Peripheral immune markers in dementia: A systematic review and meta-analysis of risk, severity, and pathological correlates.

IF 7.4 Q1 CLINICAL NEUROLOGY

Alzheimer''s and Dementia: Translational Research and Clinical Interventions Pub Date : 2026-06-01 eCollection Date: 2026-04-01 DOI:10.1002/trc2.70270

Ahmad A Toubasi, Thuraya N Al-Sayegh

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引用次数: 0

Abstract

Introduction: Systemic inflammation and innate immune activation have been implicated in dementia; however, prior studies were limited by small sample sizes. We conducted this study to evaluate the association between peripheral immune markers and the future risk of mild cognitive impairment (MCI) and dementia, their ability to differentiate between dementia causes, and their correlation with disease severity and pathological biomarkers.

Methods: On September 8, 2025, we searched PubMed, Embase, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL). Eligible articles included cohort and case-control studies assessing the association between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), or systemic inflammatory index (SII) and the risk of developing MCI or dementia, as well as their association with disease severity and pathological biomarkers. Outcomes were the risk of MCI and dementia (Alzheimer's disease, vascular dementia, and Parkinson's disease dementia), dementia severity assessed by the Mini-Mental State Examination, and cerebrospinal fluid or pathological markers including amyloid beta (Aβ)42, Aβ40, and tau. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled as effect estimates.

Results: Our analysis included 947,020 participants from 23 studies. NLR and SII, but not PLR, were associated with increased risk of dementia (NLR: HR = 1.24, 95% CI: 1.15-1.34; SII: HR = 1.08, 95% CI: 1.03-1.13) and MCI (NLR: HR = 2.78, 95% CI: 1.57-4.90; SII: HR = 1.28, 95% CI: 1.04-1.56). No differential associations were observed across dementia causes. NLR and SII were correlated with worse dementia (NLR: r = -0.22, p = 0.033; SII: r = -0.17, p = 0.041) and MCI severity (NLR: r = -0.30, p = 0.010; SII: r = -0.23, p = 0.025). NLR, but not SII, was associated with Aβ42, Aβ40, and tau.

Discussion: NLR and SII may provide valuable insights when advanced biomarker testing is limited by technological or financial barriers.

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痴呆的外周免疫标志物：风险、严重程度和病理相关性的系统回顾和荟萃分析。

全身性炎症和先天免疫激活与痴呆有关；然而，先前的研究受到样本量小的限制。我们进行了这项研究，以评估外周免疫标志物与轻度认知障碍（MCI）和痴呆的未来风险之间的关系，它们区分痴呆原因的能力，以及它们与疾病严重程度和病理生物标志物的相关性。方法：我们于2025年9月8日检索PubMed、Embase、Scopus和Cochrane Central Register of Controlled Trials （Central）。符合条件的文章包括队列和病例对照研究，评估中性粒细胞与淋巴细胞比率（NLR）、血小板与淋巴细胞比率（PLR）或全身炎症指数（SII）与发生MCI或痴呆的风险之间的关系，以及它们与疾病严重程度和病理生物标志物的关系。结果是MCI和痴呆（阿尔茨海默病、血管性痴呆和帕金森病痴呆）的风险，通过迷你精神状态检查评估的痴呆严重程度，以及脑脊液或病理标志物，包括淀粉样蛋白β (Aβ)42、Aβ40和tau。合并风险比（hr）和95%置信区间（ci）作为效果估计。结果：我们的分析包括来自23项研究的947,020名参与者。NLR和SII，但与PLR无关，与痴呆（NLR: HR = 1.24, 95% CI: 1.15-1.34; SII: HR = 1.08, 95% CI: 1.03-1.13）和MCI （NLR: HR = 2.78, 95% CI: 1.57-4.90; SII: HR = 1.28, 95% CI: 1.04-1.56）的风险增加相关。在不同的痴呆原因中没有观察到差异关联。NLR和SII与痴呆加重（NLR: r = -0.22, p = 0.033; SII: r = -0.17, p = 0.041）和MCI严重程度（NLR: r = -0.30, p = 0.010; SII: r = -0.23, p = 0.025）相关。NLR与Aβ42、Aβ40和tau相关，而与SII无关。讨论：NLR和SII可能提供有价值的见解，当先进的生物标志物检测受到技术或财务障碍的限制。

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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来源期刊

Alzheimer''s and Dementia: Translational Research and Clinical Interventions Medicine-Psychiatry and Mental Health

CiteScore

10.10

自引率

2.10%

发文量

134

审稿时长

10 weeks

期刊介绍： Alzheimer''s & Dementia: Translational Research & Clinical Interventions (TRCI) is a peer-reviewed, open access,journal from the Alzheimer''s Association®. The journal seeks to bridge the full scope of explorations between basic research on drug discovery and clinical studies, validating putative therapies for aging-related chronic brain conditions that affect cognition, motor functions, and other behavioral or clinical symptoms associated with all forms dementia and Alzheimer''s disease. The journal will publish findings from diverse domains of research and disciplines to accelerate the conversion of abstract facts into practical knowledge: specifically, to translate what is learned at the bench into bedside applications. The journal seeks to publish articles that go beyond a singular emphasis on either basic drug discovery research or clinical research. Rather, an important theme of articles will be the linkages between and among the various discrete steps in the complex continuum of therapy development. For rapid communication among a multidisciplinary research audience involving the range of therapeutic interventions, TRCI will consider only original contributions that include feature length research articles, systematic reviews, meta-analyses, brief reports, narrative reviews, commentaries, letters, perspectives, and research news that would advance wide range of interventions to ameliorate symptoms or alter the progression of chronic neurocognitive disorders such as dementia and Alzheimer''s disease. The journal will publish on topics related to medicine, geriatrics, neuroscience, neurophysiology, neurology, psychiatry, clinical psychology, bioinformatics, pharmaco-genetics, regulatory issues, health economics, pharmacoeconomics, and public health policy as these apply to preclinical and clinical research on therapeutics.