Abstract

Background:Progression trajectories of patients with mild cognitive impairment (MCI) are currently not well understood.Objective:To classify patients with incident MCI into different latent classes of progression and identify predictors of progression class.Methods:Participants with incident MCI were identified from the US National Alzheimer’s Coordinating Center Uniform Data Set (09/2005-02/2019). Clinical Dementia Rating (CDR®) Dementia Staging Instrument-Sum of Boxes (CDR-SB), Functional Activities Questionnaire (FAQ), and Mini-Mental State Examination (MMSE) score longitudinal trajectories from MCI diagnosis were fitted using growth mixture models. Predictors of progression class were identified using multivariate multinomial logistic regression models; odds ratios (ORs) and 95% confidence intervals (CIs) were reported.Results:In total, 21%, 22%, and 57% of participants (N = 830) experienced fast, slow, and no progression on CDR-SB, respectively; for FAQ, these figures were 14%, 23%, and 64%, respectively. CDR-SB and FAQ class membership was concordant for most participants (77%). Older age (≥86 versus≤70 years, OR [95% CI] = 5.26 [1.78–15.54]), one copy of APOE ɛ4 (1.94 [1.08–3.47]), higher baseline CDR-SB (2.46 [1.56–3.88]), lower baseline MMSE (0.85 [0.75–0.97]), and higher baseline FAQ (1.13 [1.02–1.26]) scores were significant predictors of fast progression versus no progression based on CDR-SB (all p < 0.05). Predictors of FAQ class membership were largely similar.Conclusion:Approximately a third of participants experienced progression based on CDR-SB or FAQ during the 4-year follow-up period. CDR-SB and FAQ class assignment were concordant for the vast majority of participants. Identified predictors may help the selection of patients at higher risk of progression in future trials.

Highlights

  • Alzheimer’s disease (AD) is a debilitating neurodegenerative disorder that greatly impairs the quality of life of patients and close family membersJ

  • All predictors identified as significant at the 5% level from the univariate analyses were subsequently included in the multivariate multinomial logistic regression (MNL) models from which we report odds ratios (ORs) and 95% confidence intervals (CIs) for all candidate predictors of latent class membership retained from the univariate analyses

  • National Alzheimer’s Coordinating Center (NACC) participants newly diagnosed with mild cognitive impairment (MCI) were classified in three latent classes of progression based on CDR-Sum of Boxes (CDR-SB) and Functional Activities Questionnaire (FAQ) score trajectories

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Summary

Introduction

Alzheimer’s disease (AD) is a debilitating neurodegenerative disorder that greatly impairs the quality of life of patients and close family membersJ. Clinical Dementia Rating (CDR®) Dementia Staging Instrument-Sum of Boxes (CDR-SB), Functional Activities Questionnaire (FAQ), and Mini-Mental State Examination (MMSE) score longitudinal trajectories from MCI diagnosis were fitted using growth mixture models. Results: In total, 21%, 22%, and 57% of participants (N = 830) experienced fast, slow, and no progression on CDR-SB, respectively; for FAQ, these figures were 14%, 23%, and 64%, respectively. CDR-SB and FAQ class membership was concordant for most participants (77%). Older age (≥86 versus ≤ 70 years, OR [95% CI] = 5.26 [1.78–15.54]), one copy of APOE ␧4 (1.94 [1.08–3.47]), higher baseline CDR-SB (2.46 [1.56–3.88]), lower baseline MMSE (0.85 [0.75–0.97]), and higher baseline FAQ (1.13 [1.02–1.26]) scores were significant predictors of fast progression versus no progression based on CDR-SB (all p < 0.05). Identified predictors may help the selection of patients at higher risk of progression in future trials

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