搜索结果：The journal of prevention of Alzheimer's disease

Consensus is consolidating around a set of lifestyle and medical factors that can promote brain health and reduce the risk of dementia for older adults and further decline for those with early Alzheimer's disease (AD) and related disorders. Little is known about the degree to which recommended brain-healthy behaviors have been adopted by patients with early AD pursuing anti-amyloid antibody therapy (AAT), a proactive group interested in doing what is under their control to help preserve cognitive and functional status. Here, initial results of a clinically relevant quality improvement study are reported. To determine the extent to which patients pursuing AAT for AD adhere to consensus-based brain health recommendations. One hundred fifty patients with mild cognitive impairment (MCI) or mild dementia due to AD seeking AAT were studied and compared to a group of 117 patients with MCI or mild dementia who were not pursuing AAT. Using a clinical survey tool developed for the project, patients were assessed on 15 modifiable risk factors for cognitive decline and dementia, including 11 via e-survey (diet, physical activity, cognitive activity, sleep, social engagement, smoking status, alcohol consumption, hearing, vision, mood/stress, and purpose in life) and 4 via electronic medical record (EMR) (blood pressure, BMI, LDL cholesterol level, and HbA1c). For each factor, the percentage of each of the two patient groups that was not optimally adhering to brain health-related guidelines was calculated. For each individual, the total number of factors not optimally being followed was determined. Less than 3% of patients with early AD pursuing AAT were following or had anthropometric measures/lab values in line with all 15 brain health recommendations. The five factors with the lowest adherence rates involved physical activity, mood/stress, HbA1c, blood pressure, and BMI, with 44-63% of the AAT group suboptimally following consensus-based guidelines. For 11 of 15 factors, >25% of the group were not adhering to guidelines. No robust differences in degree or pattern of adherence to guidelines were observed between patients pursuing and not pursuing AAT. There were no data in the EMR for HbA1c in >42% of patients and for LDL in >23% of patients in either group. Suboptimal adherence to brain health recommendations may be common among patients with early AD, whether they are pursuing AAT or not. These results suggest that healthcare systems may need to develop more effective strategies and individualized interventions for addressing modifiable risk factors for cognitive decline and dementia, and more efficacious procedures for ensuring that relevant, actionable data associated with brain health are updated in the EMR.

The emergence of disease-modifying therapies targeting amyloid pathology represents a major paradigm shift in the management of Alzheimer disease (AD). However, their implementation poses substantial organizational, infrastructural, and clinical challenges for health systems. To identify the key challenges and establish priority recommendations for the effective incorporation of amyloid-targeting therapies into the Spanish National Health System. This multiphase consensus study was conducted within the Spanish National Health System between September 2024 and July 2025. The study comprised a narrative literature review, qualitative research, regional workshops, and a modified RAND/UCLA Delphi process. A total of 56 experts participated, including a scientific committee of 6 Alzheimer disease specialists and an expert panel of 50 multidisciplinary professionals involved in AD care. Identification of key challenges across the AD care pathway; development, evaluation, and prioritization of consensus-based recommendations; and estimation of patient demand, including projected increases in day hospital activity and magnetic resonance imaging utilization. Ten key challenge areas were identified, encompassing early detection and referral, diagnostic confirmation, assessment of patient eligibility, treatment administration in day hospitals, monitoring of amyloid-related imaging abnormalities, evaluation of treatment effectiveness, infrastructure and capacity, professional training, patient information and support, and health care planning. Of the 43 recommendations assessed, 38 were rated as appropriate and necessary, with 14 prioritized for immediate implementation. Demand estimation models indicated that 11 to 26 patients per 100,000 inhabitants could be treated under current care patterns, increasing to 17 to 115 per 100,000 inhabitants under alternative eligibility scenarios. This consensus defines the clinical, organizational, and infrastructural requirements necessary to integrate amyloid-targeting therapies into routine care within the Spanish National Health System. The prioritized recommendations define immediate actions to address the challenges identified and may serve as a reference for other health systems facing similar implementation processes.

Although blood-based biomarkers are now available for diagnosing Alzheimer's disease (AD), the best biomarker for AD-specific neurodegeneration and cognitive decline remains unclear. This study aimed to determine the relative importance of four plasma biomarkers-phosphorylated tau (p-tau) 217, p-tau181, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP)-in AD-specific neurodegeneration and cognition. We analyzed cross-sectional data from two independent, ethnically distinct cohorts spanning the clinical spectrum from cognitively unimpaired to dementia: 150 participants from the SAMD cohort (100% Asian) and 284 participants from the ADNI cohort (94.0% White). Plasma biomarker levels were quantified using Single-Molecule Array (Simoa) assays. We employed dominance analysis to determine the hierarchical contributions of these biomarkers to AD signature regions of interest (ROI) thickness (entorhinal, inferior temporal, middle temporal, and fusiform regions), total cognition, and memory, stratified by amyloid-PET status. Three sensitivity analyses were further conducted to validate the findings across these cohorts, mitigating potential biases arising from differences in demographic characteristics and clinical severity. All analyses were adjusted for age, sex, education, and APOE ε4 status. The dominance hierarchy differed markedly according to the amyloid status. Plasma GFAP and p-tau217 emerged as the dominant predictors for AD signature ROI thickness and cognitive impairment in amyloid-positive participants. Specifically, GFAP demonstrated superior dominance in explaining cortical atrophy within the SAMD cohort, whereas p-tau217 was the dominant predictor in the ADNI cohort. P-tau217 generally outperformed the others in explaining total cognition and memory in the amyloid (+) group. In contrast, among amyloid (-) participants, plasma NfL showed greater explanatory power than GFAP for both neurodegeneration and cognitive decline across both cohorts. The efficacy of plasma biomarkers in reflecting AD-related neurodegeneration varies significantly depending on the presence of amyloid pathology. While GFAP and p-tau217 are robust indicators of AD-associated changes linked to plaque pathology, NfL better reflects non-specific neurodegeneration involving axonal damage. Consequently, a stratified approach based on amyloid status is essential for the optimal application of blood-based biomarkers in monitoring disease progression and evaluating therapeutic efficacy in future clinical trials and precision medicine.

Neurodegeneration in Alzheimer's disease (AD) is thought to be driven by amyloid-beta and tau deposition in the cerebral vasculature and brain. As the eye is an extension of the central nervous system, this study aimed to determine which neurovascular and neuroretinal changes in the eye are caused by AD rather than associations of the disease. Bidirectional two-sample univariable and multivariable Mendelian randomization (MR) methods were applied. Instrumental variables were derived from genome-wide association studies (GWAS) of AD and the following ocular features: thickness measurements of central macula (MT), retinal nerve fibre layer (mRNFL), ganglion cell-inner plexiform layer (mGCIPL), outer nuclear layer (ONL), inner segment layer (IS), and outer segment (OS) from macular region OCT scans; arteriolar tortuosity (AT), venular tortuosity (VT), venular width (VW), fractal dimension (FD), vertical cup-to-disc ratio (VCDR), optic cup area (OCA), and optic disc area (ODA) derived from other imaging methods. There was strong evidence that genetic liability to AD affected the retinal vasculature by specifically increasing AT (β = 0.007;95%CI=0.002,0.011;p-value=0.005) in UK Biobank participants (n=52,798). AD may influence the mRNFL (β=-0.047,95%CI=-0.119,0.023,p-value=0.18) and mGCIPL (β=-0.061;95%CI=-0.14,0.025,p-value=0.16) of the inner retina and OS layer (β = 0.044;95%CI=-0.0001,0.08;p-value=0.05) but the evidence was weak. Multivariable MR analysis showed that a causal relationship between optic disc area and AD (OR=0.76;95%CI=0.62,0.93,p-value=0.009) was probably mediated by refractive error. Early cerebrovascular signs of AD may be detected by examination of the eye. Further investigation is required to determine the clinical utility of eye screening for dementia.

About one third of amyloid positive, cognitively normal individuals develop mild cognitive impairment or clinical Alzheimer dementia (AD) over 5 years of follow-up. Sensitive cognitive measures, in addition to biomarkers of amyloid pathology, add to the efficiency of secondary prevention trials by identifying cognitively normal individuals at greatest risk of clinical progression. The Stages of Objective Memory Impairment (SOMI) system, based on the picture version of the Free and Cued Selective Reminding Test with immediate recall (pFCSRT+IR), predicted clinical progression in two observational studies. Our objective was to extend SOMI's findings to clinical trials using participants from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's(A4) study. Eligible participants were cognitively normal, had a Clinical Dementia Rating (CDR) =0, an elevated amyloid level, the pFCSRT+IR, pTau217, and longitudinal data on the CDR. Cox proportional hazards model was used to assess the association of baseline SOMI stage for clinical progression defined by time to the first of 2 consecutive CDRs > 0 or CDR>0 at last assessment. The sample was censored at 4.5 years of follow-up. Of the 911 eligible participants, mean age was 72 years, 59% were female, 62% were APOE ε4 carriers, and 37% progressed over 4.5 years. Hazard ratios (HR) for progression were estimated with follow-up time as the timescale and the SOMI 0 group as the reference. The HRs for progression across SOMI stage increased from 1.48(1.15-1.92 p=.003) for SOMI-1, to 1.83 (1.32-2.54, p ≤ 0.001) for SOMI-2, and to 3.04 (1.97-4.68, p ≤ 0.001) for SOMI 3/4. SOMI remained an independent and significant predictor when pTau217 was added to the model. SOMI's risk profile in A4 was similar to prior findings in observational cohorts. SOMI provides a low-cost, non-invasive enrichment tool for identifying individuals at risk for early cognitive decline in secondary prevention trials.

Diet and physical activity have been reported as independent risk factors for dementia, but few published studies have investigated the interactive effects of the two on dementia risk. Understanding their synergism could help shape more effective prevention strategies. Therefore, we assessed the potential interactions between MIND diet adherence and physical activity on the long-term risk of incident dementia in the population-based Rotterdam Study. Between 2009-2013, 5016 participants of the population-based Rotterdam Study were recruited (mean age 69.76 years, 57.9% women). All participants filled in questionnaires regarding their adherence to the MIND diet and time spent on moderate to vigorous physical activity (Metabolic Equivalent of Task [MET] hours per week). Participants were subsequently followed for incident dementia until January 1, 2021. We applied multivariable Cox regression models to assess interaction on both additive and multiplicative scales. Median values were 7.5 for the MIND diet score and 28.0 for MET hours per week. Of all 5016 participants, 2718 (54.2%) adhered to a high MIND diet score (≥7.5), and 2513 (50.1%) reached at least 28.0 MET hours per week. During a mean follow-up of 6.6 years, 365 participants (7.8%) developed dementia. Both higher physical activity and higher MIND-diet score were independently associated with a lower risk of dementia, but there was no significant interaction on the additive scale (RERI [95%CI]=-0.42 [-1.26 to 0.12]), nor on the multiplicative scale (HRinteraction=0.71 [0.46-1.09]). Sex-stratified analysis suggested a negative interaction between exposures in women, but not in men. Better adherence to the MIND-diet and higher levels of physical activity were each associated with a reduced risk of dementia, but overall there was no indication that their joint effects were greater than the product or sum of their individual parts. Potential sex differences warrant further exploration in different populations.

Preclinical Alzheimer's Disease stages represent possible targets for disease-modifying intervention as well as opportunity for early identification of risk for future decline. Recent research has explored the use of objectively-defined subtle cognitive decline (Obj-SCD), an emerging classification that may identify individuals at risk for neurodegeneration before the onset of mild cognitive impairment (MCI). The Edmonds/Thomas actuarial Obj-SCD criteria (> 1 SD below expectations, single cognitive test impaired per domain) aims to capture those who exhibit minimal cognitive difficulties that do not meet a MCI or dementia diagnosis. Given the novelty of the Obj-SCD classification, this narrative review provides an overview of neuroimaging, biomarker, and clinical progression studies to evaluate its biological and clinical significance. Using fluid-based biomarkers, neuroimaging, and longitudinal designs, studies have indicated that the Obj-SCD classification has the potential to capture AD-related pathological changes detectable before the clinical onset of MCI. In particular, recent studies indicate a unique pathological profile of Obj-SCD, differentiating it from the cognitively unimpaired and MCI stages. Studies comparing Obj-SCD and subjective cognitive complaints show that the Obj-SCD criteria may be more closely associated to early AD pathology. While the existing literature is limited, findings uphold Obj-SCD as a sensitive classification able to identify individuals at risk for future cognitive impairment. Studies on Obj-SCD indicate utility in research settings, although it faces challenges regarding its clinical implementation and effectiveness.

Predicting cognitive decline as a continuum, from healthy age-related decline to mild cognitive impairment and dementia, enables more precise individual-level predictions. However, the practical value of such models for early intervention and prevention depends on their ability to generalize to independent cohorts, a property that is often not evaluated. This study investigated whether adding structural magnetic resonance imaging (MRI) to non-brain data improved machine learning predictions of continuous cognitive decline and analyzed the models' generalizability. Multi-target random forest regression models predicted annual decline in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) and Mini-Mental State Examination (MMSE) using non-brain data, structural MRI data, or their combination from the Alzheimer's Disease Neuroimaging Initiative (ADNI; N = 1237) and Open Access Series of Imaging Studies (OASIS-3; N = 662) datasets. Cross-site generalizability was evaluated. Data from ADNI and OASIS-3 were used for this study. A total of 1899 participants who had demographic, clinical, and brain imaging data from a baseline session and clinical data from at least 2 follow-up sessions were included. Baseline non-brain (demographics, clinical and neuropsychological scores, information on APOE genotype, cognitive diagnosis, health, and number of sessions before baseline) and/or structural MRI data were used to predict the yearly rate of change in CDR-SOB and MMSE scores. Including structural MRI data improved prediction of CDR-SOB and MMSE change, reaching respective R2 values of .41 and .33 in ADNI and .42 and .33 in OASIS-3. Model performance for across-dataset predictions was reduced (R2 between .18 and .35), unexplained by distributional shifts of target variables. Models using only top predictive features performed similarly to full models when tested externally (R2 between .18 and .34), suggesting predictor redundancy. Incorporating structural MRI data enhances within-dataset prediction of continuous cognitive decline, allowing for more precise individual-level prediction and advancing towards precision medicine. Even though external validation remains limited, quantifying the generalizability gap is a crucial step towards the responsible use of ML models in clinical intervention and prevention.

Prior meta-analyses have suggested that training utilizing virtual reality (VR) serves as a secure and effective intervention for elderly individuals experiencing mild cognitive impairment (MCI). Nevertheless, the effectiveness of such interventions appears to differ among various populations and cognitive domains. Furthermore, there remains a significant gap in understanding the effectiveness of VR-based training, specifically among individuals diagnosed with Alzheimer's disease (AD). The researchers conducted a comprehensive search of databases, including Web of Science, PubMed, Cochrane Library, and EMBASE up until July 1, 2025, focusing on randomized controlled trials that investigated VR-based training in patients diagnosed with AD. The outcomes measured were categorized and analyzed separately, encompassing overall cognitive performance, distinct cognitive domains, psychosocial function, physical capabilities, and the execution of daily living activities within the context of AD trials. Of the 265 publications identified, 11 (4.15%) randomized controlled trials (RCTs) eventually met all eligibility criteria. Those who received VR-based training showed significantly better global cognitive function [SMD (95%CI) = 0.44 (0.21-0.68)] and Short-term memory [SMD (95%CI) = 0.62 (0.25-0.99)] than the controls. However, no significant improvements were observed in areas such as executive function, spatial memory, activities of daily living, quality of life, balance and coordination, fear of falling, risk of falls, and depression levels. VR-based interventions demonstrated beneficial effects on global cognitive function and short-term memory in AD populations. Due to the small sample size, the current research on evidence for efficacy in people with AD is weak and limited in many indicators.

Hippocampal atrophy is a key marker of Alzheimer's disease (AD)- related neurodegeneration; however, hippocampal volume alone may not fully capture heterogeneity in cognitive decline. Left-right hippocampal asymmetry may provide complementary information, but its prognostic value for long-term cognitive decline, particularly in relation to AD pathology, remains unclear. To determine whether hippocampal total volume and left-right hippocampal asymmetry provide complementary and independent information in capturing cognitive decline and clinical progression, and to examine their relationship to AD pathology. Analysis of baseline MRI and longitudinal cognitive data over 10 years in four domains of memory, language, executive, and visuospatial function, using harmonized cognitive data from the Alzheimer's Disease Sequencing Project - Phenotype Harmonization Consortium (ADSP-PHC). Participants from ADNI 1, ADNI GO, ADNI 2, and ADNI 3 PARTICIPANTS: A total of 1,142 dementia-free participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) with available baseline structural MRI, cerebrospinal fluid (CSF) amyloid-β (Aβ42) and phosphorylated tau (p-tau-181), and longitudinal cognitive follow-up. Total hippocampal volume (left + right) and hemispheric asymmetry (absolute left-right volumetric difference) were modeled simultaneously. Linear mixed-effects models examined associations with baseline performance and longitudinal change across four cognitive domains. Cox proportional hazards models assessed risk of clinical progression to clinical dementia over up to 10 years of follow-up (median follow-up 4 years; median 5 visits per participant). All analyses adjusted for age, sex, education, APOE ε4 status, and CSF biomarkers, with stratification by amyloid status. The study cohort included 546 women (47.8%), with a mean age of 72.54 ± 6.98 years. Smaller total hippocampal volume was consistently associated with worse baseline performance and faster decline across all four cognitive domains, even after adjustment for amyloid and tau. In contrast, greater left-right hippocampal asymmetry was selectively associated with worse performance and faster decline in memory, independent of total hippocampal volume. In amyloid-stratified analyses, total hippocampal volume showed broad associations with cognitive performance across multiple domains in both amyloid-positive and amyloid-negative participants, whereas hippocampal left-right asymmetry demonstrated selective associations with memory performance, which were observed only among amyloid-negative individuals. With respect to clinical progression to dementia, smaller total hippocampal volume was associated with a higher risk of progression in the overall cohort and within both amyloid groups. In contrast, hippocampal asymmetry was associated with progression risk only among amyloid-negative individuals (hazard ratio per SD increase = 1.31, 95% CI: 1.03-1.65). Hippocampal total volume and asymmetry capture distinct aspects of neurodegeneration, with asymmetry providing additional prognostic information for memory decline and clinical progression in the absence of detectable amyloid pathology.

Alzheimer's disease (AD) progression varies widely among individuals. Identifying factors influencing timing of pathology and clinical progression is crucial for optimizing early intervention trials. To investigate how the estimated age at amyloid and tau PET positivity, and the time interval between these two key events ("amyloid-tau time interval"), relate to symptom onset and clinical progression, and to assess the effects of APOE-ε4 status and sex on these associations. This analysis used data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Harvard Aging Brain Study (HABS). The ADNI is a multicenter observational cohort conducted at 55 sites across the United States; The HABS is a longitudinal, single-center observational cohort. This study included participants with at least one positive amyloid PET scan (ADNI n = 792; HABS n = 104) or at least one positive tau PET scan (ADNI n = 212; HABS n = 48). All participants had information on sex, APOE-ε4 status, and longitudinal cognitive assessments. We examined the influence of APOE-ε4 status, sex, and their interaction on the estimated age at biomarker positivity and the amyloid-tau time interval. Accelerated Failure Time (AFT) models were used to predict time to symptom onset (CDR > 0) based on estimated biomarker positivity age and the amyloid-tau time interval. Linear mixed-effects (LME) models evaluated differences in the rate of cognitive decline, as measured by CDR-SB, over five years following symptom onset according to estimated biomarker positivity age and amyloid-tau time interval. Additional models included interaction terms with sex or APOE-ε4 status. The amyloid-tau time interval varied markedly between individuals and was shorter in APOE-ε4 carriers, women, and those with older age at amyloid PET positivity. APOE-ε4 carriers and women became amyloid and tau PET positive at younger ages. Following amyloid PET positivity, a shorter time to tau PET positivity predicted earlier symptom onset. After symptom onset, faster cognitive decline was observed in individuals with younger ages at amyloid or tau PET positivity. The time to symptom onset following tau PET positivity, or the rate of cognitive decline after symptom onset, were not influenced by the amyloid-tau time interval. After becoming amyloid PET positive, APOE-ε4 carriers, women and older individuals may have a shorter window for detection and treatment before they become tau PET positive and develop symptoms. These findings should guide the identification of individuals at highest risk of rapid AD progression, enabling more efficient participant selection for clinical trials.

Plasma brain derived-p-Tau217 (BD-p-Tau217) may outperform total-p-Tau217 in detecting brain amyloid burden and warrants evaluation. To perform head-to-head comparison of plasma BD- as well as total-p-Tau181, p-Tau217 and p-Tau231 for detecting beta-amyloid positivity (Aβ+), evaluate reference ranges for Aβ+, and assess the prognostic utility of BD-p-Tau217 reference ranges. Observational study. Participants recruited from memory clinics and the community in Singapore. 213 participants, including 44 cognitively normal, 107 cognitively impaired no dementia, and 62 dementia (mean [SD] age, 73 [1] years; 121 females). Amyloid status (Aβ- [n = 139] vs Aβ+ [n = 74]) was determined by positron emission tomography (PET). Plasma BD-p-Tau and total-p-Tau were measured using the NULISAseq™ CNS Disease Panel 120. The diagnostic performance for detecting Aβ+, reference ranges (three-range: 95% specificity/95% sensitivity); binary: maximizing Youden index), and the prognostic performance of p-Tau biomarkers were evaluated. Plasma BD-p-Tau217 (AUC = 0.965) outperformed other BD- and total-p-Tau species in detecting PET Aβ+ (AUC = 0.823-0.937; all p ≤ 0.008). Using a three-range reference, BD-p-Tau217 achieved positive predictive value (PPV) and negative predictive value (NPV) of 90% and 97%, respectively. Proportion of participants in the intermediate-risk group was 7% (n = 14). Applying a binary reference, BD-p-Tau217 achieved both a specificity and sensitivity of 92%, with PPV and NPV of 86% and 96%, respectively. BD-p-Tau217-derived high-risk group exhibited faster cognitive decline than the low-risk group. Risk stratification for PET Aβ+ based on plasma BD-p-Tau217 suggests superior diagnostic and prognostic utility, warranting further validation.

Alzheimer's disease and other dementias (ADODs) are increasingly becoming a major public health concern in rapidly ageing Asia. We compared the disease burden across Japan, China, and India at different demographic stages. The Global Burden of Disease Study of 2023 was used to analyze the incidence, prevalence, mortality, and disability-adjusted life years (DALYs) in 1990-2023. Decomposition analysis identified drivers of DALYs trends. DALYs associated risk factors were quantified. The Auto-Regressive Integrated Moving Average model was used to predict future disease burden. In 2023, China had the highest absolute burden, with age-standardized incidence and prevalence rates of 156.63 (95% uncertainty interval [UI]: 136.58-175.49) and 918.83(95% UI: 784.59-1,058.24) per 100,000, respectively. Japan recorded the highest age-standardized mortality rate (31.25 [8.47-71.42] per 100,000). India had the highest annual increase in mortality and DALYs, with estimated annual percentage changes of 0.91 (95% confidence interval [95% CI] 0.80-1.03) and 0.51 (0.45-0.56), respectively. Decomposition analysis revealed distinct drivers: Japan was dominated by epidemiological changes; China was driven by both aging and epidemiological changes; India was mainly due to population growth and epidemiological changes. Ambient particulate matter was the leading risk factor across all countries, though India faced a unique household air pollution burden. DALYs are predicted to increase in all three countries significantly by 2038. The ADODs burden remains substantial, driven by distinct demographic and epidemiological factors in Japan, China, and India. Tailored strategies for prevention and management are essential to address the growing burden.

Patient safety critically influences both quality of life and disease progression in older adults with cognitive impairment, yet large-scale multicenter data remain scarce. This study aims to systematically analyze the types of safety incidents experienced by patients with Alzheimer's disease and related cognitive impairments, and explore the network associations of different safety incidents. Initiated by the Alzheimer's Disease China (ADC), this survey recruited 1057 older individuals with Alzheimer's and related cognitive impairments, along with their families, across 31 provinces, autonomous regions, and municipalities. The safety incidents evaluated in this study included falls, getting lost, medication errors, verbal aggression, physical aggression, household fire, aspiration, and choking. Incidence rates for overall and specific safety incidents were calculated. Correlation analyses and network analysis were performed to examine relationships between safety incidents. A high proportion (73.5%) of participants reported at least one safety incident in the past year, with over one-third (36.0%) experiencing three or more concurrent incidents. Medication errors (55.9%) and verbal aggression (39.6%) were most frequent, followed by falls (32.5%) and physical aggression (22.7%). Incidence rates varied significantly by cognitive impairment stage, care setting, and geographic region. Network analysis highlighted medication errors and getting lost as central nodes bridging other incidents. This study reveals an alarmingly high incidence of safety incidents among cognitively impaired patients, affecting their physical, psychological, and familial well-being. A collaborative, multidisciplinary effort involving healthcare professionals, family caregivers, fire and police emergency responders, and public health policymakers is essential to develop individualized safety strategies aligned with patient needs and contextual considerations.

Emerging evidence point to a bidirectional relationship between sleep disturbances and Alzheimer's disease (AD). Poor sleep may be an overlooked risk factor for older women, who are disproportionately affected by AD and report worse subjective sleep quality than men. High genetic AD risk-characterized by the polygenic hazard score (PHS), including apolipoprotein (APOE) &#x3b5;4 carriership-may further compound the effects of disrupted sleep on AD, particularly for older women. This study examined the moderating effect of genetic AD risk on subjective sleep as it related to memory and tau burden in a sample of older women. The sample consisted of older women (&#x2265;65 years old) from the Women Inflammation Tau Study. Participants completed the Pittsburgh Sleep Quality Index (PSQI), Rey Auditory Learning Test, and Brief Visuospatial Memory Test-Revised. They also underwent [18]F-MK6240 positron emission tomography. Tau burden was calculated in composite regions across Braak stages. Genetic risk groups were characterized by PHS stratified at the 75th percentile. PSQI global score &#xd7; PHS group interactions on memory composite scores (N = 69) and tau burden (N = 63) were examined. PSQI global score &#xd7; PHS group interactions were observed on visual memory and pathological tau in Braak regions III/IV (ps<0.10). Poorer subjective sleep was associated with worse visual memory and greater limbic tau deposition only among higher genetic risk women (ps<0.04). No significant associations were observed for verbal memory or tau in Braak regions I/II or V/VI. Older women with elevated genetic AD risk and subjective sleep difficulties may be at greater risk for visual memory deficits and tau burden in regions affected in early AD. This suggests that sleep complaints may represent a promising AD risk factor. Improving sleep may be a potential intervention target for AD mitigation and prevention, particularly for older women.

In the European Union (EU), donanemab is indicated in adults with early symptomatic Alzheimer's disease who are apolipoprotein E &#x3b5;4 non-carriers or heterozygotes. Among these, patients without superficial siderosis at baseline, uncontrolled hypertension, or anticoagulant use are eligible. To assess efficacy and safety of donanemab in the EU-eligible population. A post-hoc conservative hybrid imputation method was implemented for clinical efficacy analyses during the TRAILBLAZER-ALZ 2 placebo-controlled period. In the 78-week long-term extension (LTE) participants in the early-start (randomised to donanemab) and delayed-start (randomised to placebo with donanemab initiation during the LTE) groups were compared to a propensity-weighted external control. Participants were switched to placebo after meeting amyloid-based treatment course completion criteria. By 76 weeks, donanemab-treated participants in the EU-eligible population had a mean Clinical Dementia Rating Scale (CDR)-Sum of Boxes change from baseline difference from placebo of -0.7 points (95% confidence interval, -1.0, -0.4) and a 40.3% lower risk of disease progression to the next stage (per CDR-Global score). Treatment benefit increased over 154 weeks for non-carriers and heterozygotes, including those meeting treatment course completion criteria by 52 or 76 weeks. In the placebo-controlled period, 119 (19.5%) and 49 (8.0%) donanemab-treated eligible participants experienced amyloid-related imaging abnormalities-edema/effusion and infusion-related reactions, respectively. Safety findings were similar among donanemab-treated participants in the placebo-controlled period and LTE delayed-start group. Consistent with previous TRAILBLAZER-ALZ 2 and LTE findings, donanemab significantly slowed disease progression compared to controls with a manageable safety profile in non-carriers and heterozygotes.

Adult vaccination is inversely associated with incident Alzheimer's Disease and Related Dementias. We determined if Tetanus, Diphtheria and Pertussis (Tdap) vaccination was linked to incident Alzheimer's Disease and dementia among adults with Down Syndrome, 50% of whom develop Alzheimer's Disease by age 60. This is a retrospective cohort study using TriNetX nationally distributed electronic health records from 2013 to 2024. Historical medical record data. 5591 patients with Down Syndrome across the United States. Eligible patients were free of Alzheimer's Disease and dementia prior to index. Index date could occur 1/1/2015 to 1/1/2020 allowing for 5 to 10 years of possible follow-up time. Vaccination was measured using product name and procedure codes and Alzheimer's Disease and dementias was defined by ICD-10 codes. The mean age of the cohort was 50.0 (&#xb1;8.3), 50.1% were female and 72.1% were White. After controlling for confounding, Tdap vaccination vs. remaining without Tdap vaccination was associated with lower Alzheimer's Disease and dementia risk (HR=0.74; 95%CI:0.57-0.98). In a cohort of patients with Down Syndrome, Tdap vaccination was associated with a 26% lower risk for Alzheimer's Disease and dementia. This is a novel and important finding because existing studies of vaccination and reduced risk for Alzheimer's Disease and dementia have been among cognitively intact adults. This study reveals benefits of vaccination even among those at high risk for Alzheimer's Disease and dementia due to Down Syndrome. Future studies are needed to understand the mechanisms underlying this relationship.

The objective of this study was to provide a multimodal biomarker characterization of amnestic objective subtle cognitive decline (obj-SCD) in aging and preclinical Alzheimer's disease (AD). Prospective observational study; data from the Alzheimer's and Families+ (ALFAs+) cohort, including cognitively unimpaired (CU) individuals with available baseline CSF biomarkers (normal or AD continuum profiles) and longitudinal neuropsychological assessment (2 time points, 3-year follow-up). Amnestic obj-SCD was defined using robust longitudinal neuropsychological references with multivariate base rate thresholds of significant decline (Free and Cued Selective Reminding Test, Memory Binding Test, Wechsler Memory Scale IV: Logical Memory). Study outcomes included plasma p-tau217, NfL, and GFAP; CSF p-tau181/A&#x3b2;42, NfL, and GFAP; A&#x3b2; and tau PET; and MRI Grey Matter volume (GMv). The associations of amnestic obj-SCD with fluid (plasma and CSF) and neuroimaging biomarkers (PET and GMv) were evaluated using mixed-effects and voxel-wise linear regression models, respectively. 350 CU individuals were included (mean age 61 years; 60% female; mean education 14 years; 35% CSF A&#x3b2;-positive). Amnestic obj-SCD was identified in 10% of the sample, associated with greater AD pathology (higher plasma p-tau217, CSF p-tau181/A&#x3b2;42, global A&#x3b2; PET, medial temporal tau PET), neurodegeneration (higher plasma and CSF NfL, reduced GMv in cingulate cortex, longitudinal GMv reductions in hippocampus) and inflammation (higher plasma and CSF GFAP, longitudinal GMv increases in neocortical brain regions). These findings highlight the need for standardized clinical staging criteria to enhance early detection and risk stratification in aging and preclinical AD.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and memory impairment. Despite extensive research, the precise molecular mechanisms driving AD pathogenesis remain incompletely understood. This study sought to identify robust molecular targets and cellular basis underlying AD progression. We performed a systematic analysis of cross-regional transcriptomic datasets from AD patients, integrating differential expression analysis across 14 Gene Expression Omnibus (GEO) datasets with cross-regional intersection mapping. Single-nucleus RNA sequencing (snRNA-seq) was employed to resolve cell-type-specific expression patterns. Furthermore, cellular communication analysis and functional enrichment of astrocyte-specific genes were conducted. The biological role of the identified candidate was validated in vitro using A&#x3b2;42 oligomer-treated primary astrocytes via siRNA-mediated knockdown and plasmid-driven overexpression, with autophagic activity assessed through LC3-II and p62 expression. The transmembrane glycoprotein receptor CD44 was identified as consistently upregulated across AD-vulnerable brain regions, including the temporal cortex, frontal cortex, entorhinal cortex, and hippocampus. snRNA-seq analysis identified this upregulation primarily to astrocytes. Intercellular signaling analysis indicated that the CD44-SPP1 axis enhanced astrocyte-glial crosstalk. Functional enrichment analysis linked astrocytic CD44 to the modulation of autophagy pathways. In vitro experiments demonstrated that CD44 knockdown promoted autophagic activation (increased LC3-II and decreased p62), whereas CD44 overexpression suppressed autophagic activity. Our findings establish CD44 as a pivotal regulator of astrocytic autophagy in AD, highlighting its potential as a novel therapeutic target.