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. 2018;15(8):777-788.
doi: 10.2174/1567205015666180119092427.

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

Matthew Davis  1 , Thomas O Connell  1 , Scott Johnson  1 , Stephanie Cline  2 , Elizabeth Merikle  2 , Ferenc Martenyi  2 , Kit Simpson  3
Affiliations

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

Matthew Davis et al. Curr Alzheimer Res. 2018.

Abstract

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.

Keywords: Alzheimer’s diseases; Mild cognitive impairment; aging; apolipoprotein E; dementia; lewy bodies..

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Conflict of interest statement

CONFLICT OF INTEREST

MD, TC, and SJ were employees of Medicus Economics and received funding from Takeda Pharmaceuticals International for the study.

SC, EM, and FM were employees of Takeda Pharmaceuticals at the time of the study completion and manuscript development.

KS has received funding from Takeda Pharmaceuticals International for research unrelated to this study.

Figures

Fig. (1).
Fig. (1).
Schematic of health state transition model. Patients begin the model at age 65 years in the state of normal cognition. Patients are at risk of transitioning along the indicated paths if they have a primary etiologic diagnosis of AD at any visit. Patients are at risk of transitioning to the non-AD CI state, which includes MCI not due to AD and non-AD dementia if they do not receive a primary etiologic diagnosis of AD. All health states have a probability of transitioning to death and institutionalization. AD, Alzheimer’s disease; CI, cognitive impairment; MCI, mild cognitive impairment.
Fig. (2).
Fig. (2).
Modeling the effects of a 20% reduction in the onset of MCI due to AD in a cohort of 100 normal cognition patients at age 65 years. A: Progression with and without a 20% risk reduction in onset of MCI due to AD; B: Transitions with and without a 20% risk reduction in onset of MCI due to AD; C: Epidemiology results for 20% risk reduction in onset of MCI due to AD. AD, Alzheimer’s disease; MCI, mild cognitive impairment.
Fig. (2).
Fig. (2).
Modeling the effects of a 20% reduction in the onset of MCI due to AD in a cohort of 100 normal cognition patients at age 65 years. A: Progression with and without a 20% risk reduction in onset of MCI due to AD; B: Transitions with and without a 20% risk reduction in onset of MCI due to AD; C: Epidemiology results for 20% risk reduction in onset of MCI due to AD. AD, Alzheimer’s disease; MCI, mild cognitive impairment.
Fig. (2).
Fig. (2).
Modeling the effects of a 20% reduction in the onset of MCI due to AD in a cohort of 100 normal cognition patients at age 65 years. A: Progression with and without a 20% risk reduction in onset of MCI due to AD; B: Transitions with and without a 20% risk reduction in onset of MCI due to AD; C: Epidemiology results for 20% risk reduction in onset of MCI due to AD. AD, Alzheimer’s disease; MCI, mild cognitive impairment.
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References

    1. Alzheimer’s Association. 2015 Alzheimer’s disease facts and figures. Alzheimers Dement 11(3): 332–84 (2015a). - PubMed
    1. Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, et al. Toward defining the preclinical stages of Alzheimer’s disease:recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 7(3): 280–92 (2011). - PMC - PubMed
    1. Brookmeyer R, Corrada MM, Curriero FC, Kawas C. Survival following a diagnosis of Alzheimer disease. Arch Neurol 59(11): 1764–7 (2002). - PubMed
    1. Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM. Fore casting the global burden of Alzheimer’s disease. Alzheimers Dement 3(3): 186–91 (2007). - PubMed
    1. Morris JC. Early-stage and preclinical Alzheimer disease. Alzheimer Dis Assoc Disord 19(3): 163–65 (2005). - PubMed