Journal of Alzheimer's disease reports最新文献

Background: Early detection of preclinical Alzheimer's disease (AD) could expand preventative care. Current biomarkers are costly, invasive, or lack generalizability. Driving and sensorimotor performance may reveal prodromal changes.

Objective: We tested whether features from high-frequency driving trips detect preclinical AD and whether demographic, genetic, or sensorimotor data improve accuracy.

Methods: Drivers aged ≥ 65 (n = 254) from Driving Real-World In-Vehicle Evaluation System (DRIVES) completed cerebrospinal fluid Aβ₄₂/Aβ₄₀ and amyloid Positron emission tomography (PET) to label amyloid positive (preclinical AD) or negative. A GPS datalogger recorded location (1 Hz) and accelerometer/gyroscope (20 Hz) data between June 2022 and January 2024. Eleven driving features (e.g., average speed, jerk, idle time, turns) were extracted per trip. Vision, hearing, olfaction, gait, and grip strength were assessed. TabNet models classified amyloid status using (1) driving only, (2) driving plus age and APOE ε4, and (3) driving plus age, APOE ε4, sex, and education. LightGBM models evaluated sensorimotor features. Performance was measured on a 20% held-out test set (AUC, accuracy, precision, recall, F1).

Results: The top-performing model (driving, age, APOE ε4, sex, education) achieved an AUC of 0.84, accuracy of 0.85, and F1 score of 0.85. Key predictors were idle time, turns, and average jerk. Sensorimotor models performed modestly (AUCs of 0.66 [sensory alone] and 0.67 [sensory and sociodemographic]), with grip strength and word-in-noise scores as the top contributors.

Conclusions: A high-frequency trip's driving telemetry, combined with age and APOE ε4 status, discriminates preclinical AD, outperforming multisensory measures. Driving offers a scalable, digital biomarker to complement conventional testing. Monitoring may enable population-level screening for older adults at risk.

Background: Fosgonimeton, a small-molecule positive modulator of the neurotrophic hepatocyte growth factor (HGF) system, was studied in participants with Alzheimer's disease (AD).

Objective: To assess the efficacy and safety of fosgonimeton in AD.

Methods: LIFT-AD was a randomized, placebo-controlled, Phase 2/3 trial (NCT04488419; 23Jun2020), the primary analysis (N = 287) included participants with mild-to-moderate AD not receiving concomitant acetylcholinesterase inhibitors (AChEIs) randomized 1:1 to daily subcutaneous fosgonimeton 40 mg or placebo. The primary endpoint, the Global Statistical Test (GST) score, combined ADAS-Cog11 and ADCS-ADL23. Secondary endpoints included ADAS-Cog11, ADCS-ADL23, and NfL. Exploratory endpoints included plasma biomarkers of AD. Safety included all dosed participants, including those receiving and not receiving AChEIs or randomized to fosgonimeton 70 mg (N = 549).

Results: The trial did not achieve its primary or secondary endpoints; between-group difference in the least-square mean change (SE) from baseline to Week 26 in the GST score was -0.08 (0.10) (p = 0.70), -0.70 (0.77) (p = 0.35) in ADAS-Cog11, and +0.67 (0.92) (p = 0.61) in ADCS-ADL23. This showed small differences favoring fosgonimeton versus placebo. Nominally significant changes in plasma biomarkers were observed in p-τ217 only. Fosgonimeton had an acceptable safety profile. Serious AEs were balanced between groups (4.2% fosgonimeton, 6.9% placebo). More participants in the fosgonimeton group (14.2%) discontinued due to AEs versus placebo (4.6%), mostly from injection site reactions.

Conclusions: Fosgonimeton did not significantly improve ADAS-Cog11 or ADCS-ADL23 versus placebo. However, the consistently observed non-significant improvements favoring fosgonimeton suggests potentially relevant biological activity with fosgonimeton and that positive modulation of HGF signaling may impact components of the pathophysiologic processes of neurodegenerative diseases.

Conventional dementia screening tools, whether paper tests or static artificial intelligence (AI) models, capture only a snapshot of cognition and need to be adminstered periodically. Yet decline is dynamic, shaped by environment, comorbidities, and life history. Current approaches rarely adapt, integrate feedback, or provide transparent reasoning that clinicians can trust. We propose agentic AI systems: modular agents built on large language models (LLMs) that collaborate, adapt, and mirror interdisciplinary care. The Cognitive Agent Lab exemplifies this framework, emphasizing functional aspects (inputs, outputs, workflows) and non-functional aspects (transparency, adaptivity, robustness, clinical alignment). Embedding reasoning and collaboration, agentic AI offers a roadmap toward more personalized and explainable cognitive health tools.

Subjective cognitive decline (SCD) is an early risk marker for dementia. This study examined the 3-year incidence and predictors of SCD using the Medical Outcomes Study Cognitive Functioning Scale-Revised in a national sample of 1858 U.S. military veterans aged ≥60. Clinically significant SCD occurred in 5.4% of veterans, with an average decline of 1.73 standard deviations. Lower perceived resilience-specifically lower endorsement of "I bounce back after hardship" (35.1% relative variance explained) and "Coping with stress can make me stronger" (33.8%)-chronic pain (18.7%) and sleep difficulties (12.4%) emerged as the strongest predictors of SCD. Interventions targeting these risk factors may help mitigate SCD in veterans.

Background: In Japan, the aging population is rapidly increasing, with more older persons residing alone. Among them, individuals with dementia face unique challenges in maintaining daily life and self-identity.

Objective: This study aimed to clarify what an older woman living with Alzheimer's disease, who resided alone, experienced in her daily life based on the diaries she kept.

Methods: The contents of 13 diary books belonging to Aki (a pseudonym), an older woman with dementia who lived alone at home, were quantitatively analyzed using KH Coder, and a co-occurrence network was created. In addition, qualitative content analysis of the diary contents was performed for each subgraph obtained from this network.

Results: Across all years, most days with entries had only 1 entry. However, as the years passed, the number of days with multiple entries increased. The co-occurrence network consisted of 8 subgraphs. According to the content in each subgraph, Aki experienced "sorrow and loneliness due to forgetfulness". However, Aki made efforts such as "recording the current time," "writing in a notebook to maintain my proper character". The analyses also revealed her experience of trying to live positively, as reflected in statements such as "I will live positively even though my siblings passed away, leaving me all alone."

Conclusions: Keeping a diary may have been an important means to complement her memory function and orientation, and to inspire motivation to live positively even after the loss of her family members, moreover as well as maintaining her self-esteem.

Background: The associations between several metabolic factors, gut microbiota (GM), and cognitive performance have not been clearly identified. This study investigates their associations and GM's mediating effects.

Objective: This study aimed to investigate the causal effects of key metabolic factors on cognitive performance and to determine whether gut microbiota mediate these associations.

Methods: Genetic variants linked to four metabolic factors [body mass index (BMI), basal metabolic rate (BMR), systolic blood pressure (SBP), two-hour glucose], GM, and cognitive performance were selected from genome-wide association studies (GWAS). Univariable Mendelian randomization (MR) and mediation MR analyses were applied.

Results: We found a protective effect of body metabolic rate (β = 0.061; 95% CI: 0.029, 0.093; p = 0.0002) and risk effect of body mass index (BMI, β = -0.047; 95% CI: -0.074, -0.019; p = 0.0009), systolic blood pressure (β = -0.049; 95% CI: -0.084, -0.014; p = 0.0063), and two-hour glucose (β = -0.043; 95% CI: -0.070, -0.016; p = 0.0017) on cognitive performance. In addition, the 2-step MR analysis further showed that the BMI-effect on cognitive performance was partially mediated by Rikenellaceae family, with a mediated proportion of 14.03% (95% CI: 0.99%, 27.06%; p < 0.05).

Conclusions: Our findings suggest that several metabolic factors influence cognitive performance, with gut microbiota potentially mediating these effects. These results provide insights into potential targets and useful biomarkers for understanding the pathogenesis and developing interventions for cognitive health.

Background: Alzheimer's disease (AD) is the leading cause of dementia worldwide, with rising prevalence, high costs, and significant impact in Ecuador. Awareness and validated tools like the Alzheimer's Disease Knowledge Scale (ADKS) are crucial to improve training and early care.

Objective: To evaluate the reliability and factorial structure of the ADKS in Ecuadorian university students enrolled in health science programs.

Methods: A total of 1089 students completed the ADKS. Internal consistency was assessed using Cronbach's alpha and McDonald's omega coefficients. Confirmatory factor analysis (CFA) was conducted using a Diagonally Weighted Least Squares (DWLS) estimator to evaluate the scale's structure.

Results: The ADKS demonstrated acceptable internal consistency (α = 0.767, ω = 0.770). CFA supported the original one-factor model with strong fit indices (RMSEA = 0.047, SRMR = 0.012, CFI = 0.987, TLI = 0.973, RNI = 0.987, NFI = 0.986, RFI = 0.972, IFI = 0.987). These results confirm the scale's internal validity in this population.

Conclusions: The ADKS is a reliable and valid instrument for assessing knowledge of Alzheimer's disease among Ecuadorian university students. Its use is recommended for both clinical training and public health education strategies focused on dementia awareness.

Background: Previous observational studies have suggested a potential association between amyloid marker levels and the risk of developing cerebral small vessel disease (CSVD), but this relationship remains incompletely understood.

Objective: This study was conducted to assess the impact of amyloid marker levels on the risk of developing CSVD via Mendelian randomization (MR) design.

Methods: Using the latest genome-wide association study summary statistics for 5 plasma amyloid markers and 4 CSVD traits, a two-sample MR study was conducted to assess the genetic relationship between amyloid marker levels and CSVD risk. Furthermore, reverse MR analysis was utilized to establish the causal relationship between CSVD traits and the levels of the identified plasma amyloid markers to explore potential bidirectional causality.

Results: After FDR correction, greater amyloid-β (Aβ) 42 levels were associated with an increased risk of developing lobar cerebral microbleeds (CMBs) (odds ratio = 2.311, 95% confidence interval 1.403-3.809, p = 0.001, p FDR = 0.040). Potential positive correlations were detected between Aβ₄₀ levels and the risk of developing intracerebral hemorrhage, between Aβ₄₂ levels and the risk of developing all CMBs, and between serum amyloid P component levels and white matter fractional anisotropy status. In reverse MR analysis, no effect of CSVD traits on amyloid marker levels was detected.

Conclusions: Our study suggests potential causal relationships between amyloid marker levels and different CSVD traits. Our results contribute to a greater understanding of the pathophysiology of CSVD, particularly in relation to amyloid deposition.

Contemporary dementia-prevention campaigns inherit a century-old coupling of health with economic productivity. By framing "healthy longevity" as the capacity to sustain waged labor, they cast risk reduction as a personal duty to insure future workforce participation and overlook the structural inequities-precarious work, environmental hazards, racialized stressors-that shape brain health. We trace this genealogy, critique the individualized cognitive-reserve paradigm, and argue for prevention strategies co-created with cultural interlocutors and paired with material reforms such as fair wages, housing, and caregiver support. Decoupling health from productivity is essential for an ethically coherent dementia-prevention agenda.

The study by Kueck et al. rigorously addresses the complex pre-analytical and biological confounds underlying blood-based brain-derived neurotrophic factor (BDNF) measurement in Alzheimer's disease (AD) research. By directly comparing platelet-rich plasma and platelet-poor plasma, it distinguishes free-circulating from platelet-stored BDNF and their associations with core AD biomarkers. Findings support BDNF as a potential compensatory marker in early cognitive impairment and emphasize the critical need for biomarker-specific pre-analytic standardization protocols. This commentary contextualizes the work within existing inconsistencies and outlines key recommendations for standardizing blood-based BDNF measurements to ensure reproducibility, potential clinical utility, and translational relevance.