Measuring Alzheimer Disease Progression with Transition Probabilities: Estimates from NACC-UDS

Spackman, Eldon; Kadiyala, Srikanth; Neumann, Peter J.; Veenstra, David L.; Sullivan, Sean D.

doi:10.2174/156720512803569046

Cited by 44 publications

(61 citation statements)

References 34 publications

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“…As in other studies, some of the study patients improved from baseline to follow-up [27], which could not be explained by depressive symptoms or the use of anti-dementia medication. It might be hypothesized that the improvement can be related to optimized treatment of comorbid disorders including withdrawal of inappropriate drugs, or it can be a consequence of test-retest variability in scores for patients who were essentially stable.…”

Section: Discussionsupporting

confidence: 74%

Progression of Alzheimer’s Disease: A Longitudinal Study in Norwegian Memory Clinics

Eldholm

Barca

Persson

et al. 2018

JAD

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Abstract.Background: The course of Alzheimer's disease (AD) varies considerably between individuals. There is limited evidence on factors important for disease progression. Objective: The primary aim was to study the progression of AD, as measured by the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB). Secondary aims were to investigate whether baseline characteristics are important for differences in progression, and to examine the correlation between progression assessed using three different instruments: CDR-SB (0-18), the cognitive test Mini-Mental State Examination (MMSE, 0-30), and the functional measure Instrumental Activities of Daily Living (IADL, 0-1). Methods: The Progression of AD and Resource use (PADR) study is a longitudinal observational study in three Norwegian memory clinics. Results: In total, 282 AD patients (mean age 73.3 years, 54% female) were followed for mean 24 (16-37) months. The mean annual increase in CDR-SB was 1.6 (SD 1.8), the mean decrease in MMSE score 1.9 (SD 2.6), and the mean decrease in IADL score 0.13 (SD 0.14). Of the 282 patients, 132 (46.8%) progressed slowly, with less than 1 point yearly increase in CDR-SB. Cognitive test results at baseline predicted progression rate, and together with age, ApoE, history of hypertension, and drug use could explain 17% of the variance in progression rate. The strongest correlation of change was found between CDR-SB and IADL scores, the weakest between MMSE and IADL scores.

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Section: Discussionsupporting

confidence: 74%

Progression of Alzheimer’s Disease: A Longitudinal Study in Norwegian Memory Clinics

Eldholm

Barca

Persson

et al. 2018

JAD

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“…Several studies used an earlier version of the NACC UDS data to evaluate AD progression across more limited sets of cognitive states, with differences primarily driven by mortality rate estimates. Spackman et al [9] estimated comparable progression rates at age 77 for mild and moderate AD (77% vs. 71% likelihood of remaining in mild AD and 50% vs. 45% for moderate AD), but much higher mortality for severe AD (48% vs. 22%), and did not include patients with normal cognition or MCI. Bloudek et al [13] also estimated a much higher transition probability to death for severe AD (90%) in a study restricted to AD dementia patients.…”

Section: Discussionmentioning

confidence: 99%

“…This approach models the likelihood of the binary outcome conditional on individual risk factors to estimate age-state specific probabilities of institutionalization and death. Institutionalization was not considered a distinct health state, but was modeled separately to predict the likelihood of institutionalization for patients within each health state, as has been done in prior studies [9, 11, 13]. Age- and state-specific likelihood of progressing to death was estimated separately from the health state transitions, given the non-ordinal nature of transitioning from CI severity levels to death.…”

Section: Methodsmentioning

confidence: 99%

“…Patients who appear to improve from MCI to normal cognition remain at increased risk of transitioning to dementia [17], and patients with a previous CDR of 0.5 (which has been used to define MCI) often have AD pathology at autopsy [5]. Reversion or improvement within AD dementia ( e.g., from severe to moderate AD dementia) was estimated based on the results of prior studies of AD progression [9,11]. …”

Section: Methodsmentioning

confidence: 99%

“…Prior research has examined transition rates within AD dementia states or from normal cognition to MCI and AD without severity differentiation, but not across the full AD continuum [9–13]. To understand the impact of transitioning from normal cognition to MCI due to AD on progression to AD dementia, institutionalization, and death, the secondary objective was to develop a health state model, using the estimated progression rates, to predict the expected effect of a hypothetical disease-modifying treatment that delays onset of MCI due to AD on lifetime outcomes for a US patient cohort.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Estimating Alzheimer’s Disease Progression Rates from Normal Cognition Through Mild Cognitive Impairment and Stages of Dementia

Davis¹,

O'Connell²,

Johnson³

et al. 2018

CAR

153

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Background: Alzheimer’s Disease (AD) can be conceptualized as a continuum: patients progress from normal cognition to mild cognitive impairment (MCI) due to AD, followed by increasing severity of AD dementia. Prior research has measured transition probabilities among later stages of AD, but not for the complete spectrum. Objective: To estimate annual progression rates across the AD continuum and evaluate the impact of a delay in MCI due to AD on the trajectory of AD dementia and clinical outcomes. Methods: Patient-level longitudinal data from the National Alzheimer’s Coordinating Center for n=18,103 patients with multiple visits over the age of 65 were used to estimate annual, age-specific transitional probabilities between normal cognition, MCI due to AD, and AD severity states (defined by Clinical Dementia Rating score). Multivariate models predicted the likelihood of death and institutionalization for each health state, conditional on age and time from the previous evaluation. These probabilities were used to populate a transition matrix describing the likelihood of progressing to a particular disease state or death for any given current state and age. Finally, a health state model was developed to estimate the expected effect of a reduction in the risk of transitioning from normal cognition to MCI due to AD on disease progression rates for a cohort of 65-year-old patients over a 35-year time horizon. Results: Annual transition probabilities to more severe states were 8%, 22%, 25%, 36%, and 16% for normal cognition, MCI due to AD, and mild/moderate/severe AD, respectively, at age 65, and increased as a function of age. Progression rates from normal cognition to MCI due to AD ranged from 4% to 10% annually. Severity of cognitive impairment and age both increased the likelihood of institutionalization and death. For a cohort of 100 patients with normal cognition at age 65, a 20% reduction in the annual progression rate to MCI due to AD avoided 5.7 and 5.6 cases of MCI due to AD and AD, respectively. This reduction led to less time spent in severe AD dementia health states and institutionalized, and increased life expectancy. Conclusion: Transition probabilities from normal cognition through AD severity states are important for understanding patient progression across the AD spectrum. These estimates can be used to evaluate the clinical benefits of reducing progression from normal cognition to MCI due to AD on lifetime health outcomes.

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Cost-effectiveness of Aducanumab and Donanemab for Early Alzheimer Disease in the US

2022

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IMPORTANCE Several anti-amyloid monoclonal antibodies have been developed for slowing the progression of Alzheimer disease (AD). Among the furthest developed are aducanumab, which received accelerated approval from the US Food and Drug Administration in 2021, and donanemab, which is currently undergoing phase 3 trials. The cost-effectiveness of these treatments has not been established.OBJECTIVES To estimate the cost-effectiveness of aducanumab and donanemab relative to standard care for early AD in the US. DESIGN, SETTING, AND PARTICIPANTSA decision analytic model was used to estimate the lifetime health and economic outcomes of adults with early AD, from US healthcare sector and societal perspectives. Simulated patients had a mean (SD) age of 75.2 (5.5) years; 65% had mild cognitive impairment and 35% had mild dementia. Analyses were conducted from

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Measuring Alzheimer Disease Progression with Transition Probabilities: Estimates from NACC-UDS

Cited by 44 publications

References 34 publications

Progression of Alzheimer’s Disease: A Longitudinal Study in Norwegian Memory Clinics

Progression of Alzheimer’s Disease: A Longitudinal Study in Norwegian Memory Clinics

Estimating Alzheimer’s Disease Progression Rates from Normal Cognition Through Mild Cognitive Impairment and Stages of Dementia

Cost-effectiveness of Aducanumab and Donanemab for Early Alzheimer Disease in the US

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