, some evidence for systematic patterns in art-making for specific disorders and also find that case authors showed rather high agreement with our own assessments. More important, through opening this topic and past evidence to a systematic review, we hope to open a discussion and provide a theoretical and empirical foundation for future application and research on the intersection of art-making and the neurotypical, the changed, and the artistic brain.

Conversion Between the Mini-Mental State Examination and the Montreal Cognitive Assessment for Patients With Different Forms of Dementia.

OBJECTIVES: The Mini-Mental Status Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) are 2 frequently used brief cognitive screening tasks. Here, we provide a conversion method from MMSE to MoCA for patients with Alzheimer's dementia, frontotemporal dementia, and Parkinson dementia/Lewy body dementia, as well as for patients with dementia and with or without previous stroke. This conversion is needed as everyday clinical practice varies in their use of the 2 scales, which makes comparisons between studies, meta-analysis, and patient cohorts difficult. DESIGN: Observational cohort study. SETTING AND PARTICIPANTS: A total of 387 patients with recently diagnosed dementia in memory clinics from the Swedish registry for cognitive/dementia disorders (SveDem) from 2007 to 2018. METHODS: Overall, 387 patients of the Swedish registry for cognitive/dementia disorders with both MMSE and MoCA scores were evaluated. An equipercentile equating method was used to convert MMSE to MoCA scores in the different patient populations. Furthermore, receiver operating curves were used to examine whether MMSE or MoCA scores can distinguish between patients with different dementia types. RESULTS: MMSE scores were converted to MoCA scores for all dementia types and depicted in a conversion table. Results show that the equipercentile equating method and log-linear smoothing allow the creation of a conversion table in which for each test score of the MMSE, the equivalent score of the MoCA for each investigated group can be looked up (and vice-versa). CONCLUSIONS AND IMPLICATIONS: This study reports a reliable and easy conversion for transforming MMSE to MoCA scores (and vice-versa) in patients with Alzheimer's dementia, frontotemporal dementia, Parkinson dementia or Lewy body dementia, as well as patients with dementia with and without previous stroke.

Epidemiology and economic burden of Lewy body dementia in the United States.

OBJECTIVE: To describe the trends in epidemiology, healthcare resource use (HCRU), and costs associated with Lewy body dementia (LBD), dementia with Lewy bodies (DLB), and Parkinson's disease dementia (PDD) in the United States. METHODS: This retrospective study used administrative claims data for Medicare fee-for-service (2010-2018) and commercially-insured beneficiaries (2010-2017). The annual prevalence and incidence were calculated among the Medicare beneficiaries by dividing the number of prevalent or incident LBD, DLB, and PDD patients by the total eligible population of that calendar year. Baseline patient characteristics, HCRU, and costs over time were described for Medicare and commercially insured patients with continuous health plan enrollment for ≥12 months before and ≥24 months after first cognitive impairment (CI) diagnosis. RESULTS: From 2010 to 2016, the incidence and prevalence rates of LBD among Medicare beneficiaries ranged from 0.21%-0.18% and 0.90%-0.83%, respectively. Of 9019 Medicare patients with LBD who met other inclusion criteria, 4796 (53.2%) had DLB and 4223 (46.8%) had PDD. The mean age was 78 years and the mean Charlson Comorbidity Index score was 1.6. On average, patients with LBD incurred $18,309 in medical costs during the 1-year pre-diagnosis and $29,174 and $22,814 at years 1 and 5 after diagnosis, respectively. The main cost drivers were inpatient and outpatient visits. Similar trends were observed for DLB and PDD as well as for commercially-insured patients. CONCLUSIONS: Our findings highlight the substantial epidemiological and economic burden across the LBD spectrum and underscore a high unmet need for effective treatments to improve patient outcomes.

Assessment of autonomic symptoms may assist with early identification of mild cognitive impairment with Lewy bodies.

OBJECTIVES: Autonomic symptoms are a common feature of the synucleinopathies, and may be a distinguishing feature of prodromal Lewy body disease. We aimed to assess whether the cognitive prodrome of dementia with Lewy bodies, mild cognitive impairment (MCI) with Lewy bodies (MCI-LB), would have more severe reported autonomic symptoms than cognitively healthy older adults, with MCI due to Alzheimer's disease (MCI-AD) also included for comparison. We also aimed to assess the utility of an autonomic symptom scale in differentiating MCI-LB from MCI-AD. METHODS: Ninety-three individuals with MCI and 33 healthy controls were assessed with the Composite Autonomic Symptom Score 31-item scale (COMPASS). Mild cognitive impairment patients also underwent detailed clinical assessment and differential classification of MCI-AD or MCI-LB according to current consensus criteria. Differences in overall COMPASS score and individual symptom sub-scales were assessed, controlling for age. RESULTS: Age-adjusted severity of overall autonomic symptomatology was greater in MCI-LB (Ratio = 2.01, 95% CI: 1.37-2.96), with higher orthostatic intolerance and urinary symptom severity than controls, and greater risk of gastrointestinal and secretomotor symptoms. MCI-AD did not have significantly higher autonomic symptom severity than controls overall. A cut-off of 4/5 on the COMPASS was sensitive to MCI-LB (92%) but not specific to this (42% specificity vs. MCI-AD and 52% vs. healthy controls). CONCLUSIONS: Mild cognitive impairment with Lewy bodies had greater autonomic symptom severity than normal ageing and MCI-AD, but such autonomic symptoms are not a specific finding. The COMPASS-31 may therefore have value as a sensitive screening test for early-stage Lewy body disease.

Influence of brain atrophy using semiquantitative analysis in [123I]FP-CIT single-photon emission computed tomography by a Monte Carlo simulation study.

The specific binding ratio (SBR) is an objective indicator of N-ω-fluoropropyl-2ß-carbomethoxy-3ß-(4-[123I] iodophenyl) nortropane ([123I]FP-CIT) single-photon emission computed tomography (SPECT) that could be used for the diagnosis of Parkinson's disease and Lewy body dementia. One of the issues of the SBR analysis is that the setting position of the volume of interest (VOI) may contain cerebral ventricles and cerebral grooves. These areas may become prominent during the brain atrophy analysis; however, this phenomenon has not been evaluated enough. This study thus used Monte Carlo simulations to examine the effect of brain atrophy on the SBR analysis. The brain atrophy model (BAM) used to simulate the three stages of brain atrophy was made using a morphological operation. Brain atrophy levels were defined in the descending order from 1 to 3, with Level 3 indicating to the most severe damage. Projection data were created based on BAM, and the SPECT reconstruction was performed. The ratio of the striatal to background region accumulation was set to a rate of 8:1, 6:1, and 4:1. The striatal and the reference VOI mean value were decreased as brain atrophy progressed. Additionally, the Bolt's analysis methods revealed that the reference VOI value was more affected by brain atrophy than the striatal VOI value. Finally, the calculated SBR value was overestimated as brain atrophy progressed, and a similar trend was observed when the ratios of the striatal to background region accumulation were changed. This study thus suggests that the SBR can be overestimated in cases of advanced brain atrophy.

[Assessment of the knowledge of Lewy body disease by health care professionnels compared to Alzheimer's disease: result of a descriptive analytical study]. / Évaluation des connaissances par les professionnels de santé de la maladie à corps de Lewy comparativement à la maladie d'Alzheimer : résultat d'une étude analytique descriptive.

BACKGROUND: Dementia with Lewy body (DLB) is a common neurodegenerative disease that warrants specific care, which remains largely underdiagnosed. Our objective was to assess the knowledge of DLB by health professionals in comparison with that of Alzheimer's disease (AD), to better understand the reasons of its under-diagnosis. METHODS: We conducted a descriptive and analytical study processing the results of an online questionnaire submitted to French healthcare professionals between December 1, 2020 and March 1, 2021. RESULTS: A total of 490 healthcare professionals responded to the questionnaire. We observed a poorer knowledge of DLB compared to AD both subjective as highlighted on the self-assessment questionnaires and objective since the diagnostic criteria and therapeutic specificities were less known for DLB compared to AD. CONCLUSIONS: DLB appears as a disease that is still too poorly known by health professionals. To improve training is therefore a decisive objective in order to optimize the therapeutic care and support of patients with DLB and their relatives.

Mini-Mental State Examination (MMSE) for the early detection of dementia in people with mild cognitive impairment (MCI).

BACKGROUND: Dementia is a progressive global cognitive impairment syndrome. In 2010, more than 35 million people worldwide were estimated to be living with dementia. Some people with mild cognitive impairment (MCI) will progress to dementia but others remain stable or recover full function. There is great interest in finding good predictors of dementia in people with MCI. The Mini-Mental State Examination (MMSE) is the best-known and the most often used short screening tool for providing an overall measure of cognitive impairment in clinical, research and community settings. OBJECTIVES: To determine the accuracy of the Mini Mental State Examination for the early detection of dementia in people with mild cognitive impairment SEARCH METHODS: We searched ALOIS (Cochrane Dementia and Cognitive Improvement Specialized Register of diagnostic and intervention studies (inception to May 2014); MEDLINE (OvidSP) (1946 to May 2014); EMBASE (OvidSP) (1980 to May 2014); BIOSIS (Web of Science) (inception to May 2014); Web of Science Core Collection, including the Conference Proceedings Citation Index (ISI Web of Science) (inception to May 2014); PsycINFO (OvidSP) (inception to May 2014), and LILACS (BIREME) (1982 to May 2014). We also searched specialized sources of diagnostic test accuracy studies and reviews, most recently in May 2014: MEDION (Universities of Maastricht and Leuven, www.mediondatabase.nl), DARE (Database of Abstracts of Reviews of Effects, via the Cochrane Library), HTA Database (Health Technology Assessment Database, via the Cochrane Library), and ARIF (University of Birmingham, UK, www.arif.bham.ac.uk). No language or date restrictions were applied to the electronic searches and methodological filters were not used as a method to restrict the search overall so as to maximize sensitivity. We also checked reference lists of relevant studies and reviews, tracked citations in Scopus and Science Citation Index, used searches of known relevant studies in PubMed to track related articles, and contacted research groups conducting work on MMSE for dementia diagnosis to try to locate possibly relevant but unpublished data. SELECTION CRITERIA: We considered longitudinal studies in which results of the MMSE administered to MCI participants at baseline were obtained and the reference standard was obtained by follow-up over time. We included participants recruited and clinically classified as individuals with MCI under Petersen and revised Petersen criteria, Matthews criteria, or a Clinical Dementia Rating = 0.5. We used acceptable and commonly used reference standards for dementia in general, Alzheimer's dementia, Lewy body dementia, vascular dementia and frontotemporal dementia. DATA COLLECTION AND ANALYSIS: We screened all titles generated by the electronic database searches. Two review authors independently assessed the abstracts of all potentially relevant studies. We assessed the identified full papers for eligibility and extracted data to create two by two tables for dementia in general and other dementias. Two authors independently performed quality assessment using the QUADAS-2 tool. Due to high heterogeneity and scarcity of data, we derived estimates of sensitivity at fixed values of specificity from the model we fitted to produce the summary receiver operating characteristic curve. MAIN RESULTS: In this review, we included 11 heterogeneous studies with a total number of 1569 MCI patients followed for conversion to dementia. Four studies assessed the role of baseline scores of the MMSE in conversion from MCI to all-cause dementia and eight studies assessed this test in conversion from MCI to Alzheimer´s disease dementia. Only one study provided information about the MMSE and conversion from MCI to vascular dementia. For conversion from MCI to dementia in general, the accuracy of baseline MMSE scores ranged from sensitivities of 23% to 76% and specificities from 40% to 94%. In relationship to conversion from MCI to Alzheimer's disease dementia, the accuracy of baseline MMSE scores ranged from sensitivities of 27% to 89% and specificities from 32% to 90%. Only one study provided information about conversion from MCI to vascular dementia, presenting a sensitivity of 36% and a specificity of 80% with an incidence of vascular dementia of 6.2%. Although we had planned to explore possible sources of heterogeneity, this was not undertaken due to the scarcity of studies included in our analysis. AUTHORS' CONCLUSIONS: Our review did not find evidence supporting a substantial role of MMSE as a stand-alone single-administration test in the identification of MCI patients who could develop dementia. Clinicians could prefer to request additional and extensive tests to be sure about the management of these patients. An important aspect to assess in future updates is if conversion to dementia from MCI stages could be predicted better by MMSE changes over time instead of single measurements. It is also important to assess if a set of tests, rather than an isolated one, may be more successful in predicting conversion from MCI to dementia.

Comparison of the Caregiving Experience of Grief, Burden, and Quality of Life in Dementia with Lewy Bodies, Alzheimer's Disease, and Parkinson's Disease Dementia.

BACKGROUND: Caregivers of persons living with Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and Parkinson's disease dementia (PDD) are faced with numerous challenges. However, little is known about the caregiving experience across different dementias. OBJECTIVE: The aims of this cross-sectional study were to examine the differences in the caregiver experience between DLB, PDD, and AD. METHODS: Respondents were caregivers (N = 515; 384 DLB, 69 AD, 62 PDD) who completed a 230-question survey including sociodemographics, disease severity, neuropsychiatric symptoms, and measures of grief, burden, depression, quality of life, social support, well-being, care confidence, and mastery/self-efficacy. RESULTS: There were no differences in caregiver age, sex, race, or education, or in the distribution of disease severity between diagnostic groups. Constructs were highly intercorrelated with positive attributes (caregiver QoL, care recipient QoL, social support, well-being, mastery and care confidence) being inversely correlated with negative attributes (burden, grief, and depression). Across dementia etiologies, no differences were reported for quality of life, social support, depression, well-being, psychological well-being, mastery, care confidence, burden or grief. Instead, we found that the caregiver's experience was dependent on caregiver characteristics, person living with dementia characteristics and their most disturbing symptom, with behavior, personality changes, and sleep having the greatest effect on constructs. CONCLUSION: Caregiver ratings of psychosocial constructs may be more dependent on care recipient-caregiver dyad characteristics and the current symptoms than the underlying cause of those symptoms. Interventions to improve the caregiving experience should be developed to address specific psychosocial constructs rather than focusing on disease etiology or stage.

Introduction of an assessment toolkit associated with increased rate of DLB diagnosis.

BACKGROUND: Dementia with Lewy bodies (DLB) and dementia in Parkinson's disease (PDD) are recognised to be under-recognised in clinical practice in the UK, with only one third to a half of expected cases diagnosed. We aimed to assess whether clinical diagnostic rates could be increased by the introduction of a structured assessment toolkit for clinicians. METHODS: We established baseline diagnostic rates for DLB and PDD in four memory clinics and three movement disorder/Parkinson's disease (PD) clinics in two separate geographical regions in the UK. An assessment toolkit specifically developed to assist with the recognition and diagnosis of DLB and PDD was then introduced to the same clinical teams and diagnostic rates for DLB and PDD were reassessed. For assessing DLB diagnosis, a total of 3820 case notes were reviewed before the introduction of the toolkit, and 2061 case notes reviewed after its introduction. For PDD diagnosis, a total of 1797 case notes were reviewed before the introduction of the toolkit and 3405 case notes after it. Mean values and proportions were analysed using Student's t test for independent samples and χ2 test, respectively. RESULTS: DLB was diagnosed in 4.6% of dementia cases prior to the introduction of the toolkit, and 6.2% of dementia cases afterwards, an absolute rise of 1.6%, equal to a 35% increase in the number of DLB cases diagnosed when using the toolkit (χ2 = 4.2, P = 0.041). The number of PD patients diagnosed with PDD was not found overall to be significantly different when using the toolkit: 9.6% of PD cases before and 8.2% of cases after its introduction (χ2 = 1.8, P = 0.18), though the ages of PD patients assessed after the toolkit's introduction were lower (73.9 years vs 80.0 years, t = 19.2, p < 0.001). CONCLUSION: Introduction of the assessment toolkit was associated with a significant increase in the rate of DLB diagnosis, suggesting that a structured means of assessing symptoms and clinical features associated with DLB can assist clinicians in recognising cases. The assessment toolkit did not alter the overall rate of PDD diagnosis, suggesting that alternate means may be required to improve the rate of diagnosis of dementia in Parkinson's disease.

Characterization of symptoms and determinants of disease burden in dementia with Lewy bodies: DEvELOP design and baseline results.

BACKGROUND: The DEmEntia with LEwy bOdies Project (DEvELOP) aims to phenotype patients with dementia with Lewy bodies (DLB) and study the symptoms and biomarkers over time. Here, we describe the design and baseline results of DEvELOP. We investigated the associations between core and suggestive DLB symptoms and different aspects of disease burden, i.e., instrumental activities of daily living (IADL) functioning, quality of life (QoL), and caregiver burden. METHODS: We included 100 DLB patients (69 ± 6 years, 10%F, MMSE 25 ± 3) in the prospective DEvELOP cohort. Patients underwent extensive assessment including MRI, EEG/MEG, 123FP-CIT SPECT, and CSF and blood collection, with annual follow-up. Core (hallucinations, parkinsonism, fluctuations, RBD) and suggestive (autonomous dysfunction, neuropsychiatric symptoms) symptoms were assessed using standardized questionnaires. We used multivariate regression analyses, adjusted for age, sex, and MMSE, to evaluate how symptoms related to the Functional Activities Questionnaire, QoL-AD questionnaire, and Zarit Caregiver Burden Interview. RESULTS: In our cohort, RBD was the most frequently reported core feature (75%), while visual hallucinations were least frequently reported (39%) and caused minimal distress. Suggestive clinical features were commonly present, of which orthostatic hypotension was most frequently reported (64%). Ninety-five percent of patients showed EEG/MEG abnormalities, 88% of 123FP-CIT SPECT scans were abnormal, and 53% had a CSF Alzheimer's disease profile. Presence of fluctuations, lower MMSE, parkinsonism, and apathy were associated with higher IADL dependency. Depression, constipation, and lower IADL were associated with lower QoL-AD. Apathy and higher IADL dependency predisposed for higher caregiver burden. CONCLUSION: Baseline data of our prospective DLB cohort show clinically relevant associations between symptomatology and disease burden. Cognitive and motor symptoms are related to IADL functioning, while negative neuropsychiatric symptoms and functional dependency are important determinants of QoL and caregiver burden. Follow-up is currently ongoing to address specific gaps in DLB research.