Journal of Alzheimer's Disease最新文献

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.

Recent epidemiological evidence showed that mutations to the HFE-63 allele of this hemochromatosis-associated iron-assimilation protein improve chances of avoiding Alzheimer's disease (AD). This is unexpected since increased brain ferroptosis in gray-matter increases the risk for vascular dementia and AD. However, diffusion tensor imaging from a key Alzheimer's Disease Neuroimaging Initiative biomarker study showed that the hemochromatosis H63D allele protected white matter tracts and improved cognitive performance in individuals when APOE4 accelerates AD. H63D-carrying individuals exhibit elevated serum ferritin levels. We suggest coordinate increased levels of H-ferritin in iron-rich oligodendrocytes in H63D carriers generates sufficient neuroprotection to enhance myelin sheath integrity in white matter axons.

BackgroundEpisodic memory tests in Alzheimer's disease (AD) often depend on verbal recall or drawing.ObjectiveTo develop Visual Image Simple Recognition Test (VISRET) and evaluate its psychometric and clinical performance.MethodsWe studied 149 individuals (healthy participants [HP] = 62; AD = 53; patients with aphasia [AP] = 34). We assessed reliability (split-half Spearman-Brown [SB]), known-groups validity with age-adjusted models and age-stratified analyses, and a Bayesian logistic model (AD versus HP). A Bayesian linear model produced a composite Memory Score and highest posterior density (HPD)-based cut-offs using HP alone, subsequently evaluated by five-fold cross-validation. Convergent and discriminant validity were assessed by correlating VISRET with established neuropsychological tests in non-aphasic AD.ResultsInternal consistency was good in AD (SB = 0.87) and acceptable when pooled within-group (SB = 0.84). AD-HP discrimination was large, persisting after age adjustment, within age strata, and following aphasic AD exclusion. The Bayesian model showed excellent discrimination (posterior-mean AUC = 0.99, 95% HPD = 0.97-0.99). AP differed from HP but with trivial absolute differences (total 39.6 versus 39.4; false recognitions 0.1 versus 0.3). In non-aphasic AD, VISRET total correlated with an established episodic memory test (ρ=0.60) but demonstrated weak or near-zero correlations with non-memory domains (e.g., nonverbal reasoning, ρ=0.02). Cross-validated, HP-derived Memory-Score cut-offs achieved mean AUC = 0.98; at the 95%-HPD threshold, sensitivity = 0.87 and specificity = 0.95; at 99%-HPD, sensitivity = 0.74 and specificity = 0.98.ConclusionsVISRET is a brief, language-minimized recognition test facilitating AD-related memory impairment detection, with minimal practical impact of aphasia. The HP-derived Memory Score and cut-offs demonstrated stable cross-validation, suggesting potential clinical utility pending replication and external validation.

BackgroundType 2 diabetes (T2DM) is an independent risk factor for accelerated cognitive decline, creating a need for non-invasive biomarkers to diagnose T2DM-related mild cognitive impairment (T2DM-MCI). Circular RNAs (circRNAs), known to regulate T2DM pathophysiology, represent promising candidate biomarkers.ObjectiveWe aimed to assess the relationship between circRNAs levels and cognitive decline in T2DM patients.MethodThis study included 64 patients with T2DM-MCI and 75 patients with T2DM and normal cognition (T2DM-NC). All T2DM-MCI participants completed a 1.5-year follow-up period. Neuropsychological assessments were performed for all participants. Blood levels of circRNA were quantified using real-time quantitative polymerase chain reaction.Results(1) Whole-blood expression of hsa_circ_0015335 was significantly reduced in T2DM-MCI patients compared to T2DM-NC controls. (2) Receiver operating characteristic (ROC) curve analysis demonstrated that hsa_circ_0015335 could differentiate T2DM-MCI from T2DM-NC with an Area Under ROC Curve of 0.722. (3) Lower hsa_circ_0015335 levels showed significant negative correlations with global cognitive function, episodic memory, and executive function scores in T2DM-MCI patients. (4) A significant interaction was observed between reduced hsa_circ_0015335 expression and elevated triglyceride glucose (TyG) index, collectively contributing to global cognitive impairment in T2DM-MCI patients. (5) Mediation analysis revealed that the TyG index significantly mediated the association between baseline hsa_circ_0015335 levels and the rate of global cognitive decline during follow-up.ConclusionsPeripheral blood hsa_circ_0015335 shows potential as a biomarker for T2DM-MCI identification and cognitive decline progression in affected patients. This circRNA may contribute to cognitive impairment pathogenesis in T2DM, potentially through mechanisms involving glucose metabolism dysregulation.

BackgroundMemory loss is a core feature of typical Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI). Standard memory tests such as word lists assess verbal episodic memory with delayed recall and recognition. However, actual memory fidelity is likely variable, continuous, and has a subjective component.ObjectiveWe investigated dual-processing models of episodic memory (recollection versus familiarity) using confidence ratings in a "judgment of knowing" paradigm (JOK).MethodsThis paradigm was applied to the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) memory test as part of neuropsychological evaluation at University of Pittsburgh Alzheimer's Disease Research Center (ADRC), to generate novel indices of memory function to improve sensitivity to early memory problems and provide a memory awareness metric. On recognition testing, participants rated how sure they were of their yes/no responses to each item. We derived novel variables related to memory and metacognition, including an Accuracy-Certainty Index and the Relative Certainty Index.ResultsIn this sample of 347 participants (185 with AD, 55 with MCI, 111 cognitively unimpaired), CERAD Delayed Recall was the best single variable for discriminating groups, although multiple certainty variables also discriminated groups well.ConclusionsThe addition of certainty indices to a standard verbal memory task increased discriminative power between groups, particularly between cognitively normal controls and MCI or AD.

BackgroundIncreasing evidence suggests that the trajectory of Alzheimer's disease (AD) pathologies, such as amyloid and tau, differ between the sexes.ObjectiveGiven the higher susceptibility of females to dementia, we aimed to investigate the sex differences in the primary accumulation of tau and its subsequent spread to later cortical brain regions.MethodsWe included 315 participants in this study: 221 cognitively unimpaired individuals with normal amyloid (n = 140, A- CU) or abnormal amyloid (n = 81, A+ CU), and 94 cognitively impaired individuals with abnormal amyloid (A+ CI). Each individual received two to six tau positron emission tomography (PET) scans using the [18F]-Flortaucipir (FTP) tracer. Linear regression analyses were performed to assess sex-specific tau spreading throughout the Braak stages among three clinical groups.ResultsThe median (interquartile range) age of all samples was 73.5 (68 to 78.2) years. In total, 170 participants (54%) were female. In the A+ CU group, females exhibited higher tau-PET SUVR levels in all Braak I, III-IV, and V-VI. We found that the spreading pattern of tau may vary by sex and AD stages. In the A+ CI individuals, there was an observed interaction between the female sex and baseline tau SUVRs in Braak stages III-IV (p < 0.0001 and Bonferroni-corrected p < 0.0023), affecting longitudinal accumulation of tau in later Braak stages V-VI.ConclusionsOur findings found a sex-specific pattern of tau spreading from Braak stages III-IV to V-VI in A+ CI older adults. This disadvantage may indicate that females might experience faster tau spreading and quicker disease progression when the condition develops to more advanced disease stages.

BackgroundIncreasing numbers of studies indicate that the pathophysiological progression of Alzheimer's disease (AD) could be accelerated by chronic cerebral hypoperfusion (CCH). These findings suggest that cerebrovascular dysfunction may induce cognitive impairment in AD by expediting neurodegeneration. Dendrobium nobile Lindl. alkaloids (DNLA), the primary active components of Dendrobium nobile Lindl., have been shown to enhance cognitive function and exhibit neuroprotective effects in AD animal models.ObjectiveHowever, the impact of DNLA on AD with CCH is still elusive.MethodsIn this study, we explored the therapeutic potential and underlying mechanisms of DNLA using a novel AD plus CCH mouse model.ResultsOur results demonstrate that DNLA significantly improved cerebral blood flow, attenuated motor and cognitive decline, reduced amyloid-β deposition, mitigated neuroinflammation, and alleviated neural oxidative stress in 12-month-old AD mice with CCH.ConclusionsOur study suggests that DNLA exerts multiple neuroprotective effects, effectively preserving motor and cognitive function in AD with CCH mice of 12 months. Thus, DNLA represents a promising therapeutic candidate for the prevention and treatment of AD plus CCH.

Sumac (Rhus coriaria) is a spice and a medicinal plant that has been indicated to exert favorable effects in the management of different diseases, and it also possesses high anti-inflammatory and antioxidant properties. A plant known to be rich in bioactive molecules, including polyphenols, tannins, and flavonoids, sumac showed potent free radical scavenging activity. It thus may fight oxidative stress, which is recognized as the main cause of neurodegenerative ailments. In addition, recent investigations have also demonstrated during in vitro assays that Rhus coriaria might exert acetylcholinesterase inhibition activities, of interest in the context of therapeutic approaches for Alzheimer's disease (AD) associated with an increase of cholinergic neurotransmission supporting the cognitive processes. Furthermore, the sumac's neuroprotective activity may regulate amyloid-β (Aβ) aggregation, an important phenomenon in the AD diseased brain. Sumac may preserve neurons and synapses by blocking Aβ plaque production and neurotoxicity. That makes its anti-inflammatory activity additionally involve neuroprotective activity, largely because it reduces the pro-inflammatory cytokines level and restrains the microglial activation in the progression of AD. Given the multitarget activities, Rhus coriaria may be a potent natural candidate for preventing and treating AD. In vitro and in vivo studies are necessary to isolate its bioactive compounds, as well as preclinical and clinical studies for its effects on neurodegenerative and cognitive disorders. Dietary or medicative incorporation of sumac can supply an adjuvant choice for AD and its correlated pathogenicity.

BackgroundEmpowering people living with memory problems, including Alzheimer's disease, dementia, or mild cognitive impairment, and their carers to be engaged in the shared decision-making process about their medicines could reduce their risk of experiencing medicine-related harm. More co-designed resources to support them are needed.ObjectiveTo co-design and test a conversation-starter tool to empower people living with memory problems and their carers (consumers) to have a conversation with their healthcare professional (HCP) about their medicines.MethodsWe employed a consumer participation method with an eleven-member Steering Group consisting of six consumers and five HCPs from Australia and Maryland, United States of America. We conducted one-on-one interviews with consumers and HCPs to test the tool. We analyzed data deductively using the integrated-Promoting Action on Research Implementation in Health Services (i-PARIHS) framework and the Communication-Health Information Processing (C-HIP) model. Inductively, we also drew emergent themes that did not fit within the i-PARIHS.ResultsWe successfully co-designed the PRIME tool and recruited 35 participants (26 consumers; 9 HCPs) to improve the tool's readability and comprehensibility. We identified four major themes including: Theme 1: Variable consumer self-advocacy; Theme 2: Value of the tool; Theme 3: Changing behavior, empowerment, and motivation; Theme 4: Future use, dissemination, and implementation.ConclusionsOur participants valued the PRIME tool as an empowerment resource. They believed it would remind them of their permission to ask questions about their medicines. This may lead to a closer alignment of medicines with a person's goals of care.

BackgroundLecanemab reduces amyloid levels and modestly slows cognitive decline in a large cohort of early Alzheimer's disease (AD) but lacks real-world safety data in Chinese population.ObjectiveThe real-world study aims to analyze baseline characteristics and preliminary safety of lecanemab for AD in Zhejiang Province, and to evaluate the efficacy of plasma biomarkers for patient screening.MethodsThis multi-center study included 190 patients with AD in Zhejiang Province, who completed baseline assessments and received lecanemab treatment with follow-up.ResultsThe study included 176 participants with early AD and 14 moderate. In the early AD (mean age 68.04 years, Mini-Mental State Examination 20.03 and Montreal Cognitive Assessment 14.93), 124 (70.5%) participants were female, and 127 (72.1%) were junior high school education level or less. APOE4 heterozygote was predominant (48.9%). Logistic regression for distinguishing early AD from the Aβ negative cognitively unimpaired populations showed that p-Tau 217 independently provided better classification efficacy (area under the curve = 0.9983, p < 0.0001). In the early AD, 29 (16.5%) participants experienced infusion-related reactions (IRR) after the first-dose lecanemab, and amyloid-related imaging abnormalities (ARIA) were identified in 17 patients (9.7%), while 3 (21.4%) with IRR and none ARIA observed in the moderate AD.ConclusionsThe real-world lecanemab cohort had more females, lower educational level, and higher disease burden compared with the clinical trial cohort. Overall lecanemab exhibited a manageable short-term safety profile with no measurable cognitive efficacy. Extensive monitoring and management are required for ARIA of clinically importance. The plasma p-Tau 217 showed high accuracy for early AD screening.