Functional Outcomes of a Comprehensive, Individualized, Person-Centered Management Program in Advanced Alzheimer"™s Disease(AD): Results from a 52-Week Randomized Controlled Trial
Background: We conducted a 28-week, single-blind, randomized, controlled trial of the efficacy of Comprehensive, Individualized, Person-Centered Management (CI-PCM) and memantine treatment (Reisberg et al., Dement Geriatr Cogn Disord, 2017) in advanced AD persons. CI-PCM and memantine was approximately 7.5 times more beneficial to AD persons on the Functional Assessment Staging Tool (FAST) (Kenowsky et. al., Alzheimer"™s and Dementia, 2017) than to AD persons who received memantine alone in the memantine FDA approval pivotal trial conducted by Reisberg et. al., (NEJM 2003). We also conducted a 24-week extension study. Herein, we report the difference in functional outcomes between the CI-PCM and Usual Community Care (UCC+FC) groups at 52-weeks on the FAST and the ADCS-ADLSev-Abv. See Figures 1 and 2. Method: After screening, 20 eligible subject-carepartner dyads were randomized equally to the CI-PCM and UCC+FC groups. All 20 dyads completed the 28-week study and entered the 24-week extension study. One subject in the UCC+FC group died during the extension study. The FAST and ADCS-ADLsev-abv were conducted at baseline, and weeks 4, 12, 28, and 52. P values were calculated using the Wilcoxon Mann Whitney test. Result: The mean FAST total score from baseline (6.6±0.1SE) to week 52 (6.5±0.01SE) showed an improvement of functional limitations in the CI-PCM group. The mean FAST total score for the UCC+FC group showed a functional decline from baseline (6.6±0.1SE) to week 52 (6.8±0.1SE), displaying a robustly significant difference between the two groups (p<0.0014). The mean ADCS-ADL-sev-abv total score for the CI-PCM group demonstrated a 20.9% improvement in functioning from baseline (15.3±2.0SE) to week 52 (18.5±2.5SE). The mean ADCS-ADL-sev-abv total score for the UCC+FC group showed a decline of 48.6% from baseline (14.8±2.1SE) to week 52 (7.6±2.3SE), indicating a significant difference between the two groups (p<0.009). Conclusion: The CI-PCM program is the only evidenced-based treatment to date that can significantly improve and reverse functional deterioration in advanced AD persons. The functional success of the CI-PCM program may primarily be attributed to care partners learning to memory coach AD persons to perform daily activities such as bathing, dressing, feeding and toileting themselves, and to become/maintain urinary and fecal continence.
Evaluation of fondaparinux (Arixtra) at a large academic medical center [Meeting Abstract]
Background: Fondaparinux is FDA-approved for prophylaxis of venous thromboembolism (VTE) in patients undergoing surgery as well as for the treatment of acute deep vein thrombosis and pulmonary embolism. Off-label, fondaparinux is used as an alternative to argatroban in the treatment of suspected or confirmed heparin-induced thrombocytopenia (HIT). The Antithrombotic/Hemostatic Stewardship Committee at NYU Langone Health (NYULH) provides guidance for the safe and effective use of fondaparinux, while assuring that an evidenced-based and cost-effective approach for utilization is maintained.
Aim(s): To evaluate the utilization of fondaparinux at NYULH and to assess guideline adherence, efficacy, safety, and cost avoidance.
Method(s): This was a retrospective review of adult patients who received fondaparinux between November 2016 and June 2019 at NYULH. The primary outcome was assessment of fondaparinux utilization based on the dosing guideline. Secondary outcomes included tolerability, safety, and cost-avoidance.
Result(s): Ninety-eight patients received fondaparinux, with the most frequent indications being suspected HIT (44%), VTE prophylaxis (23%), and continuation of home therapy (14%). Based on the NYULH fondaparinux dosing guideline, 97 (99%) patients were dosed appropriately. One patient (1%) received fondaparinux while on hemodialysis. Thromboembolic events occurred in 3 (3%) patients, major bleeding occurred in 4 (4%) patients and clinically relevant non-major bleeding occurred in 2 (2%) patients. In the 52 patients with suspected or confirmed HIT, the cost-avoidance of utilizing fondaparinux instead of argatroban was approximately $100,000.
Conclusion(s): The majority of fondaparinux utilization at NYULH is for suspected HIT, and dosing guidelines were followed in most cases. A low thromboembolic event rate with the use of fondaparinux was observed. The major and clinically relevant non-major bleeds experienced in six patients may be attributed to these patients' baseline high bleeding risk. Fondaparinux was a cost-effective alternative to argatroban in patients with suspected or confirmed HIT in this patient population. (Table Presented)
Psychometric Cognitive Decline Precedes the Advent of Subjective Cognitive Decline in the Evolution of Alzheimer's Disease
BACKGROUND:We have described the clinical stages of the brain aging and Alzheimer's disease (AD) continuum. In terms of the pre-dementia stages of AD, we introduced the terminology "mild cognitive impairment" (MCI) for the first pre-dementia stage and "subjective cognitive decline" (SCD) for the pre-MCI stage. We now report the characteristics of a pre-SCD condition eventuating in likely AD. OBJECTIVE:The aim of this study was to characterize a pre-SCD condition eventuating in AD. METHOD/METHODS:Sixty healthy persons with "no cognitive decline" (NCD) were recruited and 47 were followed (mean baseline age, 64.1 Â± 8.9 years; mean follow-up time, 6.7 Â± 3.1 years). Outcome was determined at the final assessment prior to 2002 as "decliner," if SCD or worse, or "nondecliner" if NCD. RESULTS:After controlling for age, gender, years of education, and follow-up time, there was a between-group difference in the decline rate (p < 0.001). Also, after controlling for demographic variables and follow-up time, the combinatorial psychometric score was lower at baseline in the future decliners (p = 0.035). Of the 9 psychometric variables, after controlling for demographic variables and follow-up time, 3 were significantly lower at baseline in future decliners. Since AD is known to be age related and all subjects in this study were otherwise healthy, we also did an analysis without controlling for age. The combinatorial psychometric score was highly significantly better at baseline in the future nondecliners than in the future decliners (p = 0.008). CONCLUSION/CONCLUSIONS:This is ostensibly the first study to link psychometric cognitive decline to the subsequent SCD stage of eventual AD.
Two Year Outcomes, Cognitive and Behavioral Markers of Decline in Healthy, Cognitively Normal Older Persons with Global Deterioration Scale Stage 2 (Subjective Cognitive Decline with Impairment)
BACKGROUND:Little is known with respect to behavioral markers of subjective cognitive decline (SCD), a condition initially described in association with Global Deterioration Scale (GDS) stage 2. OBJECTIVE:Two-year interval behavioral markers were investigated herein. METHODS:Subjects from a published 7-year outcome study of GDS stage 2 subjects were selected. This study had demonstrated a hazard ratio of 4.5 for progression of GDS stage 2, in comparison with GDS stage 1 (no subjective or objective cognitive decline) subjects, after controlling for demographic and temporal variables. Because GDS 2 subjects have previously demonstrated impairment in comparison with healthy persons free of complaints, we herein suggest the terminology "SCD(I)" for these persons. 98 SCD(I) persons, 63 women and 35 men, mean baseline age, 67.12Â±8.75 years, with a mean educational background of 15.55Â±2.60 years, and mean baseline MMSE scores of 28.9Â±1.24 were followed for 2.13Â±0.30 years. RESULTS:Observed annual decline on the GDS was 6.701% per annum, very close to a 1986 published estimate. At follow up, the MMSE, and 7 of 8 psychometric tests did not decline significantly. Of 21 Hamilton Depression Scale items, 2 improved and the remainder were unchanged. Anxieties declined from multiple perspectives. The Brief Cognitive Rating Scale (BCRS) declined significantly (pâ€Š<â€Š0.001), with component declines in Remote memory (pâ€Š<â€Š0.01), and Functioning/self-care (pâ€Š=â€Š0.01). CONCLUSION/CONCLUSIONS:SCD(I) persons decline at an annual rate of approximately 6.7% /year from several recent studies. The BCRS assessments and the Digit Symbol Substitution Test can be sensitive measures for future studies of progression mitigation.