Journal of Alzheimer's Disease最新文献

BackgroundVarious functional impairments in eye movements have been observed in Alzheimer's disease (AD) and other neurodegenerative disorders. Detecting abnormal eye movements may help identify individuals at risk of memory diseases even when evident clinical symptoms are absent.ObjectiveTo investigate the earliest possible stage at which the risk of memory impairment can be detected using computer-based eye-tracking (ET) analysis of King-Devick (KD) test performance.MethodsWe recruited a total of 34 healthy controls and 33 participants with a Clinical Dementia Rating-Sum of Boxes (CDR-SOB) score of 0.5 or higher. They all underwent a neurological examination, the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological test battery (CERAD-NB), and a CDR interview. The KD reading test was performed using computer-based ET. We analyzed fixation durations, saccade durations, and saccade amplitudes. For this study, test results were analyzed in relation to CDR-SOB.ResultsThe mean duration of saccades was significantly shorter in the CDR-SOB 0.5 group compared to healthy controls (p = 0.001), and this difference remained significant across groups with CDR-SOB >0.5. The mean amplitude of saccades was significantly lower in individuals with CDR-SOB scores ranging from 1 to 4, as well as those with scores exceeding 4.5, in comparison to healthy controls (p = 0.007).ConclusionsThese findings suggest that ET analysis of the KD test may help detect individuals with very early cognitive problems. Therefore, this method shows promise as a supportive or potentially indicative biomarker for future studies aimed at developing user-friendly tools to identify individuals at risk for AD or other memory diseases.

The growing prevalence of Alzheimer's disease (AD) requires strategies that go beyond risk identification to active prevention. In a recent large cohort study, Lee and colleagues demonstrated a "dose-dependent" relationship between cumulative lifestyle risk and AD incidence, thus underlining the power of modifiable factors in modulating cognitive trajectories. This commentary explores the clinical and public health implications, highlighting how sustained behavioral interventions, early risk assessment, integrated care models, and population-level policies can reduce the burden of AD and improve cognitive health outcomes across aging societies.

Alzheimer's disease involves impairment of all cognitive capabilities. Although the cognitive capabilities in humans are equipped in parallel in the form of modules, individual cognitive capabilities function via language, and human cognitive functions are vulnerable, by nature, to linguistic disturbances. Therefore, for elucidating the pathogenesis of Alzheimer's disease, it is important to analyze not only biological factors, but also linguistic factors. In this position paper, I discuss the relationship between cognitive capabilities and language, as well as the nature of language which creates cognitive capabilities, in order to acquire the prerequisite knowledge for analysis of linguistic factors in Alzheimer's disease.

BackgroundMultiscale dispersion entropy (MDEnt) is a nonlinear EEG measure that quantifies brain complexity across time scales, reflecting both local and global brain dynamics. Previous research indicates lower complexity at short time scales in Alzheimer's disease (AD) compared to mild cognitive impairment (MCI) and healthy controls (HCs), with MCI also showing lower values than HCs. Major depressive disorder (MDD) has also been preliminarily linked to reduced complexity during acute episodes.ObjectiveTo assess whether MDEnt at short time scales can distinguish AD from MCI and HCs, and to examine complexity differences across additional groups, remitted MDD (rMDD) and rMDD + MCI, while exploring associations with cognitive performance.MethodsThe study included 316 older adults: 44 HCs, 46 with rMDD, 114 with MCI, 71 with rMDD + MCI, and 41 with AD. Resting-state, eyes-closed EEGs were analyzed using MDEnt at 24 ms (short) and 60 ms (long) time scales. Cognitive function was measured with the Montreal Cognitive Assessment and a composite cognitive score.ResultsShort time scale complexity was lowest in AD, followed by MCI, and highest in HCs; rMDD presence had no impact. Only AD showed reduced complexity at long time scales. Complexity at both time scales was significantly correlated with cognitive performance.ConclusionsThis study highlights the value of MDEnt to assess complexity at short time scale and differentiate individuals with AD, MCI, or HCs. Reduced complexity in these individuals may underlie their cognitive impairment. In contrast, our study suggests that any MDD impact on complexity is likely related to active depressive symptoms.

BackgroundNeuropsychiatric signs and symptoms (NPS) are highly prevalent in Alzheimer's disease (AD), but whether co-occurring symptom constellations relate to regional amyloid deposition remains unclear.ObjectiveTo identify reproducible NPS clusters in AD and examine their associations with regional amyloid deposition using ¹⁸F-FC119S positron emission tomography (PET).MethodsWe included 143 patients with probable AD and positive amyloid PET. NPS were assessed with the Korean Neuropsychiatric Inventory, and hierarchical cluster analysis (Yule's Q, average linkage) identified symptom clusters. Regional amyloid burden in frontal, temporal, and parietal cortices was quantified by automated SUVRs. Clinical characteristics were compared using t tests, and associations between clusters and regional amyloid patterns were examined with Pearson's χ².ResultsFour clusters emerged: Group 1 (delusion, agitation-aggression, disinhibition, aberrant motor behavior); Group 2 (depression, anxiety, irritability); Group 3 (hallucination, euphoria, nighttime behavior, apathy); and Group 4 (eating abnormalities). Group 1 patients were older with worse global status (lower K-MMSE, higher CDR, lower Barthel); Group 2 showed higher GDS15 scores; Group 3 showed selectively lower K-MMSE; Group 4 showed no significant differences. On PET, Group 1 was associated with right frontal and right temporal positivity; Group 2 with left parietal negativity; Group 3 with right frontal positivity plus left parietal negativity; Group 4 showed no significant association.ConclusionsIn amyloid-confirmed, drug-naïve AD, distinct NPS clusters map onto specific regional amyloid patterns and global clinical profiles. These findings support a network-oriented view of NPS pathophysiology and may inform phenotyping and individualized management.

BackgroundEarly detection of Alzheimer's disease (AD) is critical for timely intervention. Subjective cognitive decline (SCD), defined as self-perceived cognitive worsening while objective performance on standardized tests remains normal, when accompanied by neurodegenerative changes on brain imaging (e.g., hippocampal atrophy), can be classified as SCD with neurodegeneration of AD form (SCD-NDAD). This phenotype may represent an early stage of AD.ObjectiveInvestigate the prevalence and clinical characteristics of SCD-NDAD in general population.Methods: This multicenter, community-based cross-sectional study was conducted from 2013 to 2019 across 31 communities in eight major cities of northern, eastern, southern, and western China. Community-dwelling adults aged 50 years and older were recruited through cluster sampling. Participants underwent standardized interviews, neuropsychological assessments, and magnetic resonance imaging, on the basis of which SCD-NDAD was identified. The prevalence of SCD-NDAD was estimated with age- and sex-standardized weights.ResultsOf 5054 participants (mean age 69.4 years, 60.6% women), 2886 completed MRI. In participants aged ≥50 years, the prevalence of SCD-NDAD was 4.9% (95% confidence interval: 4.1% to 5.8%). In participants aged 65 years and older, prevalence increased to 6.5% (95% confidence interval: 5.5% to 7.7%). While these individuals exhibited preserved cognitive function across all domains, they demonstrated significant hippocampal atrophy, a key marker of AD-related neurodegeneration.ConclusionsSCD-NDAD is common among older adults in China, with an estimated prevalence affecting 12.4 million individuals aged ≥65 years. Identifying this cohort may offer a critical window for early intervention and holds significant implications for public health strategies aimed at dementia prevention.

BackgroundNeuropsychiatric symptoms (NPS) are increasingly recognized as core features of Alzheimer's disease (AD), often emerging preclinically. Adults with Down syndrome (DS) represent a genetically determined population at high risk for AD (DS-associated AD, DSAD), yet their neuropsychiatric profiles remain undercharacterized and seldom compared with sporadic AD (sAD).ObjectiveTo delineate and compare NPS profiles across the AD continuum in adults with and without DS, examining their relationships with amyloid-tau (AT) biomarker status, neuroimaging, and neurophysiological markers.MethodsWe conducted a cross-sectional study of 293 adults (138 with DS, ≥ 18 years; 155 non-DS, ≥ 50 years) stratified by cognitive stage. NPS were assessed via Neuropsychiatric Inventory (NPI). A subset underwent cerebrospinal fluid biomarker analysis, MRI, and EEG. Linear models explored NPI associations with AT status, MRI/EEG findings, sex, and psychotropic medication use.ResultsNPS severity increased with cognitive decline in both cohorts; affective and behavioral domains were most prevalent. Individuals with DS showed significantly higher NPI total scores across all stages, particularly disinhibition and aberrant motor behaviors during dementia. Positive AT biomarker status and abnormal EEG/MRI findings independently associated with greater NPI burden, including in cognitively unimpaired individuals. Polypharmacy and female sex were additional predictors in DS. Caregiver distress paralleled NPI severity.ConclusionsThis study identifies shared and syndrome-specific NPS trajectories in DSAD and sAD, with clear associations to AD biomarkers and neurophysiological dysfunction. Findings support NPS as early indicators of AD pathology and underscore the importance of personalized, developmentally informed behavioral assessment and care.

BackgroundLecanemab and donanemab are anti-amyloid-β monoclonal antibodies recently approved in the United States and Europe for the treatment of early Alzheimer's disease (AD). Their modest clinical benefit, safety profile, and cost raise debate about real-world applicability. Fortasyn Connect (Souvenaid^TM), a multi-nutrient intervention, has shown potential clinical benefits in prodromal AD.ObjectiveTo compare the clinical effect sizes (Cohen's d) and estimated months of preserved independence in instrumental activities of daily living (IADLs) for lecanemab, donanemab, and Souvenaid™, based on published pivotal clinical trial data.MethodsCohen's d on the Clinical Dementia Rating-Sum of Boxes (CDR-SB) was computed using standardized mean differences and 95% confidence intervals (CIs) derived from published trials. Times of functional independence were estimated using the Hartz approach.ResultsPoint estimates of Cohen's d effect sizes on CDR-SB were -0.34, -0.33, and -0.52 for lecanemab, donanemab, and Souvenaid™, respectively, with no statistically significant differences between drugs. Estimated gains in IADL independence were 10 months for lecanemab, 8 months for donanemab, and 27 months for Souvenaid™.ConclusionsDespite differences in study designs, Souvenaid^TM demonstrated comparable clinical efficacy with superior safety, accessibility, and cost profile. These findings support further evaluation of Souvenaid^TM as a non-invasive, scalable option in early AD management.

BackgroundPredementia, encompassing subjective cognitive decline (SCD) and mild cognitive impairment (MCI), represents an early phase of neurodegeneration with a heightened risk of progression to dementia. This stage offers a critical window for intervention. Virtual reality (VR) enhances neuroplasticity in predementia via multisensory stimulation, addressing research gaps.​​ObjectiveTo assess the impact of VR-based interventions on cognitive abilities, emotional well-being, and instrumental activities of daily living (IADL) in individuals with predementia conditions.MethodsA search of seven databases identified studies involving seniors aged ≥65 with SCD or MCI. Eligible studies compared conventional cognitive training or usual care as controls. Quality was assessed using the Cochrane Risk of Bias Tool, and evidence certainty was graded using the GRADE framework.ResultsTwelve randomized controlled trials were included. The meta-analysis revealed that, in comparison to control groups, VR-based cognitive interventions had superior effects on subjective cognitive complaints (SMD = -4.06, 95% CI [-4.86, -3.25]), learning and memory (SMD = 0.41, 95% CI [0.02, 0.80]), working memory (SMD = -0.06, 95% CI [-0.08, -0.03]), verbal fluency (SMD = 0.49, 95% CI [0.03, 0.94]), spatial cognition (SMD = 1.43, 95% CI [0.77, 2.10]), and IADL (SMD = 0.77, 95% CI [0.14, 1.40]).ConclusionsVR-based cognitive interventions could improve objective cognitive performance, subjective cognitive complaints, and IADL in predementia. Future research should prioritize optimizing the intervention protocols and enhancing the geriatric-specific VR-based cognitive intervention.

BackgroundThe cerebrospinal fluid (CSF) and plasma amyloid-β (Aβ)_40/42 ratio, p-217tau and p-181tau, and neurofilament light chain are biomarkers of Aβ proteinopathy, tau proteinopathy, and neuronal injury, respectively, in Alzheimer's disease (AD). However, direct biomarkers of cognitive function have yet to be identified.ObjectiveTherefore, the present study investigated the potential of CSF and plasma levels of drebrin, a postsynaptic protein, as biomarkers of synaptic activity and cognitive function in the human brain in clinical settings.MethodsWe developed a novel ELISA to measure CSF and plasma levels of drebrin and analyzed 68 CSF and 128 plasma samples from patients with AD and other neurological diseases.ResultsCSF drebrin levels were significantly reduced in samples of mild cognitive impairment due to AD, the dementia stages of AD, and idiopathic normal pressure hydrocephalus. Plasma drebrin levels were also significantly reduced in samples of MCI due to AD.ConclusionsCSF and plasma drebrin levels are specific biomarkers of cognitive decline in the MCI stage of AD.