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Abstract Background Understanding the relationship among changes in Clinical Dementia Rating (CDR), patient outcomes, and probability of progression is crucial for evaluating the long-term benefits of disease-modifying treatments. We examined associations among changes in Alzheimer’s disease (AD) stages and outcomes that are important to patients and their care partners including activities of daily living (ADLs), geriatric depression, neuropsychiatric features, cognitive impairment, and the probabilities of being transitioned to a long-term care facility (i.e., institutionalization). We also estimated the total time spent at each stage and annual transition probabilities in AD. Methods The study included participants with unimpaired cognition, mild cognitive impairment (MCI) due to AD, and mild, moderate, and severe AD dementia in the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set (UDS) database. The associations among change in AD stages and change in relevant outcomes were estimated using linear mixed models with random intercepts. The probability of transitioning to long-term care facilities was modeled using generalized estimating equations. The total length of time spent at AD stages and annual transition probabilities were estimated with multistate Markov models. Results The estimated average time spent in each stage was 3.2 years in MCI due to AD and 2.2, 2.0, and 2.8 years for mild, moderate, and severe AD dementia, respectively. The annual probabilities of progressing from MCI to mild, moderate, and severe AD dementia were 20, 4, and 0.7%, respectively. The incremental change to the next stage of participants with unimpaired cognition, MCI, and mild, moderate, and severe AD dementia (to death) was 3.2, 20, 26.6, 31, and 25.3%, respectively. Changes in ADLs, neuropsychiatric features, and cognitive measures were greatest among participants who transitioned from MCI and mild AD dementia to more advanced stages. Participants with MCI and mild and moderate AD dementia had increasing odds of being transitioned to long-term care facilities over time during the follow-up period. Conclusions The findings demonstrated that participants with early stages AD (MCI or mild dementia) were associated with the largest changes in clinical scale scores. Early detection, diagnosis, and intervention by disease-modifying therapies are required for delaying AD progression. Additionally, estimates of transition probabilities can inform future studies and health economic modeling.

Background: Evidence on health and social care resource utilisation and associated costs, and how this varies across people with Alzheimer's disease (AD) dementia is limited. Methods: Retrospective cohort, using the Discover dataset, which includes linked health and social care records for approximately 2.5 million people in North-West London. Individuals were followed up from the latter of 2010 or from diagnosis of AD dementia (index) up to 2019. Outcomes were overall survival, care home admission, health and social care utilisation and associated costs, and cardiovascular outcomes. Variation was explored in subpopulations and by stratifying by cost quintile. Generalised linear modelling was used to estimate the association between clinical and demographic characteristics and healthcare costs. Results: The cohort included 18,116 people diagnosed with AD dementia whose mean age at index was 81 years, 62 % were female and 65 % were of white ethnicity. Median survival from index was 4.9 years (95 %CI: 4.8–5.0). Mean healthcare costs were £4,548(£4,491–£4,604) per person year(ppy). Healthcare costs for the 48 % who used social care were £5,433ppy(£5,353–£5,514) and social care costs were £24,374ppy(£24,372–£24,376). In the overall cohort costs in the highest cost quintile were £13,665ppy(£13,420–£13,911), of which 70 % was from inpatient hospitalisation. Subpopulations admitted to care home (£7,535 £7,362–£7,709), with cardiovascular disease (£6,106;£5,990–£6,222) and with type 2 diabetes (£6,049;£5,901–£6,198) accrued the highest healthcare costs. Factors most strongly associated with cost were dying during follow up (+£2,224;£2,010–£2,493), being frail (+£1,246;£1,051–£1,440) and prior stroke (+£1,207;£908–£1,507). Conclusion: Characteristics of individuals with high healthcare costs include requirement for social care and cardiometabolic comorbidities. Identifying individuals early in their disease course may improve health outcomes and reduce the cost of AD dementia in later life.

Abstract Background Management guidelines for obesity suggest maintaining a minimum of 5% body weight reduction to help prevent or lower the risk of developing conditions such as hypertension and type 2 diabetes. However, achieving long‐term weight control is difficult with lifestyle modification alone, making it essential to combine pharmacotherapy with diet and exercise in individual cases. Semaglutide 2.4 mg has demonstrated significant reductions in body weight and cardiometabolic risk factors in clinical trials, but information on outcomes in a real‐world setting is limited. Objective To assess changes in body weight and other clinical outcomes at 6‐month follow‐up among adults on semaglutide 2.4 mg in a real‐world setting in the United States (US). Methods Observational and retrospective cohort study of patients initiating treatment between 15 June 2021, and 31 March 2022, using a large US claims‐linked electronic health record database. Results Mean (±SD) body mass index (BMI) of the 343 patients included in the analysis was 37.9 ± 5.5 kg/m2. After 6 months, mean body weight change was −10.5 ± 6.8 kg (95% CI: −11.2; −9.8, p

Abstract INTRODUCTION We examined associations between the Clinical Dementia Rating Scale (CDR) and function (Functional Assessment Scale [FAS]), neuropsychiatric symptoms (Neuropsychiatric Inventory Questionnaire [NPI‐Q]), and cognitive impairment in Alzheimer's disease (AD). METHODS We used data from the National Alzheimer's Coordinating Center Uniform Data Set and defined cognitively unimpaired and AD stages using CDR‐global. RESULTS Functional and neuropsychiatric symptoms occur as early as the mild cognitive impairment (MCI) phase. The adjusted lest square mean FAS (95% confidence interval [CI]) was lowest in cognitively unimpaired (3.88 [3.66, 4.11] to 5.01 [4.76, 5.26]) and higher with more advanced AD (MCI: 8.17 [6.92, 9.43] to 20.87 [19.53, 22.20]; mild: 18.54 [17.57, 19.50] to 28.13 [27.14, 29.12]; moderate: 26.01 [25.31, 26.70] to 29.42 [28.73, 30.10]). FAS and NPI‐Q scores increased steeply with MCI (NPI‐Q: 5.55 [4.89, 6.20] to 7.11 [6.43, 7.78]) and mild AD dementia (NPI‐Q: 6.66 [5.72, 7.60] to 8.32 [7.32, 9.33]). DISCUSSION CDR‐global staged AD by capturing differences in relevant outcomes along AD progression. Highlights There were strong associations among CDR and the various outcomes relevant to healthcare providers, patients, and their care givers, such as activities of daily living. Overall, activities of daily living, neuropsychiatric symptoms, and cognitive function outcomes deteriorated over time and can be observed in early stages of AD (MCI or mild dementia). Our findings directly inform the current understanding of AD progression and can aid in care planning and benefit assessments of early AD interventions to delay the progression of AD to more advanced stages.

ContextMagnetic resonance imaging (MRI) is currently the most accurate imaging modality to assess local prostate cancer stage. Despite a growing body of evidence, incorporation of MRI images into decision-making process concerning surgical template of radical prostatectomy, is complex and still poorly understood.ObjectiveWe sought to determine the value of MRI in preoperative planning before radical prostatectomy.Materials and methodsSystematic search through electronic PubMed, EMBASE, and Cochrane databases from 2000 up to April 2018 was performed. Only studies that used preoperative MRI in decision-making process regarding extension of resection in patients with prostate cancer, in whom radical prostatectomy was an initial form of treatment were included into analysis. Their quality was scored by Risk Of Bias In Non-Randomized Studies of Interventions system. Meta-analysis was performed to calculate the weighted summary proportion under the fixed or random effects model as appropriate and pooled effects were depicted on forest plots.ResultsThe results showed that the preoperative MRI led to the modification of initial surgical template in one third of cases (35%). This occurred increasingly with the rising prostate cancer-risk category: 28%, 33%, 52% in low-, intermediate- and high-risk group, respectively. Modification of neurovascular bundle-sparing surgery based on MRI appeared to have no impact on the positive surgical margin rate. The decision based on MRI was correct on average in 77% of cases and differed across prostate cancer-risk categories: 63%, 75% and 91% in low-, intermediate- and high-risk group, accordingly.ConclusionsIn summary, MRI has a considerable impact on the decision-making process regarding the extent of resection during radical prostatectomy. Adaptation of MRI images by operating surgeons has at worst no significant impact on surgical margin status, however its ability to decrease the positive surgical margin rates remains unconfirmed.