Disease Assessment Scale-Cognition Research Articles

MicroRNA biomarkers in cerebrospinal fluid and plasma are associated with reduced cognitive decline in Alzheimer's Disease

AbstractBackgroundDespite the promising prospects of using microRNAs in Alzheimer's disease (AD) research, several challenges remain unresolved.MethodOur study analyzed the changes in microRNA expression levels in cerebrospinal fluid (CSF) and plasma samples and their association with concurrent cognitive decline and hippocampal volume changes in patients with AD using the Alzheimer's Disease Neuroimaging Initiative database.ResultWe observed a significant decrease in plasma hsa‐mir‐125b‐5p levels (P=0.018), significant increase in plasma hsa‐mir‐26a‐5p levels (P=0.017), and significant decrease in mir‐185b‐5p levels in CSF (P=0.017). However, these microRNAs showed no significant differences between the control and AD groups across various ATN subtypes. Lower plasma hsa‐mir‐125b‐5p and hsa‐mir‐26a‐5p concentrations and CSF mir‐185b‐5p concentrations were associated with a faster increase in Alzheimer’s Disease Assessment Scale Cognition 13‐item scale scores (P= 0.011, P=0.009, P=0.018, respectively) and a decline in hippocampal volume (P=0.25, P=0.052, P=0.044, respectively), suggesting a potentially detrimental influence on cognitive and memory impairment in AD progression. CSF mir‐185b‐5p concentrations were positive for amyloid deposition (P= 0.0451, r=0.1754) and negative for fibrillar amyloid levels (P= 0.0392, r=‐0.1647), indicating their potential relevance in AD pathology and the development of AD.ConclusionThese results highlight the role of CSF and plasma microRNA biomarkers in predicting cognitive and clinical decline in patients with AD.

Diosgenin-rich Yam (rhizome of Dioscorea batatas) extract ameliorates cognitive functions and plasma biomarkers for mild cognitive impairment and mild Alzheimer's disease: A randomized controlled trial

IntroductionIn Alzheimer's disease (AD), neural circuit disconnection primarily causes memory dysfunction, which leads to the hypothesis that repairing neural networks may be an appropriate treatment strategy for AD. We previously found that diosgenin stimulated neurite regeneration and synapse formation in AD model mice, and diosgenin-rich Yam extract enhanced cognitive function in healthy people and normal mice. In this study, we investigated the efficacy and safety of Yam extract in patients with mild cognitive impairment (MCI) and mild AD. MethodsPatients were administered either diosgenin-rich Yam extract or placebo, respectively, for 24 weeks. The primary outcome was cognitive function, which was evaluated using the Mini Mental State Examination Japanese version (MMSE-J), Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog), and verbal fluency test; the secondary outcomes were plasma biomarker levels [neurofilament light chain (NfL); axonal marker, glial fibrillary acidic protein levels; reactive astrocyte marker, and the Aβ42/40 ratio; marker of brain Aβ]. ResultsDiosgenin-rich Yam extract improved the ADAS-Cog Praxis domain score and plasma NfL (12 to 24 weeks) in all patients. The number of patients with improved/maintained ADAS-Cog total, Praxis or Memory scores was high in the Yam extract group, but not in placebo group. Divided by severity of pathology, diosgenin-rich Yam extract also improved the total and Memory domain in ADAS-Cog, and plasma NfL levels in patients with MCI. In the Yam extract group, improvement of MMSE-J was related to plasma Aβ42/40 increase, and improvement of plasma NfL was related to better MMSE-J. ConclusionTreatment with diosgenin-rich Yam extract for 24 weeks resulted in modest cognitive improvement and a decrease in plasma NfL levels, which may suggest axonal protection in the brain.

A randomized sham-controlled trial of transcranial and intranasal photobiomodulation in Japanese patients with mild cognitive impairment and mild dementia due to Alzheimer's disease: a protocol.

Photobiomodulation (PBM) is a novel strategy for cognitive enhancement by improving brain metabolism and blood flow. It is potentially beneficial for patients with Alzheimer's disease (AD). We present a study protocol for a randomised controlled trial designed to evaluate the efficacy and safety of PBM. This is a single-centre, parallel-group, randomised, sham-controlled study. We enroll patients with mild cognitive impairment or dementia due to AD and assigned them to receive either active or sham stimulation at home for 12 weeks, with three sessions per week (20 min each). The stimulation involves invisible near-infrared light delivered by five applicators (one in a nostril, one on the frontal scalp, and three on the occipital scalp). The primary outcome will be the mean change in the Alzheimer Disease Assessment Scale-cognition from baseline to Week 12. We will also measure cognitive function, activity of daily living, behavioral and psychological symptoms, and caregiver burden. We will collect data at clinics at baseline and Week 12 and remotely at home. We estimate a sample size of 30 (20 active and 10 sham) based on an expected mean difference of -6.9 and an SD of 4.8. We use linear models for the statistical analysis. The National Center of Neurology and Psychiatry Clinical Research Review Board (CRB3200004) approved this study. The results of this study will be published in a scientific peer-reviewed journal. Trial registration details Japan Registry of Clinical Trials jRCTs032230339.

Efficacy of donepezil plus hydrogen-oxygen mixture inhalation for treatment of patients with Alzheimer disease: A retrospective study.

To investigate the clinical effect of donepezil combined with hydrogen-oxygen mixture inhalation in the treatment of patients with Alzheimer disease (AD), a total of 273 AD patients admitted to our hospital from March 2018 to March 2022 were retrospectively analyzed and assigned into an observation group (n = 138) and a control group (n = 135) according to the different treatment that they received. The control group was treated with donepezil tablets, while the observation group was treated with donepezil tablets combined with hydrogen-oxygen mixture inhalation. The scores of mini-mental state examination (MMSE), Montreal Cognitive Assessment (MoCA), Alzheimer's Disease Assessment Scale-Cognition, activity of daily living scale (ADL) and the P300 event-related potential were compared between the 2 groups. After treatment, MMSE score, MoCA score, and ADL score in both groups increased after treatment (P < .01), while the improvement in the observation group was more significant than that in the control group (P < .001 for MMSE, P = .003 for MoCA, and P = .013 for ADL). The scores of Alzheimer's Disease Assessment Scale-Cognition in the observation group decreased after treatment (P < .05), while the improvement in the observation group was more significant than that in the control group (P = .005). After treatment, the latency of P300 in both groups was shortened (P < .01), and the improvement in the observation group was more significant than that in the control group (P < .001). The amplitude of the observation group increased after treatment (P < .01), and the improvement of the observation group was significant than that of the control group (P = .007). The clinical efficacy of donepezil combined with hydrogen-oxygen mixture inhalation in the treatment of AD is better than that of donepezil alone, which is worthy of further study.

Targeting the Correct Population for Trials: A Post‐hoc Analysis of Trial of Solanezumab for Mild Dementia Due to Alzheimer’s disease.

AbstractBackgroundUp to 50% of placebo treated participants in AD clinical trials do not show clinically meaningful cognitive decline (CMCD) over the course of study. Inclusion of these individuals makes it more difficult to demonstrate the benefits of treatments intended to slow cognitive decline. Here, we used data from the trial of solanezumab for mild AD (EXPEDITION3) to investigate effectiveness of predictive models for enrichment of trials.MethodA total of 1072 patients with mild dementia and biomarker evidence of amyloid by PET or CSF studies were enrolled in the placebo arm of EXPEDITION3 trial. 893 patients completed the trial and had baseline structural MRIs making them eligible for this analysis. We identified cognitive decliners, individuals with CMCD, based on the score of the 14‐item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS‐cog14; Range 0‐90; change of ≥4 from baseline to week 80) versus stable cognition, individuals without CMCD (change of &lt;4 from baseline to week 80). Random forest classifiers were trained to classify participants into cognitive decliners vs. stable cognition groups using 3 feature‐sets: Model‐1) Demographics + Neuropsychological test (NP); Model‐2) Demographics + biomarkers (APOE4 alleles and volumetric MRI); Model‐3) All available measures. 70% of data was used for training and 30% for validation.ResultSample characteristics are summarized in Table 1. CMCD was observed in 55.8% of participants at week 80. In the validation sample, model 2 had the best performance in differentiating the two subgroups (AUC = 0.70), followed by model 3 (AUC = 0.68). Model 1 had poor performance in differentiating the two subgroups with AUC = 0.56. Table 2 summarizes performance metrics of models. Positive predictive value of the best performing model (model 2) was approximately 12% higher than the base prevalence of cognitive decline, and negative predictive value of it was approximately 20% higher than the base prevalence of participants who had stable cognition.ConclusionA large portion of biomarker confirmed AD cases enrolled in this trial did not show CMCD on placebo treatment. Predictive models have the potential to improve the design of AD trials through selective inclusion criteria for participants expected to decline and exclusion of those expected to remain stable.

Effect of acupuncture with donepezil based on syndrome differentiation on cognitive function in patients with mild-to-moderate Alzheimer’s disease: a study protocol for a multicenter randomized controlled trial

BackgroundThere has been a rapid increase in the worldwide prevalence of Alzheimer’s disease (AD). Previous studies have shown that acupuncture can improve neurological and cognitive function; however, the utility of applying acupuncture in patients with AD remains unclear. This study protocol describes a clinical trial for evaluating the efficacy and safety of acupuncture based on syndrome differentiation with donepezil hydrochloride on cognitive function in patients with AD.Methods/designThis multicenter randomized controlled trial commenced on February 1, 2019, at the Shanghai Longhua Hospital of TCM, Shanghai Huashan Hospital of Fudan University, and Shanghai Mental Health Center, and will conclude on June 30, 2022. The study will recruit 184 patients randomly divided into an acupuncture group or a control group at a 1:1 ratio. All participants will receive donepezil hydrochloride (5 mg/day), and those in the acupuncture group will receive acupuncture based on syndrome differentiation with donepezil for 12 weeks. The primary outcome will be the post-treatment change in the Alzheimer’s Disease Assessment Scale-cognition score at 12 weeks. The secondary outcomes will be the efficacy scores of the Minimum Mental State Examination, Alzheimer’s Disease Cooperative Research Activity-Daily Life, and Quality of Life-Alzheimer’s Disease. All assessments will be performed at baseline, after treatment (week 12), and at follow-up (weeks 24 and 36).DiscussionThis trial may provide high-quality evidence for the efficacy of acupuncture in the treatment of AD. The results of this study will be published in peer-reviewed journals.Trial registrationClinicalTrials.govNCT03810794. Registered on 17 January 2019.

Microglial Activation, Tau Pathology, and Neurodegeneration Biomarkers Predict Longitudinal Cognitive Decline in Alzheimer's Disease Continuum.

PurposeBiomarkers used for predicting longitudinal cognitive change in Alzheimer’s disease (AD) continuum are still elusive. Tau pathology, neuroinflammation, and neurodegeneration are the leading candidate predictors. We aimed to determine these three aspects of biomarkers in cerebrospinal fluid (CSF) and plasma to predict longitudinal cognition status using Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort.Patients and MethodsA total of 430 subjects including, 96 cognitive normal (CN) with amyloid β (Aβ)-negative, 54 CN with Aβ-positive, 195 mild cognitive impairment (MCI) with Aβ-positive, and 85 AD with amyloid-positive (Aβ-positive are identified by CSF Aβ42/Aβ40 < 0.138). Aβ burden was evaluated by CSF and plasma Aβ42/Aβ40 ratio; tau pathology was evaluated by CSF and plasma phosphorylated-tau (p-tau181); microglial activation was measured by CSF soluble TREM2 (sTREM2) and progranulin (PGRN); neurodegeneration was measured by CSF and plasma t-tau and structural magnetic resonance imaging (MRI); cognition was examined annually over the subsequent 8 years using the Alzheimer’s Disease Assessment Scale Cognition 13-item scale (ADAS13) and Mini-Mental State Exam (MMSE). Linear mixed-effects models (LME) were applied to assess the correlation between biomarkers and longitudinal cognition decline, as well as their effect size on the prediction of longitudinal cognitive decline.ResultsBaseline CSF Aβ42/Aβ40 ratio was decreased in MCI and AD compared to CN, while CSF p-tau181 and t-tau increased. Baseline CSF sTREM2 and PGRN did not show any differences in MCI and AD compared to CN. Baseline brain volumes (including the hippocampal, entorhinal, middle temporal lobe, and whole-brain) decreased in MCI and AD groups. For the longitudinal study, there were significant interaction effects of CSF p-tau181 × time, plasma p-tau181 × time, CSF sTREM2 × time, and brain volumes × time, indicating CSF, and plasma p-tau181, CSF sTREM2, and brain volumes could predict longitudinal cognition deterioration rate. CSF sTREM2, CSF, and plasma p-tau181 had similar medium prediction effects, while brain volumes showed stronger effects in predicting cognition decline.ConclusionOur study reported that baseline CSF sTREM2, CSF, and plasma p-tau181, as well as structural MRI, could predict longitudinal cognitive decline in subjects with positive AD pathology. Plasma p-tau181 can be used as a relatively noninvasive reliable biomarker for AD longitudinal cognition decline prediction.

Validity of the Web-Based, Self-Directed, NeuroCognitive Performance Test in Mild Cognitive Impairment.

Digital cognitive tests offer several potential advantages over established paper-pencil tests but have not yet been fully evaluated for the clinical evaluation of mild cognitive impairment. The NeuroCognitive Performance Test (NCPT) is a web-based, self-directed, modular battery intended for repeated assessments of multiple cognitive domains. Our objective was to examine its relationship with the Alzheimer's Disease Assessment Scale-Cognition Subscale (ADAS-Cog) and Mini-Mental State Examination (MMSE) as well as with established paper-pencil tests of cognition and daily functioning in mild cognitive impairment (MCI). We used Spearman correlations, regressions and principal components analysis followed by a factor analysis (varimax rotated) to examine our objectives. In MCI subjects, the NCPT composite is significantly correlated with both a composite measure of established tests (r = 0.78, p < 0.0001) as well as with the ADAS-Cog (r = -0.55, p < 0.0001). Both NCPT and paper-pencil test batteries had a similar factor structure that included a large "g" component with a high eigenvalue. The correlation for the analogous tests (e.g., Trails A and B, learning memory tests) were significant (p < 0.0001). Further, both the NCPT and established tests significantly (p < 0.0001) predicted the University of California San Diego Performance-Based Skills Assessment and Functional Activities Questionnaire, measures of daily functioning. The NCPT, a web-based, self-directed, computerized test, shows high concurrent validity with established tests and hence offers promise for use as a research or clinical tool in MCI. Despite limitations such as a relatively small sample, absence of control group and cross-sectional nature, these findings are consistent with the growing literature on the promise of self-directed, web-based cognitive assessments for MCI.

Ginkgo Biloba Extract Is Comparable With Donepezil in Improving Functional Recovery in Alzheimer's Disease: Results From a Multilevel Characterized Study Based on Clinical Features and Resting-State Functional Magnetic Resonance Imaging.

Background: Ginkgo biloba extract (GBE) and donepezil have been reported to be effective in patients with Alzheimer’s disease (AD). Nonetheless, how these drugs impact spontaneous brain activities and how they consequently improve functional recovery are currently unclear.Objectives: This study was to explore the efficacy of GBE vs. donepezil and their add-on efficacy on functional recovery and the adaption of spontaneous brain activities following pharmacologic treatment in patients with AD.Methods: Patients with AD were enrolled and assigned to the GBE group (n = 50), the donepezil group (n = 50), or the combined group (n = 50). Neuropsychological assessments, including minimum mental state examination (MMSE), Alzheimer’s disease assessment scale-cognition (ADAS-Cog), instrumental activity of daily living (IADL), geriatric depression scale (GDS), neuropsychiatric inventory (NPI), and quality of life in Alzheimer’s disease (QOL-AD), were conducted at baseline, 1 month, 3 months, and 6 months. Resting-state functional magnetic resonance imaging (rs-fMRI) was collected to compare the amplitude of low-frequency fluctuation (ALFF), percent amplitude of fluctuation (PerAF), regional homogeneity (ReHo), and degree centrality (DC) at baseline and 6 months.Results: No major significant differences were detected in all comparisons between groups across all follow-up time points. For intragroup comparison, MMSE and ADAS-Cog scores differed significantly across all follow-ups in three groups. The combined group showed significant improvement of GDS scores between baseline and 6 months (p = 0.007). The GBE group (p = 0.044) and donepezil group (p = 0.012) demonstrated significant improvement of NPI scores between baseline and 6 months. Significant correlations were observed between IADL and ALFF in the right gyrus rectus (p = 0.03) and in the left superior cerebellum gyrus (p = 0.01), between GDS and ALFF in the right middle temporal gyrus (p = 0.01), between NPI and PerAF in the left fusiform gyrus (p = 0.03), and between MMSE and ReHo in right superior frontal gyrus (p = 0.04).Conclusion: GBE was comparable with donepezil in the improvement of functional recovery in patients with AD while the combined application of GBE and donepezil seems unnecessary. GBE-mediated improvement of functional recovery was characterized by decreased ALFF values in the right gyrus rectus and decreased PerAF values in the left fusiform gyrus. These featured variations of imaging metrics in specific brain regions may serve as biomarkers in the monitoring of the therapeutic efficacy of GBE.

Association of Tau Pathology With Clinical Symptoms in the Subfields of Hippocampal Formation.

Objective: To delineate the relationship between clinical symptoms and tauopathy of the hippocampal subfields under different amyloid statuses.Methods: One hundred and forty-three subjects were obtained from the ADNI project, including 87 individuals with normal cognition, 46 with mild cognitive impairment, and 10 with Alzheimer’s disease (AD). All subjects underwent the tau PET, amyloid PET, T1W, and high-resolution T2W scans. Clinical symptoms were assessed by the Neuropsychiatric Inventory (NPI) total score and Alzheimer’s Disease Assessment Scale cognition 13 (ADAS-cog-13) total score, comprising memory and executive function scores. The hippocampal subfields including Cornu Ammonis (CA1–3), subiculum (Sub), and dentate gyrus (DG), as well as the adjacent para-hippocampus (PHC) and entorhinal cortex (ERC), were segmented automatically using the Automatic Segmentation of Hippocampal Subfields (ASHS) software. The relationship between tauopathy/volume of the hippocampal subfields and assessment scores was calculated using partial correlation analysis under different amyloid status, by controlling age, gender, education, apolipoprotein E (APOE) allele ɛ4 carrier status, and, time interval between the acquisition time of tau PET and amyloid PET scans.Results: Compared with amyloid negative (A−) group, individuals from amyloid positive (A+) group are more impaired based on the Mini-mental State Examination (MMSE; p = 3.82e-05), memory (p = 6.30e-04), executive function (p = 0.0016), and ADAS-cog-13 scores (p = 5.11e-04). Significant decrease of volume (CA1, DG, and Sub) and increase of tau deposition (CA1, Sub, ERC, and PHC) of the hippocampal subfields of both hemispheres were observed for the A+ group compared to the A- group. Tauopathy of ERC is significantly associated with memory score for the A- group, and the associated regions spread into Sub and PHC for the A+ group. The relationship between the impairment of behavior or executive function and tauopathy of the hippocampal subfield was discovered within the A+ group. Leftward asymmetry was observed with the association between assessment scores and tauopathy of the hippocampal subfield, which is more prominent for the NPI score for the A+ group.Conclusion: The associations of tauopathy/volume of the hippocampal subfields with clinical symptoms provide additional insight into the understanding of local changes of the human HF during the AD continuum and can be used as a reference for future studies.

Intranasal Insulin Reduces White Matter Hyperintensity Progression in Association with Improvements in Cognition and CSF Biomarker Profiles in Mild Cognitive Impairment and Alzheimer\u2019s Disease

BackgroundIntranasally administered insulin has shown promise in both rodent and human studies in Alzheimer’s disease; however, both effects and mechanisms require elucidation.ObjectiveWe assessed the effects of intranasally administered insulin on white matter health and its association with cognition and cerebral spinal fluid biomarker profiles in adults with mild cognitive impairment or Alzheimer’s disease in secondary analyses from a prior phase 2 clinical trial (NCT01767909).DesignA randomized (1:1) double-blind clinical trial.SettingTwelve sites across the United States.ParticipantsAdults with mild cognitive impairment or Alzheimer’s disease.InterventionParticipants received either twice daily placebo or insulin (20 IU Humulin R U-100 b.i.d.) intranasally for 12 months. Seventy-eight participants were screened, of whom 49 (32 men) were enrolled.MeasurementsChanges from baseline in global and regional white matter hyperintensity volume and gray matter volume were analyzed and related to changes in cerebral spinal fluid biomarkers, Alzheimer’s Disease Assessment Scale-Cognition, Clinical Disease Rating-Sum of Boxes, Alzheimer’s Disease Cooperative Study-Activities of Daily Living Scale, and a memory composite.ResultsThe insulin-treated group demonstrated significantly reduced changes in white matter hyperintensity volume in deep and frontal regions after 12 months, with a similar trend for global volume. White matter hyperintensity volume progression correlated with worsened Alzheimer’s disease cerebral spinal fluid biomarker profile and cognitive function; however, patterns of correlations differed by treatment group.ConclusionIntranasal insulin treatment for 12 months reduced white matter hyperintensity volume progression and supports insulin’s potential as a therapeutic option for Alzheimer’s disease.

Effects of multisession transcranial direct current stimulation as an augmentation to cognitive tasks in patients with neurocognitive disorders in Japan: a study protocol for a randomised controlled trial

IntroductionTranscranial direct current stimulation (tDCS) is a potentially novel strategy for cognitive enhancement in patients with disorders. We present a study protocol for a randomised controlled trial designed to evaluate...

Progressive task-oriented circuit training for cognition, physical functioning and societal participation in individuals with dementia.

Dementia is commonly associated with cognitive deficit, functional decline and societal participation restriction across multiple domains of functioning. The decline impacts not only on the individual, but also on their informal caregivers, healthcare and the social system. This clinical random controlled study investigated the efficacy of 12-week Progressive Task-oriented circuit training on cognition, physical functioning and societal participation of individuals with dementia. This study involved 31 individuals living with dementia recruited from a tertiary health institution in Lagos Nigeria. They were randomized into two groups: Progressive Task-oriented circuit training (involved in 12-week circuit training, two times a week for 70 min per session consisting of six workstations) and Control group (training with conventional treatment and home programmes). They were assessed at baseline, mid-intervention and post-intervention using Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog), Bristol ADLs, Community integration Questionnaire, 6-min walk test. Data analysed using the independent-samples t tests, paired t tests, Friedman two-way analysis of variance and Mann-Whitney U test (p ≤ .05). Participants were aged 69.61 ± 3.44 years. There was significant improvement from baseline to post-intervention in cognition (30.77 ± 1.02 vs. 28.77 ± 3.30), physical functioning (28.19 ± 3.90 vs. 25.84 ± 6.26) and societal participation (3.64 ± 0.73 vs. 5.59 ± 2.76). However, the progressive Task-oriented circuit training had more significant improvement than the control group within the group in cognition (p = .000), physical functioning (p = .000), and societal participation (p = .000). There was no statistical difference within the Control group with cognition (p = .097), Physical functioning (p = 1.000). Meanwhile there was statistically significant effect between both groups on cognition, physical functioning and societal participation post-intervention (p < .005). Although both Task-oriented Circuit Training and conventional treatment with home exercise programmes are efficacious, Progressive Task-oriented Circuit Training is more efficacious in enhancing and developing therapeutic strategies to train cognition, improve functional performance and societal participation in the rehabilitation of individuals with dementia.

Associations of Subsyndromal Symptomatic Depression with Cognitive Decline and Brain Atrophy in Elderly Individuals without Dementia: A Longitudinal Study

BackgroundSubsyndromal symptomatic depression (SSD) is prevalent in older adults. However, it remains unclear whether there are effects of SSD on brain aging outcomes (cognition and brain structures), especially in the presence of Alzheimer's Disease (AD) pathology. MethodsA total of 1,188 adults without dementia were recruited from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Participants with SSD were measured using the 15-item Geriatric Depression Scale (GDS-15). In multivariable models, the cross-sectional and longitudinal associations of SSD with brain aging outcomes were explored. We further evaluated whether baseline amyloid-β (Aβ) load modifies the relations between SSD and brain aging outcomes. ResultsSSD at baseline was associated with significantly longitudinal decline in cognition and displayed significantly accelerated atrophy in hippocampus (β = –29.53, p = 0.001) and middle temporal gyrus (β = – 77.82, p = 0.006) among all participants and Aβ-Positive individuals. SSD interacted with baseline Aβ load in predicting longitudinal decline in Mini Mental State Examination (MMSE) (β = – 0.327, p = 0.023), episodic memory (β = –0.065, p = 0.004) and increase in Alzheimer's Disease Assessment Scale Cognition 13-item scale (ADAS-cog13) (β = 0.754, p = 0.026). LimitationsOur study didn't look at AD diagnosis but Aβ status. ConclusionsOur findings suggested that older people without dementia with both SSD and a high level of Aβ load may have higher risk of cognitive deterioration and brain atrophy. Therapeutic mitigation of depressive symptoms, especially in those with abnormal Aβ levels, may help delay progressive decline in cognition.

Effectiveness of Acupuncture for Alzheimer’s Disease: An Updated Systematic Review and Meta-analysis

Acupuncture has reportedly improved memory and cognitive impairment in both animal and clinical studies. It may be an effective treatment for Alzheimer's disease (AD). The purpose of this meta-analysis was to review the effectiveness of acupuncture for the treatment of AD. Eight databases were searched for articles published up to and including July 2017, and 13 studies fulfilling the inclusion criteria were identified. The main outcomes assessed were clinical efficacy rate, Mini-Mental State Examination score, Ability of Daily Living Scale score, Alzheimer's Disease Assessment Scale-Cognition score, Hasegawa's Dementia Scale (HDS) score, and adverse events. The methodological quality of the articles was assessed using Cochrane's risk of bias. All the studies compared the efficacy of acupuncture with that of medication, and were published in Chinese journals. Meta-analysis revealed that acupuncture yielded positive results as determined via all the indexes scored except the HDS (95% CI -0.26 to 0.90, Z=0.35, P=0.73). Only one of the studies reported adverse events associated with acupuncture and medication. The rate of adverse events in the medication group was 13%. In most of the studies assessed in the current meta-analysis, acupuncture alone was better than conventional western medicines for the treatment of AD.

A Meta-Analysis of the Effect of Multisession Transcranial Direct Current Stimulation on Cognition in Dementia and Mild Cognitive Impairment.

There have been increasing efforts to investigate the effects of neuromodulation techniques, such as transcranial direct current stimulation (tDCS), on cognitive impairment in dementia and related conditions. In this systematic review and meta-analysis, we assessed the efficacy of multisession anodal tDCS compared with sham stimulation for improving global cognition and specific cognitive domains in both Alzheimer's disease and mild cognitive impairment. Eight articles meeting the criteria for inclusion in the meta-analysis were selected. Five studies used the Mini-Mental State Examination to examine mild cognitive impairment and dementia. In a fixed-effect model, there was a mean difference in the change score of -0.13 points. Three trials for dementia using the Alzheimer's Disease Assessment Scale-Cognition showed a mean difference of -0.53 points. At present, there is a lack of clear evidence concerning the efficacy of multisession anodal tDCS due to the small number of studies and different measures used. This underscores the need for further investigations using larger samples and common outcome measures.

Real-World, Multinational, Retrospective Observational Survey of the ADAS-Cog and Associations with Healthcare Resource Utilization in Patients with Alzheimer's Disease.

Alzheimer's disease (AD) is one of the most costly conditions, both economically and regarding patient disability and dependency. The huge costs coupled with the predicted increase in prevalence worldwide are likely to challenge healthcare systems in the future. The classic version of the Alzheimer's Disease Assessment Scale-Cognition subscale (ADAS-Cog) is generally seen as the current gold standard primary outcome measure of cognitive symptom progression in dementia clinical trials. This study evaluated the relationship between ADAS-Cog scores as a measure of clinical progression and the healthcare resource utilization (HCRU)-measured burden of cognitive impairment in patients with mild cognitive impairment, AD, or suspected AD in the real world. A retrospective observational survey of physicians and their consulting patients with multiple ADAS-Cog scores. Regression models were constructed for HCRU variables (e.g., consultations, hospitalizations, caregiving requirements) with ADAS-Cog rate of change, baseline ADAS-Cog, and their interaction included as exposure variables. 651 patient records were completed by 154 physicians. Approximately 70% of patients had mild to moderate dementia. In 56.7% of patients, clinical progression was maintained/stable from baseline. Mean change in ADAS-Cog (adjusted to 12 months) was 2.8 points and change scores increased with increasing dementia severity. Most HCRU variables increased significantly (p < 0.05; joint test) with increasing ADAS-Cog scores (indexing clinical deterioration). The results suggest that further understanding the relationship between HCRU and ADAS-Cog changes in real-world clinical practice could potentially provide a baseline upon which the success of disease-modifying, as well as newer symptomatic, dementia therapies can be judged.

The effect of electroacupuncture combined with donepezil on cognitive function in Alzheimer\u2019s disease patients: study protocol for a randomized controlled trial

BackgroundAlzheimer’s disease is a progressive neurodegenerative disease. Although some of the current treatments offer some symptomatic relief, this disease cannot be cured at present. Electroacupuncture may be effective for Alzheimer’s disease for cognitive function, but the evidence for its effectiveness is still limited. The aim of this study is to evaluate the add-on effect of electroacupuncture to donepezil for improving the cognitive function of Alzheimer’s disease.Methods/designA total of 334 participants with Alzheimer’s disease will be randomly assigned to either an electroacupuncture combined with donepezil group or a donepezil group with a ratio of 1:1. Participants in the electroacupuncture combined with donepezil group will receive electroacupuncture in addition to donepezil for 12 weeks and will keep taking donepezil for the following 24 weeks. Participants in the control group will take donepezil only. The primary outcome is the change from baseline in the total score of the Alzheimer’s Disease Assessment Scale-cognition at week 12. A follow-up will be conducted 24 weeks after the treatment.DiscussionWe expect to verify the hypothesis that acupuncture in addition to donepezil is better than donepezil in improving the cognitive function of patients with Alzheimer’s disease. This trial has a limitation that participant blinding is impossible.Trial registrationClinical Trials.gov: ID: NCT02305836. Registered on 13 November 2014.

Effects of Regular and Long-Acting Insulin on Cognition and Alzheimer’s Disease Biomarkers: A Pilot Clinical Trial

Background: Long acting insulin detemir administered intranasally for three weeks enhanced memory for adults with Alzheimer’s disease dementia (AD) or amnestic mild cognitive impairment (MCI). The investigation of longer-term administration is necessary to determine whether benefits persist, whether they are similar to benefits provided by regular insulin, and whether either form of insulin therapy affects AD biomarkers.Objective: The present study aimed to determine whether four months of treatment with intranasal insulin detemir or regular insulin improves cognition, daily functioning, and AD biomarkers for adults with MCI or AD.Methods: This randomized, double-blind, placebo-controlled trial included an intent-to-treat sample consisting of 36 adults diagnosed with MCI or mild to moderate AD. Participants received placebo (n = 12), 40 IU of insulin detemir (n = 12), or 40 IU of regular insulin (n = 12) daily for four months, administered with a nasal delivery device. A cognitive battery was administered at baseline and after two and four months of treatment. MRI was administered for all participants and lumbar puncture for a subset (n = 20) at baseline and four months. The primary outcome was change from baseline to four months on a memory composite (sum of Z scores for delayed list and story recall). Secondary outcomes included: global cognition (Alzheimer’s Disease Assessment Scale-Cognition), daily functioning (Dementia Severity Rating Scale), MRI volume changes in AD-related regions of interest, and cerebrospinal fluid AD markers.Results: The regular insulin treated group had better memory after two and four months compared with placebo (p < 0.03). No significant effects were observed for the detemir-assigned group compared with the placebo group, or for daily functioning for either group. Regular insulin treatment was associated with preserved volume on MRI. Regular insulin treatment was also associated with reduction in the tau-P181/Aβ42 ratio.Conclusion: Future research is warranted to examine the mechanistic basis of treatment differences, and to further assess the efficacy and safety of intranasal insulin.

Cognitive Stimulation as a Therapeutic Modality for Dementia: A Meta-Analysis.

ObjectiveAlthough cognitive stimulation (CS) is one of the most popular non-pharmacological interventions for people with dementia, its efficacy is still debatable. We performed a meta-analysis of randomized controlled trials (RCTs) on the efficacy of CS in people with dementia.MethodsData sources were identified by searching PubMed, MEDLINE, Embase, psychINFO, and Cochrane Reviews Library. A total of 7,354 articles were identified, and of these, 30 RCTs were selected based on the selection criteria. Of these 30 RCTs, 14 were finally included in our meta-analysis [731 participants with dementia; 412 received CS (CS group) and 319 received usual care (control group)].ResultsWe found that the people with dementia had a moderate benefit from CS. The mean difference between the CS and control groups was 2.21 [95% CI (0.93, 3.49), Z=3.38, p=0.00007] in the Alzheimer's Disease Assessment Scale-Cognition and 1.41 [95% CI (0.98, 1.84), Z=6.39, p<0.00001] in the Mini-Mental State Examination. CS also improved quality of life in people with dementia [95% CI (0.72, 3.38), Z=3.02, p=0.003].ConclusionCS is effective for improving cognition and quality of life in people with dementia; however, its effects were small to moderate.