Assessment and management of delirium in a tertiary hospital-Improvements in cognitive screening and use of non-pharmacological strategies with a multidisciplinary approach.

OBJECTIVE: This series of audits aimed to determine current best practice in delirium management in a tertiary teaching hospital and to identify strategies to improve the quality of care in delirium with a focus on prevention. METHODS: We completed a series of audits following the formation of the Cognitive Impairment Reference Group, a multidisciplinary team that was created to implement delirium management guidelines and monitor compliance. Audit 1 focused on antipsychotic use in patients aged 66 years and older. Audit 2 reviewed delirium care in the Acute Medical Ward. Audit 3 included ethnographic data and investigated the use of non-pharmacological methods to prevent and manage delirium in the Geriatric Ward. Two years on, Audit 4 is a repeat of Audit 1. RESULTS: There were improved rates of cognitive screening between Audits 2 and 3 from 65% n = 40 to 86% n = 102, respectively. Most patients had one form of non-pharmacological strategy in place to prevent delirium however few had a multicomponent approach. Fewer patients were prescribed benzodiazepines alongside antipsychotics 28.57% n = 35 in Audit 1 compared to Audit 4 12.5% n = 32. CONCLUSIONS: Improved quality of care in delirium management is achievable via a co-ordinated multidisciplinary approach. These audits demonstrated improvements in both rates of cognitive screening, and use of non-pharmacological strategies prior to antipsychotic medication use and better adherence to guidelines for antipsychotic prescribing. Areas for further development in delirium prevention include the uptake of screening and individualised non-pharmacological strategies.

Screening, Assessment, and Pharmacologic Treatment of Mild Cognitive Impairment and Early Alzheimer's Disease: The Role for Monoclonal Antibodies.

The Psychiatric Consultation Service at Massachusetts General Hospital sees medical and surgical inpatients with comorbid psychiatric symptoms and conditions. During their twice-weekly rounds, Dr Stern and other members of the Consultation Service discuss diagnosis and management of hospitalized patients with complex medical or surgical problems who also demonstrate psychiatric symptoms or conditions. These discussions have given rise to rounds reports that will prove useful for clinicians practicing at the interface of medicine and psychiatry.Prim Care Companion CNS Disord. 2023;25(6):23f03544. Author affiliations are listed at the end of this article.

Dipeptidyl peptidase-4 inhibitors alleviate cognitive dysfunction in type 2 diabetes mellitus.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are commonly at high risk for developing cognitive dysfunction. Antidiabetic agents might be repurposed for targeting cognitive dysfunction in addition to modulation on glucose homeostasis. This study aimed to evaluate the impact of dipeptidyl peptidase-4 inhibitors (DPP-4i) on cognitive function in T2DM. METHODS: PubMed, Embase, Cochrane Library and Web of Science were systematically searched from inception to September 30, 2023. Weighted mean differences were calculated using the Mantel-Haenszel (M-H) fixed or random effects model based on the degree of heterogeneity among studies. Heterogeneity was evaluated using a Chi-squared test and quantified with Higgins I2. Sensitivity analysis was performed with the leave-one-out method, and publication bias was evaluated according to Begg's and Egger's tests. RESULTS: Six clinical trials involving 5,178 participants were included in the pooled analysis. Administration of DPP-4i generally correlated with an increase of Mini-Mental State Examination (MMSE) scores (1.09, 95% CI: 0.22 to 1.96). DPP-4i alleviated cognitive impairment in the copying skill subdomain of MMSE (0.26, 95% CI: 0.12 to 0.40). Treatment with DPP-4i also resulted in an increase of Instrumental Activities of Daily Living (IADL) scores (0.82, 95% CI: 0.30 to 1.34). However, DPP-4i produced no significant effects on Barthel Activities of Daily Living (BADL) scores (0.37, 95% CI: -1.26 to 1.99) or other test scores. CONCLUSIONS: DPP-4i treatment favourably improved cognitive function in patients with T2DM. Further trials with larger samples should be performed to confirm these estimates and investigate the association of different DPP-4i with cognitive function among diabetic patients. TRIAL REGISTRATION IN PROSPERO: CRD42023430873.

Analysis of Costs for Imaging-Assisted Pharmaceutical Intervention in Alzheimer's Disease with Lecanemab: Snapshot of the First 3 Years.

BACKGROUND: The approval of lecanemab for the treatment of Alzheimer's disease (AD) by the Food and Drug Administration in the United States has sparked controversy over issues of safety, cost, and efficacy. Furthermore, the prognostication of cognitive decline is prohibitively difficult with current methods. The inability to forecast incipient dementia in patients with biological AD suggests a prophylactic scenario wherein all patients with cognitive decline are prescribed anti-AD drugs at the earliest manifestations of dementia; however, most patients with mild cognitive impairment (approximately 77.7%) do not develop dementia over a 3-year period. Prophylactic response therefore constitutes unethical, costly, and unnecessary treatment for these patients. OBJECTIVE: We present a snapshot of the costs associated with the first 3 years of mass availability of anti-AD drugs in a variety of scenarios. METHODS: We consider multiple prognostication scenarios with varying sensitivities and specificities based on neuroimaging studies in patients with mild cognitive impairment to determine approximate costs for the large-scale use of lecanemab. RESULTS: The combination of fluorodeoxyglucose and magnetic resonance was determined to be the most cost-efficient at $177,000 for every positive outcome every 3 years under an assumed adjustment in the price of lecanemab to $9,275 per year. CONCLUSIONS: Imaging-assisted identification of cognitive status in patients with prodromal AD is demonstrated to reduce costs and prevent instances of unnecessary treatment in all cases considered. This highlights the potential of this technology for the ethical prescription of anti-AD medications under a paradigm of imaging-assisted early detection for pharmaceutical intervention in the treatment of AD.

Cognitive impairment according to Montreal Cognitive Assessment independently predicts the ability of chronic obstructive pulmonary disease patients to maintain proper inhaler technique.

BACKGROUND: Maintaining correct inhaler technique is crucial in the management of chronic obstructive pulmonary disease (COPD). We aimed to investigate the inhaler technique in patients with COPD, to compare it immediately after and at 1 month after training, and to identify the predictors of incorrect inhaler use at 1 month after training. METHODS: This prospective study was conducted at the COPD clinic of Siriraj Hospital (Bangkok, Thailand). Patients demonstrating improper inhaler use were trained face-to-face by pharmacists. Inhaler technique was re-assessed immediately after and at 1 month after training. The Montreal Cognitive Assessment (MoCA) score, pulmonary function tests, 6-min walk distance (6 MWD), modified Medical Research Council scale score, and COPD Assessment Test (CAT) score were evaluated. RESULTS: Sixty-six patients with COPD who demonstrated at least one critical error during the use of any controller inhaler were enrolled. The mean age was 73.0 ± 9.0 years, and 75.8% patients had moderate/severe COPD. Immediately after training, all patients used dry powder inhalers correctly and 88.1% used pressurized metered-dose inhalers correctly. At 1 month, the number of patients demonstrating the correct technique decreased across all devices. Multivariable analysis revealed that MoCA score ≤ 16 was independently associated with a critical error at 1 month after training (adjusted odds ratio: 12.7, 95% confidence interval: 1.8-88.2, p = 0.010). At 1 month, CAT score (11.4 ± 8.9 vs. 8.4 ± 5.5, p = 0.018) and 6 MWD (351 ± 93 m vs. 372 ± 92 m, p = 0.009) had significantly improved in patients demonstrating the correct technique, and CAT score met the minimal clinically important difference. CONCLUSIONS: Face-to-face training by pharmacists improved patient performance. However, the number of patients following proper technique had decreased at 1 month after training. Cognitive impairment (MoCA score ≤ 16) independently predicted the ability of COPD patients to maintain proper inhaler technique. Assessment of cognitive function combined with technical re-assessment and repeated training should improve COPD management.

The value of maintaining cognition in patients with mild cognitive impairment: The innovation headroom and potential cost-effectiveness of roflumilast.

INTRODUCTION: Early health-technology assessment can support discussing scarce resource allocation among stakeholders. We explored the value of maintaining cognition in patients with mild cognitive impairment (MCI) by estimating: (1) the innovation headroom and (2) the potential cost effectiveness of roflumilast treatment in this population. METHODS: The innovation headroom was operationalized by a fictive 100% efficacious treatment effect, and the roflumilast effect on memory word learning test was assumed to be associated with 7% relative risk reduction of dementia onset. Both were compared to Dutch setting usual care using the adapted International Pharmaco-Economic Collaboration on Alzheimer's Disease (IPECAD) open-source model. RESULTS: The total innovation headroom expressed as net health benefit was 4.2 (95% bootstrap interval: 2.9-5.7) quality-adjusted life years (QALYs). The potential cost effectiveness of roflumilast was k€34 per QALY. DISCUSSION: The innovation headroom in MCI is substantial. Although the potential cost effectiveness of roflumilast treatment is uncertain, further research on its effect on dementia onset is likely valuable.

[Assessment of the safety and clinical efficacy of the Brainmax in therapy of non-demented patients with a mild cognitive impairment]. / Otsenka klinicheskoi effektivnosti i bezopasnosti preparata Breinmaks v terapii patsientov s nedementnymi kognitivnymi narusheniyami.

OBJECTIVE: The assessment of the clinical efficiency and safety of the drug Brainmax and its influence on the degree of functional recovery in the treatment of patients with non-dementia cognitive disorders with this drug. MATERIAL AND METHODS: An open multicenter randomized study included 60 patients of 18-55 years with light and moderate CI, having complaints of the cognitive spectrum. They used a clinical and neurological study using generally accepted scales and tests (MoCA, MMSE, MFI-20 tests, Schulta, DSST tests and an assessment of the quality of life of SF-36). Patients were randomized in two groups comparable by age and gender. Group 1 was treated with Brainmax per os twice every day for 14 days. After 10-days rest they received same medication for another 14 days. Group 2 was treated with Brainmax per os twice every day for 14 days, without the continuation. The total duration of the study was 40 days, the assessment of their condition was carried out on the 1st day (visit 1), after 15 days (visit 2) and after 40 days (visit 3) using the indicators of the above scales and tests in comparison with the background data. Safety assessment was carried out by the presence and structure of undesirable phenomena. RESULTS: The use of Brainmax led to a significant improvement in cognitive performance according to all generally accepted scales and tests (concentration and maintaining of attention, working memory, visual-constructive skills, volume and speed of attention speed, information processing and executive functions), as well as to the decrease severity of asthenia and improvement of the quality of life. CONCLUSION: Brainmax has shown a good safety profile, tolerability and clinical efficacy in the treatment of young and middle-aged patients with non-demented cognitive impairment. Significant improvement was observed both with single and double course administration of the drug, but a significantly better effect was noted after its repeated course, which reflects, among other things, the cumulative effect of the active substances of this drug and makes longer use of the drug Brainmax justified and appropriate in these categories of patients. The data obtained allow us to recommend the wider use of the drug Brainmax in clinical practice for the treatment of CI in patients of different ages, which will optimize therapy and improve the course and outcome of the disease.

Multitargeting approaches to cognitive impairment: Synthesis of aryl-alkylpiperazines and assessment at cholinesterases, histamine H3 and dopamine D3 receptors.

Multitargeting ligands on enzymes and receptors may generate a profile for a potential treatment of cognitive impairment. Considering this, a set of 21 substituted aryl-alkyl-piperazines were designed, prepared and tested for their binding affinities at histamine H3 and dopamine D3 receptors (H3R and D3R, respectively) as well as acetyl- and butyrylcholinesterases (AChE/BChE) as potentially synergistic profile. Initial screening of the compounds at H3R and D3R was done at 1 or 10 µM and 100 µM at AChE and BChE assays. The most promising compounds were then evaluated in full concentration-response curves to estimate the Ki and IC50 values. Results showed that several compounds were ligands at H3R (n = 10), D3R (n = 6), AChE (n = 3), and BChE (n = 9). Compounds LINS05006 (Ki H3R 2.8 µM; D3R 0.7 µM; IC50 BChE 26.3 µM) and LINS05015 (Ki H3R 1.1 µM; D3R 3.1 µM; IC50 AChE 97.8 µM; BChE 43.7 µM) are highlighted since presented affinity in three different. These results suggest that methylpiperazine moiety led to balanced activity at all three classes of targets, and longer linker provided the best affinities. These compounds presented high ligand efficiency values (LE > 0.3) and may have adequate pharmacokinetic profile as suggested by calculated physicochemical properties.

Medication management and treatment adherence in Parkinson's disease patients with mild cognitive impairment.

INTRODUCTION: The key feature that distinguishes mild cognitive impairment (MCI) from dementia is the absence of significant functional decline because of cognitive impairment. In Parkinson's disease patients (PD) with MCI (PD-MCI), the effect of cognitive impairment on complex instrumental daily activities, such as medication management, is not well established. METHOD: 26 patients with PD-MCI (diagnosed to Level 2 Movement Disorders Society diagnostic criteria) and 32 idiopathic PD patients without cognitive impairment participated in the study. A detailed neuropsychological testing battery (including tests for attention and working memory, executive functions, language, visuospatial functions, episodic memory) and various prospective memory tasks were applied to the patients. Medication taking behaviors were evaluated using two different methods based on the performance (medication management ability assessment) and self-reporting (adherence scale). RESULTS: The PD-MCI group obtained significantly lower scores in medication management assessment and made more mistakes on following prescription instructions (e.g., they took more or less tablets and did not use medications as instructed with regard to meal times). Cognitive areas predicting success in medication management performance were language, event-based prospective memory and visuospatial functions. There was no significant difference between the two groups' self-reporting of adherence. CONCLUSION: Mild cognitive impairment in patients with PD adversely affects medication management. Diagnosing MCI in PD is important to ensure that the appropriate measures can be taken to provide support and improve the medication management process. Adherence assessments based on self-reporting may not provide reliable and sensitive information in patients with PD-MCI.

Estimated Annual Spending on Aducanumab in the US Medicare Program.

This cross-sectional study examines upper bound and lower bound annualized Medicare costs for administering aducanumab to beneficiaries with the approved indications of mild cognitive impairment or mild dementia.

The complementary utility of cognitive testing and the medication management ability assessment in older adults.

OBJECTIVE: Older adults are susceptible to cognitive declines that may limit independence. Though neuropsychologists opine about risk of functional decline, the degree to which cognitive testing and in-office simulations approximate everyday behavior is unclear. We assessed the complementary utility of cognitive testing and the face-valid Medication Management Ability Assessment (MMAA) to predict medication management among older adults. METHOD: This was a retrospective study of 234 older adults (age = 72 ± 7.7 years; 59% women) who completed the MMAA during outpatient neuropsychological evaluations. Based on comprehensive clinical assessment, most participants (n = 186) were independent in medication management, while 48 received assistance. Demographically adjusted composite scores were derived for attention/processing speed (A/PS), executive functioning (EF), visuospatial/constructional ability (VC), language, and memory domains. Univariate differences in cognition were examined across Assisted versus Independent groups. Logistic regression assessed which cognitive domains independently predicted group status. The incremental value of the MMAA was assessed, holding uniquely associated cognitive test scores constant. RESULTS: Those receiving assistance with medication management performed worse across all neurocognitive domains and the MMAA compared with independent counterparts. EF was the only unique cognitive predictor of medication management status. When modeled alone, EF and MMAA performance correctly classified 79.5% and 80.8% of cases, respectively. When modeled together, both were independently associated with medication management status and correctly classified 83.3% of cases. CONCLUSIONS: EF uniquely predicted medication management status beyond other cognitive domains. The MMAA provided complementary predictive utility. Concurrent interpretation of executive functioning and MMAA performance is advised when assessing older adults suspected of medication mismanagement. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Design and optimization of myricetin encapsulated nanostructured lipid carriers: In-vivo assessment against cognitive impairment in amyloid beta (1-42) intoxicated rats.

AIMS: This research aimed to evaluate the potential of MY loaded nanostructured lipid carrier (MY-NLCs) to ameliorate the bioavailability in the brain and cognitive impairment in Aß induced Alzheimer''s model. MATERIALS AND METHODS: MY-NLCs were prepared with precirol ATO 5, labrafac lipophile WL 1349, and tween 80 as solid lipid, liquid lipid, and surfactant respectively. The formulation was optimized with central composite design (CCD) and characterized by different parameters. Cellular toxicity and uptake studies were evaluated in SH-SY5Y cells. MY concentration in plasma and brain was analyzed after the i.p. administration of MYS and MY-NLCs (40 mg/kg) in Sprague-Dawley rats (n = 3). Further, the pharmacodynamic studies were evaluated in the (Aß1--42) induced (5 µg/5 µl, ICV, unilateral) Alzheimer''s rat model (n = 6) and cognitive performance was assessed using Morris water maze test followed by histological and neurotransmitters analyses in rats'' brain. KEY FINDINGS: The optimized MY-NLCs exhibited 89.7 ± 26.0 nm particle size, 80.81 ± 10.39% entrapment efficiency, and 5.08 ± 1.0% of drug loading capacity. The in-vitro release studies revealed a biphasic release pattern and also demonstrated distinct cellular internalization in SH-SY5Y cells. MY-NLCs exhibited 2.77 folds higher AUC 0-24 in plasma and drug targeting efficiency for MY into the brain was found 127.05% as compared to MYS. The mitigating potential of MY-NLCs (10 mg/kg) was also significantly observed in behavioral parameters and in the regulation of neurotransmitters levels in rat brain. SIGNIFICANCE: MY-NLCs would be explored as an alternative promising drug delivery platform for several neurodegenerative payloads.

Trend and effects of high-deductible health insurance plans in the health care system: financial access problems in management of cognitive impairment.

BACKGROUND: High-deductible health plans (HDHPs) are characterized by higher deductibles and lower monthly premiums compared with a typical health plan. HDHPs may reduce, or delay, needed care, which will ultimately lead to poorer access to care for chronically affected participants. OBJECTIVES: To (1) investigate the HDHP enrollment trend and (2) determine the effects of HDHPs on financial access problems for individuals with self-reported cognitive impairment. METHODS: Data between 2010 and 2018 were obtained from the National Health Interview Survey (NHIS). Individuals with cognitive impairment were identified if they were limited by memory difficulties. Problems regarding financial access to health care were assessed based on 6 survey questions from the Centers for Disease Control and Prevention. Multivariable logistic regressions were implemented to evaluate the effects of HDHPs. RESULTS: This study identified 1,148 individuals with cognitive impairment, representing 3.9 million individuals in the United States from 2010 to 2018. A nearly 2-fold increase in HDHP enrollment with cognitive impairment was observed from 2010 (20.9%) to 2018 (41.9%). This increase is similar to that reported for noncognitively impaired individuals. After controlling for possible confounding variables, cognitively impaired individuals with HDPHs were more likely to have overall financial access difficulties compared with those without HDHPs (OR = 1.17, 95% CI = 0.88-1.56, P = 0.271), but this likelihood was not statistically significant. CONCLUSIONS: HDHPs are intended to support effective care options and reduce health care costs. However, our research found that among individuals with cognitive impairment, those with HDHPs experienced some financial access problems, such as affording medical care, follow-up care, and specialists, than those without HDHPs, indicating that HDHPs might have unintended consequences for health care usage. DISCLOSURES: No outside funding supported this study. The authors have no conflicts of interest or financial interests to disclose.

Caregiver and provider perspectives on dual VA and Medicare Part D medication use in veterans with suspected dementia or cognitive impairment.

PURPOSE: Many older veterans with dementia fill prescriptions through both Veterans Affairs (VA) and Medicare Part D benefits. Dual VA/Part D medication use may have unintended negative consequences in terms of prescribing safety and quality. We aimed to characterize benefits and drawbacks of dual VA/Part D medication use in veterans with dementia or cognitive impairment from the perspectives of caregivers and providers. METHODS: This was a qualitative study based on semistructured telephone interviews of 2 groups: (1) informal caregivers accompanying veterans with suspected dementia or cognitive impairment to visits at a VA Geriatric Evaluation and Management clinic (n = 11) and (2) VA healthcare providers of veterans with dementia who obtained medications via VA and Part D (n = 12). We conducted semistructured telephone interviews with caregivers and providers about benefits and drawbacks of dual VA/Part D medication use. Interview transcripts were subjected to qualitative content analysis to identify key themes. RESULTS: Caregivers and providers both described cost and convenience benefits to dual VA/Part D medication use. Caregivers reported drawbacks including poor communication between VA and non-VA providers and difficulty managing medications from multiple systems. Providers reported potential safety risks including communication barriers, conflicting care decisions, and drug interactions. CONCLUSION: Results of this study allow for understanding of potential policy interventions to better manage dual VA/Part D medication use for older veterans with dementia or cognitive impairment at a time when VA is expanding access to non-VA care.

Caregivers' willingness to pay for Alzheimer's disease medications in Taiwan.

BACKGROUND: Alzheimer's disease (AD) exerts significant financial expenses on caregivers, and knowledge of caregivers' support for out-of-pocket payment is of great importance for policymaking on the insurance coverage of future AD medication in Taiwan. We aimed to investigate caregivers' willingness to pay (WTP) for a hypothetical curative AD medication and the effect of different factors on the amount of WTP. METHODS: Informal caregivers of patients with AD and informants of patients with amnestic mild cognitive impairment (MCI) were included. An iterative bidding game technique, followed by a dichotomous choice question and a final open-ended question were used to elicit caregivers' maximum WTP. The correlations between the WTP and characteristics of caregiver and patient were analyzed, including sex, educational level, severity of dementia, neuropsychiatric symptoms assessed by Neuropsychiatric Inventory, time needed to support patients assessed by Caregiver Activity Survey, and caregivers' monthly income. RESULTS: A total of 1134 informal caregivers of patients with AD or MCI were included. Caregivers of patients with AD were willing to pay for a curative AD medication, and their maximum WTP value was higher than informants of MCI patients. Among patients with AD and patients with MCI, caregivers' monthly income was positively correlated with WTP. Apathy subsyndrome was the only factor correlated with percentage of WTP in caregiver's income in the MCI group. CONCLUSION: Support for out-of-pocket WTP for a hypothetical curative AD medication was significantly related to caregiver's income.

The clinical and educational outcomes of an inter-professional student-led medication review team, a pilot study.

AIMS: The involvement of an inter-professional healthcare student team in the review of medications used by geriatric patients could not only provide patients with optimized therapy but also provide students with a valuable inter-professional learning experience. We describe and evaluate the clinical and learning outcomes of an inter-professional student-run mediation review program (ISP). SUBJECT AND METHOD: A variable team consisting of students in medicine, pharmacy, master advanced nursing practice, and master physician assistant reviewed the medication lists of patients attending a specialized geriatric outpatient clinic. RESULTS: During 32 outpatient visits, 188 medications were reviewed. The students identified 14 medication-related problems, of which 4 were not recognized by healthcare professionals. The ISP team advised 95 medication changes, of which 68 (71.6%) were directly implemented. Students evaluated this pilot program positively and considered it educational (median score 4 out of 5) and thought it would contribute to their future inter-professional relationships. CONCLUSION: An inter-professional team of healthcare students is an innovative healthcare improvement for (academic) hospitals to increase medication safety. Most formulated advices were directly incorporated in daily practice and could prevent future medication-related harm. The ISP also offers students a first opportunity to work in an inter-professional manner and get insight into the perspectives and qualities of their future colleagues.

The Effects of COVID-19 Home Confinement in Dementia Care: Physical and Cognitive Decline, Severe Neuropsychiatric Symptoms and Increased Caregiving Burden.

PURPOSE: This study aims to analyze home confinement impact on individuals with neurocognitive disorders (NCD) through informal caregiver's perspective and examine how it has affected caregiving burden. METHODS: Thirty-six caregivers (64.94 ± 13.54 years, 41.7% female) of individuals with NCD (74.28 ± 6.76 years, 66.7% female) selected from the Body & Brain exercise program were interviewed over the phone. The following instruments were used: Barthel Index (BI) to assess care recipients' ability to function independently on activities of daily living (ADL), the Neuropsychiatric Inventory (NPI) to evaluate neuropsychiatric symptoms, and the CarerQol-7D/ CarerQol-VAS to determine caregiver subjective burden/well-being. RESULTS: Pre and post-confinement comparisons showed that care recipients significantly declined their independence in ADL (p = 0.003) and increased NPI total score (MD = 5.72; 95% CI: 1.19 to 10.25, p = 0.015). As for caregivers, results also showed an increased caregiving burden (MD = -0.17; 95% CI: -0.27 to -0.08; p = 0.001) and a decline in their well-being (p = 0.015). DISCUSSION: COVID-19 crisis sheds light on how imperative it is to find solutions and design contingency plans for future crisis, in order to ensure properly sustained support to dementia caregiving dyads and mitigate caregivers' burden.

Treatment of Cognitive Impairment and the Role of Demographic Factors in Disease Progression: The Final Results of the Russian Observational Program "DIAMANT".

BACKGROUND: Chronic cerebral ischemia (CCI) is a form of cerebrovascular disease manifested as a vascular cognitive impairment (VCI). The management of the patients with CCI is determined by a healthy lifestyle and early therapy aimed at correcting and preventing this disease. Divaza is a drug with endothelial protective and nootropic effects. We present the final efficacy and safety analysis of all-Russian, open-label, prospective, observational, multicenter study of Divaza and emphasize the role of demographic and socioeconomic factors in cognitive disorder (CD) progression. METHODS: CCI patients (n = 2,583) with or without CD were enrolled. Patients received Divaza (2 tablets 3 times per day for 12 weeks). Montreal Cognitive Assessment (MoCA) testing was required. The change in the mean MoCA score post-treatment was used as the primary endpoint. As the secondary endpoints, the number of patients with a MoCA <26 and ≤17 (dementia); the percentage of patients with a MoCA score improvement in different age groups; the dynamics of mean MoCA score in age groups; and the relationship between CD and sex or regional social/economic factors were assessed. RESULTS: Divaza therapy led to a significant improvement: the mean MoCA score was up to 20% higher post-treatment (Wilcoxon test, p < 0.0001 vs. baseline). The number of participants with MoCA ≥26 increased by 33.6%. The number of patients with dementia was 4.1 times less after therapy (p < 0.00001 vs. baseline). Divaza improved cognitive functions of patients in each age group. Findings demonstrate that regional socioeconomic factors contribute to CD development and severity. The observed divergence between sexes was a result of a larger number of women enrolled. The study confirmed the safety of Divaza. CONCLUSIONS: In the study, we observed the efficacy of Divaza for the treatment of CD: a therapy contributed to an increase in the mean MoCA score and the positive dynamics in the number of patients with cognitive improvement.

The University of California San Diego performance-based skills assessment: a useful tool to detect mild everyday functioning difficulties in HIV-infected patients with very good immunological condition.

Everyday functioning (EF) impairment is frequent in people living with HIV (PLWH). Our aim was to better explore EF and its association with PLWH cognition, by administering both the IADL scale, the most common functional scale, and a new and ecologic multi-domain (communication and financial skills) tool to measure EF as the University of California San Diego (UCSD) Performance-Based Skills Assessment-Brief Version (UPSA-B). Eighty-five PLWH on cART with very good immunological condition and 23 age- and education-matched healthy controls (HC) were enrolled. PLWH underwent a standardized neuropsychological battery plus IADL, and cognitive impairment was defined according to Frascati criteria. Both groups underwent the UPSA-B. Only 6 subjects (7%) were affected by cognitive impairment (asymptomatic profile). While IADL score was at ceiling for all patients, the UPSA-B total score was significantly worse in PLWH when compared with HC [mean 82.1 (SD 9.3) vs 89.2 (SD 6.2); p < 0.001]. At communication subtest, PLWH group and HC were significantly different (p = 0.002), while no difference emerged at financial skills (p = 0.096). Higher score at UPSA-B was independently associated with better global cognitive performance (composite Z-score) (ß 7.79; p < 0.001). Also considering each single cognitive domain, UPSA-B performance (both total and at subtests) confirmed the association with neurocognitive performance. In conclusion, UPSA-B seems to better discriminate EF impairment than IADL in PLWH, and it was associated with cognitive functions, also in the absence of symptomatic cognitive impairment. Thus, it appears a promising tool in the context of HIV infection to avoid misdiagnosis and to better detect also mild EF.