Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring最新文献

Introduction: This survey investigated perspectives of research and clinical professionals on optimal content and features of measurement of self-perceived cognitive functioning.

Methods: Respondents were professionals working with older adults with self-reported cognitive concerns. The survey addressed views on harmonization and preferences for items, response formatting, practical features, and instrument validation. We evaluated item preferences in consideration of a previous statistical harmonization.

Results: Ninety professionals from 20 different countries completed the survey. Most professionals (87%) indicated a need for a harmonized instrument. Respondents agreed that an instrument should measure current ability alongside change therein, focus on memory, and adopt Likert scale responses. Recommendations for assessment timeframe, practical features, and validation priorities varied. Respondents differentially endorsed items previously found to be statistically informative.

Discussion: Respondents agreed on overarching measurement topics, with varying recommendations for specific content and features. Together with statistical information, these results provide a starting point for a harmonized instrument.

Highlights: Professionals see a need for a harmonized tool to measure cognitive concerns.Professionals have diverse preferences for measurement content and its validation.Item relevance as seen by professionals aligned considerably with statistical value.Integration of statistical information with expert and patient opinion is crucial.

Introduction: To address uncertainty about long-term clinical and economic impacts of an accurate dementia diagnosis, we evaluated the cost-effectiveness of adding amyloid positron emission tomography (PET) to memory clinic workup over 5 years.

Methods: Inverse probability weighting was used to balance covariates between PET (n = 440) and no-PET (n = 460) participants from the Amsterdam Dementia Cohort. Time in community following diagnosis, time alive, and costs were combined in cost-effectiveness analyses.

Results: PET participants lived longer in community (0.26 years, 95% confidence interval [CI]: 0.05 to 0.45) and overall (0.15, CI: 0.02 to 0.27), but did not have statistically different health insurance (€703, CI: -3974 to 5045) or total costs including institutionalization (-€8258, CI: -20,622 to 3377). The probability that PET was cost-effective for extending time in community was 76% at a €2530 willingness-to-pay threshold. The probability that PET yielded cost savings and was more effective for extending time alive was 90%.

Discussion: Findings in this observational cohort suggest that using amyloid PET in memory clinics may be cost-effective.

Highlights: Participants with an amyloid PET in a memory clinic work-up were compared to those without.The amyloid PET group spent more time in community and alive over 5 years of follow-up.Amyloid PET had a 76% chance to cost-effectively extend time in community in uncertainty analysis.

Background: This study piloted and evaluated the feasibility of ARISE (Awareness Raising Interventions in Schools), a non-randomized training program designed to enhance teachers' knowledge and attitudes toward aging and dementia in two Brazilian public schools.

Methods: A single-group pre-post design was used to assess changes in dementia knowledge and stigma-related beliefs among 62 teachers from two public schools and an adult literacy program in Brazil.

Results: Despite challenges related to workload and retention, the program was well-received by participants, who reported high satisfaction with both the content and structure. Quantitative data demonstrated significant improvements in attitudes toward aging and knowledge of dementia. No significant changes were found in attitudes toward dementia.

Discussion: This study supports the feasibility and effectiveness of the proposed program in improving attitudes toward aging and increasing dementia knowledge in schoolteachers. Future efforts should prioritize flexible implementation and streamlined content to enhance engagement and scalability.

Highlights: First teacher-focused training on aging and dementia in Brazil.Feasibility confirmed with high satisfaction despite workload challenges.Significant gains in dementia knowledge and attitudes toward aging.Qualitative data revealed motivators, barriers, and perceived impact.Scalable approach to reduce stigma and promote brain health literacy.

Introduction: A definitive diagnosis of Alzheimer's disease (AD) requires the identification of pathological changes. Plasma miRNAs have emerged as potential AD diagnostic biomarkers.

Methods: A matched case-control study was conducted using convenience sampling to evaluate the ability of candidate miRNAs in differentiating probable AD patients with mild cognitive impairment (MCI) or mild dementia (MD) stages. The initial sample included 29 patients and 58 controls. Plasma levels of miRNAs were measured by real-time polymerase chain reaction (RT-PCR) and their associations with scores from a comprehensive neuropsychological battery of cognitive tests analyzed by Spearman's correlation.

Results: A miR-181a, miR-181c, and miR-495 signature showed area-under-curve values indicative of strong diagnostic capacity and biomarker-based staging. Higher levels of these miRNAs were associated with worse scores in the different assessed cognitive tests.

Discussion: This study reports for the first-time alterations in plasma miR-495 levels in both MCI and MD patients. Future studies with larger cohorts are essential to validate the findings.

Highlights: Alterations in plasma miR-495 levels are reported for the first time in AD patients.miR-181a, miR-181c, and miR-495 levels were higher in AD patients compared to controls.Higher levels of these miRNAs were related to worse cognitive test scores.miRNA signature was able to distinguish AD stages.

Introduction: Alzheimer's disease (AD) diagnosis has been based largely on clinical symptoms, despite their limited sensitivity and specificity. Biomarker use was proposed to support a more accurate and timely diagnosis. However, neuroimaging or cerebrospinal fluid (CSF) is rarely used in primary care due to their perceived invasiveness, cost, and need for appropriate infrastructure. Blood-based biomarkers (BBMs) could represent an economical, minimally invasive alternative, but barriers exist to a seamless translation to the clinic.

Methods: Ten international experienced AD clinicians and biomarker experts participated in a diagnostic roundtable to discuss the implementation of BBMs for diagnosing early symptomatic AD.

Results: The participants proposed an optimal AD diagnostic pathway and highlighted three main gaps to implementing BBMs for early symptomatic AD diagnosis: limited real-world data, resource gaps, and system barriers.

Discussion: Although BBMs could streamline the AD diagnostic pathway, further real-world evidence and collaboration among multiple stakeholders are needed.

Highlights: Early symptomatic Alzheimer's disease (AD) diagnosis improves treatment strategy and lowers costs.Currently available biomarkers are not widely used across all clinical settings.Blood-based biomarkers (BBMs) could be a cost-effective, minimally invasive alternative.BBMs could accelerate an accurate AD diagnosis.There are barriers to the inclusion of BBMs in clinical practice.

Introduction: M0 images were missing in Siemens ASL data in Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, prohibiting cerebral blood flow (CBF) quantification.

Methods: A conditional latent diffusion model was trained and evaluated on in-house datasets, then applied to the Siemens data in ADNI-3. Regional CBF differences by Alzheimer's disease (AD) stages, their accuracy for AD classification, and CBF trajectory slopes were compared between generated data (Siemens) and acquired data (General Electric).

Results: The diffusion model generated M0 images with high fidelity (SSIM = 0.918 ± 0.023, PSNR = 31.361 ± 2.537) and minimal CBF bias (mean difference is 0.21 ± 1.58 mL/100 g/min). Both generated and acquired CBF showed similar spatial patterns and decreasing trends with AD progression in specific AD-related regions. Generated CBF also improved accuracy in classifying AD stages compared to qualitative perfusion images.

Conclusion: This study shows the potential of diffusion models for imputing missing modalities in large-scale studies exploring the use of ASL as a biomarker of AD.

Highlights: Using latent diffusion model, we can generate M0 image from control image in arterial spin labeling (ASL) with high fidelity.The generated M0 can be used for cerebral blood flow (CBF) quantification in Alzheimer's Disease Neuroimaging Initiative dataset.The performance of classification between Alzheimer's disease (AD) patients and cognitive normal people is better when using generated CBF maps than using non-quantitative perfusion images.ASL CBF decreases with AD progression in key AD-related brain regions.

Introduction: A previous study of non-demented presenilin-1 (PSEN1) E280A carriers found basal forebrain and hippocampus, but not the thalamus, to be preserved. This study tested the hypothesis of preservation in an independent PSEN1 E280A sample and explored associations with amyloid and tau pathology.

Methods: We analyzed multimodal neuroimaging data from 57 individuals in the Colombia-Boston (COLBOS) cohort (non-carriers: 30 and carriers: 27). We used Bayesian multiple regression with priors to test our hypothesis.

Results: Carrier status had no effect on basal forebrain (Bayes factor [BF₁₀] = 0.54) and hippocampal volume (BF₁₀ = 1.05). However, smaller volumes were found in the thalamus of mutation carriers (BF₁₀ = 8.74). We found evidence against an effect of amyloid and tau pathology on basal forebrain, but evidence for an effect on the thalamus.

Discussion: Our results support the preservation of the cholinergic basal forebrain and hippocampus, while highlighting early thalamic involvement in PSEN1 E280A carriers. This has implications for future selection of treatment targets.

Highlights: Basal forebrain volume preserved in non-demented presenilin-1 (PSEN1) E280A carriers.Hippocampal volume preserved in non-demented PSEN1 E280A carriers.Thalamic atrophy observed in non-demented PSEN1 E280A carriers.No link between amyloid/tau pathology and basal forebrain volume.Tau burden linked to hippocampal and thalamic volume loss.

Background: Racial and/or ethnic differences in neuropsychological test performance are understudied in frontotemporal degeneration (FTD) but their identification is critical to identifying ways to improve care of representative FTD populations.

Methods: Differences in cognitive scores between Black (n = 56) and Hispanic (n = 76) relative to White (n = 2281) participants and the likelihood of impairment status in cognitive test performance were evaluated.

Results: Minoritized individuals had lower scores and/or greater likelihood of impairment on measures of lexical retrieval, processing speed, cognitive flexibility, and working memory but not global cognition, verbal recall, attention, and category fluency. Addition of severity, age (M = 65.18), sex (40% female), education (M = 15.62), and vascular comorbidities attenuated group differences.

Discussion: Racial/ethnic differences on neuropsychological tests used in diagnosis and monitoring of FTD were substantially attenuated when accounting for potential contributing factors. To address these differences in FTD, future efforts must increase representative research participation of patients and understand social determinants of health.

Highlights: Racially/ethnically minoritized individuals with frontotemporal dementia are severely underrepresented in the National Alzheimer's Coordinating Center datasetRacially/ethnically minoritized individuals with frontotemporal dementia obtained lower scores and greater likelihood of impairment on common neuropsychological testsThe effect of racial/ethnic group on neuropsychological test scores was substantially attenuated when adjusting for disease severity, education level, sex, and age.

Introduction: Dementia is a rising global health challenge. Advances in large-scale proteomics and genetic databases have enabled high-throughput screening approaches to uncover novel mechanistic pathways and therapeutic targets.

Methods: This study used a Mendelian randomization framework to examine genetic associations of 2172 plasma proteins (UK Biobank, n = 54,219) with: (1) dementia subtypes (FinnGen, n = 429,209), including Alzheimer's disease (n = 12,348), vascular dementia (n = 2667), and Parkinson's disease dementia (n = 589); and (2) global neuroimaging markers (UK Biobank), including white matter hyperintensities (n = 42,310), fractional anisotropy (n = 17,663), and mean diffusivity (n = 17,467).

Result: Multiple potential causal protein-outcome relationships were identified, corroborating known associations (e.g., apolipoprotein E, synaptosomal-associated protein 25) and uncovering more novel proteins (e.g., butyrophilin subfamily 3 member A2, granzyme A, contactin-2, and trefoil factor 3) potentially involved in dementia disease processes.

Discussion: The identified proteins have diverse functions spanning immune regulation, cellular proliferation, neuronal stability, and neuroinflammation. The findings increase our understanding of disease processes governing cognitive health and highlight candidate proteins with potential as new disease biomarkers or therapeutic targets.

Highlights: We used Mendelian randomization to link 2172 plasma proteins to dementia and brain imaging traits.Apolipoprotein E, triggering receptor expressed on myeloid cells 2, and Fc receptor-like 3 showed protective associations across dementia subtypes.Butyrophilin subfamily 3 member A2, granzyme A, contactin-2, and trefoil factor 3 were uncovered as novel dementia-associated proteins.Immune, metabolic, and vascular pathways were implicated in the etiology of dementia.