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. 2024 Mar 21;16(1):e12574.
doi: 10.1002/dad2.12574. eCollection 2024 Jan-Mar.

Exploring cognitive progression subtypes in the Framingham Heart Study

Huitong Ding  1   2 , Biqi Wang  3 , Alexander P Hamel  3 , Cody Karjadi  1   2 , Ting F A Ang  1   2   4 , Rhoda Au  1   2   4   5   6 , Honghuang Lin  3
Affiliations

Exploring cognitive progression subtypes in the Framingham Heart Study

Huitong Ding et al. Alzheimers Dement (Amst). .

Abstract

Introduction: Alzheimer's disease (AD) is a heterogeneous disorder characterized by complex underlying neuropathology that is not fully understood. This study aimed to identify cognitive progression subtypes and examine their correlation with clinical outcomes.

Methods: Participants of this study were recruited from the Framingham Heart Study. The Subtype and Stage Inference (SuStaIn) method was used to identify cognitive progression subtypes based on eight cognitive domains.

Results: Three cognitive progression subtypes were identified, including verbal learning (Subtype 1), abstract reasoning (Subtype 2), and visual memory (Subtype 3). These subtypes represent different domains of cognitive decline during the progression of AD. Significant differences in age of onset among the different subtypes were also observed. A higher SuStaIn stage was significantly associated with increased mortality risk.

Discussion: This study provides a characterization of AD heterogeneity in cognitive progression, emphasizing the importance of developing personalized approaches for risk stratification and intervention.

Highlights: We used the Subtype and Stage Inference (SuStaIn) method to identify three cognitive progression subtypes.Different subtypes have significant variations in age of onset.Higher stages of progression are associated with increased mortality risk.

Keywords: Alzheimer's disease; age of onset; cognitive progression; heterogeneity; machine learning; mortality.

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Conflict of interest statement

R.A. is a scientific advisor to Signant Health and NovoNordisk, and a consultant to the Davos Alzheimer's Collaborative. The other authors declare no conflicts of interest. Author disclosures are available in the supporting information.

Figures

FIGURE 1
FIGURE 1
The sample selection diagram of this study. AD, Alzheimer's disease; MCI, mild cognitive impairment; NP, neuropsychological
FIGURE 2
FIGURE 2
Three cognitive progression subtypes identified in this study. The x axis represents the SuStaIn stages of cognitive decline, while the y axis represents the cognitive functions. At each SuStaIn stage, a new z score event occurs when a cognitive function declines to a new severity level, as indexed by a z score with respect to the participants who are cognitively intact; z scores of z = 1 red) and z = 2 (magenta). Higher opacity represents a higher confidence in the ordering.
FIGURE 3
FIGURE 3
Correlation between SuStaIn stage and different cognitive function scores. SuStaIn, Subtype and Stage Inference method
See this image and copyright information in PMC

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