Explore the vast range of titles available.

With U.S. Food and Drug Administration (FDA)-approved anti-amyloid, partially disease-modifying treatments now available, the ethical justification for randomly assigning patients to placebo has become controversial. The idea of twin-controls (or virtual-controls) has gained significant attention in recent years, with the aim of creating twin patient cohorts that can be used as a surrogate to evaluate the effects of treatment on a personalized level. While promising, the feasibility of digital twins techniques remains largely untested. I-CONECT is a multi-site, single-blind, randomized controlled trial (RCT) examining the effects of conversational interactions on cognition among socially isolated subjects aged ≥ 75 years (normal cognition; mild cognitive impairment). 186 participants were randomized into experimental or control groups. The experimental group engaged in video chats with study staff 4 times/week for 6 months, while the control groups received weekly 10-minute phone calls. The current analysis focused on the efficacy-shown Montreal Cognitive Assessment (MoCA; global cognition) and category fluency animals (CFA; language-based executive function) at 6-month follow-up. Data from the National Alzheimer's Coordinating Center-Uniform Data Set (NACC-UDS) were used to create digital twins for treatment participants through two methods. Method 1 involved twin mapping, matching participants with 1 to 20 twins who had similar demographic, biological, and social factors, and comparing change scores between each participant and their twins. Method 2 used direct modeling by building random forest models to predict change scores as if participants were assigned to a \"usual care\" control group. Effect sizes were compared between original and twin-controls trials, as well as between the two methods. Approximately 10% of NACC-UDS participants (5,332 out of 50,259) were eligible for I-CONECT. For parallel-group designs, treatment effect sizes on MoCA closely aligned between original (β=1.67) and twin-control (β=1.46-1.97) trials when the Euclidean distance mapping was applied. Similar findings were found in CFA (original trial β=2.56; twin-control trial β=2.31-3.34). For single-case, n-of-1 designs, methods 1 and 2 showed substantial agreement in identifying treatment responders (Cohen's Kappa=1 for MoCA; 0.68 for CFA). Digital twins from publicly available datasets enhance the rigor of RCTs by providing mapped twins as controls for early-phase dementia trials.

Residual negative symptoms and cognitive impairment are common for chronic schizophrenia patients. The aim of this study was to investigate the efficacy of a mindfulness-based intervention (MBI) on negative and cognitive symptoms of schizophrenia patients with residual negative symptoms. In this 6-week, randomized, single-blind, controlled study, a total of 100 schizophrenia patients with residual negative symptoms were randomly assigned to the MBI or control group. The 6-week MBI group and the control group with general rehabilitation programs maintained their original antipsychotic treatments. The scores for the Positive and Negative Syndrome Scale (PANSS), the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and the Symptom Checklist 90 (SCL-90) were recorded at baseline and week 6 to assess psychotic symptoms, cognitive performance, and emotional state, respectively. Compared with general rehabilitation programs, MBI alleviated the PANSS-negative subscore, general psychopathology subscore, and PANSS total score in schizophrenia patients with residual negative symptoms ( = 33.77, < 0.001; = 42.01, < 0.001; = 52.41, < 0.001, respectively). Furthermore, MBI improved RBANS total score and immediate memory subscore ( = 8.80, = 0.024; = 11.37, = 0.006), as well as SCL-90 total score in schizophrenia patients with residual negative symptoms ( = 18.39, < 0.001). Our results demonstrate that MBI helps schizophrenia patients with residual negative symptoms improve clinical symptoms including negative symptom, general psychopathology symptom, and cognitive impairment. ChiCTR2100043803.

INTRODUCTION ABvac40 is an investigational active immunotherapy (vaccine) targeting Aβ40. This study assessed the safety and immunogenicity of ABvac40 in patients with amnestic mild cognitive impairment or very mild Alzheimer's disease. METHODS AB1601 was a multicenter, randomized, double‐blind, placebo‐controlled phase 2 study. Patients (n = 124) received five monthly injections plus a 10‐month booster of ABvac40 or placebo, with 18–24 months of follow‐up. Primary endpoints included safety, tolerability, and immunogenicity. Secondary endpoints assessed immune response, neuropsychological changes, and disease biomarkers. RESULTS Treatment‐emergent adverse events (TEAEs) and serious TEAEs were comparable between ABvac40 (90.6% and 26.6%) and placebo (93.3% and 26.7%). Amyloid‐related imaging abnormalities‐hemorrhage (ARIA‐H) were similar (12.5% ABvac40; 15.0% placebo), with no ARIA‐edema (ARIA‐E) or meningoencephalomyelitis. ABvac40 induced a specific, sustained immune response in plasma, with detectable antibodies in CSF. DISCUSSION These findings support further investigation of ABvac40 as a potential disease‐modifying therapy. Clinical Trial Registration Number: NCT03461276 (ClinicalTrials.gov) Highlights ABvac40 was safe and well‐tolerated in early‐stage Alzheimer's disease patients. No amyloid‐related imaging abnormalities‐edema (ARIA‐E) or encephalitis observed; ARIA‐hemorrhage (ARIA‐H) rates were similar across groups. Specific, sustained immune response to ABvac40 in plasma, with cerebrospinal fluid (CSF) antibody penetration. Cognitive scales and magnetic resonance imaging (MRI) volumetric data favored ABvac40 over placebo. Results support further development of ABvac40 as a disease‐modifying therapy.

Mild cognitive impairment (MCI) represents the symptomatic pre-dementia stage of Alzheimer's disease (AD). Given the increasing prevalence of AD and its socioeconomic burden, delaying the progression of MCI to AD is critical. Modulating the microbiota-gut-brain (MGB) axis has emerged as a promising therapeutic approach. This study aimed to evaluate the efficacy and safety of MT104, a dietary supplement containing Cuscuta seeds and heat-killed probiotics, in regulating the MGB axis in patients with MCI. This multicenter, randomized, double-blind, placebo-controlled study involved participants randomly assigned in a 1:1 ratio to receive MT104 or placebo. Cognitive function was assessed using the Korean-Montreal Cognitive Assessment (K-MoCA) and Korean-Mini Mental State Examination at baseline and after 12 weeks of treatment. Visuospatial and memory functions were evaluated using the Rey Complex Figure Test and Seoul Verbal Learning Test (SVLT). Statistical analyses included t-tests, Mann-Whitney U tests, analysis of covariance (ANCOVA), and ranked ANCOVA. The mean changes in verbal memory function, as measured by SVLT delayed recall, showed clinically significant improvement in the MT104 group compared with the placebo group in the intention-to-treat and per-protocol groups. The global cognition, as measured by the K-MoCA, also significantly improved in the per-protocol group. Additionally, there were no significant findings regarding the safety profile of MT104. MT104 improved memory performance and global cognition in patients with MCI without safety concerns. These findings support the potential of dietary therapeutic strategies to reduce the risk of progression from MCI to AD dementia. Further studies are needed to confirm these results and explore the long-term benefits of MT104.

Background Post‐stroke cognitive impairment (PSCI) is a common complication following stroke, with limited effective treatments. This randomized controlled trial aims to evaluate the efficacy of two non‐pharmacological interventions—electroacupuncture therapy (EA) and herbal olfactory therapy (HOT)—in improving cognitive function in PSCI patients, both as standalone treatments and in combination. Methods This parallel‐group, assessor‐blinded, randomized controlled trial will recruit 210 PSCI patients, randomly assigned to one of six groups: control, EA, HOT, combination therapy, sham therapy, or the healthy (ratio 1:1:1:1:1:1). All participants will receive standard cognitive training and basic medical care. The EA group will receive 4 weeks of electro‐acupuncture at specific acupoints. The HOT group will receive 4 weeks of aromatic inhalation therapy using Acorus tatarinowii volatile oil. The combination group will receive both interventions. The primary outcome measure is cognitive function, assessed using the Montreal cognitive assessment (MoCA) at baseline, week 4, and week 8. Secondary outcomes include the mini‐mental state examination (MMSE), functional magnetic resonance imaging (fMRI), near‐infrared spectroscopy (fNIRS), and anxiety assessment using the state‐trait anxiety inventory (STAI) at baseline and week 4. Data analysis will be conducted using a modified intention‐to‐treat approach. Aims This study aims to evaluate the clinical efficacy of EA at cervical acupoints combined with HOT for PSCI, with a specific focus on determining the therapeutic superiority of this combined approach over monotherapy interventions. Conceptual schematic illustrating the trial design and mechanisms. Electroacupuncture (EA) targets cervical acupoints (GB20/Gongxue) to improve cerebral blood flow and neural connectivity. HOT (herbal olfactory therapy) delivers Acorus Tatarinowii volatile oil via inhalation to penetrate the blood‐brain barrier, reduce neuroinflammation, and enhance synaptic plasticity. Combined therapy synergistically modulates LRPs/ARF1 signaling, promotes mitochondrial function, and clears Aβ plaques. Outcomes are assessed via MoCA/MMSE (cognition), fMRI/fNIRS (brain activity), and STAI (anxiety). Healthy controls provide normative brain function baselines.

Older adults with subjective cognitive decline (SCD) recruited from memory clinics have an increased risk of developing dementia and regularly experience reduced psychological well-being related to memory concerns and fear of dementia. Research on improving well-being in SCD is limited and lacks non-pharmacological approaches. We investigated whether mindfulness-based and health education interventions can enhance well-being in SCD. The SCD-Well trial (ClinicalTrials.gov: NCT03005652) randomised 147 older adults with SCD to an 8-week caring mindfulness-based approach for seniors (CMBAS) or an active comparator (health self-management programme [HSMP]). Well-being was assessed at baseline, post-intervention, and 6-month post-randomisation using the Psychological Well-being Scale (PWBS), the World Health Organisation's Quality of Life (QoL) Assessment psychological subscale, and composites capturing meditation-based well-being dimensions of awareness, connection, and insight. Mixed effects models were used to assess between- and within-group differences in change. CMBAS was superior to HSMP on changes in connection at post-intervention. Within both groups, PWBS total scores, psychological QoL, and composite scores did not increase. Exploratory analyses indicated increases in PWBS autonomy at post-intervention in both groups. Two non-pharmacological interventions were associated with only limited effects on psychological well-being in SCD. Longer intervention studies with waitlist/retest control groups are needed to assess if our findings reflect intervention brevity and/or minimal base rate changes in well-being.

In a randomized trial, patients with brain amyloid deposition but no dementia who received a β-site amyloid precursor protein–cleaving enzyme 1 inhibitor had no benefit with respect to clinical outcomes and worsening on some measures of cognition and daily function.

Neuropsychological functioning turns out to be a rate-limiting factor in psychiatry. However, little is known when comparing neuropsychological and psychosocial functioning in inpatients with schizophrenia or severe depression in their treatment pathways including add-on psychoeducation or the latter combined with cognitive behavioral therapy up to 2-year follow-up. To evaluate this question, we investigated these variables in two randomised controlled trials including 196 patients with DSM-IV schizophrenia and 177 patients with major depression. Outcome measures were assessed in the hospital at pre- and posttreatment and following discharge until 2-year follow-up. We focused on neuropsychological and psychosocial functioning regarding its differences and changes over time in data of two pooled trials. There were significant time effects indicating gains in knowledge about the illness, short and medium-term memory (VLMT) and psychosocial functioning (GAF), however, the latter was the only variable showing a time x study/diagnosis interaction effect at 2-year follow-up, showing significant better outcome in depression compared to schizophrenia. Moderator analysis showed no changes in psychosocial and neuropsychological functioning in schizophrenia and in affective disorders due to age, duration of illness or sex. Looking at the rehospitalisation rates there were no significant differences between both disorders. Both groups treated with psychoeducation or a combination of psychoeducation and CBT improved in neuropsychological and psychosocial functioning as well as knowledge about the illness at 2-year follow-up, however, patients with major depression showed greater gains in psychosocial functioning compared to patients with schizophrenia. Possible implications of these findings were discussed.

Background The increase in cases of mild cognitive impairment (MCI) underlines the urgency of finding effective methods to slow its progression. Given the limited effectiveness of current pharmacological options to prevent or treat the early stages of this deterioration, non-pharmacological alternatives are especially relevant. Objective To assess the effectiveness of a cognitive-motor intervention based on immersive virtual reality (VR) that simulates an activity of daily living (ADL) on cognitive functions and its impact on depression and the ability to perform such activities in patients with MCI. Methods Thirty-four older adults (men, women) with MCI were randomized to the experimental group ( n  = 17; 75.41 ± 5.76) or control ( n  = 17; 77.35 ± 6.75) group. Both groups received motor training, through aerobic, balance and resistance activities in group. Subsequently, the experimental group received cognitive training based on VR, while the control group received traditional cognitive training. Cognitive functions, depression, and the ability to perform activities of daily living (ADLs) were assessed using the Spanish versions of the Montreal Cognitive Assessment (MoCA-S), the Short Geriatric Depression Scale (SGDS-S), and the of Instrumental Activities of Daily Living (IADL-S) before and after 6-week intervention (a total of twelve 40-minutes sessions). Results Between groups comparison did not reveal significant differences in either cognitive function or geriatric depression. The intragroup effect of cognitive function and geriatric depression was significant in both groups ( p  < 0.001), with large effect sizes. There was no statistically significant improvement in any of the groups when evaluating their performance in ADLs (control, p  = 0.28; experimental, p  = 0.46) as expected. The completion rate in the experimental group was higher (82.35%) compared to the control group (70.59%). Likewise, participants in the experimental group reached a higher level of difficulty in the application and needed less time to complete the task at each level. Conclusions The application of a dual intervention, through motor training prior to a cognitive task based on Immersive VR was shown to be a beneficial non-pharmacological strategy to improve cognitive functions and reduce depression in patients with MCI. Similarly, the control group benefited from such dual intervention with statistically significant improvements. Trial registration ClinicalTrials.gov NCT06313931; https://clinicaltrials.gov/study/NCT06313931 .

To examine the effect of multicomponent exercise program on memory function in older adults with mild cognitive impairment (MCI), and identify biomarkers associated with improvement of cognitive functions. Subjects were 100 older adults (mean age, 75 years) with MCI. The subjects were classified to an amnestic MCI group (n = 50) with neuroimaging measures, and other MCI group (n = 50) before the randomization. Subjects in each group were randomized to either a multicomponent exercise or an education control group using a ratio of 1∶1. The exercise group exercised for 90 min/d, 2 d/wk, 40 times for 6 months. The exercise program was conducted under multitask conditions to stimulate attention and memory. The control group attended two education classes. A repeated-measures ANOVA revealed that no group × time interactions on the cognitive tests and brain atrophy in MCI patients. A sub-analysis of amnestic MCI patients for group × time interactions revealed that the exercise group exhibited significantly better Mini-Mental State Examination (p = .04) and logical memory scores (p = .04), and reducing whole brain cortical atrophy (p<.05) compared to the control group. Low total cholesterol levels before the intervention were associated with an improvement of logical memory scores (p<.05), and a higher level of brain-derived neurotrophic factor was significantly related to improved ADAS-cog scores (p<.05). The results suggested that an exercise intervention is beneficial for improving logical memory and maintaining general cognitive function and reducing whole brain cortical atrophy in older adults with amnestic MCI. Low total cholesterol and higher brain-derived neurotrophic factor may predict improvement of cognitive functions in older adults with MCI. Further studies are required to determine the positive effects of exercise on cognitive function in older adults with MCI. UMIN-CTR UMIN000003662 ctr.cgi?function = brows&action = brows&type = summary&recptno = R000004436&language = J.