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

medRxiv : the preprint server for health sciences Pub Date : 2024-11-28 DOI:10.1101/2024.11.26.24317918

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 Centers (NACC) into distinct subtypes. Linear mixed effects modeling was used to determine the effect of problem history subtype on cognitive decline over two years.

Results: 2754 individuals were partitioned into three subtypes: minimal (n = 1380), substance use (n = 1038), and cardiovascular (n = 336) subtypes. The cardiovascular problem history subtype had significantly worse cognitive decline over a two-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.

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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是有用的。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。方法：使用自我报告的医疗和物质使用史（即问题史）将来自国家阿尔茨海默病协调中心（NACC）的参与者聚类为不同的亚型。采用线性混合效应模型确定问题史亚型对两年内认知能力下降的影响。结果：2754人被分为三个亚型：最小（n = 1380），物质使用（n = 1038）和心血管（n = 336）亚型。在两年的随访期间，心血管病史亚型的认知能力下降明显加重（p = 0.013）。讨论：我们的研究强调需要考虑问题史，以减少阿尔茨海默病临床试验结果的异质性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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medRxiv : the preprint server for health sciences

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