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

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.

Background: Alzheimer's disease (AD) blood biomarkers could improve the diagnostic process for patients with cognitive complaints presenting to primary care. We investigated general practitioners' (GPs') perspectives on facilitating and hindering factors associated with the use and implementation of AD blood biomarkers.

Method: In this qualitative, semi-structured interview study, we used purposive sampling to recruit a heterogeneous group of 18 Dutch GPs. Qualitative data analysis of interview transcripts was based on the Theoretical Domains Framework.

Results: GPs believed that AD blood biomarkers could have both positive and negative consequences. Mentioned positive consequences included facilitating an accessible diagnostic process, clarity about the etiology, and life planning. Mentioned negative consequences were imposing a psychological burden on patients and possible AD over- or underdiagnosis.

Conclusion: While AD blood biomarkers may have potential benefits according to GPs, additional evidence, definition of context of use and logistics, and adoption of guidelines are needed for eventual implementation.

Highlights: GPs experience a knowledge gap regarding AD and AD blood biomarkersAD blood biomarkers could inform GPs, enabling decision-making in primary careGPs perceive various harms and benefits associated with the use of AD biomarkersInformation, education and guidelines are key factors for successful implementation.

Introduction: Counseling for early Alzheimer's disease (AD) detection is essential, especially regarding emerging blood-based biomarkers. The increasing need for counseling requires innovative approaches and simultaneously consideration of ethical issues.

Ethical considerations: Telemedicine is discussed as a means of providing more accessible and fairer health care. Nevertheless, barriers to accessing telemedicine are important to consider, such as required technical hardware and ethical criteria regarding interpersonal counseling, including individual adaptation of information to ensure self-determined decision-making. Regarding resource allocation, issues must be considered before telemedicine is implemented.

Theoretical reflection: Fair counseling structures require the discussion of resource allocation. To avoid justifying telemedical counseling based solely on cost-effectiveness and overlooking further ethical demands, we propose a ranked approach. To strengthening self-determined decisions, we argue that equal care structures can be built on these prerequisite aspects and enable realization of fair resource allocation as a last step.

Highlights: Blood-based biomarkers in Alzheimer's disease (AD) facilitate easier access to risk assessment and early detection. Currently, insufficient pre-diagnostic counseling structures exist which support informed decision-making. Telemedicine may be a meaningful approach for innovative counseling services. However, unresolved ethical and legal issues regarding telemedical counseling services for the early detection of AD must first be addressed.Telemedical counseling in the early detection of AD is yet rarely discussed in the literature. Therefore, we combine insights from ethical analysis of telemedical counseling with the ethical issues of fair and empowering counseling in the early detection of AD separately. In a second step, we discuss the use of telemedical counseling for the early detection of AD inductively to highlight ethically relevant aspects and present our considerations in light of the principles of autonomy, non-maleficence, beneficence, and justice.To provide ethical guidance for possible future implementation without overprioritizing one approach to counseling for the early detection of AD, considerations regarding fair resource allocation are required. We argue that three major ethical topics should be considered in the future: Strengthening individuals' autonomy, equal care structures, and fair resource allocation.

Introduction: Amyloid beta (Aβ), a hallmark of early Alzheimer's disease (AD), disrupts white matter (WM) microstructure, but its spatial patterns and transcriptomic links in cognitively normal individuals remain underexplored.

Methods: We compared the WM microstructure between Aβ-positive (Aβ+) and Aβ-negative (Aβ-) individuals at the cognitively normal stage. We investigated the relationship between the fibers and the cortical and subcortical regions to which they are connected, as well as the underlying gene expression.

Results: WM damage observed in Aβ+ individuals was characterized across eight fiber tracts, even prior to the evidence of atrophy and during the cognitive normal stage. This damage is primarily associated with cortical Aβ accumulation and may be linked to genes that regulate oligodendrocyte function and myelination.

Discussion: Cortical Aβ-related WM changes precede gray matter atrophy in preclinical AD, highlighting their potential as early biomarkers. Oligodendrocyte dysfunction and myelination pathways may underlie Aβ-driven WM vulnerability, offering targets for intervention.

Highlights: WM microstructural changes precede gray matter atrophy in preclinical AD.Aβ-driven WM damage persists even after adjusting for age.WM microstructural damage is primarily linked to cortical Aβ burden in cognitively normal individuals.Oligodendrocytes and myelin underlie the vulnerability of WM-related to Aβ.