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. 2025 Jan;21(1):e14393.
doi: 10.1002/alz.14393. Epub 2024 Nov 19.

Conversion to Alzheimer's disease dementia from normal cognition directly or with the intermediate mild cognitive impairment stage

Xinlin Lu  1 , Yahui Zhang  1 , Yichen Tang  2 , Charles Bernick  3 , Guogen Shan  1
Affiliations

Conversion to Alzheimer's disease dementia from normal cognition directly or with the intermediate mild cognitive impairment stage

Xinlin Lu et al. Alzheimers Dement. 2025 Jan.

Abstract

Introduction: Progression to Alzheimer's disease (AD) dementia from normal cognition (NC) can follow different trajectories, with most progressing through a recognizable mild cognitive impairment stage (NC-MCI-AD), while some individuals transition quickly from NC to AD dementia (NC-AD).

Methods: We compared demographic characteristics, health factors, and cognitive and functional assessments across three time points: the first NC visit, the last NC visit, and the first AD dementia visit.

Results: The NC-MCI-AD group showed greater impairment in cognitive and functional scores at AD dementia diagnosis, despite maintaining better cognitive function during the NC stage. Analysis of yearly changes revealed negligible differences during NC. However, the yearly change during the AD dementia stage suggested potentially more rapid functional decline in the NC-AD group.

Discussion: These findings highlight the heterogeneity in AD disease progression and emphasize the importance of considering diverse progression patterns in AD research and clinical practice.

Highlights: We investigated the disease progression difference between patients who converted to Alzheimer's disease (AD) dementia from normal cognition (NC) directly or through the mild cognitive impairment (MCI) stage. We found that the NC-MCI-AD group showed greater impairment in cognitive and functional scores at AD dementia diagnosis. We discovered that the NC-AD group had rapid functional decline once patients were confirmed with AD onset.

Keywords: Alzheimer's disease; cognitive decline; disease progression; functional impairment; mild cognitive impairment; neuropsychiatric symptoms.

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Conflict of interest statement

All authors reported no conflicts of interest for this study. Author disclosures are available in the supporting information.

Figures

FIGURE 1
FIGURE 1
Distribution of cognitive and functional measures across disease progression stages for the NC–AD group and the NC–MCI–AD group. AD, Alzheimer's disease; CDR‐SB, Clinical Dementia Rating Sum of Boxes; FAQ, Functional Activities Questionnaire; MCI, mild cognitive impairment; MMSE, Mini‐Mental State Examination; NC, normal cognition; NPI‐Q, Neuropsychiatric Inventory Questionnaire.
See this image and copyright information in PMC

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