Alzheimer's & Dementia最新文献

Introduction: In preclinical Alzheimer's disease (AD), amyloid accumulates in the brain while individuals remain cognitively unimpaired (Clinical Dementia Rating^® [CDR] = 0). Differentiating trajectories of healthy aging and preclinical AD is challenging as both are associated with age-related impairments (e.g., falls).

Methods: Longitudinal cohort study. We monitored falls for 1 year among 125 CDR 0 older adults and assessed preclinical AD status (amyloid). We continued to evaluate CDR annually (median 10 years). The cohort was grouped: Preclinical AD-Fall-, Preclinical AD-Fall+, Preclinical AD+Fall-, and Preclinical AD+Fall+. Survival analysis examined time to progression to CDR 1 (mild dementia) by group.

Results: Participants were 74 years (mean) at baseline, 62% female, 96% White. Preclinical AD+Fall+ progressed to CDR 1 most rapidly. Preclinical AD-Fall- progressed least quickly. Preclinical AD+Fall- and Preclinical AD-Fall+ had similar progression rates.

Discussion: Falls may associate with faster progression of AD dementia, potentially reflecting motor and gait dysfunction intrinsic to disease progression.

Introduction: Automated cerebrospinal fluid (CSF) biomarker assays have largely replaced manual immunoassays for measuring amyloid pathology in CSF. We refitted and validated the ABIDE model, predicting progression from mild cognitive impairment (MCI) to dementia, with CSF measurements from the automated Elecsys platform.

Methods: We included 2413 MCI participants (998 [41%] amyloid-positive) from seven observational cohorts. Elecsys was used in 958 (40%) participants. The parameters of the previous ABIDE Cox model were re-estimated. Model discrimination and calibration were evaluated with leave-one-cohort-out cross-validation.

Results: During follow-up, 1034 (42%; 585 [58%] amyloid-positive) participants developed dementia. Discrimination was good with Harrell's C of 0.70 (95% confidence interval [CI]: 0.66-0.73). Calibration was good in the total population and amyloid-positive subgroup, with substantial predicted progression risks for all amyloid-positive participants.

Discussion: We refitted the ABIDE model, predicting MCI to dementia progression, with automated CSF measurements. The model was well calibrated in amyloid-positive patients and may support clinical discussions regarding ATTs.

Introduction: While positron emission tomography (PET) is the standard for pathological staging, its limited availability necessitates accessible alternatives. We evaluated plasma biomarkers for detecting PET-based stages using single-axis (Thal/Braak) and integrated A/T composite models.

Methods: We enrolled 237 AD spectrum participants undergoing multimodal assessments including amyloid/tau PET and plasma biomarker analysis (phosphorylated tau [p-tau] 217, %p-tau217, and amyloid beta [Aβ] 42/40 ratio). Detecting and discriminative performance was assessed using receiver operating characteristics (ROC) analysis and probability-based stage prediction.

Results: Plasma p-tau217-based biomarkers showed excellent detecting performance for early amyloid (Thal I-II; area under the curve values > 0.96) and intermediate tau (Braak III-IV; area under the curve values > 0.92). Probability-based prediction identified therapeutic window thresholds of 1.895-5.077 pg/mL. Notably, integrated A/T composite staging yielded highly consistent thresholds (< 3% variance).

Discussion: Plasma p-tau217-based biomarkers accurately reflect PET-based staging across frameworks. The convergent therapeutic window thresholds demonstrate robust biological transitions, enabling accessible identification of optimal candidates for disease-modifying therapies.

Introduction: This paper presents the development of a framework to assess the use and experiences of non-pharmacological interventions (NPIs) supporting sleep, including technological and indoor environmental quality (IEQ) measures. Sleep disturbances are common in people with dementia (PwD) and increase caregiver burden. Pharmacological treatments pose risks, highlighting the need for effective NPIs.

Methods: The framework was designed through literature review and expert consensus, and piloted over three weeks with two community-dwelling PwD and one caregiver.

Results: Findings were analyzed to improve the framework on explanation of NPIs, questionnaires, and sleep monitoring. The framework integrates methods to assess user experiences and to monitor sleep and IEQ parameters, due to their impact on sleep.

Discussion: The final framework, DESMEE-CAP, has demonstrated validity and utility in capturing experiences without disrupting routines. While promising, the small sample size limits generalizability.

Highlights: Development of a framework, in co-creation, that supports research on the use of non-pharmacological interventions (NPIs) for sleep support for community-living people with dementia and their caregivers. Attention to sleep quality and appropriate support is needed, and insights are provided through the use of the developed framework. Contribution to the development of appropriate, non-pharmacological support for sleep of people with dementia and their caregivers at home.

Introduction: PARO, a baby seal robot, has shown promise in addressing behavioral and psychological symptoms of dementia (BPSD) in clinical settings. However, little is known about PARO's benefits when used independently of health professionals. This study examined that scenario in older adults with dementia.

Methods: Applying a cluster-randomized design, we randomly assigned six facilities to once- or thrice-weekly self-directed PARO sessions for a month. BPSD severity and caregiver burden scores of the Neuropsychiatric Inventory Brief Questionnaire were measured.

Results: Findings from 85 participants indicated a significant reduction in caregiver burden in the thrice-weekly group (least-squares [LS] mean: -3.29, 95% confidence interval [CI]: [-6.26, -0.32], p = 0.030). For BPSD severity, while clinically meaningful improvement was observed, no significant difference was found (adjusted LS mean: -1.98, 95% CI: [-4.10, 0.15], p = 0.068) due to insufficient statistical power.

Discussion: Increasing robot use frequency reduced the caregiver burden and demonstrated a clinically significant improvement trend in the BPSD severity.