Association of a multiplex immune marker panel with incident cognitive impairment and dementia: The Northern Manhattan Study

Mohammad Abdurrehman Sheikh; Michelle P Moon; Clinton B Wright; Jose Gutierrez; Minghua Liu; Tatjana Rundek; Ken Cheung; Mady Hornig; Mitchell S V Elkind

doi:10.1016/j.bbih.2024.100937

Association of a multiplex immune marker panel with incident cognitive impairment and dementia: The Northern Manhattan Study

Brain Behav Immun Health. 2024 Dec 24:43:100937. doi: 10.1016/j.bbih.2024.100937. eCollection 2025 Feb.

Authors

Mohammad Abdurrehman Sheikh¹, Michelle P Moon², Clinton B Wright³, Jose Gutierrez², Minghua Liu², Tatjana Rundek⁴, Ken Cheung⁵, Mady Hornig⁶, Mitchell S V Elkind^{2

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Affiliations

¹ Department of Neurology, Louisiana State University Health Sciences Center at Shreveport, Shreveport, LA, USA.
² Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
³ National Institute of Neurological Disorders and Stroke, USA.
⁴ Departments of Neurology, Epidemiology, and Human Genetics, University of Miami, Miami, FL, USA.
⁵ Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY, USA.
⁶ Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.

Abstract

Objective: To determine whether a panel of immune markers adds significant information to known correlates of risk of dementia and cognitive impairment.

Background: The impact of immune mechanisms on dementia risk is incompletely characterized.

Design/methods: A subsample of the Northern Manhattan Study, a prospective cohort study in the racially/ethnically diverse population of New York City, underwent comprehensive neuropsychological testing up to three times, at approximately 5-year intervals. Cognitive outcomes were adjudicated as no cognitive impairment, mild cognitive impairment (MCI), or dementia. Immune markers were assessed using a multiplex immunoassay on plasma samples collected at the time of the first neuropsychological test. Least absolute shrinkage and selection operator (LASSO) techniques were employed to yield a panel of immune markers linearly related to the outcome of dementia/MCI vs. no cognitive impairment. Nested logistic regression models were run to determine the independent association of the immune marker panel with dementia/MCI after adjusting for other predictors of risk.

Results: Among 1179 participants (mean age 70.0 ± 8.9 years, 60% women, 68% Hispanic), immune markers improved model fit above demographic and vascular risk factors (p-value for likelihood ratio test <0.0001) as correlates of MCI/dementia. Individual immune markers found to be associated with dementia/MCI were C-X-C Motif Chemokine Ligand 9 (CXCL9) and C-C Motif Chemokine Ligand 2 (CCL2). The effect of the immune markers was comparable to traditional risk factors, with CCL2 (per SD) having almost the same effect as 1 year of aging and CXCL9 (per SD) showing approximately twice this magnitude.

Conclusion: Immune markers are associated with cognitive decline and dementia outcomes in a multi-ethnic cohort. More work is needed to further characterize these associations and determine therapeutic strategies. (Funded by the National Institute of Health/National Institute of Neurological Disorders and Stroke; grant number R01 29993 (Sacco/Elkind)).

Keywords: Dementia; Epidemiology; Inflammation; Mild cognitive impairment.