Alzheimer's Disease Assessment Scale-Cognitive Research Articles

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.

Pathogenetic therapy of cognitive impairment: results of a multicenter placebo-controlled clinical trial of the efficacy and safety of Miladean

Evaluation of the efficacy and safety of the use of the drug Miladean in the treatment of patients with cognitive disorders (CDs) of vascular genesis. In during the double-blind multicenter prospective randomized placebo-controlled phase III clinical trial, 300 patients with CDs and chronic cerebral ischemia were randomized into 3 groups: group 1 (n=100) received Miladean (daily dose: memantine 10 mg + melatonin 6 mg), group 2 (n=101) - memantine (10 mg/day), group 3 - placebo (n=99) for 8 weeks. The dynamics of the overall score (the primary criterion of effectiveness) and the proportion of patients with improvement on the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog), the dynamics of visual-spatial orientation disorders (Benton test), sleep quality (Pittsburgh Sleep Quality Index scale) and the safety of therapy were evaluated. Miladean demonstrated efficacy in the treatment of CDs: a statistically and clinically significant decrease in the overall score on the ADAS-Sod scale was shown (by 6.1 versus 4.7 and 3.5 points in the 2nd (p=0.009) and 3rd (p<0.05) groups) and an increase in the proportion of patients (96.9%) with clinically and statistically a significant improvement compared to the 2nd and 3rd groups (p=0.019 and p<0.001 respectively). Miladean significantly improved the performance in the Benton test (1.20±1.66 vs. 0.64±1.69 points in group 3, p=0.026) and sleep quality (84.7% of patients with CDs), compared to placebo (63.9%) and memantine (64.3%) (p=0.002 in both cases). Miladean was well tolerated, there were no cases of interaction with basic therapy drugs. The combination of many different pathogenetic effects of Miladean suggests that it has the ability to slow down the rate of progression of CDs and stabilize the condition of patients. The unique combination of active substances in Miladean has been proven to be effective and safe in the treatment of patients with CDs.

Associations of erythrocyte omega-3 fatty acids with cognition, brain imaging and biomarkers in the Alzheimer’s disease neuroimaging initiative: cross-sectional and longitudinal retrospective analyses

The association between omega-3 (ω-3) PUFAs and cognition, brain imaging and biomarkers is still not fully established. The aim was to analyze the cross-sectional and retrospective longitudinal associations between erythrocyte ω-3 index and cognition, brain imaging, and biomarkers among older adults. A total of 832 Alzheimer's Disease Neuroimaging Initiative 3 (ADNI-3) participants, with a mean (SD) age of 74.0 (7.9) y, 50.8% female, 55.9% cognitively normal, 32.7% with mild cognitive impairment, and 11.4% with Alzheimer disease (AD) were included. A low ω-3 index (%EPA + %DHA) was defined as the lowest quartile (≤3.70%). Cognitive tests [composite score, AD Assessment Scale Cognitive (ADAS-Cog), Wechsler Memory Scale (WMS), Trail Making Test, Category Fluency, Mini-Mental State Examination, Montreal Cognitive Assessment] and brain variables [hippocampal volume, white matter hyperintensities (WMHs), positron emission tomography (PET) amyloid-β (Aβ) and tau] were considered as outcomes in regression models. Low ω-3 index was not associated with cognition, hippocampal, and WMH volume or brain Aβ and tau after adjustment for demographics, ApoEε4, cardiovascular disease, BMI, and total intracranial volume in the cross-sectional analysis. In the retrospective analysis, low ω-3 index was associated with greater Aβ accumulation (adjusted β = 0.02; 95% CI: 0.01, 0.03; P=0.003). The composite cognitive score did not differ between groups; however, low ω-3 index was significantly associated with greater WMS-delayed recall cognitive decline (adjusted β = -1.18; 95% CI: -2.16, -0.19; P=0.019), but unexpectedly lower total ADAS-Cog cognitive decline. Low ω-3 index was cross-sectionally associated with lower WMS performance (adjusted β = -1.81, SE=0.73, P=0.014) and higher tau accumulation among ApoE ε4 carriers. Longitudinally, low ω-3 index was associated with greater Aβ accumulation and WMS cognitive decline but unexpectedly with lower total ADAS-Cog cognitive decline. Although no associations were cross-sectionally found in the whole population, low ω-3 index was associated with lower WMS cognition and higher tau accumulation among ApoE ε4 carriers. The Alzheimer's Disease Neuroimaging Initiative (ADNI) is registered at clinicaltrials.gov as NCT00106899.

Does Resting Motor Threshold correlate with severity of Alzheimer's disease?

Conflicting results have emerged from studies examining the potential of resting motor threshold (RMT) as a neurophysiological marker for Alzheimer's disease (AD) diagnosis and progression. In this study, we estimated the strength of the association between RMT measurements and severity of cognitive impairment in a relatively large sample (N=128) of clinical trial participants with mild (Clinical Dementia Rating - CDR=1) to moderate (CDR=2) AD. RMT for each participant was determined by applying single-pulse transcranial magnetic stimulation repeated at varying intensities over left and right sides of the primary motor cortex. RMT is the minimum intensity that evoked a visible contralateral involuntary finger twitch and RMT asymmetry is the absolute difference between the left and right RMT measurements. Cognitive impairment was measured with the Montreal Cognitive Assessment (MoCA) and the Alzheimer Disease Assessment Scale - Cognitive (ADAS-Cog) scores. Although the left and right RMT was lower in CDR 2 than in CDR 1 participants, neither RMT nor RMT asymmetry correlated significantly with cognitive test scores. In conclusion, our study in a large sample size does not support the idea that RMT is a sensitive marker of cognitive decline/severity in AD. Clinical Relevance- This study provides evidence that RMT may not be useful for AD progression monitoring.

Research on predicting the risk of mild cognitive impairment in the elderly based on the joint model

Objective: To construct and compare the dynamic prediction models of the risk of mild cognitive impairment (MCI) in the elderly based on six different cognitive function scales. Methods: Based on longitudinal data from the Alzheimer's Disease Neuroimaging Initiative from 2005 to 2020, Mini-mental state examination (MMSE), functional activities questionnaire (FAQ), Alzheimer's disease assessment scale-cognitive (ADAS-Cog) 11, ADAS-Cog13, ADAS delayed word recall (ADASQ4), and Rey auditory verbal learning test (RAVLT)_immediate were used as longitudinal cognitive function evaluation indicators to assess the longitudinal changes in cognitive function. The joint model was used to analyze association between indicators variation trajectory and survival outcome MCI, and construct the risk prediction model of MCI in the elderly, the linear mixed model was constructed the longitudinal sub-model which described the evolution of a repeated measure over time, a proportional hazards model was constructed the survival sub-model, and the two sub-models were connected through the correlation parameter (α). The areas under the receiver operator characteristic curve (AUC) were used to evaluate the predictive efficacy of the model in the follow-up period of (t, t+Δt). The starting point t was selected at the 30th, 42nd, and 54th month, and the Δt was selected as 15 and 21 months. Based on the prediction model, an example of the research object was selected for dynamic individual predictions of the risk of MCI. Results: Finally, 544 older adults (aged 60 years and above) with normal baseline cognitive status were included, of which 119 cases (21.9%) had MCI during the follow-up process were regarded as the case group, and 425 cases remained normal as the control group. The joint model suggests that the longitudinal trajectories of the six evaluation indicators are all related to the risk of MCI (P<0.001). The risk of MCI decreased by 32.3% (HR=0.677, 95%CI: 0.541-0.846) and 10.8% (HR=0.892, 95%CI: 0.865-0.919) for each one-point increase of MMSE and RAVLT_immediate longitudinal scores. The risk of MCI increased by 53.2% (HR=1.532, 95%CI: 1.393-1.686), 36.2% (HR=1.362, 95%CI: 1.268-1.462), 23.2% (HR=1.232, 95%CI: 1.181-1.285), and 85.1% (HR=1.851, 95%CI:1.629-2.104) for each one-point increase of FAQ, ADAS-Cog11, ADAS-Cog13, and ADASQ4 longitudinal scores. AUC results show that RAVLT_immediate (0.760 2) and ADASQ4 (0.755 8) have higher average prediction efficiency, followed by ADAS-Cog13 (0.743 7), ADAS-Cog11 (0.715 3), FAQ (0.700 8) and MMSE (0.629 5). ADASQ4 joint model was used to provide a dynamic individual prediction of the risk of MCI. The average probability of MCI after five years of follow-up and ten years of follow-up in the example individuals were 8% and 40%, respectively. Conclusions: The RAVLT_immediate and ADASQ4 scales, which are only for memory tests, have high accuracy in predicting the risk of MCI. Using the RAVLT_immediate and ADASQ4 scales as longitudinal cognitive function evaluation indicators to construct a joint model, the results can provide a basis for realizing MCI risk prediction for the elderly.

LncRNA HOTAIR in exercise-induced neuro-protective function in Alzheimer's disease.

Exercise is effective in Alzheimer's disease (AD), which is characterized by neuro-degenerative progress with increasing morbidity. The present study aimed to explore whether HOTAIR participated in the regulation of exercise in AD. Arelative expression of serum HOTAIR was detected using quantitative real-time polymerase chain reaction (PCR). The diagnostic significance of HOTAIR on distinguishing AD patients was evaluated by receiver operating characteristic (ROC) curve. Correlations between HOTAIR expression and Mini-Mental State Examination (MMSE) score or Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) score were analyzed with Pearson's test. Logistic regression analysis was applied to investigate factors as independent indicators for HOTAIR expression. In AD patients, the expression of HOTAIR was increased, and it could function as adiagnostic marker in AD patients. The expression of HOTAIR was associated with MMSE score and ADAS-Cog score in AD patients before exercise. Exercise ameliorated the cognitive impairment and reduced the relative serum expression of HOTAIR. Exercise was proved to be an independent indicator of HOTAIR expression. HOTAIR was apossible biomarker for indicating AD patients, and it was correlated with MMSE scores and ADAS-Cog results. Exercise might moderate AD progress via controlling HOTAIR.

Filipino Multicomponent Intervention to Maintain Cognitive Performance in High-Risk Population (FINOMAIN): Study Protocol for a Cluster Randomized Controlled Trial.

Background: More than half of the people with dementia live in lower-middle income countries (LMIC), yet we lack research and evidence-based knowledge to guide health promotion and prevention strategies for cognitive decline. In the Philippines, the prevalence of mild cognitive impairment (MCI) and cardiovascular risk factors among older persons are high, making this population at high risk for developing dementia. This protocol describes a cluster randomized controlled trial that aims to investigate the efficacy of a multicomponent intervention to maintain cognitive performance among high-risk population.Methods: This is a cluster-randomized, two-arm, single-blind trial of a multicomponent intervention that combines dance called INDAK (Improving Neurocognition through Dance and Kinesthetics), nutrition counseling, and vascular risk management. The intervention arm will receive 12 months (1-h, twice per week) of INDAK and every 3 months of nutrition counseling and intensive vascular risk management and monitoring. The control group will receive the usual vascular care advice and referral. A total of 605 (20–25 clusters per arm) community-dwelling Filipino older adults aged ≥ 60 years old with MCI will participate in the study and will be assessed at baseline, 6th- and 12th-month follow-up. The primary outcome is cognitive performance assessed by the Alzheimer's Disease Assessment Scale—Cognitive (ADAS-Cog), Mnemonic Similarity Tasks (MST), and executive function composite (EFC). Secondary outcomes are functional connectivity assessed through brain imaging, and measures of behavioral, functional level, and quality of life.Discussion: The study aims to provide scientific evidence on a public health intervention that is contextualized in a community setting to reduce dementia risk among older adults with MCI. This model can be an ecological, low-cost, and effective program, thereby conducive to widespread implementation in the Philippines as well as in other low-resource settings with similar public health challenges. The pilot phase was underway with eight villages (clusters), but temporarily interrupted by the pandemic. The full study is anticipated to start after community restrictions are eased.

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.

Predicting Alzheimer's disease based on survival data and longitudinally measured performance on cognitive and functional scales

This study assessed how well longitudinally taken cognitive and functional scales from people with mild cognitive impairment (MCI) predict conversion to Alzheimer's disease (AD). Participants were individuals with baseline MCI from the Alzheimer's Disease Neuroimaging Initiative. Scales included the Alzheimer Disease Assessment Scale-Cognitive (ADAS-Cog) 11 and 13, the Mini Mental State Examination (MMSE), and the Functional Assessment Questionnaire (FAQ). A joint modelling approach compared performance on the four scales for dynamic prediction of risk for AD. The goodness of fit measures included log likelihood, the Akaike Information Criterion (AIC) and the Bayesian Information Criterion (BIC). The area under the curve (AUC) of the receiver operating characteristic assessed predictive accuracy. The parameter α in the ADAS-Cog11, ADAS-Cog13, MMSE, and FAQ joint models was statistically significant. Joint MMSE and FAQ models had better goodness of fit. FAQ had the best predictive accuracy. Cognitive and functional impairment assessment scales are strong screening predictors when repeated measures are available. They could be useful for predicting risk for AD in primary healthcare.

Inter-individual differences in the responses to aerobic exercise in Alzheimer's disease: Findings from the FIT-AD trial

BackgroundDespite the strong evidence of aerobic exercise as a disease-modifying treatment for Alzheimer's disease (AD) in animal models, its effects on cognition are inconsistent in human studies. A major contributor to these findings is inter-individual differences in the responses to aerobic exercise, which was well documented in the general population but not in those with AD. The purpose of this study was to examine inter-individual differences in aerobic fitness and cognitive responses to a 6-month aerobic exercise intervention in community-dwelling older adults with mild-to-moderate dementia due to AD. MethodsThis study was a secondary analysis of the Effects of Aerobic Exercise for Treating Alzheimer's Disease (FIT-AD) trial data. Aerobic fitness was measured by the shuttle walk test (SWT), the 6-min walk test (6MWT), and the maximal oxygen consumption (VO2max) test, and cognition by the AD Assessment Scale-Cognition (ADAS-Cog). Inter-individual differences were calculated as the differences in the standard deviation of 6-month change (SDR) in the SWT, 6MWT, VO2max, and ADAS-Cog between the intervention and control groups. ResultsSeventy-eight participants were included in this study (77.4 ± 6.3 years old, mean ± SD; 15.7 ± 2.8 years of education; 41% were female). VO2max was available for 26 participants (77.7 ± 7.1 years old; 14.8 ± 2.6 years of education; 35% were female). The SDR was 37.0, 121.1, 1.7, and 2.3 for SWT, 6MWT, VO2max, and ADAS-Cog, respectively. ConclusionThere are true inter-individual differences in aerobic fitness and cognitive responses to aerobic exercise in older adults with mild-to-moderate dementia due to AD. These inter-individual differences likely underline the inconsistent cognitive benefits in human studies.

The efficacy of statins in the treatment of Alzheimer's disease: a meta-analysis of randomized controlled trial.

Alzheimer's disease (AD) is a common type of dementia, which has caused heavy global economic and health burden, and the using of statins to treat AD has caused widely debated. The purpose of this meta-analysis is to explore the effect of statins in the treatment of Alzheimer's disease. Studies were retrieved by searching PubMed, Embase, Cochrane library, OvisdSP, Web of Science, Chinese Nation Knowledge Infrastructure (CNKI) and Chinese Biomedical Database (CBM) databases before March 31, 2019. We extracted the Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-cognitive (ADAS-Cog), Neuropsychiatric Inventory (NPI), Activities of Daily Living (ADL) scale score, and other information. The pooled Weighted Mean Difference (WMD) and their 95% confidence intervals (95% CI) were calculated with random effect model or fixed random effect model. A total of nine randomized controlled trials were included that contained 1489 patients; of them, 742 patients in the statins group, 747 patients in the control group. There were nine studies used the MMSE scale, five studies used the ADAS-Cog scale, four studies used the NPI scale, and six studies used the ADL scale. Meta-analysis of the nine studies that reported the MMSE scale scores indicated that there is no significant effect of statins as compared with control group (the pooled WMD = 1.09, 95% CI, - 0.00, 2.18, p = 0.05, I2= 87.9%). Meta-analysis of the five studies that reported the ADAS-Cog scale scores also indicated that there is no significant effect of statins as compared with control group (the pooled WMD = - 0.16, 95% CI, - 2.67, 2.36, p = 0.90, I2= 80.1%). Meta-analysis of the four studies that reported the NPI scale scores indicated that treatment with statins could slow the rise in the NPI scale scores (the pooled WMD = - 1.16, 95% CI, - 1.88, - 0.44, p = 0.002, I2= 45.4%). Meta-analysis of the six studies that reported the ADL scale scores indicated that treatment with statins could improve patients' daily living ability (the pooled WMD = - 4.06, 95% CI, - 6.88, - 1.24, p = 0.005, I2= 86.7%). Results of subgroup analysis indicated that the use of statins in the short term (≤ 12months) associated with the change of the MMSE scale scores (the pooled WMD = 1.78, 95% CI, 0.53, 3.04, p = 0.005, I2= 79.6%). Sensitivity analysis and publication bias test were both negative, and the results were relatively reliable and stable. Statins used in AD patients had beneficial effects on the scores of MMSE scale in the short term (≤ 12months), and statins could slow the deterioration of neuropsychiatric status and significantly improve activities of daily living ability in AD patients, but statins did not show an advantage in the change of the ADAS-Cog scale scores.

Saving cognitive outcome data in Alzheimer's disease clinical trials during the COVID-19 pandemic: Commentary on the virtual administration of the ADAS-Cog.

Elderly participants in Alzheimer's disease (AD) clinical trials are at high risk of morbidity and mortality with interpersonal exposure to COVID‐19, a situation that is likely to continue for the foreseeable future. Yet, in‐person neuropsychological assessments remain the mainstay primary outcomes for clinical trials seeking prevention and cure for AD. The Alzheimer's Disease Assessment Scale‐Cognitive (ADAS‐Cog) is among the most commonly used cognitive assessment in AD clinical trials, and though currently lacking specific guidelines for virtual administrations, it can be used remotely with appropriate modifications and considerations. Here we propose a novel method of virtual administration of the ADAS‐Cog, which considers workarounds for technological and human limitations imposed when the participant is no longer sitting across from the test administrator.

Effects of a combined transcranial magnetic stimulation (TMS) and cognitive training intervention in patients with Alzheimer's disease

IntroductionThis clinical trial evaluates the efficacy and safety of a 6-week course of daily neuroAD™ therapy. Methods131 subjects between 60 and 90 years old, unmedicated for Alzheimer's disease (AD), or on stable doses of an acetylcholinesterase inhibitor and/or memantine, with Mini–Mental State Examination scores between 18 and 26, clinical dementia rating scale scores of 1 or 2, enrolled for a prospective, randomized, double-blind, sham-controlled, multicenter clinical trial. Structural brain MRIs were obtained for transcranial magnetic stimulation targeting. Baseline Alzheimer's disease assessment scale—cognitive (ADAS-Cog) and Clinical Global Impression of Change were assessed. 129 participants were randomized to active treatment plus standard of care (SOC) or sham treatments plus SOC. ResultsSubjects with baseline ADAS-Cog ≤ 30 (~85% of study population) showed a statistically significant benefit favoring active over sham. Responder analysis showed 31.7% participants in the active group with ≤ −4 point improvement on ADAS-Cog versus 15.4% in the sham group. DiscussionneuroAD™ Therapy System provides a low-risk therapeutic benefit for patients with milder AD (baseline ADAS-Cog ≤30) beyond pharmacologic SOC.

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.

Barriers to early detection of cognitive impairment in the elderly despite the availability of simple cognitive screening tools and the pharmacist's role in early detection and referral

AbstractAimThe aim of this review is to identify a suitable cognitive screening tool that can be used by the pharmacist during home medication review in addition to calculating the medications’ total anticholinergic burden (ACB).Data sourcesA search of the literature was conducted using PubMed, Embase, Medline and Google Scholar databases to identify relevant studies using the following keywords: ‘cognitive impairment’, ‘cognitive impairment AND diagnosis’, ‘cognitive scales’, ‘dementia’, ‘delirium’, ‘pharmacist role’, ‘mini‐mental state examination (MMSE)’, ‘the Rowland dementia assessment scale (RUDAS)’, ‘the Alzheimer's Disease Assessment Scale ‐ Cognition (ADAS‐Cog)’ and ‘barriers and problems’. Only informational websites, clinical trials and review articles were included.ResultsThe MMSE, RUDAS, ADAS‐Cog, Psychogeriatric Assessment Scale (PAS) and Kimberley Indigenous Cognitive Assessment (KICA‐Cog) require specialist training. The anxiety and depression checklist (K10) and ‘worried about your memory’ (WAYM) can be self‐administered without prior training. The ACB scoring system can also be used to determine the total medications ACB.ConclusionThe K10 and WAYM can be used by the pharmacist during medication reviews to detect cognitive impairment early and refer the elderly for further medical care supported by the calculated score for the patient‘s total medications‘ ACB.

DESIGN AND EXECUTION OF THE NILVAD STUDY

NILVAD is an investigator driven phase III clinical trial of nilvadipine in mild to moderate Alzheimer's disease. Nilvadipine, a dihyropyridine calcium channel blocker, is a licensed antihypertensive and is being repurposed for AD based on clinical and basic science evidence for its potential as a disease-modifying agent in AD. 511 subjects with mild to moderate AD were recruited across 23 sites in 9 different European countries. Subjects received 8 mg over encapsulated nilvadipine or matching placebo over a period of 18 months. The sponsor of the trial was St. James's Hospital, Dublin. Academic trial units were used to monitor the trial in each country. The primary outcome measures were Alzheimer's disease Assessment Scale Cognitive (ADAS-Cog) and Clinical Dementia Rating Scale sum of boxes (CDR-sb). There were a number of challenges to overcome in successfully completing this trial including: recruitment and exclusion of patients on multiple antihypertensive agents, in particular other calcium channel blockers and beta blockers; IMP manufacture: sourcing and over capsulation of study drug and matching placebo and independently establishing blindedness and stability testing of the over encapsulated repurposed agent; safety monitoring and pharmacovigilance. NILVAD is an example of an investigator driven repurposing program for an antihypertensive in AD. The NILVAD trial provides multiple learnings that can be captured and help inform future efforts in this challenging area of drug discovery.

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.