Distinct medical and substance use histories associate with cognitive decline in Alzheimer's disease

IF 11.1 1区医学 Q1 CLINICAL NEUROLOGY Alzheimer's & Dementia Pub Date : 2025-03-20 DOI:10.1002/alz.70017

Clayton Mansel, Diego R. Mazzotti, Ryan Townley, Mihaela E. Sardiu, Russell H. Swerdlow, Robyn A. Honea, Olivia J. Veatch

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Abstract

INTRODUCTION

Phenotype clustering reduces patient heterogeneity and could be useful when designing precision clinical trials. We hypothesized that the onset of early cognitive decline in patients would exhibit variance predicated on the clinical history documented prior to an Alzheimer's disease (AD) diagnosis.

METHODS

Self-reported medical and substance use history (i.e., problem history) was used to cluster participants from the National Alzheimer's Coordinating Center (NACC) into distinct subtypes. Linear mixed effects modeling was used to determine the effect of problem history subtype on cognitive decline over 2 years.

RESULTS

Two thousand seven hundred fifty-four individuals were partitioned into three subtypes: minimal (n = 1380), substance use (n = 1038), and cardiovascular (n = 336). The cardiovascular problem history subtype had significantly worse cognitive decline over a 2 year follow-up period (p = 0.013).

DISCUSSION

Our study highlights the need to account for problem history to reduce heterogeneity of outcomes in AD clinical trials.

Highlights

Clinical data were used to identify subtypes of patients with Alzheimer's disease (AD) in the National Alzheimer's Coordinating Center dataset.
Three problem history subtypes were found: minimal, substance use, and cardiovascular.
The mean change in Clinical Dementia Rating Sum of Boxes (CDR-SB) was assessed over a 2 year follow-up.
The cardiovascular subtype was associated with the worst cognitive decline.
The magnitude of change in CDR-SB was similar to recent AD clinical trials.

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不同的医疗和物质使用史与阿尔茨海默病的认知能力下降有关

表型聚类减少了患者的异质性，在设计精确的临床试验时可能有用。我们假设，患者早期认知能力下降的发病将根据阿尔茨海默病（AD）诊断前的临床病史表现出差异。

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来源期刊

Alzheimer's & Dementia 医学-临床神经学

CiteScore

14.50

自引率

5.00%

发文量

299

审稿时长

3 months

期刊介绍： Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.