Modeling Alzheimer's disease progression using the disease system analysis approach

Goméni, Roberto; Simeoni, Monica; Zvartau-Hind, Marina; Irizarry, Michael C.; Austin, Daren; Gold, Michael

doi:10.1016/j.jalz.2010.12.012

Cited by 17 publications

(13 citation statements)

References 32 publications

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“…If (22) and (23) then problem has a unique local minimum. Note that, by Proposition 3, constraint (22) guarantees the existence of a finite optimal solution for , and .…”

Section: ) Special Casementioning

confidence: 84%

“…That is, assumption A1 implies that after units of time the cost rate of a hidden failure stabilizes at value , i.e., for . Assumptions similar to A1 can be found in various disease progression models (see, e.g., [22] and [23]). Setting (note that if then for ) yields a constant penalty cost rate as in [20] & [21], which is commonly used in the majority of existing relevant literature (see, e.g., [8], [13], [15]- [18], [20], [21]).…”

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confidence: 99%

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Scheduling Preventive Maintenance as a Function of an Imperfect Inspection Interval

Maillart

Prokopyev

2015

IEEE Trans. Rel.

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This paper considers a system with periodic inspections and periodic preventive maintenance (PM) to detect and correct hidden failures that generate a penalty cost per unit time undetected. Imperfect periodic inspections (IPIs) occur at a chosen interval , and detect hidden failures with probability . Both reactive maintenance (RM), performed when a hidden failure is detected by an IPI, and PM, performed at a chosen time , renew the system. The objective is to determine the optimal frequency and quantity of imperfect inspections between PM such that the expected cost (which includes the costs of undetected failures, IPIs, PM, and RM) per unit time is minimized over an infinite horizon. We analytically establish conditions for the existence of a finite optimal for a given value of , and discuss the asymptotic behavior of the objective function for large and . These results are further exploited to describe convergence properties of a proposed approach for finding a globally optimal solution. Also, for the special case of a Weibull time-to-failure distribution, we derive conditions that guarantee the uniqueness of a locally optimal solution for a given value of . Index Terms-Imperfect inspections, maintenance optimization, preventive maintenance (PM). ACRONYMS AND ABBREVIATIONSPM preventive maintenance IPI imperfect periodic inspection RM reactive maintenance cdf cumulative distribution function pdf probability density function TTF time to failure NOTATION probability that an IPI detects an underlying failure cost per PM or RM cost per IPI instantaneous cost of a hidden failure cost rate of a hidden failure when the length of the undetected time period is ,

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“…If (22) and (23) then problem has a unique local minimum. Note that, by Proposition 3, constraint (22) guarantees the existence of a finite optimal solution for , and .…”

Section: ) Special Casementioning

confidence: 84%

mentioning

confidence: 99%

Scheduling Preventive Maintenance as a Function of an Imperfect Inspection Interval

Maillart

Prokopyev

2015

IEEE Trans. Rel.

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“…The 12-month decline in the placebo group was similar to that reported in other clinical trials involving patients with mild to moderate dementia. 28 The baseline ADAS-cog SD was 11.4 points, and the 12-month between-groups mean difference of 0.3 points represented a standardized difference (standardized effect size) of only 0.03 (95% CI 20.39 to 0.44). Effects were similar in subgroups defined by baseline severity (mild vs moderate dementia; interaction p value 5 0.44, 2-tailed analysis of covariance).…”

Section: Classification Of Evidence This Interventional Study Providesmentioning

confidence: 95%

Raloxifene for women with Alzheimer disease

et al. 2015

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Objective: To determine whether raloxifene, a selective estrogen receptor modulator, improves cognitive function compared with placebo in women with Alzheimer disease (AD) and to provide an estimate of cognitive effect.Methods: This pilot study was conducted as a randomized, double-blind, placebo-controlled trial, with a planned treatment of 12 months. Women with late-onset AD of mild to moderate severity were randomly allocated to high-dose (120 mg) oral raloxifene or identical placebo provided once daily. The primary outcome compared between treatment groups at 12 months was change in the Alzheimer's Disease Assessment Scale, cognitive subscale (ADAS-cog).Results: Forty-two women randomized to raloxifene or placebo were included in intent-to-treat analyses (mean age 76 years, range 68-84), and 39 women contributed 12-month outcomes. ADAS-cog change scores at 12 months did not differ significantly between treatment groups (standardized difference 0.03, 95% confidence interval 20.39 to 0.44, 2-tailed p 5 0.89). Raloxifene and placebo groups did not differ significantly on secondary analyses of dementia rating, activities of daily living, behavior, or a global cognition composite score. Caregiver burden and caregiver distress were similar in both groups. Conclusions:Results on the primary outcome showed no cognitive benefits in the raloxifenetreated group. Classification of evidence:This study provides Class I evidence that for women with AD, raloxifene does not have a significant cognitive effect. The study lacked the precision to exclude a small effect. Neurology ® 2015;85:1937-1944 GLOSSARY AD 5 Alzheimer disease; ADAS-cog 5 Alzheimer's Disease Assessment Scale, cognitive subscale; CI 5 confidence interval; SERM 5 selective estrogen receptor modulator.The burden of Alzheimer disease (AD) falls heavily on women. By virtue of greater longevity, more women than men survive to an older age when risk is greater. AD pathology is more likely to be expressed as dementia in women than men, 1 and cognitive symptoms appear to be more severe.2 Estrogens have attracted interest as potential treatment for women with AD, but relatively small therapeutic trials have generally failed to confirm efficacy.3 A number of compounds that lack the 4-ring cyclopentanophenanthrene structure characteristic of steroid hormones interact with estrogen receptors or exhibit estrogen-like properties. The selective estrogen receptor modulators (SERMs) have estrogenic effects in some tissues but antiestrogenic effects or no estrogenic effect in other tissues. Raloxifene, an oral SERM, is approved for treatment of osteoporosis in postmenopausal women. In the Multiple Outcomes of Raloxifene Evaluation trial, high-dose (120 mg/d) raloxifene reduced the risk of mild cognitive impairment (relative risk 0.67, 95% confidence interval [CI] 0.46-0.98) and led to a nonsignificant reduction in AD risk (0.51, 95% CI 0.21-1.21). 4 Studies of raloxifene effects on cognition in womenFrom the

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“…When looking at the standard primary outcome variable in AD clinical trials, the Alzheimer's Disease Assessment Scale-cognitive portion (ADAS-Cog), it is interesting to note the factors that can influence rate of change or progression [35]. Covariate analyses indicate that baseline Mini-Mental State Examination (MMSE) score, education, age, and apolipoprotein3/4 genotype had a significant effect on the level and shape of the trajectories of the mean model predicted ADAS-Cog change from baseline.…”

Section: Have Researchers Failed To Consider the Impact Of Important mentioning

confidence: 99%

Why the Negative Studies in Alzheimer’s Disease?

Möbius¹

2014

Global Clinical Trials for Alzheimer's Disease

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Modeling Alzheimer's disease progression using the disease system analysis approach

Cited by 17 publications

References 32 publications

Scheduling Preventive Maintenance as a Function of an Imperfect Inspection Interval

Scheduling Preventive Maintenance as a Function of an Imperfect Inspection Interval

Raloxifene for women with Alzheimer disease

Why the Negative Studies in Alzheimer’s Disease?

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