Plasma Amyloid Beta 40/42, Phosphorylated Tau 181, and Neurofilament Light Are Associated with Cognitive Impairment and Neuropathological Changes Among World Trade Center Responders: A Prospective Cohort Study of Exposures and Cognitive Aging at Midl

Details

• Personal Author:
  Bennett DA ; Bromet EJ ; Carr MA ; Clouston SAP ; Diminich ED ; Finch CE ; Gandy SE ; Kotov R ; Kritikos M ; Kuan P-F ; Luft BJ ; Meliker J ; Mielke M ; Yang X
• Description:
  Introduction: World Trade Center (WTC) responders are experiencing a high risk of mild cognitive impairment (MCI) and dementia, though the etiology remains inadequately characterized. This study investigated whether WTC exposures and chronic post-traumatic stress disorder (PTSD) were correlated with plasma biomarkers characteristic of Alzheimer's disease (AD) neuropathology. Methods: Eligible participants included WTC-exposed individuals with a baseline cognitive assessment and available plasma sample. We examined levels of the amyloid beta (Aß)40/42 ratio, phosphorylated tau 181 (p-tau181), and neurofilament light chain (NfL) and associations with a WTC exposures (duration on site ≥15 weeks, dust cloud), the PTSD Symptom Checklist for Diagnostic and Statistical Manual of Mental Disorders, 4th edition PTSD, and classification of amyloid/tau/neurodegeneration (AT[N]) profiles. Multinomial logistic regressions assessed whether biomarkers predicted increased risk of MCI or dementia. Results: Of 1179 eligible responders, 93.0% were male, mean (standard deviation) age 56.6 years (7.8). Aß40/42, p-tau181, and NfL intercorrelated and increased with age. In subgroup analyses of responders with available neuroimaging data (n = 75), Aß40/42 and p-tau181 were further associated with decreased hippocampal volume (Spearman's p = -0.3). Overall, 58.08% of responders with dementia had ≥1 elevated biomarker, and 3.45% had elevations across all biomarkers. In total, 248 (21.05%) had MCI and 70 (5.94%) had dementia. Increased risk of dementia was associated with plasma AT(N) profile T+ or A+N+. Exposure on site ≥15 weeks was independently associated with T+ (adjusted risk ratio [aRR] = 1.03 [1.01-1.05], P = 0.009), and T+N+ profile (aRR = 2.34 [1.12-4.87]). The presence of PTSD was independently associated with risk of A+ (aRR = 1.77 [1.11-2.82]). Discussion: WTC exposures and chronic PTSD are associated with plasma biomarkers consistent with neurodegenerative disease. [Description provided by NIOSH]
• Subjects:
  Aging Biomarkers Cohort Studies Nervous System Occupational Health Safety September 11 Terrorist Attacks
• Keywords:
  Cognitive Function Cohort Studies Neuropathology Post-traumatic Stress Disorder PTSD World Trade Center WTC
• ISSN:
  2352-8729
• Document Type:
  Text
• Funding:
  Contract
• Genre:
  Journal Article
• Place as Subject:
  California ; Illinois ; New York ; North Carolina ; OSHA Region 2 ; OSHA Region 4 ; OSHA Region 5 ; OSHA Region 9
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  15
• Issue:
  1
• NIOSHTIC Number:
  nn:20067690
• Citation:
  Alzheimers Dement Diagn Assess Dis Monit 2023 Jan-Mar; 15(1):e12409
• Contact Point Address:
  Sean A. P. Clouston, Program in Public Health, 101 Nichols Rd., Health Sciences Center, #3-071, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY 11794, USA
• Email:
  sean.clouston@stonybrookmedicine.edu
• Federal Fiscal Year:
  2023
• Peer Reviewed:
  True
• Source Full Name:
  Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:321101b92ed8e63959c1a959f7e59b72a6dae10add1a3ded8b31e52ffb02e35c696f87685757ab108390d49f4fe83bfce419876e091910e0f07a7fb53dd77d03
• Download URL:
  https://stacks.cdc.gov/view/cdc/229954/cdc_229954_DS1.pdf
• File Type:
  [PDF - 438.05 KB ]