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

Background: Primary care offers ideal opportunities for early detection of cognitive impairment, yet clinics face significant barriers to routine screening. MyCog is an electronic health record-integrated tablet application self-administered during a primary care visit designed to overcome barriers to screening.

Methods: We compared MyCog performance between 65 adults age 65+ with diagnosed cognitive impairment and 80 cognitively normal adults. Five modeling approaches achieved consensus to select consistently discriminative variables for the final detection algorithm. Performance was primarily assessed via receiver operating characteristic area under the curve (AUC), sensitivity, specificity, and accuracy.

Results: All models demonstrated strong diagnostic performance (AUC 0.817 to 0.873). Memory accuracy and executive function efficiency scores were consistently selected as predictors of impairment across models. The final logistic regression achieved AUC 0.890, with sensitivity 0.723 to 0.831, specificity 0.788 to 0.912, and accuracy 0.807 to 0.828 depending on threshold.

Discussion: Findings suggest MyCog accurately detects cognitive impairment via a streamlined self-administered app that efficiently fits into primary care workflows.

Introduction: Differentiating dementia with Lewy bodies (DLB) from Alzheimer's disease (AD) is challenging. Seed amplification assay (SAA) is sensitive for the detection of misfolded α-synuclein.

Methods: Patients with DLB (N = 31) and AD (N = 25) were recruited and evaluated. Misfolded α-synuclein was assessed in cerebrospinal fluid (CSF), skin, urine, and olfactory mucosa using SAA.

Results: The accuracy of α-synuclein-SAA for DLB was 87% (95% confidence interval [CI]: 77% to 98%) in CSF, 85% (95% CI: 75% to 98%) in skin, 58% (95% CI: 47% to 69%) in olfactory mucosa, and 59% (95% CI: 51% to 66%) in urine. The core symptoms - fluctuations, REM sleep behavior disorder, and parkinsonism - had accuracies for SAA positivity of ≥79%. Notably, 95% of SAA-positive patients also had hyposmia.

Discussion: These findings support the use of CSF and skin α-synuclein-SAAs as diagnostic tools for DLB, with strong associations between SAA and clinical phenotype. In particular, intact olfactory function is associated with a lower risk of SAA positivity.

Highlights: CSF and skin biopsies show high diagnostic accuracy for α-synuclein, demonstrating good concordance.Strong correlations exist between core symptoms of DLB and pathological α-synuclein.A very high sensitivity of hyposmia for pathological α-synuclein is observed.A novel proof-of-concept is offered for the potential detection of pathological α-synuclein in urine, marking the first such comparative analysis between patients with DLB and AD.

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.