An Analysis of the Public Financial Support Eligibility Rule for French Dependent Elders with Alzheimer’s Disease

AbstractBackgroundIt is crucial to define health policies that target patients with the highest needs. In France, public financial support is provided to dependent patients: it can be used to finance informal care time and nonmedical care use. Eligibility for public subsidies and reimbursement of costs is associated with a specific tool: the autonomie gérontologie groupes iso-ressources (AGGIR) scale score.ObjectiveOur objective was to explore whether patients with Alzheimer’s disease who are eligible for public financial support have greater needs than do noneligible patients.MethodsUsing data from the Dépendance des patients atteints de la maladie d’Alzheimer en France study, we calculated nonmedical care expenditures (in €) using microcosting methods and informal care time demand (hours/month) using the Resource Use in Dementia questionnaire. We measured the burden associated with informal care provision with Zarit Burden Interview. We used a modified two-part model to explore the correlation between public financial support eligibility and these three variables.ResultsWe find evidence of higher informal care use, higher informal caregivers’ burden, and higher care expenditures when patients have an AGGIR scale score corresponding to public financial support eligibility.ConclusionsThe AGGIR scale is useful to target patients with the highest costs and needs. Given our results, public subsidies could be used to further sustain informal caregivers networks by financing programs dedicated to lowering informal caregivers’ burden

Prospectives

Tiré de: Prospectives, vol. 22, no 1, février 1986.Titre de l'écran-titre (visionné le 24 janv. 2013

Further Analyses of the Safety of Verubecestat in the Phase 3 EPOCH Trial of Mild-To-Moderate Alzheimer’s Disease

Background: Verubecestat, a BACE1 inhibitor that reduces Aβ levels in the cerebrospinal fluid of humans, was not effective in a phase 3 trial (EPOCH) of mild-to-moderate AD and was associated with adverse events. To assist in the development of BACE1 inhibitors, we report detailed safety findings from EPOCH. Methods: EPOCH was a randomized, double-blind, placebo-controlled 78-week trial evaluating verubecestat 12 mg and 40 mg in participants with mild-to-moderate AD diagnosed clinically. The trial was terminated due to futility close to its scheduled completion. Of 1957 participants who were randomized and took treatment, 652 were assigned to verubecestat 12 mg, 652 to verubecestat 40 mg, and 653 to placebo. Adverse events and relevant laboratory, vital sign, and ECG findings were assessed. Results: Verubecestat 12 mg and 40 mg were associated with an increase in the percentage of participants reporting adverse events versus placebo (89 and 92% vs. 82%), although relatively few participants discontinued treatment due to adverse events (8 and 9% vs. 6%). Adverse events that were increased versus placebo included falls and injuries, suicidal ideation, weight loss, sleep disturbance, rash, and hair color change. Most were mild to moderate in severity. Treatment differences in suicidal ideation emerged within the first 3 months but did not appear to increase after 6 months. In contrast, treatment differences in falls and injuries continued to increase over time. Conclusions: Verubecestat was associated with increased risk for several types of adverse events. Falls and injuries were notable for progressive increases over time. While the mechanisms underlying the increased adverse events are unclear, they may be due to BACE inhibition and should be considered in future clinical development programs of BACE1 inhibitors

A bloodâ based nutritional risk index explains cognitive enhancement and decline in the multidomain Alzheimer prevention trial

IntroductionMultinutrient approaches may produce more robust effects on brain health through interactive qualities. We hypothesized that a bloodâ based nutritional risk index (NRI) including three biomarkers of diet quality can explain cognitive trajectories in the multidomain Alzheimer prevention trial (MAPT) over 3â years.MethodsThe NRI included erythrocyte nâ 3 polyunsaturated fatty acids (nâ 3 PUFA 22:6nâ 3 and 20:5nâ 3), serum 25â hydroxyvitamin D, and plasma homocysteine. The NRI scores reflect the number of nutritional risk factors (0â 3). The primary outcome in MAPT was a cognitive composite Z score within each participant that was fit with linear mixedâ effects models.ResultsEighty percent had at lease one nutritional risk factor for cognitive decline (NRI â ¥1: 573 of 712). Participants presenting without nutritional risk factors (NRI=0) exhibited cognitive enhancement (β = 0.03 standard units [SU]/y), whereas each NRI point increase corresponded to an incremental acceleration in rates of cognitive decline (NRIâ 1: β = â 0.04 SU/y, P = .03; NRIâ 2: β = â 0.08 SU/y, P < .0001; and NRIâ 3: β = â 0.11 SU/y, P = .0008).DiscussionIdentifying and addressing these wellâ established nutritional risk factors may reduce ageâ related cognitive decline in older adults; an observation that warrants further study.Highlightsâ ¢Multiâ nutrient approaches may produce more robust effects through interactive propertiesâ ¢Nutritional risk index can objectively quantify nutritionâ related cognitive changesâ ¢Optimum nutritional status associated with cognitive enhancement over 3â yearsâ ¢Suboptimum nutritional status associated with cognitive decline over 3â yearsâ ¢Optimizing this nutritional risk index may promote cognitive health in older adultsPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152935/1/trc2jtrci201911004.pd

Cross-sectional Associations of Fatigue with Cerebral &#946;-Amyloid in Older Adults at Risk of Dementia

Fatigue is a common symptom in the elderly and has also been associated with impaired cognition in older adults. Hence, we sought to explore the cross-sectional relationship between fatigue and cerebral \u3b2-amyloid (A\u3b2) in 269 elderly individuals reporting subjective memory complaints from the Multidomain Alzheimer Preventive Trial. Standard uptake value ratios (SUVRs) were generated by [18F] florbetapir positron emission tomography (PET) using the cerebellum as a reference. Cortical-to-cerebellar SUVRs (cortical-SUVRs) were obtained using the mean signal from the frontal cortex, temporal cortex, parietal cortex, precuneus, anterior cingulate, and posterior cingulate. Other brain regions independently assessed were the anterior cingulate, anterior putamen, caudate, hippocampus, medial orbitofrontal cortex, occipital cortex, parietal cortex, pons, posterior cingulate, posterior putamen, precuneus, semioval center, and temporal cortex. Fatigue was defined according to two questions retrieved from the Center for Epidemiological Studies-Depression scale. Chronic fatigue was defined as meeting fatigue criteria at two consecutive clinical visits 6 months apart between study baseline and 1 year (visits were performed at baseline, 6 months and 1 year then annually). Cross-sectional associations between fatigue variables and cerebral A\u3b2 were explored using fully adjusted multiple linear regression models. We found no statistically significant cross-sectional associations between fatigue assessed at the clinical visit closest to PET and A\u3b2 in any brain region. Similarly, chronic fatigue was not significantly associated with A\u3b2 load. Sensitivity analysis in subjects with a Clinical Dementia Rating of 0.5 showed that fatigue reported at the clinical visit closest to PET was, however, weakly associated with increased A\u3b2 in the hippocampus (B-coefficient: 0.07, 95% CI: 0.01, 0.12, p\u2009=\u20090.016). These preliminary results suggest that fatigue might be associated with A\u3b2 in brain regions associated with Alzheimer's disease in subjects in the early stages of disease

Alzheimers Dement

Introduction: The free and cued selective reminding test is used to identify memory deficits in mild cognitive impairment and demented patients. It allows assessing three processes: encoding, storage, and recollection of verbal episodic memory. Methods: We investigated the neural correlates of these three memory processes in a large cohort study. The Memento cohort enrolled 2323 outpatients presenting either with subjective cognitive decline or mild cognitive impairment who underwent cognitive, structural MRI and, for a subset, fluorodeoxyglucose-positron emission tomography evaluations. Results: Encoding was associated with a network including parietal and temporal cortices; storage was mainly associated with entorhinal and parahippocampal regions, bilaterally; retrieval was associated with a widespread network encompassing frontal regions. Discussion: The neural correlates of episodic memory processes can be assessed in large and standardized cohorts of patients at risk for Alzheimer's disease. Their relation to pathophysiological markers of Alzheimer's disease remains to be studied

AMYPAD Diagnostic and Patient Management Study:Rationale and design

Introduction: Reimbursement of amyloid–positron emission tomography (PET) is lagging due to the lack of definitive evidence on its clinical utility and cost-effectiveness. The Amyloid Imaging to Prevent Alzheimer's Disease–Diagnostic and Patient Management Study (AMYPAD-DPMS) is designed to fill this gap. Methods: AMYPAD-DPMS is a phase 4, multicenter, prospective, randomized controlled study. Nine hundred patients with subjective cognitive decline plus, mild cognitive impairment, and dementia possibly due to Alzheimer's disease will be randomized to ARM1, amyloid-PET performed early in the diagnostic workup; ARM2, amyloid-PET performed after 8 months; and ARM3, amyloid-PET performed whenever the physician chooses to do so. Endpoints: The primary endpoint is the difference between ARM1 and ARM2 in the proportion of patients receiving a very-high-confidence etiologic diagnosis after 3 months. Secondary endpoints address diagnosis and diagnostic confidence, diagnostic/therapeutic management, health economics and patient-related outcomes, and methods for image quantitation. Expected Impacts: AMYPAD-DPMS will supply physicians and health care payers with real-world data to plan management decisions

EU/US/CTAD Task Force: Lessons Learned from Recent and Current Alzheimer's Prevention Trials

At a meeting of the EU/US/Clinical Trials in Alzheimer’s Disease (CTAD) Task Force in December 2016, an international group of investigators from industry, academia, and regulatory agencies reviewed lessons learned from ongoing and planned prevention trials, which will help guide future clinical trials of AD treatments, particularly in the pre-clinical space. The Task Force discussed challenges that need to be addressed across all aspects of clinical trials, calling for innovation in recruitment and retention, infrastructure development, and the selection of outcome measures. While cognitive change provides a marker of disease progression across the disease continuum, there remains a need to identify the optimal assessment tools that provide clinically meaningful endpoints. Patient- and informant-reported assessments of cognition and function may be useful but present additional challenges. Imaging and other biomarkers are also essential to maximize the efficiency of and the information learned from clinical trials