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Abstract Alzheimer’s Disease (AD), a neurodegenerative disorder escalating worldwide, remains incurable with existing interventions merely mitigating symptoms. Hydralazine, an antihypertensive agent, has displayed neuroprotective potential in AD animal models via amplification of mitochondrial functionality and stimulation of stress management and repair pathways. Nevertheless, its effectiveness and tolerability in human AD cohorts are yet to be confirmed. This study protocol describes the design of an ongoing, single-center, randomized, triple-blind, placebo-controlled trial to assess hydralazine’s effects on cognitive function in mild to moderate -stage AD patients. We will enroll 424 patients aged 50 and older, meeting NINCDS-ADRDA criteria for probable AD with Mini-Mental State Examination scores from 12–26. They’ll be randomly assigned to receive either hydralazine HCL (25 mg, thrice daily) or a placebo for 12 months. The primary outcome is the Alzheimer’s Disease Assessment Scale change from baseline to 12 months. Secondary outcomes include various measures using Lawton instrumental activities of daily living scale, neuropsychiatry inventory, and caregiver activity survey. This trial will explore the potential benefits and risks of hydralazine in mild to moderate AD treatment. It’s the first trial examining hydralazine’s impact on mild to moderate -stage AD in human and is registered at the Iranian Registry of Clinical Trials (IRCT20200711048075N1, registered 29/07/2020) and ClinicalTrials.gov (NCT 04,842,552AQ, registered 13/04/2021). Ethics approval was granted by the Research Ethics Committee of the National Institute for Medical Research Development (IR.NIMAD.REC.1398.424), following the SPIRIT Statement guidelines. Findings will be disseminated via peer-reviewed publications and conferences. This inaugural human clinical trial evaluates hydralazine’s impact on patients in the mild to moderate AD. Executed with a randomized, triple-blind, placebo-controlled methodology, this study incorporates a significant sample size and an extended monitoring duration. Multiple parameters, including cognitive capabilities, will be assessed. Potential limitations include the inherent homogeneity of the AD cohort, the lack of biomarker assays, and the unpredictable progression of the disease. Notably, the study might not elucidate the protracted effects of hydralazine beyond a 12-month period. Another limitation of our clinical trial is that patients were diagnosed with Alzheimer’s disease based solely on clinical evaluation and MRI findings, without the inclusion of specific biomarkers, which may impact the accuracy and specificity of the diagnosis. Trial registration: Iranian Registry of Clinical Trials (IRCT20200711048075N1, registered 29/07/2020) and ClinicalTrials.gov (NCT 04,842,552, registered 13/04/2021).

Positive effects of new anti-amyloid-β (Aβ) monoclonal antibodies in Alzheimer's disease (AD) have been attributed to brain amyloid reduction. However, most anti-Aβ antibodies also increase the CSF levels of the 42-amino acid isoform (Aβ42). We evaluated the associations of changes in CSF Aβ42 and brain Aβ-PET with cognitive and clinical end points in randomized trials of anti-Aβ drugs that lowered (β- and γ-secretase inhibitors) or increased CSF Aβ42 levels (anti-Aβ monoclonal antibodies) to test the hypothesis that post-treatment increases in CSF Aβ42 levels are independently associated with cognitive and clinical outcomes. From long-term (≥12 months) randomized placebo-controlled clinical trials of anti-Aβ drugs published until November 2023, we calculated the post-treatment versus baseline difference in ADAS-Cog (cognitive subscale of the Alzheimer's Disease Assessment Scale) and CDR-SB (Clinical Dementia Rate-Sum of Boxes) and z -standardized changes in CSF Aβ42 and Aβ-PET Centiloids (CL). We estimated the effect size [regression coefficients (RCs) and confidence intervals (CIs)] and the heterogeneity (I2) of the associations between AD biomarkers and cognitive and clinical end points using random-effects meta-regression models. We included 25 966 subjects with AD from 24 trials. In random-effects analysis, increases in CSF Aβ42 were associated with slower decline in ADAS-Cog (RC: −0.55; 95% CI: −0.89, −0.21, P = 0.003, I2 = 61.4%) and CDR-SB (RC: −0.16; 95% CI: −0.26, −0.06, P = 0.002, I2 = 34.5%). Similarly, decreases in Aβ–PET were associated with slower decline in ADAS-Cog (RC: 0.69; 95% CI: 0.48, 0.89, P < 0.001, I2 = 0%) and CDR-SB (RC: 0.26; 95% CI: 0.18, 0.33, P < 0.001, I2 = 0%). Sensitivity analyses yielded similar results. Higher CSF Aβ42 levels after exposure to anti-Aβ drugs are independently associated with slowing cognitive impairment and clinical decline. Increases in Aβ42 may represent a mechanism of potential benefit of anti-Aβ monoclonal antibodies in AD. [ABSTRACT FROM AUTHOR]

Successful clinical development of new therapeutic interventions is notoriously difficult, especially in neurodegenerative diseases, where predictive biomarkers are scarce and functional improvement is often based on patient's perception, captured by structured interviews. As a consequence, mechanistic modeling of the processes relevant to therapeutic interventions in CNS disorders has been lagging behind other disease indications, probably because of the perceived complexity of the brain. However in this report, we develop the argument that a combination of Computational Neurosciences and Quantitative Systems Pharmacology (QSP) modeling of molecular pathways is a powerful simulation tool to enhance the probability of successful drug development for neurodegenerative diseases. Computational Neurosciences aims to predict action potential dynamics and neuronal circuit activation that are ultimately linked to behavioral changes and clinically relevant functional outcomes. These processes can not only be affected by the disease state, but also by common genotype variants on neurotransmitter-related proteins and the psycho-active medications often prescribed in these patient populations. Quantitative Systems Pharmacology (QSP) modeling of molecular pathways allows to simulate key pathological drivers of dementia, such as protein aggregation and neuroinflammatory responses. They often impact neurotransmitter homeostasis and voltage-gated ion-channels or lead to mitochondrial dysfunction, ultimately leading to changes in action potential dynamics and clinical readouts. Combining these two modeling approaches can lead to better actionable understanding of the many non-linear pharmacodynamic processes active in the human diseased brain. Practical applications include a rational selection of the optimal doses in combination therapies, identification of subjects more likely to respond to treatment, a more balanced stratification of treatment arms in terms of comedications, disease status and common genotype variants and re-analysis of small clinical trials to uncover a possible clinical signal. Ultimately this will lead to a higher success rate of bringing new therapeutics to the right patient populations. [ABSTRACT FROM AUTHOR]

Despite extensive use of the Alzheimer's Disease (AD) Assessment Scale – Cognitive Subscale (ADAS-Cog) in AD research, exploration of memory subtests or process scores from the measure has been limited. The current study sought to establish validity for the ADAS-Cog Word Recall Immediate and Delayed Memory subtests and learning slope scores by showing that they are sensitive to AD biomarker status. Word Recall subtest and learning slope scores were calculated for 441 participants from the Alzheimer's Disease Neuroimaging Initiative (aged 55 to 90). All participants were categorized using the NIA-AA Research Framework – based on PET-imaging of β-amyloid (A) and tau (T) deposition – as Normal AD Biomarkers (A-T-), Alzheimer's Pathologic Change (A + T-), or Alzheimer's disease (A + T+). Memory subtest and learning slope performances were compared between biomarker status groups, and with regard to how well they discriminated samples with (A + T+) and without (A-T-) biomarkers. Lower Word Recall memory subtest scores – and scores for a particular learning slope calculation, the Learning Ratio – were observed for the AD (A + T+) group than the other biomarker groups. Memory subtest and Learning Ratio scores further displayed fair to good receiver operator characteristics when differentiating those with and without AD biomarkers. When comparing across learning slopes, the Learning Ratio metric consistently outperformed others. ADAS-Cog memory subtests and the Learning Ratio score are sensitive to AD biomarker status along the continuum of the NIA-AA Research Framework, and the results offer criterion validity for use of these subtests and process scores as unique markers of memory capacity. [ABSTRACT FROM AUTHOR]

(1) Background: Alzheimer's disease (AD) is a progressive and fatal neurodegenerative disorder. Hydrogen gas (H2) is a therapeutic medical gas with multiple functions such as anti-oxidant, anti-inflammation, anti-cell death, and the stimulation of energy metabolism. To develop a disease-modifying treatment for AD through multifactorial mechanisms, an open label pilot study on H2 treatment was conducted. (2) Methods: Eight patients with AD inhaled 3% H2 gas for one hour twice daily for 6 months and then followed for 1 year without inhaling H2 gas. The patients were clinically assessed using the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog). To objectively assess the neuron integrity, diffusion tensor imaging (DTI) with advanced magnetic resonance imaging (MRI) was applied to neuron bundles passing through the hippocampus. (3) Results: The mean individual ADAS-cog change showed significant improvement after 6 months of H2 treatment (−4.1) vs. untreated patients (+2.6). As assessed by DTI, H2 treatment significantly improved the integrity of neurons passing through the hippocampus vs. the initial stage. The improvement by ADAS-cog and DTI assessments were maintained during the follow-up after 6 months (significantly) or 1 year (non-significantly). (4) Conclusions: This study suggests that H2 treatment not only relieves temporary symptoms, but also has disease-modifying effects, despite its limitations. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) dementia is the most frequent cause of neurodegenerative dementia. The cognitive and behavioral symptoms associated with this disorder often have overlapping characteristics, potentially resulting in delayed diagnosis or misdiagnosis. This study aimed to assess the level of peripheral blood neurofilament light chain (NfL) and total tau (t-tau) protein in AD patients and investigate their relationship with cognitive impairment. The study included 80 participants of both sexes between the ages of 60 to 85 years. The participants were divided into two groups, consisting of 40 individuals in the control group (mean age 75±6.6 years) who had no cognitive or functional impairments and 40 AD patients (mean age 74.98±5.03 years). This study utilized the DSM-5 diagnostic criteria for major or mild neurocognitive disorder attributed to Alzheimer's disease (AD). The clinical and biochemical features of all participants were documented, and the Alzheimer's disease Assessment Scale cognitive subscale (ADAS-cog) scores were evaluated. Sandwich ELISA was employed to determine serum NfL and t-tau protein levels. The median serum NfL and t-tau protein levels in AD patients were significantly higher than those of the controls (47.84 pg/ml versus 17.66 pg/ml and 12.05 pg/ml versus 11.13 pg/ml, respectively). Age was positively correlated with NfL, t-tau levels, and ADAS-cog. Although elevated NfL and t-tau protein levels may play a role in disease progression, their diagnostic value for AD was limited. [ABSTRACT FROM AUTHOR]

Introduction: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive deterioration in cognition, memory and activities of daily living. Selective blockade of serotonin-6 (5-HT6) receptors, which are exclusively localized to the central nervous system, is reported to play an important role in learning and memory. Masupirdine is a potent and selective 5-HT6 receptor antagonist with pro-cognitive properties in animal models of cognition. Methods: The efficacy and safety of masupirdine were evaluated in patients with moderate AD concurrently treated with donepezil and memantine. A total of 564 patients were randomized in a 1:1:1 ratio. The study consisted of a 26-week double-blind treatment period. The primary efficacy outcome was the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog 11). Changes from baseline were analyzed using a mixed effects model for repeated measures (MMRM). In exploratory post hoc analyses, patients were subdivided based on the use of memantine dosage forms and memantine plasma concentrations, to evaluate the impact of memantine on the efficacy of masupirdine. Results: In an exploratory post hoc analysis, less worsening in cognition (ADAS-Cog 11 scores) was observed with masupirdine treatment as compared with placebo in patients whose trough memantine plasma concentrations were ≤ 100 ng/mL. Conclusions: Although prespecified study endpoints of the phase 2 study were not met, these exploratory post hoc subgroup observations are hypothesis-generating and suggest that the efficacy of masupirdine was adversely affected by concurrent therapy with memantine. Further assessment of masupirdine to determine its potential role as a treatment option for cognitive deficits associated with AD is warranted. Trial Registration: The study was registered at ClinicalTrials.gov (NCT02580305). [ABSTRACT FROM AUTHOR]

Background: Several medications have been applied to Alzheimer's dementia patients (AD) but their efficacies have been insufficient. The efficacy and safety of 4 weeks of repetitive transcranial magnetic stimulation (rTMS) in Japanese AD were evaluated in this exploratory clinical trial. Methods: Forty-two patients, aged 60-93 years (average, 76.4 years), who were taking medication (> 6 months) and had Mini-Mental State Examination (MMSE) scores ≤ 25 and Clinical Dementia Rating Scale scores (CDR-J) of 1 or 2, were enrolled in this single-center, prospective, randomized, three-arm study [i.e., 120% resting motor threshold (120% RMT), 90% RMT for the bilateral dorsolateral prefrontal cortex, and Sham]. Alzheimer's Disease Assessment Scale-Japanese Cognitive (ADAS-J cog), Montreal Cognitive Assessment (MoCA-J), Clinical Global Impression of Change (CGIC), Neuropsychiatric inventory (NPI), and EuroQOL 5 Dimensions 5-Level (EQ-5D-5L) were administered. The primary endpoint was the mean change from baseline in the MMSE score (week 4). An active rTMS session involved applying 15 trains bilaterally (40 pulses/train at 10 Hz; intertrain interval, 26 s). Participants received ≥ 8 interventions within the first 2 weeks and at least one intervention weekly in the 3rd and 4th weeks. Full Analysis set (FAS) included 40 patients [120% RMT (n = 15), 90% RMT (n = 13), and Sham (n = 12)]. Results: In the FAS, MMSE, ADAS-J cog, MoCA-J, CDR-J, CGIC, NPI, and EQ-5D-5L scores between the three groups were not significantly different. Two patients were erroneously switched between the 120% RMT and 90% RMT groups, therefore, "as treated" patients were mainly analyzed. Post hoc analysis revealed significant treatment efficacy in participants with MMSE scores ≥ 15, favoring the 120% RMT group over the Sham group. Responder analysis revealed 41.7% of the 120% RMT group had a ≥ 3-point improvement in the ADAS-J cog versus 0% in the Sham group (Fisher's exact test, p = 0.045). The MoCA-J showed the same tendency but was not significant. Efficacy disappeared in week 20, based on the ADAS-cog and MoCA-J. No intervention-related serious adverse events occurred. Conclusion: This paper is the first report of using rTMS in Japanese AD patients. The treatment seems safe and moderate-mild stage AD should be target population of pivotal clinical trial with 120% RMT rTMS. [ABSTRACT FROM AUTHOR]

Background: Although repetitive transcranial magnetic stimulation (rTMS) has been extensively studied in patients with Alzheimer's disease (AD), the clinical evidence remains inconsistent. The purpose of this meta-analysis was to evaluate the effects of rTMS on global cognitive function in patients with AD. Methods: An integrated literature search using 4 databases (PubMed, Web of Science, Embase, and Cochrane Library) was performed to identify English language articles published up to October 6, 2021. We pooled Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) scores using a random-effects model via RevMan 5.4 software. We calculated estimates of mean differences (MD) with 95% confidence intervals (CI). The primary outcomes were pre-post treatment changes in global cognition as measured using MMSE and ADAS-Cog immediately after rTMS treatment, and the secondary outcome was duration of cognitive improvement (1-1.5 and ≤3 months). Results: Nine studies with 361 patients were included in this meta-analysis. The results showed that rTMS significantly improved global cognitive function immediately following rTMS treatment [(MD) 1.82, 95% confidence interval (CI) 1.41-2.22, p < 0.00001, MMSE; 2.72, 95% CI, 1.77-3.67, p < 0.00001, ADAS-Cog], and the therapeutic effects persisted for an extended duration (2.20, 95% CI, 0.93-3.47, p =0.0007, MMSE; 1.96, 95% CI, 0.96-2.95, p = 0.0001, ADAS-Cog). Subgroup analyses showed that high frequency rTMS targeted to the left dorsolateral prefrontal cortex (DLPFC) for over 20 sessions induced the greatest cognitive improvement, with effects lasting formore than 1 month after the final treatment. There were no significant differences in dropout rate (p > 0.05) or adverse effect rate (p > 0.05) between the rTMS and control groups. Conclusions: Repetitive TMS is a potentially effective treatment for cognitive impairment in AD that is safe and can induce long-lasting effects. Our results also showed that ADAS-cog and MMSE differed in determination of global cognitive impairment. [ABSTRACT FROM AUTHOR]

Introduction: Appropriate tools and references are essential for evaluating individuals' cognitive levels. This study validated the Taiwan version of the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-cog) and provided normative data for the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), and ADAS-cog in community-dwelling older adults. Methods: MMSE, MoCA, and ADAS-cog were administered to 150 nondemented healthy adults aged 55–85 years during 2018–2020 as part of the Northeastern Taiwan Community Medicine Research Cohort. ADAS-cog was translated from the original English version to traditional Chinese with cultural and language considerations in Taiwan. Cronbach's alpha (α) tested the reliability of ADAS-cog, and Pearson correlations examined its external validity using MMSE and MoCA as comparisons. Normative data were generated and stratified by age and education, and the one-way analysis of variance compared scores between age and education groups. Another 20 hospital-acquired participants with cognitive impairment joined the 150 healthy participants. Comparisons in the Clinical Dementia Rating (CDR) tiers tested the discriminability of the tests for different cognitive levels. The area under the receiver operating characteristic curve (AUROC) analyzed the power of ADAS-cog in predicting CDR 0.5 from CDR 0. Results: The Taiwan version of ADAS-cog had fair reliability between items (α = 0.727) and good correlations to MMSE (r = −0.673, p < 0.001) and MoCA (r = −0.746, p < 0.001). The normative data of MMSE, MoCA, and ADAS-cog showed ladder changes with age (p = 0.006, 0.001, and 0.437) and education (p < 0.001, <0.001, and <0.001) in the 150 nondemented older adults. Next, in the 170 mixed participants from the communities and the hospital, MMSE, MoCA, and ADAS-cog scores were well differentiable between CDR 0, 0.5, and 1. In addition, ADAS-cog discriminated CDR 0.5 from 0 by an AUROC of 0.827 (p < 0.001). Discussion/Conclusion: The three structured cognitive tests consistently reflect cognitive levels of healthy older adults. The Taiwan version of ADAS-cog is compatible with MMSE and MoCA to distinguish people with mildly impaired from normal cognition. In addition, this study derived MMSE, MoCA, and ADAS-cog norms tailored to demographic factors. The findings highlight the need for stratification of age and education rather than applying a fixed cutoff for defining normal and abnormal cognition. [ABSTRACT FROM AUTHOR]

Disease modification trials in dementia and mild cognitive impairment (MCI) have not met with success. One potential criticism of these trials is the lack of sensitive outcome measures. A large number of outcome measures have been employed in dementia and MCI trials. This review aims to describe and analyze the utility of cognitive/clinical outcome measures in Alzheimer's disease (AD) and MCI trials. Methods: A PubMed search was conducted using relevant MeSH terms and exploded keywords. The search was confined to English language publications of human studies from the last five years which describe the latest trends in the use of outcome measures. Results: Despite broad use, the outcome measures employed are heterogeneous, with little data on correlations between scales. Another problem is that most studies are over-reliant on clinician/researcher assessment and cognitive outcomes, and there is a definite lack of stakeholder input. Finetuning of the paradigm is also required for people with early-stage disease, mild to moderate disease, and advanced dementia, as the outcome measures in these subgroups have varying relevance. Disease modification/prevention is an appropriate goal in early disease, whereas palliation and freedom from discomfort are paramount in later stages. The outcome measures selected must be suitable for and sensitive to these particular care goals. Although there is a shift to enrich MCI cohorts using a biomarker-based approach, the clinical relevance of such outcome measures remains uncertain. Conclusions: Outcome measures in dementia/MCI trials remain inhomogeneous and diverse, despite extensive use. Outcome measures fall within several paradigms, including cognitive, functional, quality-of-life, biomarker-based, and patient-reported outcome measures. The success of future disease-modifying trials is reliant to a large extent on the selection of outcome measures which combine all outcomes of clinical relevance as well as clinical meaning. Outcome measures should be tied to the type and stage of dementia and to the specific interventions employed. [ABSTRACT FROM AUTHOR]

Objective We aimed to evaluate the clinical efficacy and safety of Jianpi Yishen Huazhuo formula in patients with mild and moderate vascular dementia(VaD) with syndrome of spleen and kidney deficiency and mutual obstruction of phlegm and blood stasis. Methods A total of 90 patients with mild and moderate VaD with syndrome of spleen and kidney deficiency and mutual obstruction of phlegm and blood stasis treated at Dongfang Hospital of Beijing University of Chinese Medicine, Shanxi Traditional Chinese Medical Hospital, and The Affiliated Hospital to Changchun University of Chinese Medicine between December 2017 and February 2021 were enrolled. The patients were randomly divided into the control group (n =45) and the experimental group(n =45). Patients in the control group were given conventional basic treatment, and patients in the experimental group were additionally given Jianpi Yishen Huazhuo formula. Patients in both groups were treated for 180 days. The changes of Alzheimer's Disease Assessment Scale-Cognitive section (ADAS-cog) scores and traditional Chinese medicine symptoms were compared between the two groups before and after treatment. Results During the treatment, four cases fell off in the experimental group and five cases in the control group. Finally, 41 cases in the experimental group and 40 cases in the control group completed this study. The ADAS-cog scores of the experimental group were decreased after treatment compared with those before treatment(P<0. 01). The difference in ADAS-cog scores between before and after treatment and the difference in memory and language scores between before and after treatment were larger in the experimental group compared with the control group(P<0. 01). The number of patients with depression, misspeaking, and poor speech was lower in the experimental group after treatment compared with that before treatment(P<0. 05, P<0. 01). The number of patients with poor speech was lower in the experimental group after treatment compared with the control group(P<0. 05). The scores of nine peripheral symptoms, i. e., headache, dizziness, fatigue, palpitations, soreness of waist and knee, tiredness and weight of limbs, chilly sensation and cold limbs, frequent nocturnal urination, and residual leach after urination, were lower in the experimental group after treatment compared with those before treatment (P<0. 05, P<0. 01). The scores of four peripheral symptoms, i. e., sallow complexion, sighing often, chilly sensation and cold limbs, and frequent nocturnal urination, were lower in the experimental group after treatment compared with the control group(P<0. 05). Total peripheral symptom scores were lower in the experimental group after treatment compared with those before treatment(P<0. 01). The total scores of the experimental group were lower after treatment compared with the control group(P<0. 05). Conclusion Jianpi Yishen Huazhuo formula can improve cognitive function and related clinical symptoms in patients with mild and moderate VaD with syndrome of spleen and kidney deficiency and mutual obstruction of phlegm and blood stasis. It is safe and has certain advantages over conventional basic treatment. [ABSTRACT FROM AUTHOR]

Recent clinical trials in mild Alzheimer disease (AD) have enriched for amyloid-specific positron emission tomography (PET) imaging and used extended versions of the AD Assessment Scale-Cognitive Subscale (ADAS-Cog) in an effort to increase the sensitivity to detect treatment effects. We used data from mild AD participants in the AD Neuroimaging Initiative to model trial effect sizes for 12- and 24-month trials using 3 versions of the ADAS-Cog and increased standardized uptake value ratio (SUVR) cutoffs for amyloid imaging inclusion criteria. For 12-month trials, extended ADAS-Cog versions improved effect sizes. The ADAS-Cog11 elicited larger effect sizes when enriching for SUVR 1.1 only, whereas the ADAS-Cog12 and ADAS-Cog13 were associated with larger effect sizes with higher SUVR thresholds. For 24-month trials, extended ADAS-Cog versions increased effect sizes for trials not enriched for amyloid and trials enriched for SUVR 1.1. Only enriching for higher SUVR thresholds (1.3 and 1.4, not 1.1) increased trial power. We conclude that extended versions of the ADAS-Cog improve mild AD trial effect sizes for both 12- and 24-month long studies, whereas amyloid imaging criteria may be most valuable for 12-month trials.

BackgroundDevelopment of new treatments for Alzheimer's disease (AD) has broadened into early interventions in individuals with modest cognitive impairment and a slow decline. The 11-item version of the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) was originally developed to measure cognition in patients with mild to moderate AD. Attempts to improve its properties for early AD by removing items prone to ceiling and/or by adding cognitive measures known to be impaired early have yielded a number of ADAS-Cog variants. Using Alzheimer's Disease Neuroimaging Initiative data, we compared the performance of the 3-, 5-, 11- and 13-item ADAS-Cog variants in subjects with early AD. Given the interest in enrichment strategies, we also examined this aspect with a focus on cerebrospinal fluid (CSF) markers.MethodsSubjects with mild cognitive impairment (MCI) and mild AD with available ADAS-Cog 13 and CSF data were analysed. The decline over time was defined by change from baseline. Direct cross-comparison of the ADAS-Cog variants was performed using the signal-to-noise ratio (SNR), with higher values reflecting increased sensitivity to detect change over time.ResultsThe decline over time on any of the ADAS-Cog variants was minimal in subjects with MCI. Approximately half of subjects with MCI fulfilled enrichment criteria for positive AD pathology. The impact of enrichment was detectable but subtle in MCI. The annual decline in mild AD was more pronounced but still modest. More than 90 % of subjects with mild AD had positive AD pathology. SNRs were low in MCI but greater in mild AD. The numerically largest SNRs were seen for the ADAS-Cog 5 in MCI and for both the 5- and 13-item ADAS-Cog variants in mild AD, although associated confidence intervals were large.ConclusionsThe possible value of ADAS-Cog expansion or reduction is less than compelling, particularly in MCI. In mild AD, adding items known to be impaired at early stages seems to provide more benefit than removing items on which subjects score close to ceiling.

• Psychometric networks of cognitive impairment in Alzheimer's disease were examined • Analysis of three pivotal double-blind randomized clinical trials of donepezil • Previously unknown treatment effects emerged via network differences • For those treated with donepezil cognition was a more unified construct • Central network elements (e.g. language comprehension) may define treatment targets Psychometric network analysis is an alternative theoretically-driven analytic approach that has the potential to conceptualize cognitive impairment in Alzheimer's disease differently than was previously assumed and consequently detect unknown treatment effects. Based on individual participant data, extracted from three double-blind, randomized placebo-controlled clinical trials, psychometric networks were computed on observed Alzheimer's Disease Assessment Scale Cognitive Subscale scores at baseline (N=1,554) and on predicted change scores at 24 weeks of follow-up for participants who received donepezil (N=797) or placebo (N=484). A novel conceptualization of cognitive impairment in Alzheimer's disease was displayed through the baseline network, that had 90% (n=27) positive statistically significant (p<0.05) associations, and a most central aspect of ideational praxis. Following 24 weeks, treatment effects emerged via the differences between the change score networks. The donepezil network had more statistically significant (p<0.05) positive associations and a higher global strength (n=15; S=1.22; p=0.03), than the placebo network (n=8; S=0.57). This suggests that for those who were treated with donepezil compared with placebo, cognition is a more unified construct. The main aspects of change in cognitive impairment were comprehension of spoken language for the donepezil network and spoken language ability for the placebo network. Comprehension of spoken language apears to be most sensitive to psychopharmaceutical interventions and should therefore be closely monitored. Overall, our psychometric network analysis presents a new conceptualization of cognitive impairment in Alzheimer's disease, points to previously unknown treatment effects and highlights well-defined aspects of cognitive impairment that may translate into future treatment targets. [ABSTRACT FROM AUTHOR]

Currently no standardized tools are available in the Indian languages to assess changes in cognition. Our objectives are to culturally adapt the Alzheimer's disease Assessment Scale–Cognitive Subscale (ADAS-Cog) for use in India and to validate the Tamil version in an urban Tamil-speaking older adult population. Two panels of key stakeholders and a series of qualitative interviews informed the cultural and linguistic adaptation of the ADAS-Cog-Tamil. Issues related to levels of literacy were considered during the adaptation. Validation of the ADAS-Cog-Tamil was completed with 107 participants − 54 cases with a confirmed diagnosis of mild-moderate dementia, and 53 age, gender and education matched controls. Concurrent validity was examined with the Vellore Screening Instrument for Dementia (VSID) in Tamil. Internal consistency using Cronbach's alpha, sensitivity and specificity data using the Area under the Receiver Operating Characteristics (AUROC) curve values were computed. Inter-rater reliability was established in a subsample. The ADAS-Cog-Tamil shows good internal consistency (α = 0.91), inter-rater reliability and concurrent validity (with VSID-Patient version: r = –0.84 and with VSID-Caregiver version: r = –0.79). A cut-off score of 13, has a specificity of 89% and sensitivity of 90% for the diagnosis of dementia. ADAS-Cog-Tamil, derived from a rigorous, replicable linguistic and cultural adaptation process involving service users and experts, shows good psychometric properties despite the limitations of the study. It shows potential for use in clinical settings with urban Tamil speaking populations. The English version of the tool derived from the cultural adaptation process could be used for further linguistic adaptation across South Asia. [ABSTRACT FROM AUTHOR]

Background: Filipino normative data for neuropsychological tests are lacking. Objectives: This study aimed to determine the Filipino normative data for the Filipino Norming Project (FNP) Neuropsychological Battery, combining the Alzheimer’s Disease Assessment Scale – Cognitive (ADAS-Cog) and the Neuropsychological Test Battery from the Uniform Dataset of Alzheimer’s Disease Center (UDS-ADC). Methods: We recruited participants 60 years and older with normal cognition (MMSE score of 25 and above and did not fulfill criteria for dementia according to DSM-IV criteria). Psychologists administered the tests to the study participants. We conducted multivariate analyses to study the effect of age, gender, and education on test performance. Results: A total of 191 participants underwent the FNP Neuropsychological Test Battery. The mean age was 68.8 years (SD 5.4). The majority were female (84.1%). The mean score of ADAS-Cog was 9.98 (SD 4.74). The effect of education was prominent throughout the cognitive domains tested while the effect of age was limited to a few cognitive domains. The mean ADAS-Cog scores were 11.80 ± 4.40 for primary education, 9.93 ± 5.08 for secondary, and 8.15 ± 3.95 for tertiary. On average, women scored 2.75 points lower than men and performed better on the verbal components. Men performed better on the constructional praxis component. The same effect of education and gender was observed for the UDS-ADC. Conclusion: For the first time, normative data are available for the ADAS-Cog and UDS-ADC for a Filipino older population. This study stresses the importance of establishing population-specific normative data, taking into account the specific sociocultural and linguistic context of that population.

While heart disease remains a common cause of mortality, cerebrovascular disease also increases with age, and has been implicated in Alzheimer's disease and related dementias (ADRD). We have described hydrogen sulfide (H2S), a signaling molecule important in vascular homeostasis, as a biomarker of cardiovascular disease. We hypothesize that plasma H2S and its metabolites also relate to vascular and cognitive dysfunction in ADRD. We used analytical biochemical methods to measure plasma H2S metabolites and MRI to evaluate indicators of microvascular disease in ADRD. Levels of total H2S and specific metabolites were increased in ADRD versus controls. Cognition and microvascular disease indices were correlated with H2S levels. Total plasma sulfide was the strongest indicator of ADRD, and partially drove the relationship between cognitive dysfunction and white matter lesion volume, an indicator of microvascular disease. Our findings show that H2S is dysregulated in dementia, providing a potential biomarker for diagnosis and intervention. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The Clinician's Interview‐Based Impression of Change Plus caregiver input (CIBIC‐Plus) has been widely used in dementia drug trials to evaluate cognition, behavior, and function. New trials of symptomatic drugs forecast renewed interest in this measure. METHODS: To test its clinical meaningfulness, we examined how CIBIC‐Plus performed in two cholinesterase inhibitor trials compared to goal attainment scaling Scale (GAS) scores, a patient‐reported outcome measure. RESULTS: Net goal attainment was seen for all but one GAS domains in subjects who improved on the CIBIC‐Plus. Subjects who improved initially on CIBIC‐Plus scores were likely to remain improved across all other outcomes for each trial's duration, except for Disability Assessment for Dementia scores. DISCUSSION: The initial response to treatment, as assessed by CIBIC‐Plus, remained stable for most outcome measures. Even small CIBIC‐Plus improvement changes are associated with clinically meaningful change as assessed by GAS. Other tests detect decline better than improvement. [ABSTRACT FROM AUTHOR]

Focal repetitive transcranial magnetic stimulation (rTMS) has been applied to improve cognition in Alzheimer's disease (AD) with conflicting results. We applied rTMS in AD in a pilot placebo-controlled study using the H2-coil. H-coils are suitable for targeting wider neuronal structures compared with standard focal coils, in particular the H2-coil stimulates simultaneously the frontal-parietal-temporal lobes bilaterally. Thirty patients (mean age 70.9 year, SD 8.1; mean MMSE score 16.9, SD 5.5) were randomized to sham or real 10 Hz rTMS stimulation with the H2-coil. Each patient underwent 3 sessions/week for 4 weeks, followed by 4 weeks with maintenance treatment (1 session/week). Primary outcome was improvement of ADAS-cog at 4 and 8 weeks compared with baseline. A trend toward an improved ADAS-cog score over time was observed for patients undergoing real rTMS, with actively treated patients experiencing a mean decrease of −1.01 points at the ADAS-Cog scale score per time point (95% CIs −0.02 to −3.13, p < 0.04). This trend was no longer evident 2 months after the end of treatment. Real rTMS showed no significant effect on MMSE and BDI changes over time. These preliminary findings suggest that rTMS with H-coil is feasible and safe in patients with probable AD and might provide beneficial, even though transient, effects on cognition. This study prompts larger studies in the early stages of AD, combining rTMS and cognitive rehabilitation.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT04562506.

Focal repetitive transcranial magnetic stimulation (rTMS) has been applied to improve cognition in Alzheimer's disease (AD) with conflicting results. We applied rTMS in AD in a pilot placebo-controlled study using the H2-coil. H-coils are suitable for targeting wider neuronal structures compared with standard focal coils, in particular the H2-coil stimulates simultaneously the frontal-parietal-temporal lobes bilaterally. Thirty patients (mean age 70.9 year, SD 8.1; mean MMSE score 16.9, SD 5.5) were randomized to sham or real 10 Hz rTMS stimulation with the H2-coil. Each patient underwent 3 sessions/week for 4 weeks, followed by 4 weeks with maintenance treatment (1 session/week). Primary outcome was improvement of ADAS-cog at 4 and 8 weeks compared with baseline. A trend toward an improved ADAS-cog score over time was observed for patients undergoing real rTMS, with actively treated patients experiencing a mean decrease of −1.01 points at the ADAS-Cog scale score per time point (95% CIs −0.02 to −3.13, p < 0.04). This trend was no longer evident 2 months after the end of treatment. Real rTMS showed no significant effect on MMSE and BDI changes over time. These preliminary findings suggest that rTMS with H-coil is feasible and safe in patients with probable AD and might provide beneficial, even though transient, effects on cognition. This study prompts larger studies in the early stages of AD, combining rTMS and cognitive rehabilitation. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT04562506. [ABSTRACT FROM AUTHOR]

To evaluate reliability and concurrent validity of the Alzheimer's Disease Assessment Scale - Cognitive Subscale, Chinese Version (ADAS-Cog-C) among Chinese community older adults. Three groups, comprising of 1,276 community-dwelling older adults, were included in this study: a normal control (NC), a mild cognitive impairment (MCI), and an Alzheimer's disease (AD) group. All participants were assessed through ADAS-Cog-C, clinical interviews, physical examinations, Mini Mental State Examination (MMSE), and the Clinical Dementia Rating Scale (CDR). Internal consistency was assessed to evaluate the reliability of ADAS-Cog-C. Pearson and Spearman correlation coefficients were calculated to evaluate the concurrent validity between ADAS-Cog-C, MMSE, and CDR. Overall, the Cronbach's alpha coefficients of ADAS-Cog-C for the AD and MCI groups were 0.843 and 0.554, respectively. The split-half reliability coefficients for the AD and MCI groups were 0.860 and 0.539, respectively. ADAS-Cog-C scores were negatively correlated with MMSE scores (r = −0.706, p < 0.001) and positively associated with CDR scores (r = 0.546, p < 0.001). After excluding the MCI group from the analysis, the internal consistency of ADAS-Cog-C for the total population improved (α = 0.813, rhh = 0.852, all p < 0.001), as did the correlation between ADAS-Cog-C and MMSE (r = −0.828, p < 0.001) and CDR (r = 0.429, all p < 0.001) scores. ADAS-Cog-C has good internal consistency and concurrent validity for assessing Chinese community older adults with AD, but poor consistency, good concurrent validity with the MMSE while moderate concurrent validity with the CDR for MCI. [ABSTRACT FROM AUTHOR]

Introduction: This clinical trial evaluates the efficacy and safety of a 6‐week course of daily neuroAD™ therapy. Methods: 131 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. Results: Subjects 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. Discussion: neuroAD™ Therapy System provides a low‐risk therapeutic benefit for patients with milder AD (baseline ADAS‐Cog ≤30) beyond pharmacologic SOC. [ABSTRACT FROM AUTHOR]

Objective: Our study aimed to verify the validity of the Chinese version of Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) for the community-dwelling older people in China.Methods: A total of 1276 individuals composed by 628 normal controls (NCs), 572 people living with mild cognitive impairment (MCI), and 76 people living with Alzheimer's disease (AD) were recruited for the current study. All of the participants underwent ADAS-Cog, clinical interview and examination, Quick Cognitive Screening Scale for the Elderly, and Activities of Daily Living Scale. The sensitivity and specificity of ADAS-Cog were calculated, and a receiver operating characteristic curve (ROC curve) was drawn to decide the optimal cutoff points of ADAS-Cog for screening MCI and AD.Results: Statistically significant differences were observed among the three groups (P <. 001, NC < MCI Conclusion: The present study illustrates that the Chinese version of the ADAS-Cog total score is able to detect cognitive impairment of AD patients in Chinese communities but has a lower efficacy for MCI. [ABSTRACT FROM AUTHOR]

Background: Various types of cognitive dysfunction could make it difficult to use multiple objects properly in Alzheimer's disease (AD). Aim: To observe the qualitative feature of action deficits during a widely used praxis task and to clarify cognitive dysfunctions underlying the deficits. Methods: We examined 80 patients with mild cognitive impairment (MCI), 84 patients with AD (69 mild and 15 moderate AD) and 40 healthy controls (HC) using the Alzheimer's Disease Assessment Scale cognitive subscale—Japanese version (ADAS‐J cog) and the Mini‐Mental State Examination (MMSE). Errors in the "praxis task" of ADAS‐J cog were classified into 4 types: apraxic, attentional, visuospatial and writing errors based on their qualitative features. The ratio of each error type was calculated and compared with each other. Results: Participants with mild and moderate AD made significantly more errors in the praxis task compared with those in the HC and MCI groups. Qualitative analysis revealed that attentional errors occur more frequently in the MCI group than those in the HC group. For apraxic errors, there were significant differences between the MCI group and the mild/moderate AD groups. The more severe their general cognitive dysfunctions, the greater the variety of errors patients exhibit in the praxis task. Conclusion: The results indicate that a main factor affecting the praxis task in MCI patients was attentional deficits, while various cognitive dysfunctions were related to action deficits in patients with AD. Our qualitative analysis for the praxis task revealed difference in action deficits in MCI and AD patients. [ABSTRACT FROM AUTHOR]

Although considerate progress was obtained by adding imagistic and laboratory test, clinical examination remains the core of the diagnosis for Alzheimer`s disease. After 20 years of experience with anticholinergic drugs we know that only one third of the patients respond to the treatment; the treatment is more efficient in the initial stages of the neurocognitive decline. It is important to evaluate the efficacy of drugs as soon as possible. We examined patients with mild and moderate Alzheimer`s disease referred through our outpatient clinic. They fulfilled the NINCDS-ADRDA criteria for Alzheimer`s disease and they scored at baseline 21 to 26 points on MMSE. The patients were treated with Galantamine, 8 mg/day for the first month and then 16 mg/day. We evaluated the patients after 2 and 6 months of treatment; we performed MMSE and ADAS-Cog in order to see if a more complex evaluation would be helpful. We considered that the treatment was efficient if MMSE score did not decrease after 6 months of treatment. We also evaluated clinical disability using DAD (Disability Assessment for Dementia Scale) and the difficulty of living with a patient with dementia using CBS (Caregiver Burden Scale). The examination using MMSE and ADAS-Cog after two months of treatment does not have a predictable value. ADAS-Cog examination can be useful for patients that have a stable MMSE score after six months of treatment. Although the evolution of ADAS-Cog and MMSE scores were significantly positive, clinical disability of the patients progressed, rising concerns for their caregivers.

Late-onset Alzheimer's disease (AD) differs substantially from early-onset AD. In this cross sectional study we investigated brain perfusion changes after 18 months of treatment with cholinesterase inhibitors (ChEIs) donepezil or galantamine. Twenty-five drug-naïve late-onset AD patients were recruited from outpatient clinics. We examined brain perfusion using single photon emission computed tomography (SPECT) and used three-dimensional stereotactic surface projection (3D-SSP) and the stereotactic extraction estimation method (SEE) level 3 to analyze classified gyrus level segments. We assessed cognitive function using the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) grouped into three subgroup domains, language, memory, and praxis. In the follow-up data, some regions were further hypoperfused, reflecting worsening of the disease, while other regions showed alleviated hypoperfusion, potentially related to the ChEIs treatment. Regional cerebral blood flow (rCBF) decreased in the parietal cortex and increased in the frontal and the limbic cortices. Increased hypoperfusion significantly correlated with ADAS-cog scores changes were seen in the superior parietal lobule, inferior parietal lobule, angular gyrus, and supramarginal gyrus of the parietal cortex. Alleviated hypoperfusion significantly related to recovery of ADAS-cog scores were seen in the rectal and paracentral lobule of the frontal cortex, and the anterior cingulate of the limbic cortex. These regions showed significant relationships with total ADAS-cog and language, memory and praxis subscales scores. The current longitudinal study indicates prominent rCBF changes and their relationships with changes in ADAS-cog scores in late-onset AD patients. [ABSTRACT FROM AUTHOR]

Background: 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.Objective: 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.Methods: 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.Results: 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).Conclusion: 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. [ABSTRACT FROM AUTHOR]

The Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) was developed in the 1980s to assess the level of cognitive dysfunction in Alzheimer's disease. Advancements in the research field have shifted focus toward pre-dementia populations, and use of the ADAS-Cog has extended into these pre-dementia studies despite concerns about its ability to detect important changes at these milder stages of disease progression. If the ADAS-Cog cannot detect important changes, our understanding of pre-dementia disease progression may be compromised and trials may incorrectly conclude that a novel treatment approach is not beneficial. The purpose of this review was to assess the performance of the ADAS-Cog in pre-dementia populations, and to review all modifications that have been made to the ADAS-Cog to improve its measurement performance in dementia or pre-dementia populations. The contents of this review are based on bibliographic searches of electronic databases to locate all studies using the ADAS-Cog in pre-dementia samples or subsamples, and to locate all modified versions. Citations from relevant articles were also consulted. Overall, our results suggest the original ADAS-Cog is not an optimal outcome measure for pre-dementia studies; however, given the prominence of the ADAS-Cog, care must be taken when considering the use of alternative outcome measures. Thirty-one modified versions of the ADAS-Cog were found. Modification approaches that appear most beneficial include altering scoring methodology or adding tests of memory, executive function, and/or daily functioning. Although modifications improve the performance of the ADAS-Cog, this is at the cost of introducing heterogeneity that may limit between-study comparison. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the clinical evidence for traditional medicines (TMs) used in East Asia on measures of cognition in Alzheimer disease, determine the effect sizes at different time points for the TMs and pharmacotherapies, and assess the tolerability of the TMs.Methods: We searched 12 databases in English, Chinese, and Japanese for eligible randomised controlled trials that compared orally administered TMs with pharmacotherapy and reported cognitive outcomes. Meta-analyses were conducted for Alzheimer's Disease Assessment Scale-cognitive subscale and/or Mini-Mental State Examination (MMSE). Mean differences and 95% confidence intervals were calculated to evaluate treatment effects.Results: Thirty randomised controlled trials met inclusion criteria. Twenty-nine compared TMs with donepezil. Single studies provided comparisons with galantamine, rivastigmine, or memantine. There were no significant differences between the TM and donepezil groups at 12 or 24 weeks for Alzheimer's Disease Assessment Scale-cognitive subscale or MMSE. Improvements over baseline were significant for MMSE at 12 and 24 weeks within the TM and donepezil groups and remained significant at 1 year. Effect sizes were reduced in the 3 double-blind studies. At 24 weeks, donepezil 10 mg/d generally produced greater improvements in MMSE than 5 mg/d. Tolerability reporting was incomplete and inconsistent between studies.Conclusions: The results suggested that the clinical benefits of the TMs were not less than donepezil at comparable time points, with both groups showing improvements. However, lack of blinding in most studies and other design and measurement issues are likely to have resulted in overestimation of effect sizes in both groups. Further well-designed studies are needed. [ABSTRACT FROM AUTHOR]

Objective: The Alzheimer's disease assessment scale-Cognitive Subscale (ADAS-Cog) is a battery to assess cognitive performance in Alzheimer's disease (AD) and was developed according to the core characteristics of cognitive decline in AD: memory, language, praxis, constructive ability, and orientation. The aim of this study was to explore the diagnostic accuracy and discriminative capacity of the ADAS-Cog for Mild Cognitive Impairment (MCI) and AD, using cut-off points for the Portuguese population. Method: The European Portuguese version of the ADAS-Cog was administrated to 650 participants, divided into a control group (n = 210), an MCI group (n = 240), and an AD group (n = 200). The clinical groups fulfilled standard international diagnostic criteria. Controls were healthy cognitive participants actively integrated in the community. The neuropsychological assessment protocol included the ADAS-Cog, the Mini Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), and the Adults and Older Adults Functional Assessment Inventory (IAFAI). Results: The ADAS-Cog revealed good psychometric indicators, and the total scores were significantly different between the three groups (p < .001: Control < MCI < AD). The optimal cut-off points established were: MCI > 9 points (AUC = .835; sensitivity = 58% and specificity = 91%) and AD > 12 points (AUC = .996; sensitivity = 94% and specificity = 98%). Conclusions: Our findings confirmed the capacity of the ADAS-Cog total score to identify cognitive impairment in AD patients, with poor sensitivity for MCI, in a Portuguese cohort. [ABSTRACT FROM AUTHOR]

Review presents the cur rent approach of us ing short repeatable neuropsychological batteries and refers to recent literature focused on this type of dia gnostic proces s. The trend of the last decade highlights the need for the development of neuropsychological dia gnostic measures, which would show good psychometric qualities and at the same time respond to the demand of a more expedient as ses sment and repeatability of results over time with a lower risk of the practice eff ect. First of al l, the article proposes desirable characteristics of cognitive batteries and proposes the pos sibilities of interpretation of their outcomes. Secondly, the characteristics of the existing short repeatable neuropsychological batteries are discus sed, based on the criteria of 1. availability of paral lel versions; 2. time duration less than 45 min; 3. cognitive profi le as an outcome based on the results; and 4. availability in Czech clinical or research practice. The follow ing methods will be discus sed: Repeatable Battery for the As ses sment of Neuropsychological Status (RBANS), Neuropsychological As ses sment Battery - Screen ing Module (NAB-SM), Dementia Rat ing Scale - 2 (DRS-2), Alzheimer's Dis ease As ses sment Scale Cognitive Subscale (ADASCog), MATRICS Consensus Cognitive Battery (MCCB), and Screen for Cognitive Impairment in Psychiatry (SCIP). [ABSTRACT FROM AUTHOR]

Introduction The clinical meaningfulness of Alzheimer's Disease Assessment Scale–Cognitive subscale (ADAS-Cog) subscale change is disputed. We compared 2- to 4-point ADAS-Cog changes with changes in Goal Attainment Scaling (GAS) and everyday function across initial ADAS-Cog scores and treatment responses. Methods This exploratory analysis evaluated mild-moderate Alzheimer's disease patients treated with donepezil (12 months) or galantamine (8 months). Clinical meaningfulness was defined as concomitant ADAS-Cog and GAS changes of ±3 points and/or functional improvement. Results Patients with ≥3-point ADAS-Cog improvement significantly improved on GAS but not on standard tests of everyday function. ADAS-Cog “no change” (≤±3 points) was seen with mean GAS improvement. Initial ADAS-Cog improvement made endpoint improvement (ADAS-Cog 3 points and GAS 1 point) more likely (odds ratio = 6.9; 95% confidence interval = 2.5–19.5). In contrast, initial deterioration made endpoint improvement unlikely (0.33; 0.14–0.64). Discussion ADAS-Cog improvement and no change were each associated with GAS improvement. Initial ADAS-Cog worsening was unlikely to result in later improvement. Clinical trial registration number ISRCTN26167328. [ABSTRACT FROM AUTHOR]

Objective: Obsessive compulsive disorder (OCD) is cha racterized by recurrent intrusive thoughts and repetitive behaviors or mental acts compulsions. Previous studies obviously indicate that OCD patients have several impairments in memory and other neurocognitive functions. Our primary aim is to assess the cognitive impairment in OCD patients through Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog) which is widely used in Alzheimer's Dementia. Method: Thirty two patients with a diagnosis of OCD and twenty six healthy controls were administrated Structured Clinical Interview for DSM Disorders (SCID-I), Yale Brown Obsessive Compulsive Scale (Y-BOKS), ADAS-Cog Scale, Mini Mental Status Examination (MMSE), Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Rating Scales (HARS). Results: When we compared two groups, OCD subjects performed significantly worse in the fields of ADAS-Cog Total (p<0.0001), Word Recall (p<0.0001), Word Recognition (p<0.0001) Commands (p<0.0001), Constructional Praxis (p<0.05) and Orientation (p<0.05) Tests of ADAS-Cog compared to the healthy control group. Conclusion: We suggest that ADAS-Cog might be used as an available tool to assess some neurocognitive deficits in OCD patients. Further studies in larger samples of OCD patients are needed to assess the availability of ADAS-Cog in measuring the neurocognitive impairments. [ABSTRACT FROM AUTHOR]

The purpose of this study was to estimate and examine ways to improve the reliability of change scores on the Alzheimer’s Disease Assessment Scale, Cognitive Subtest (ADAS-Cog). The sample, provided by the Alzheimer’s Disease Neuroimaging Initiative, included individuals with Alzheimer’s disease (AD) (n = 153) and individuals with mild cognitive impairment (MCI) (n = 352). All participants were administered the ADAS-Cog at baseline and 1 year, and change scores were calculated as the difference in scores over the 1-year period. Three types of change score reliabilities were estimated using multivariate generalizability. Two methods to increase change score reliability were evaluated: reweighting the subtests of the scale and adding more subtests. Reliability of ADAS-Cog change scores over 1 year was low for both the AD sample (ranging from .53 to .64) and the MCI sample (.39 to .61). Reweighting the change scores from the AD sample improved reliability (.68 to .76), but lengthening provided no useful improvement for either sample. The MCI change scores had low reliability, even with reweighting and adding additional subtests. The ADAS-Cog scores had low reliability for measuring change. Researchers using the ADAS-Cog should estimate and report reliability for their use of the change scores. The ADAS-Cog change scores are not recommended for assessment of meaningful clinical change. [ABSTRACT FROM PUBLISHER]

Background/Aims: The objective of this study was to determine whether treatment with acetylcholinesterase inhibitors would provide cognitive benefit for patients with vascular dementia. Methods: Studies in patients with vascular dementia, who had not taken acetylcholinesterase inhibitors or memantine for at least 6 weeks, were included. Results: Twelve studies were included in the final analysis. Donepezil showed significant improvement in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) as compared to placebo, at the doses tested, that is, 5 and 10 mg/day (difference in means –1.389 and –1.680, respectively, p ≤ 0.008), but not on the Mini Mental State Examination (MMSE) (p ≥ 0.259). Galantamine also improved the ADAS-cog in comparison to the placebo (difference in means –2.191, p < 0.001), whereas, rivastigmine did not show any benefit on ADAS-cog. However, the findings with rivastigmine are difficult to interpret, given there were only 2 studies. Treatment with cholinesterase inhibitors was associated with a twofold increase in the odds of discontinuation, due to adverse events (pooled OR 1.966, 95% CI 1.630–2.371, p < 0.001). Conclusion: The present results reveal the therapeutic benefits of donepezil and galantamine in patients with vascular dementia. Interestingly, the ADAS-cog and MMSE varied considerably in detecting cognitive improvement. [ABSTRACT FROM AUTHOR]

Backgrounds and Objectives: Currently, no consensus has been reached on the therapeutic implications of monoclonal antibodies against amyloid-beta (Aβ) in Alzheimer's disease (AD). This study aimed to examine the effectiveness and safety of monoclonal antibodies against Aβ as a whole and also to determine the superiority of individual antibodies vis-à-vis placebo in mild or moderate AD., Methods: Literature retrieval, article selection, and data abstraction were performed independently and in duplicate. Cognition and function were appraised by the Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Disability Assessment for Dementia (DAD), and Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB). Effect sizes are expressed as standardized mean difference (SMD) with a 95% confidence interval (CI)., Results: Twenty-nine articles involving 108 drug-specific trials and 21,383 participants were eligible for synthesis. Of the four assessment scales, only CDR-SB was significantly reduced after using monoclonal antibodies against Aβ relative to placebo (SMD: -0.12; 95% CI: -0.2 to -0.03; p = 0.008). Egger's tests indicated a low likelihood of publication bias. At individual levels, bapineuzumab was associated with a significant increase in MMSE (SMD: 0.588; 95% CI: 0.226-0.95) and DAD (SMD: 0.919; 95% CI: 0.105-1.943), and a significant decrease in CDR-SB (SMD: -0.15; 95% CI: -0.282-0.018). Bapineuzumab can increase the significant risk of serious adverse events (OR: 1.281; 95% CI: 1.075-1.525)., Conclusion: Our findings indicate that monoclonal antibodies against Aβ can effectively improve instrumental activities of daily life in mild or moderate AD. In particular, bapineuzumab can improve cognition and function, as well as activities of daily life, and meanwhile, it triggers serious adverse events., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hao, Dong, Sun, Duan and Niu.)

Although considerate progress was obtained by adding imagistic and laboratory test, clinical examination remains the core of the diagnosis for Alzheimer`s disease. After 20 years of experience with anticholinergic drugs we know that only one third of the patients respond to the treatment; the treatment is more efficient in the initial stages of the neurocognitive decline. It is important to evaluate the efficacy of drugs as soon as possible. We examined patients with mild and moderate Alzheimer`s disease referred through our outpatient clinic. They fulfilled the NINCDS-ADRDA criteria for Alzheimer`s disease and they scored at baseline 21 to 26 points on MMSE. The pa- tients were treated with Galantamine, 8 mg/day for the first month and then 16 mg/day. We evaluated the patients after 2 and 6 months of treatment; we performed MMSE and ADAS-Cog in order to see if a more complex evaluation would be helpful. We considered that the treatment was efficient if MMSE score did not decrease after 6 months of treatment. We also evaluated clinical disability using DAD (Disability Assessment for Dementia Scale) and the difficulty of living with a patient with dementia using CBS (Caregiver Burden Scale). The examination using MMSE and ADAS-Cog after two months of treatment does not have a predictable value. ADAS-Cog examination can be useful for patients that have a stable MMSE score after six months of treatment. Although the evolution of ADAS-Cog and MMSE scores were significantly positive, clinical disability of the patients progressed, rising concerns for their caregivers. [ABSTRACT FROM AUTHOR]

The role of nonsteroidal anti-inflammatory drugs (NSAIDs) in prevention of Alzheimer’s disease (AD) has been evaluated in many studies. We performed a meta-analysis to summarize the existing evidence on the relation between use of classical NSAIDs and AD. Randomized controlled trials (RCTs) evaluating the role of classical NSAIDs in AD was searched using different search engines. The RCTs in patients who had the degree of AD measured on Mini-Mental State Examination (MMSE) or AD Assessment Scale-Cognitive subscale (ADAS-cog) were included in the study. The RCTs and data (AD scores) were independently assessed by 2 reviewers, and data were included in meta-analysis only after a common consensus was reached. The pooled results from the ADAS-cog and MMSE scores failed to show any difference between the treatment and the placebo groups as opposed to findings from some observational studies. However, in view of heterogeneity of results, there is a need to conduct more RCTs to arrive at confirmatory findings. [ABSTRACT FROM AUTHOR]

Background: MLC601 and MLC901 showed neuroprotective and neuroregenerative properties and positive results in the treatment of dementia and cognitive impairment. This study aimed to investigate the long-term benefits of monotherapy with MLC601 and MLC901 in patients with Alzheimer's disease (AD)., Methods: In this study, patients with AD, diagnosed by DSM-IV criteria, were enrolled. Patients have received MLC601 for four years, and their regimen has changed to MLC901 for another four years. Recruited patients were followed to assess the efficacy and safety first of MLC601 and MLC901. Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale- Cognitive Subscale (ADAS-Cog) were used to assess cognitive function. Safety was evaluated by monitoring adverse events (AEs) and abnormal findings in physical examinations or lab tests., Results: At the end of the trial, the changes in the mean (±SD) MMSE and ADAS-Cog scores were 5.1 (3.09) and 12.5 (10.89), respectively. Both scores showed a significant change in repeated measure analysis, with the ADAS-Cog score indicating a higher change than the MMSE score (P < 0.001)., Conclusion: For more than eight years, we studied monotherapy with NeuroAid (MLC601, MLC901) in patients with AD. The study contributes further to the long-term safety and efficacy data of MLC in patients with AD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Repetitive transcranial magnetic stimulation (rTMS) uses a magnetic coil to induce an electric field in brain tissue. As a pilot study, we investigated the effect of rTMS treatment on 10 volunteers with Alzheimer's disease (AD) in a two-stage study. The first stage consisted of a double-blind crossover study with real and sham treatments. Each treatment block consisted of 13 sessions over 4 weeks. During each session, 2000 TMS pulses at 90%-100% of resting motor threshold were applied to dorsolateral prefrontal cortex bilaterally, and the patients were kept cognitively active by object/action naming during the treatment. The second stage was an open-label study, in which the same treatments were performed in 2-week blocks (10 sessions) approximately every 3 months as follow-up treatments on six of the volunteers, who completed the first stage of the study. Primary outcome measures were the Montreal Cognitive Assessment (MOCA) and the Alzheimer's Disease Assessment Scale-cognitive subscale. The secondary outcome measures were the Revised Memory and Behavior Checklist as well as our team's custom-designed cognitive assessments. The results showed a noticeably stronger improvement on all assessments during the real treatment as compared to the sham treatment. The changes in MOCA scores as well as our designed cognitive assessment were found to be statistically significant, with particularly strong results in the six volunteers who were in the early stages of the disease. The long-term trends observed in the second stage of the study also showed generally less decline than would be expected for their condition. It appears that rTMS can be an effective tool for improving the cognitive abilities of patients with early to moderate stages of AD. However, the positive effects of rTMS may persist for only up to a few weeks. Specific skills being practiced during rTMS treatment may retain their improvement for longer periods. [ABSTRACT FROM AUTHOR]