Dataset Information

Single-cell transcriptomics analysis of mild cognitive impairment in World Trade Center disaster responders.

ABSTRACT:

Introduction

Recent research has found that World Trade Center (WTC) responders in their mid-50s have an elevated prevalence of mild cognitive impairment (MCI) that is associated with neural degeneration and subcortical thinning. This article extends our understanding of the molecular complexity of MCI through gene expression profiling of blood.

Methods

The transcriptomics of 40 male WTC responders were profiled across two cohorts (discovery: nine MCI and nine controls; replication: 11 MCI and 11 controls) using CITE-Seq at single-cell resolution in blood.

Results

Comparing the transcriptomic signatures across seven major cell subpopulations, the largest differences were observed in monocytes in which 226 genes were differentially expressed. Pathway analysis on the genes unique to monocytes identified processes associated with cerebral immune response.

Discussion

Our findings suggested monocytes may constitute a key cell type to target in blood-based biomarker studies for early detection of risk of MCI and development of new interventions.

SUBMITTER: Kuan PF

PROVIDER: S-EPMC7896635 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Single-cell transcriptomics analysis of mild cognitive impairment in World Trade Center disaster responders.

Kuan Pei-Fen PF Clouston Sean S Yang Xiaohua X Che Chang C Gandy Samuel S Kotov Roman R Bromet Evelyn E Luft Benjamin J BJ

Alzheimer's & dementia (Amsterdam, Netherlands) 20210220 1

<h4>Introduction</h4>Recent research has found that World Trade Center (WTC) responders in their mid-50s have an elevated prevalence of mild cognitive impairment (MCI) that is associated with neural degeneration and subcortical thinning. This article extends our understanding of the molecular complexity of MCI through gene expression profiling of blood.<h4>Methods</h4>The transcriptomics of 40 male WTC responders were profiled across two cohorts (discovery: nine MCI and nine controls; replicatio ...[more]

PMID: 33665344

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Project description:BackgroundThe emergency personnel who responded to the World Trade Center (WTC) attacks endured severe occupational exposures, yet the prevalence of cognitive impairment remains unknown among WTC-exposed-FDNY-responders. The present study screened for mild and severe cognitive impairment in WTC-exposed FDNY responders using objective tests, compared prevalence rates to a cohort of non-FDNY WTC-exposed responders, and descriptively to meta-analytic estimates of MCI from global, community, and clinical populations.MethodsA sample of WTC-exposed-FDNY responders (n = 343) was recruited to complete an extensive battery of cognitive, psychological, and physical tests. The prevalences of domain-specific impairments were estimated based on the results of norm-referenced tests, and the Montreal Cognitive Assessment (MoCA), Jak/Bondi criteria, Petersen criteria, and the National Institute on Aging and Alzheimer's Association (NIA-AA) criteria were used to diagnose MCI. NIA-AA criteria were also used to diagnose severe cognitive impairment. Generalized linear models were used to compare prevalence estimates of cognitive impairment to a large sample of WTC-exposed-non-FDNY responders from the General Responder Cohort (GRC; n = 7102) who completed the MoCA during a similar time frame.ResultAmong FDNY responders under 65 years, the unadjusted prevalence of MCI varied from 52.57% to 71.37% depending on the operational definition of MCI, apart from using a conservative cut-off applied to MoCA total scores (18 < MoCA < 23), which yielded a markedly lower crude prevalence (24.31%) compared to alternative criteria. The prevalence of MCI was higher among WTC-exposed-FDNY-responders, compared to WTC-exposed-non-FDNY-GRC-responders (adjusted RR = 1.53, 95% C.I. = [1.24, 1.88], p < .001) and meta-analytic estimates from different global, community, and clinical populations. Following NIA-AA diagnostic guidelines, 4.96% of WTC-exposed-FDNY-responders met the criteria for severe impairments (95% CI = [2.91% to 7.82%]), a prevalence that remained largely unchanged after excluding responders over the age of 65 years.DiscussionThere is a high prevalence of mild and severe cognitive impairment among WTC-responders highlighting the putative role of occupational/environmental and disaster-related exposures in the etiology of accelerated cognitive decline.

Dataset Information

Single-cell transcriptomics analysis of mild cognitive impairment in World Trade Center disaster responders.

Introduction

Methods

Results

Discussion

Publications

Single-cell transcriptomics analysis of mild cognitive impairment in World Trade Center disaster responders.

Similar Datasets

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