Explore the vast range of titles available.

The broad importance of dementia is undisputed, with Alzheimer's disease justifiably getting the most attention. However, dementia with Lewy bodies and Parkinson's disease dementia, now called Lewy body dementias, are the second most common type of degenerative dementia in patients older than 65 years. Despite this, Lewy body dementias receive little attention and patients are often misdiagnosed, leading to less than ideal management. Over the past 10 years, considerable effort has gone into improving diagnostic accuracy by refining diagnostic criteria and using imaging and other biomarkers. Dementia with Lewy bodies and Parkinson's disease dementia share the same pathophysiology, and effective treatments will depend not only on successful treatment of symptoms but also on targeting the pathological mechanisms of disease, ideally before symptoms and clinical signs develop. We summarise the most pertinent progress from the past 10 years, outlining some of the challenges for the future, which will require refinement of diagnosis and clarification of the pathogenesis, leading to disease-modifying treatments.

BackgroundLate onset depression (LOD) may precede the diagnosis of Parkinson’s disease (PD) or dementia with Lewy bodies (DLB). We aimed to determine the rate of clinical and imaging features associated with prodromal PD/DLB in patients with LOD.MethodsIn a cross-sectional design, 36 patients with first onset of a depressive disorder (Diagnostic and Statistical Manual of Mental Disorders IV criteria) diagnosed after the age of 55 (LOD group) and 30 healthy controls (HC) underwent a detailed clinical assessment. In addition, 28/36 patients with LOD and 20/30 HC underwent a head MRI and 29/36 and 25/30, respectively, had dopamine transporter imaging by 123I-ioflupane single-photon emission computed tomography (SPECT) imaging. Image analysis of both scans was performed by a rater blind to the participant group. Results of clinical assessments and imaging results were compared between the two groups.ResultsPatients with LOD (n=36) had significantly worse scores than HC (n=30) on the PD screening questionnaire (mean (SD) 1.8 (1.9) vs 0.8 (1.2); p=0.01), Movement Disorder Society Unified Parkinson’s Disease Rating Scale total (mean (SD) 19.2 (12.7) vs 6.1 (5.7); p<0.001), REM-sleep behaviour disorder screening questionnaire (mean (SD) 4.3 (3.2) vs 2.1 (2.1); p=0.001), Lille Apathy Rating Scale (mean (SD) −23.3 (9.6) vs −27.0 (4.7); p=0.04) and the Scales for Outcomes in PD-Autonomic (mean (SD) 14.9 (8.7) vs 7.7 (4.9); p<0.001). Twenty-four per cent of patients with LOD versus 4% HC had an abnormal 123I-ioflupane SPECT scan (p=0.04).ConclusionsLOD is associated with increased rates of motor and non-motor features of PD/DLB and of abnormal 123I-ioflupane SPECTs. These results suggest that patients with LOD should be considered at increased risk of PD/DLB.

Background Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue currently approved for type 2 diabetes and obesity. Preclinical evidence in transgenic models of Alzheimer’s disease suggests that liraglutide exerts neuroprotective effects by reducing amyloid oligomers, normalising synaptic plasticity and cerebral glucose uptake, and increasing the proliferation of neuronal progenitor cells. The primary objective of the study is to evaluate the change in cerebral glucose metabolic rate after 12 months of treatment with liraglutide in participants with Alzheimer’s disease compared to those who are receiving placebo. Methods/design ELAD is a 12-month, multi-centre, randomised, double-blind, placebo-controlled, phase IIb trial of liraglutide in participants with mild Alzheimer’s dementia. A total of 206 participants will be randomised to receive either liraglutide or placebo as a daily injection for a year. The primary outcome will be the change in cerebral glucose metabolic rate in the cortical regions (hippocampus, medial temporal lobe, and posterior cingulate) from baseline to follow-up in the treatment group compared with the placebo group. The key secondary outcomes are the change from baseline to 12 months in z scores for clinical and cognitive measures (Alzheimer’s Disease Assessment Scale—Cognitive Subscale and Executive domain scores of the Neuropsychological Test Battery, Clinical Dementia Rating Sum of Boxes, and Alzheimer’s Disease Cooperative Study—Activities of Daily Living) and the incidence and severity of treatment-emergent adverse events or clinically important changes in safety assessments. Other secondary outcomes are 12-month change in magnetic resonance imaging volume, diffusion tensor imaging parameters, reduction in microglial activation in a subgroup of participants, reduction in tau formation and change in amyloid levels in a subgroup of participants measured by tau and amyloid imaging, and changes in composite scores using support machine vector analysis in the treatment group compared with the placebo group. Discussion Alzheimer’s disease is a leading cause of morbidity worldwide. As available treatments are only symptomatic, the search for disease-modifying therapies is a priority. If the ELAD trial is successful, liraglutide and GLP-1 analogues will represent an important class of compounds to be further evaluated in clinical trials for Alzheimer’s treatment. Trial registration ClinicalTrials.gov, NCT01843075 . Registration 30 April 2013.

Purpose We aim to report the quality of accuracy studies investigating the utility of [ 18 F]fluorodeoxyglucose (FDG)-PET in supporting the diagnosis of prodromal Alzheimer’s Disease (AD), frontotemporal lobar degeneration (FTLD) and prodromal dementia with Lewy bodies (DLB) in mild cognitive impairment (MCI) subjects, and the corresponding recommendations made by a panel of experts. Methods Seven panellist, four from the European Association of Nuclear Medicine, and three from the European Academy of Neurology, produced recommendations taking into consideration the incremental value of FDG-PET, as added on clinical-neuropsychological examination, to ascertain the aetiology of MCI (AD, FTLD or DLB). A literature search using harmonized population, intervention, comparison, and outcome (PICO) strings was performed, and an evidence assessment consistent with the European Federation of Neurological Societies guidance was provided. The consensual recommendation was achieved based on Delphi rounds. Results Fifty-four papers reported the comparison of interest. The selected papers allowed the identification of FDG patterns that characterized MCI due to AD, FTLD and DLB. While clinical outcome studies supporting the diagnosis of MCI due to AD showed varying accuracies (ranging from 58 to 100%) and varying areas under the receiver-operator characteristic curves (0.66 to 0.97), no respective data were identified for MCI due to FTLD or for MCI due to DLB. However, the high negative predictive value of FDG-PET and the existence of different disease-specific patterns of hypometabolism support the consensus recommendations for the clinical use of this imaging technique in MCI subjects. Conclusions FDG-PET has clinical utility on a fair level of evidence in detecting MCI due to AD. Although promising also in detecting MCI due to FTLD and MCI due to DLB, more research is needed to ultimately judge the clinical utility of FDG-PET in these entities.

Dementia is on the rise globally due to increasing life expectancies and population growth. Digital technologies may help detect early signs, enabling timely interventions to slow or reverse cognitive decline. However, to support the successful implementation of these digital technologies into health care settings, they must be acceptable to target users. Older adults and those with mild cognitive impairment (MCI) are at risk of developing dementia in later life and need to be able to use these technologies in order for this intervention to be approved and implemented in clinical practice. This study explored the perspectives of older adults and those living with a clinical diagnosis of MCI on the acceptability of using various digital technologies that have the potential to support early dementia detection. Participants were recruited from Boston University's Alzheimer's Disease Research Center. Participants selected at least 2 technologies from 9 different wearables and software to use for 2 weeks, at 3-month intervals, over a total duration of 2 years. A subgroup of self-selecting participants was interviewed after the first 2 weeks of use to gather initial perspectives regarding the acceptability of using the digital technologies. An inductive framework thematic analysis approach was used, assisted by NVivo (version 14.23.2; QSR International). In total, 13 individuals living with a clinical diagnosis of MCI and 11 adults aged 65 years and older were interviewed. Our analysis identified five key themes: (1) gamification, (2) wearability, (3) user guidance, (4) burden of use, and (5) usefulness. Gamified apps were generally liked, although users with little experience of digital games needed time to adjust. Wearables resembling everyday accessories (eg, watches) were preferred, but complaints about tight or uncomfortable straps were frequently reported. Clear instructions were critical to support correct use, but many participants would have liked more troubleshooting support when technical issues arose. The use of 5 or more devices led to a high burden, especially when devices had practicality issues such as not being waterproof. Devices offering personal feedback were perceived as useful to satisfy personal interests, though some questioned their usefulness within health care. Participants raised concerns about losing valued personal interactions with health care professionals and questioned how their existing health conditions and treatment for such conditions may affect the validity of the data collected by the devices. These findings can guide researchers in choosing appropriate devices and minimizing burden. Future work should explore the views of those experiencing digital exclusion to ensure equitable access to dementia-detection technologies.

Digital biomarkers are gaining interest as proxy markers for mental health, as they enable passive and continuous data collection. However, the association between digital biomarkers of health and anxiety, both generalized anxiety disorder and anxiety symptoms, remains unknown. This systematic review and meta-analysis examined the association between digital biomarkers of health obtained from wrist-worn wearables and anxiety in adults. Systematic literature searches were conducted across 6 databases, including unpublished gray literature. The final search was done on September 21, 2025. Cross-sectional or longitudinal studies investigating the association between digital biomarkers from wrist-worn wearables and anxiety were eligible. Studies using inferential statistics or machine learning methods were both eligible. Studies were excluded if participants received diagnoses of neurodegenerative disorders or physical health conditions. Two risk-of-bias tools were used: the National Heart, Lung, and Blood Institute assessment tool for inferential statistical studies, and the modified version of the Quality Assessment of Diagnostic Accuracy Studies-2 for machine learning studies. Whenever possible, effect sizes were combined across studies, for each digital biomarker of health separately, using random-effects meta-analyses. Sensitivity analyses were performed to assess whether results differed according to anxiety type (state or trait) and age group. Otherwise, studies were synthesized narratively. A total of 44 studies from 42 articles were eligible. Among these, 36 studies used inferential statistical approaches for analysis (21 reporting sleep characteristics, 8 reporting physical activity, 2 reporting heart rate variability, and 5 reporting more than 1 type), and 8 studies used machine learning approaches. Sample size ranged from 17 to 170,320. Meta-analyses on 4 sleep metrics found no associations: sleep efficiency (Fisher z=-0.07, 95% CI -0.14 to 0.002; P=.06; PI -0.19 to 0.05), wake after sleep onset (Fisher z=0.13, 95% CI -0.04 to 0.30; P=.11; PI -0.15 to 0.41), total sleep time (Fisher z=0.009, 95% CI -0.01 to 0.03; P=.28; PI -0.02 to 0.03), and sleep onset latency (Fisher z=0.04, 95% CI -0.07 to 0.15; P=.08; PI -0.19 to 0.27). Qualitative syntheses revealed that lower physical activity levels and higher heart rate were associated with greater anxiety symptoms. Machine learning studies using wrist-worn wearable data alone showed varied performance, with predictive performance improving when wearable data were combined with other data sources. This is the first review to synthesize evidence from inferential statistical (mostly fair quality) and machine learning studies examining association between wearable-derived digital biomarkers and anxiety. Meta-analyses found no associations between sleep metrics and anxiety. Although based on limited studies, lower physical activity levels and elevated heart rate were associated with greater anxiety symptoms. Digital biomarkers may be more useful when integrated with other data sources (eg, self-report and clinical data) rather than used as stand-alone screening tools. PROSPERO CRD42023409995; https://www.crd.york.ac.uk/PROSPERO/view/CRD42023409995.

Background: The study aim was to conduct a systematic review of the evidence from randomized, placebo controlled trials related to the efficacy of donepezil, rivastigmine and galantamine in the treatment of behavioral and psychological symptoms of Alzheimer's disease. Methods: Electronic database searches of MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were carried out using multiple search terms. Articles included were original publications of randomized, placebo-controlled trials of monotherapy of donepezil, rivastigmine or galantamine that reported a behavioral outcome measure. Results: 14 studies were identified that matched inclusion criteria. Nine were of donepezil, three of galantamine and two of rivastigmine. Median study treatment length was 24 weeks (range 12–170). Most studies used the Neuropsychiatric Inventory as a behavioral outcome measure although three used specific scales for either agitation or apathy. Four studies were specifically designed to assess behavioral outcomes whilst in the majority of studies behavioral outcomes were only secondary measures. Three studies found statistically significant, albeit modest, differences in the change of NPI total score between drug and placebo. The interpretation of the results of many studies is limited by methodological considerations, including generally low NPI scores at baseline and the investigation of behavioral and psychological symptoms of dementia (BPSD) as secondary outcomes. Conclusions: The evidence base regarding the efficacy of cholinesterase inhibitors in BPSD is limited, in part due to methodological considerations. In the absence of alternative safe and effective management options, the use of cholinesterase inhibitors is an appropriate pharmacological strategy for the management of BPSD in Alzheimer's disease.

Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are common forms of dementia that substantially affect quality of life. Currently, the only treatment licensed for PDD is rivastigmine, and there are no licensed treatments for DLB. We aimed to test the safety and efficacy of the N-methyl D-aspartate (NMDA) receptor antagonist memantine in patients with PDD or DLB. We did a parallel-group, 24-week, randomised controlled study of memantine (20 mg per day) versus placebo at four psychiatric and neurological outpatient clinics in Norway, Sweden, and the UK during 2005–08. Patients were included if they fulfilled the UK Parkinson's Disease Society Brain Bank clinical diagnostic criteria for Parkinson's disease (PD) and developed dementia according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM IV) criteria at least 1 year after the onset of motor symptoms (PDD) or met the revised consensus operationalised criteria for DLB. Patients were assigned to a computer-generated randomisation list. All physicians who had contact with patients were masked to treatment allocation. The primary outcome measure was clinical global impression of change (CGIC), which ranged from 1 to 7 points, and a low score means a better outcome. Analysis was by intention to treat based on the last observation carried forward. This trial is registered, number ISRCTN89624516. 72 patients with PDD or DLB were randomly assigned and started treatment: 34 with memantine and 38 with placebo. 56 (78%) completed the study. All withdrawals were owing to adverse events, but the proportion of withdrawals was similar in both groups. At week 24 the patients in the memantine group had better CGIC scores than those taking placebo (mean difference 0·7, 95% CI 0·04–1·39; p=0·03). With the exception of improved speed on attentional tasks in the memantine group (a quick test of cognition [AQT] form: difference 12·4, 95% CI 6·0–30·9; p=0·004), there were no significant differences between the groups in secondary outcome measures. Patients with DLB or PDD might benefit from treatment with memantine, which was well tolerated. Large-scale studies are now required to confirm our preliminary findings. The Western Norway Regional Health Authority; H Lundbeck A/S.

Background The research criteria for subjective cognitive decline (SCD) exclude mild cognitive impairment (MCI), but do not stipulate the use of specific MCI criteria. This study compared different approaches to defining (i.e., excluding) MCI during the ascertainment of SCD, focusing on the impact on dementia incidence rates in SCD. Methods This cohort study utilized routine healthcare data collected in the Essex Memory Clinic from 1999 to 2023. Two different operationalizations of the SCD criteria were used to categorize the cohort into two SCD patient samples. One sample was based on local clinical practice – MCI was excluded according to the Winblad criteria (this sample was termed SCD Winblad ). The other sample was created via the retrospective application of the Jak/Bondi criteria for the exclusion of MCI (termed SCD Jak/Bondi ). Only patients aged ≥ 55 years at baseline with ≥ 12 months follow-up were considered for inclusion. The initial clinical/demographic characteristics of the samples were compared. Rates of incident dementia were calculated for each sample, and unadjusted and Mantel-Haenszel-adjusted incidence rate ratios were calculated to compare dementia incidence between the SCD samples. Results The Essex Memory Clinic database included 2,233 patients in total. The SCD and study eligibility criteria were used to select SCD Winblad ( n  = 86) and SCD Jak/Bondi ( n  = 185) samples from the database. Median follow-up (3 years) did not differ between the two samples. The SCD Jak/Bondi sample was significantly older than the SCD Winblad at first assessment (median age: 74 versus 70 years) and had poorer scores on tests of global cognition, immediate and delayed verbal recall, and category fluency. Following adjustment for age, the dementia incidence rate ratio [95% confidence interval] was 3.7 [1.5 to 9.3], indicating a significantly greater rate of progression to dementia in SCD Jak/Bondi . Conclusions This study highlights that the approach used to ascertain SCD has important implications for both SCD phenotypes and prognosis. This underscores the importance of how MCI is operationalized within SCD studies. More broadly, the findings add to a growing body of work indicating that objective cognition should not be overlooked in SCD, and offer a potential explanation for the heterogeneity across the SCD prognostic literature.

Purpose A joint effort of the European Association of Nuclear Medicine (EANM) and the European Academy of Neurology (EAN) aims at clinical guidance for the use of FDG-PET in neurodegenerative diseases. This paper addresses the diagnostic utility of FDG-PET over clinical/neuropsychological assessment in the differentiation of the three forms of primary progressive aphasia (PPA). Methods Seven panelists were appointed by the EANM and EAN and a literature search was performed by using harmonized PICO (Population, Intervention, Comparison, Outcome) question keywords. The studies were screened for eligibility, and data extracted to assess their methodological quality. Critical outcomes were accuracy indices in differentiating different PPA clinical forms. Subsequently Delphi rounds were held with the extracted data and quality assessment to reach a consensus based on both literature and expert opinion. Results Critical outcomes for this PICO were available in four of the examined papers. The level of formal evidence supporting clinical utility of FDG-PET in differentiating among PPA variants was considered as poor. However, the consensual recommendation was defined on Delphi round I, with six out of seven panelists supporting clinical use. Conclusions Quantitative evidence demonstrating utility or lack thereof is still missing. Panelists decided consistently to provide interim support for clinical use based on the fact that a typical atrophy or metabolic pattern is needed for PPA according to the diagnostic criteria, and the synaptic failure detected by FDG-PET is an earlier phenomenon than atrophy. Also, a normal FDG-PET points to a non-neurodegenerative cause.