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Cognitive impairment and World Trade Centre-related exposures

Nature Reviews Neurology volume 18, pages 103–116 (2022)Cite this article

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Abstract

On 11 September 2001 the World Trade Center (WTC) in New York was attacked by terrorists, causing the collapse of multiple buildings including the iconic 110-story ‘Twin Towers’. Thousands of people died that day from the collapse of the buildings, fires, falling from the buildings, falling debris, or other related accidents. Survivors of the attacks, those who worked in search and rescue during and after the buildings collapsed, and those working in recovery and clean-up operations were exposed to severe psychological stressors. Concurrently, these ‘WTC-affected’ individuals breathed and ingested a mixture of organic and particulate neurotoxins and pro-inflammogens generated as a result of the attack and building collapse. Twenty years later, researchers have documented neurocognitive and motor dysfunctions that resemble the typical features of neurodegenerative disease in some WTC responders at midlife. Cortical atrophy, which usually manifests later in life, has also been observed in this population. Evidence indicates that neurocognitive symptoms and corresponding brain atrophy are associated with both physical exposures at the WTC and chronic post-traumatic stress disorder, including regularly re-experiencing traumatic memories of the events while awake or during sleep. Despite these findings, little is understood about the long-term effects of these physical and mental exposures on the brain health of WTC-affected individuals, and the potential for neurocognitive disorders. Here, we review the existing evidence concerning neurological outcomes in WTC-affected individuals, with the aim of contextualizing this research for policymakers, researchers and clinicians and educating WTC-affected individuals and their friends and families. We conclude by providing a rationale and recommendations for monitoring the neurological health of WTC-affected individuals.

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Fig. 1: WTC-related exposures and their potential routes to the brain.
Fig. 2: Theoretical mechanisms linking exposure to WTC activities and cognitive symptoms.
Fig. 3: Cortical atrophy in cognitively impaired WTC responders.
Fig. 4: WTC responder cortical thickness change from normative data.

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References

  1. Ground Zero stops burning, after 100 days. Guardian (Lond.) https://www.theguardian.com/world/2001/dec/20/september11.usa (2001).

  2. Plumer, B. Nine facts about terrorism in the United States since 9/11. Washington Post https://www.washingtonpost.com/news/wonk/wp/2013/09/11/nine-facts-about-terrorism-in-the-united-states-since-911/ (2013).

  3. September 11 terror attacks fast facts. CNN https://www.cnn.com/2013/07/27/us/september-11-anniversary-fast-facts/ (2020).

  4. Dahlgren, J., Cecchini, M., Takhar, H. & Paepke, O. Persistent organic pollutants in 9/11 World Trade Center rescue workers: reduction following detoxification. Chemosphere 69, 1320–1325 (2007).

    Article  CAS  PubMed  Google Scholar 

  5. Lippmann, M., Cohen, M. D. & Chen, L. C. Health effects of World Trade Center (WTC) dust: an unprecedented disaster’s inadequate risk management. Crit. Rev. Toxicol. 45, 492–530 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Toom, V. Whose body is it? Technolegal materialization of victims’ bodies and remains after the World Trade Center terrorist attacks. Sci. Technol. Hum. Values 41, 686–708 (2015).

    Article  Google Scholar 

  7. Lioy, P. J. et al. Characterization of the dust/smoke aerosol that settled east of the World Trade Center (WTC) in lower Manhattan after the collapse of the WTC 11 September 2001. Env. Health Perspect. 110, 703–714 (2002).

    Article  CAS  Google Scholar 

  8. Kahn, L. G. et al. Adolescents exposed to the World Trade Center collapse have elevated serum dioxin and furan concentrations more than 12 years later. Env. Int. 111, 268–278 (2018).

    Article  CAS  Google Scholar 

  9. Dick, F. D. Solvent neurotoxicity. Occup. Env. Med. 63, 221–226, 179 (2006).

    Article  CAS  Google Scholar 

  10. Rao, D. B., Jortner, B. S. & Sills, R. C. Animal models of peripheral neuropathy due to environmental toxicants. ILAR J. 54, 315–323 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Wilkenfeld, M., Fazzari, M., Segelnick, J. & Stecker, M. Neuropathic symptoms in World Trade Center disaster survivors and responders. J. Occup. Env. Med. 58, 83–86 (2016).

    Article  Google Scholar 

  12. Marmor, M. et al. Paresthesias among community members exposed to the World Trade Center disaster. J. Occup. Env. Med. 59, 389–396 (2017).

    Article  CAS  Google Scholar 

  13. Thawani, S., Wang, B., Shao, Y., Reibman, J. & Marmor, M. Time to onset of paresthesia among community members exposed to the World Trade Center disaster. Int. J. Env. Res. Public. Health 16, 1429 (2019).

    Article  CAS  Google Scholar 

  14. Colbeth, H. L. et al. Post-9/11 peripheral neuropathy symptoms among World Trade Center-exposed firefighters and emergency medical service workers. Int. J. Environ. Res. Public Health 16, 1727 (2019).

    Article  PubMed Central  Google Scholar 

  15. Galea, S. et al. Psychological sequelae of the September 11 terrorist attacks in New York City. N. Engl. J. Med. 346, 982–987 (2002).

    Article  PubMed  Google Scholar 

  16. Diagnostic and Statistical Manual of Mental Disorders: DSM-5 5th edn (American Psychiatric Association, 2013).

  17. Liu, B., Tarigan, L. H., Bromet, E. J. & Kim, H. World Trade Center disaster exposure-related probable posttraumatic stress disorder among responders and civilians: a meta-analysis. PLoS ONE 9, e101491 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  18. Stern, Y. et al. Whitepaper: Defining and investigating cognitive reserve, brain reserve, and brain maintenance. Alzheimers Dement. 16, 1305–1311 (2020).

    Article  PubMed  Google Scholar 

  19. Spiro, A. III, Schnurr, P. P. & Aldwin, C. M. Combat-related posttraumatic stress disorder symptoms in older men. Psychol. Aging 9, 17–26 (1994).

    Article  PubMed  Google Scholar 

  20. Haghani, A., Morgan, T. E., Forman, H. J. & Finch, C. E. Air pollution neurotoxicity in the adult brain: emerging concepts from experimental findings. J. Alzheimers Dis. 76, 773–797 (2020).

    Article  PubMed  Google Scholar 

  21. Lucchini, R. G. et al. Neurofunctional dopaminergic impairment in elderly after lifetime exposure to manganese. Neurotoxicology 45, 309–317 (2014).

    Article  CAS  PubMed  Google Scholar 

  22. Lucchini, R. G., Dorman, D. C., Elder, A. & Veronesi, B. Neurological impacts from inhalation of pollutants and the nose–brain connection. Neurotoxicology 33, 838–841 (2012).

    Article  CAS  PubMed  Google Scholar 

  23. Landrigan, P. J. et al. Health and environmental consequences of the World Trade Center disaster. Env. Health Perspect. 112, 731–739 (2004).

    Article  CAS  Google Scholar 

  24. Forman, H. J. & Finch, C. E. A critical review of assays for hazardous components of air pollution. Free Radic. Biol. Med. 117, 202–217 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Riediker, M. et al. Particle toxicology and health — where are we? Part. Fibre Toxicol. 16, 19 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  26. Mumaw, C. L. et al. Microglial priming through the lung–brain axis: the role of air pollution-induced circulating factors. FASEB J. 30, 1880–1891 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Zeliger, H. I. Exposure to lipophilic chemicals as a cause of neurological impairments, neurodevelopmental disorders and neurodegenerative diseases. Interdiscip. Toxicol. 6, 103–110 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  28. Best, E. A. et al. Biomarkers of exposure to polycyclic aromatic hydrocarbons and cognitive function among elderly in the United States (National Health and Nutrition Examination Survey: 2001–2002). PLoS ONE 11, e0147632 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  29. Jedrychowski, W. A. et al. Prenatal exposure to polycyclic aromatic hydrocarbons and cognitive dysfunction in children. Env. Sci. Pollut. Res. Int. 22, 3631–3639 (2015).

    Article  CAS  Google Scholar 

  30. Peterson, B. S. et al. Effects of prenatal exposure to air pollutants (polycyclic aromatic hydrocarbons) on the development of brain white matter, cognition, and behavior in later childhood. JAMA Psychiat. 72, 531–540 (2015).

    Article  Google Scholar 

  31. Perera, F. P. et al. Prenatal airborne polycyclic aromatic hydrocarbon exposure and child IQ at age 5 years. Pediatrics 124, e195–e202 (2009).

    Article  PubMed  Google Scholar 

  32. Perera, F. P. et al. Early-life exposure to polycyclic aromatic hydrocarbons and ADHD behavior problems. PLoS ONE 9, e111670 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  33. Bromet, E. et al. DSM-IV post-traumatic stress disorder among World Trade Center responders 11–13 years after the disaster of 11 September 2001 (9/11). Psychol. Med. 46, 771–783 (2016).

    Article  CAS  PubMed  Google Scholar 

  34. Hall, K. S., Hoerster, K. D. & Yancy, W. S. Jr Post-traumatic stress disorder, physical activity, and eating behaviors. Epidemiol. Rev. 37, 103–115 (2015).

    Article  PubMed  Google Scholar 

  35. Bonanno, G. A. Resilience in the face of potential trauma. Curr. Dir. Psychol. Sci. 14, 135–138 (2005).

    Article  Google Scholar 

  36. Kornfield, S. L., Klaus, J., McKay, C., Helstrom, A. & Oslin, D. Subsyndromal posttraumatic stress disorder symptomatology in primary care military veterans: treatment implications. Psychol. Serv. 9, 383–389 (2012).

    Article  PubMed  Google Scholar 

  37. Shelby, R. A., Golden-Kreutz, D. M. & Andersen, B. L. PTSD diagnoses, subsyndromal symptoms, and comorbidities contribute to impairments for breast cancer survivors. J. Trauma. Stress. 21, 165–172 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  38. Wallace, D., Moss, A. S. & Hodges, S. Sub-syndromal PTSD: what is important to know in military personnel and veterans? Australas. Psychiat. 28, 254–256 (2019).

    Article  Google Scholar 

  39. Pietrzak, R. H., Goldstein, M. B., Malley, J. C., Johnson, D. C. & Southwick, S. M. Subsyndromal posttraumatic stress disorder is associated with health and psychosocial difficulties in veterans of operations Enduring Freedom and Iraqi Freedom. Depress. Anxiety 26, 739–744 (2009).

    Article  PubMed  Google Scholar 

  40. Abdallah, C. G. et al. The neurobiology and pharmacotherapy of posttraumatic stress disorder. Annu. Rev. Pharmacol. Toxicol. 59, 171–189 (2019).

    Article  CAS  PubMed  Google Scholar 

  41. Sherin, J. E. & Nemeroff, C. B. Post-traumatic stress disorder: the neurobiological impact of psychological trauma. Dialogues Clin. Neurosci. 13, 263–278 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  42. Pitman, R. K. et al. Biological studies of post-traumatic stress disorder. Nat. Rev. Neurosci. 13, 769–787 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Malikowska-Racia, N. & Salat, K. Recent advances in the neurobiology of posttraumatic stress disorder: a review of possible mechanisms underlying an effective pharmacotherapy. Pharmacol. Res. 142, 30–49 (2019).

    Article  PubMed  Google Scholar 

  44. Livingston, G. et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet 396, 413–446 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  45. Chen, J. C. et al. Ambient air pollution and neurotoxicity on brain structure: evidence from Women’s Health Initiative Memory Study. Ann. Neurol. 78, 466–476 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  46. Ailshire, J. A. & Clarke, P. Fine particulate matter air pollution and cognitive function among U.S. older adults. J. Gerontol. B 70, 322–328 (2015).

    Article  Google Scholar 

  47. Gatto, N. M. et al. Components of air pollution and cognitive function in middle-aged and older adults in Los Angeles. Neurotoxicology 40, 1–7 (2014).

    Article  CAS  PubMed  Google Scholar 

  48. Gonzalez-Maciel, A., Reynoso-Robles, R., Torres-Jardon, R., Mukherjee, P. S. & Calderon-Garciduenas, L. Combustion-derived nanoparticles in key brain target cells and organelles in young urbanites: culprit hidden in plain sight in Alzheimer’s disease development. J. Alzheimers Dis. 59, 189–208 (2017).

    Article  CAS  PubMed  Google Scholar 

  49. Wilker, E. H. et al. Long-term exposure to fine particulate matter, residential proximity to major roads and measures of brain structure. Stroke 46, 1161–1166 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Wallin, C. et al. Alzheimer’s disease and cigarette smoke components: effects of nicotine, PAHs, and Cd(II), Cr(III), Pb(II), Pb(IV) ions on amyloid-beta peptide aggregation. Sci. Rep. 7, 14423 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  51. Shaffer, R. M. et al. Fine particulate matter exposure and cerebrospinal fluid markers of vascular injury. J. Alzheimers Dis. 71, 1015–1025 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Campbell, A. et al. Particulate matter in polluted air may increase biomarkers of inflammation in mouse brain. Neurotoxicology 26, 133–140 (2005).

    Article  CAS  PubMed  Google Scholar 

  53. Cacciottolo, M. et al. Traffic-related air pollutants (TRAP-PM) promote neuronal amyloidogenesis through oxidative damage to lipid rafts. Free Radic. Biol. Med. 147, 242–251 (2020).

    Article  CAS  PubMed  Google Scholar 

  54. Justice, N. J. et al. Posttraumatic stress disorder-like induction elevates β-amyloid levels, which directly activates corticotropin-releasing factor neurons to exacerbate stress responses. J. Neurosci. 35, 2612–2623 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  55. Filiano, A. J., Gadani, S. P. & Kipnis, J. Interactions of innate and adaptive immunity in brain development and function. Brain Res. 1617, 18–27 (2015).

    Article  CAS  PubMed  Google Scholar 

  56. Andrews, J. A. & Neises, K. D. Cells, biomarkers, and post-traumatic stress disorder: evidence for peripheral involvement in a central disease. J. Neurochem. 120, 26–36 (2012).

    Article  CAS  PubMed  Google Scholar 

  57. Glaser, R. & Kiecolt-Glaser, J. K. Stress-induced immune dysfunction: implications for health. Nat. Rev. Immunol. 5, 243–251 (2005).

    Article  CAS  PubMed  Google Scholar 

  58. Kuan, P. F. et al. Cell type-specific gene expression patterns associated with posttraumatic stress disorder in World Trade Center responders. Transl. Psychiat. 9, 1 (2019).

    Article  CAS  Google Scholar 

  59. Deslauriers, J., Powell, S. & Risbrough, V. B. Immune signaling mechanisms of PTSD risk and symptom development: insights from animal models. Curr. Opin. Behav. Sci. 14, 123–132 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  60. Felmingham, K. et al. Duration of posttraumatic stress disorder predicts hippocampal grey matter loss. Neuroreport 20, 1402–1406 (2009).

    Article  PubMed  Google Scholar 

  61. Ousdal, O. T. et al. The association of PTSD symptom severity with amygdala nuclei volumes in traumatized youths. Translat. Psychiat. 10, 1–10 (2020).

    Article  Google Scholar 

  62. Yehuda, R. Advances in understanding neuroendocrine alterations in PTSD and their therapeutic implications. Ann. N. Y. Acad. Sci. 1071, 137–166 (2006).

    Article  CAS  PubMed  Google Scholar 

  63. Wingenfeld, K. & Wolf, O. T. HPA axis alterations in mental disorders: impact on memory and its relevance for therapeutic interventions. CNS Neurosci. Ther. 17, 714–722 (2011).

    Article  CAS  PubMed  Google Scholar 

  64. Yehuda, R. Post-traumatic stress disorder. N. Engl. J. Med. 346, 108–114 (2002).

    Article  CAS  PubMed  Google Scholar 

  65. Gill, J. M., Saligan, L., Woods, S. & Page, G. PTSD is associated with an excess of inflammatory immune activities. Perspect. Psychiatr. Care 45, 262–277 (2009).

    Article  PubMed  Google Scholar 

  66. Akiyama, H. et al. Cell mediators of inflammation in the Alzheimer disease brain. Alzheimer Dis. Assoc. Disord. 14, S47–S53 (2000).

    Article  CAS  PubMed  Google Scholar 

  67. Leyns, C. E. G. & Holtzman, D. M. Glial contributions to neurodegeneration in tauopathies. Mol. Neurodegener. 12, 50 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  68. Clouston, S. A. et al. Cognitive impairment among World Trade Center responders: long-term implications of re-experiencing the 9/11 terrorist attacks. Alzheimers Dement. 4, 67–75 (2016).

    Google Scholar 

  69. Alzheimer’s Disease Fact Sheet https://www.nia.nih.gov/health/alzheimers-disease-fact-sheet (National Institute on Aging, 2021)

  70. Daviglus, M. L. et al. National Institutes of Health State-of-the-Science Conference statement: preventing Alzheimer disease and cognitive decline. Ann. Intern. Med. 153, 176–181 (2010).

    Article  PubMed  Google Scholar 

  71. Clouston, S. et al. Traumatic exposures, posttraumatic stress disorder, and cognitive functioning in World Trade Center responders. Alzheimers Dement. 3, 593–602 (2017).

    Article  Google Scholar 

  72. Clouston, S. A. P. et al. Reduced cortical thickness in World Trade Center responders with cognitive impairment. Alzheimers Dement. 12, e12059 (2020).

    Google Scholar 

  73. Chen, A. P. F. et al. A deep learning approach for monitoring parietal-dominant Alzheimer’s disease in World Trade Center responders at midlife. Brain Commun. 3, fcab145 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  74. Singh, A. et al. World Trade Center exposure, post-traumatic stress disorder, and subjective cognitive concerns in a cohort of rescue/recovery workers. Acta Psychiat. Scand. 141, 275–284 (2020).

    Article  CAS  PubMed  Google Scholar 

  75. Singh, A. et al. PTSD and depressive symptoms as potential mediators of the association between World Trade Center exposure and subjective cognitive concerns in rescue/recovery workers. Int. J. Environ. Res. Public Health 17, 5683 (2020).

    Article  PubMed Central  Google Scholar 

  76. Seil, K., Yu, S. & Alper, H. A cognitive reserve and social support-focused latent class analysis to predict self-reported confusion or memory loss among middle-aged World Trade Center health registry enrollees. Int. J. Environ. Res. Public Health 16, 1401 (2019).

    Article  PubMed Central  Google Scholar 

  77. Clouston, S. A. P. et al. Incidence of mild cognitive impairment in World Trade Center responders: long-term consequences of re-experiencing the events on 9/11/2001. Alzheimers Dement. 11, 628–636 (2019).

    Google Scholar 

  78. Huang, C. et al. White matter connectivity in incident mild cognitive impairment: a diffusion spectrum imaging study of world trade center responders at midlife. J. Alzheimers Dis. 80, 1209–1219 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Deri, Y. et al. Neuroinflammation and mild cognitive impairment in World Trade Center responders at midlife: a pilot study using [18F]-FEPPA PET imaging. Brain Behav. Immun. Health 16, 100287 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  80. Mukherjee, S., Clouston, S., Kotov, R., Bromet, E. & Luft, B. Handgrip strength of World Trade Center (WTC) responders: the role of re-experiencing posttraumatic stress disorder (PTSD) symptoms. Int. J. Environ. Res. Public Health 16, 1128 (2019).

    Article  PubMed Central  Google Scholar 

  81. Clouston, S. A. P., Guralnik, J. M., Kotov, R., Bromet, E. J. & Luft, B. J. Functional limitations among responders to the World Trade Center attacks 14 years after the disaster: implications of chronic posttraumatic stress disorder. J. Trauma. Stress. 30, 443–452 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  82. Diminich, E. D. et al. Chronic posttraumatic stress disorder and comorbid cognitive and physical impairments in World Trade Center responders. J. Trauma. Stress. 34, 616–627 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  83. Massy-Westropp, N. M., Gill, T. K., Taylor, A. W., Bohannon, R. W. & Hill, C. L. Hand grip strength: age and gender stratified normative data in a population-based study. BMC Res. Notes 4, 127 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  84. Ling, C. H. et al. Handgrip strength and mortality in the oldest old population: the Leiden 85-plus study. CMAJ 182, 429–435 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  85. Taekema, D. G., Gussekloo, J., Maier, A. B., Westendorp, R. G. & de Craen, A. J. Handgrip strength as a predictor of functional, psychological and social health. A prospective population-based study among the oldest old. Age Ageing 39, 331–337 (2010).

    Article  PubMed  Google Scholar 

  86. Fukumori, N. et al. Association between hand-grip strength and depressive symptoms: locomotive syndrome and health outcomes in Aizu Cohort Study (LOHAS). Age Ageing 44, 592–598 (2015).

    Article  PubMed  Google Scholar 

  87. Lino, V. T. et al. Handgrip strength and factors associated in poor elderly assisted at a primary care unit in Rio de Janeiro, Brazil. PLoS ONE 11, e0166373 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  88. Firth, J. et al. Association between muscular strength and cognition in people with major depression or bipolar disorder and healthy controls. JAMA Psychiat. 75, 740–746 (2018).

    Article  Google Scholar 

  89. Firth, J. et al. Grip strength is associated with cognitive performance in schizophrenia and the general population: a UK Biobank study of 476559 participants. Schizophr. Bull. 44, 728–736 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  90. Ganzel, B., Casey, B., Glover, G., Voss, H. U. & Temple, E. The aftermath of 9/11: effect of intensity and recency of trauma on outcome. Emotion 7, 227 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  91. Ganzel, B. L., Kim, P., Glover, G. H. & Temple, E. Resilience after 9/11: multimodal neuroimaging evidence for stress-related change in the healthy adult brain. NeuroImage 40, 788–795 (2008).

    Article  PubMed  Google Scholar 

  92. Deri, Y. et al. Neuroinflammation in World Trade Center responders at midlife: A pilot study using [18F]-FEPPA PET imaging. Brain Behav. Immun. Health 16, 100287 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  93. Deri, Y. et al. Selective hippocampal subfield volume reductions in World Trade Center responders with cognitive impairment. Alzheimer’s & dementia: diagnosis. Assess. Dis. Monit. 13, e12165 (2021).

    Google Scholar 

  94. Potvin, O., Dieumegarde, L., Duchesne, S. & Initiative, A. S. D. N. Normative morphometric data for cerebral cortical areas over the lifetime of the adult human brain. Neuroimage 156, 315–339 (2017).

    Article  PubMed  Google Scholar 

  95. Clouston, S. A. P. et al. A cortical thinning signature to identify World Trade Center responders with possible dementia. Intelligence-based Medicine 5, 100032 (2021).

    Article  Google Scholar 

  96. Aldrich, T. K. et al. Lung function in rescue workers at the World Trade Center after 7 years. N. Engl. J. Med. 362, 1263–1272 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Rosen, R. L. et al. Elevated C-reactive protein and posttraumatic stress pathology among survivors of the 9/11 World Trade Center attacks. J. Psychiatr. Res. 89, 14–21 (2017).

    Article  PubMed  Google Scholar 

  98. Bello, G. A. et al. Development of a physiological frailty index for the World Trade Center general responder cohort. Curr. Gerontol. Geriatr. Res. 2018, 3725926 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  99. Clouston, S. A., Edelman, N. H., Aviv, A., Stewart, C. & Luft, B. J. Shortened leukocyte telomere length is associated with reduced pulmonary function and greater subsequent decline in function in a sample of World Trade Center responders. Sci. Rep. 9, 8148 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  100. Kuan, P. F. et al. Gene expression associated with PTSD in World Trade Center responders: an RNA sequencing study. Transl. Psychiat. 7, 1297 (2017).

    Article  Google Scholar 

  101. Kuan, P.-F. et al. Molecular linkage between post-traumatic stress disorder and cognitive impairment: a targeted proteomics study of World Trade Center responders. Transl. Psychiat. 10, 269 (2020).

    Article  CAS  Google Scholar 

  102. Jack, C. R. Jr. et al. NIA-AA Research Framework: toward a biological definition of Alzheimer’s disease. Alzheimers Dement. 14, 535–562 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  103. Albert, M. S. et al. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging–Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 7, 270–279 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  104. McKhann, G. M. et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging–Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 7, 263–269 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  105. Ismail, Z. et al. The Mild Behavioral Impairment Checklist (MBI-C): a rating scale for neuropsychiatric symptoms in pre-dementia populations. J. Alzheimers Dis. 56, 929–938 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  106. Zammit, A. R. et al. A coordinated multi-study analysis of the longitudinal association between handgrip strength and cognitive function in older adults. J. Gerontol. B 76, 229–241 (2021).

    Article  Google Scholar 

  107. Duggan, E. C. et al. A multi-study coordinated meta-analysis of pulmonary function and cognition in aging. J. Gerontol. A. 74, 1793–1804 (2019).

    Article  Google Scholar 

  108. Association, A. S. 2019 Alzheimer’s disease facts and figures. Alzheimers Dement. 15, 321–387 (2019).

    Article  Google Scholar 

  109. Gorelick, P. B. et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 42, 2672–2713 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  110. Lim, E. W. et al. Amyloid-β and Parkinson’s disease. J. Neurol. 266, 2605–2619 (2019).

    Article  CAS  PubMed  Google Scholar 

  111. Chin, K. S., Yassi, N., Churilov, L., Masters, C. L. & Watson, R. Prevalence and clinical associations of tau in Lewy body dementias: a systematic review and meta-analysis. Parkinsonism Relat. Disord. 80, 184–193 (2020).

    Article  PubMed  Google Scholar 

  112. Crary, J. F. et al. Primary age-related tauopathy (PART): a common pathology associated with human aging. Acta Neuropathol. 128, 755–766 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Jack, C. R. Jr. et al. Suspected non-Alzheimer disease pathophysiology — concept and controversy. Nat. Rev. Neurol. 12, 117–124 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Power, M. C. et al. Combined neuropathological pathways account for age-related risk of dementia. Ann. Neurol. 84, 10–22 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Jack, C. R. Jr. et al. Tracking pathophysiological processes in Alzheimer’s disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol. 12, 207–216 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Bäckman, L., Jones, S., Berger, A.-K., Laukka, E. J. & Small, B. J. Cognitive impairment in preclinical Alzheimer’s disease: a meta-analysis. Neuropsychology 19, 520 (2005).

    Article  PubMed  Google Scholar 

  117. Li, G. et al. Cerebrospinal fluid biomarkers for Alzheimer’s and vascular disease vary by age, gender, and APOE genotype in cognitively normal adults. Alzheimers Res. Ther. 9, 48 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Petersen, R. Mild cognitive impairment: transition between aging and Alzheimer’s disease. Neurologia 15, 93–101 (2000).

    CAS  PubMed  Google Scholar 

  119. Bondi, M. W. et al. Neuropsychological criteria for mild cognitive impairment improves diagnostic precision, biomarker associations, and progression rates. J. Alzheimers Dis. 42, 275–289 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  120. Lopez, O. L., Becker, J. T. & Sweet, R. A. Non-cognitive symptoms in mild cognitive impairment subjects. Neurocase 11, 65–71 (2005).

    Article  PubMed  Google Scholar 

  121. Martin, E. & Velayudhan, L. Neuropsychiatric symptoms in mild cognitive impairment: a literature review. Dement. Geriatr. Cogn. Disord. 49, 146–155 (2020).

    Article  PubMed  Google Scholar 

  122. Roberto, N. et al. Neuropsychiatric profiles and conversion to dementia in mild cognitive impairment, a latent class analysis. Sci. Rep. 11, 6448 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. US Preventive Services Task Force. Screening for cognitive impairment in older adults: US Preventive Services Task Force recommendation statement. JAMA 323, 757–763 (2020).

    Article  Google Scholar 

  124. Liss, J. L. et al. Practical recommendations for timely, accurate diagnosis of symptomatic Alzheimer’s disease (MCI and dementia) in primary care: a review and synthesis. J. Intern. Med. 290, 310–334 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Sliwinski, M. J. et al. Reliability and validity of ambulatory cognitive assessments. Assessment 25, 14–30 (2018).

    Article  PubMed  Google Scholar 

  126. Luis, C. A., Keegan, A. P. & Mullan, M. Cross validation of the Montreal Cognitive Assessment in community dwelling older adults residing in the southeastern US. Int. J. Geriatr. Psychiat. 24, 197–201 (2009).

    Article  Google Scholar 

  127. Wittich, W., Phillips, N., Nasreddine, Z. S. & Chertkow, H. Sensitivity and specificity of the Montreal Cognitive Assessment modified for individuals who are visually impaired. J. Vis. Impair. Blind. 104, 360–368 (2010).

    Article  Google Scholar 

  128. Deri, Y. et al. Selective hippocampal subfield volume reductions in World Trade Center responders with cognitive impairment. Alzheimers Dement. 13, e12165 (2021).

    Google Scholar 

  129. Chen, A. P. F. et al. A deep learning approach for monitoring parietal-dominant Alzheimer’s disease in World Trade Center responders at midlife. Brain Commun. 3, fcab145 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  130. Yoncheva, Y. N. et al. Computerized cognitive training for children with neurofibromatosis type 1 (NF1): a pilot study. Psychiat. Res. Neuroimag. 266, 53–78 (2017).

    Article  Google Scholar 

  131. Stricker, N. H. et al. Longitudinal comparison of in clinic and at home administration of the Cogstate Brief Battery and demonstrated practice effects in the Mayo Clinic Study Of Aging. J. Prev. Alzheimers Dis. 7, 21–28 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  132. Sanderson, W. C. & Scherbov, S. Measuring the speed of aging across population subgroups. PLoS ONE 9, e96289 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  133. Clouston, S. et al. Posttraumatic stress-related cognitive and physical impairment: clinical characterization of a novel disorder. J. Trauma. Stress. 34, 616–627 (2020).

    PubMed  PubMed Central  Google Scholar 

  134. Anor, C. J. et al. Neuropsychiatric symptoms in Alzheimer disease, vascular dementia, and mixed dementia. Neurodegener. Dis. 17, 127–134 (2017).

    Article  PubMed  Google Scholar 

  135. Mavounza, C., Ouellet, M.-C. & Hudon, C. Caregivers’ emotional distress due to neuropsychiatric symptoms of persons with amnestic mild cognitive impairment or Alzheimer’s disease. Aging Ment. Health 24, 423–430 (2020).

    Article  PubMed  Google Scholar 

  136. Isik, A. T., Soysal, P., Solmi, M. & Veronese, N. Bidirectional relationship between caregiver burden and neuropsychiatric symptoms in patients with Alzheimer’s disease: a narrative review. Int. J. Geriatr. Psychiat. 34, 1326–1334 (2019).

    Article  Google Scholar 

  137. Hongisto, K. et al. Quality of life in relation to neuropsychiatric symptoms in Alzheimer’s disease: 5-year prospective ALSOVA cohort study. Int. J. Geriatr. Psychiat. 33, 47–57 (2018).

    Article  Google Scholar 

  138. Coughlan, G., Laczó, J., Hort, J., Minihane, A.-M. & Hornberger, M. Spatial navigation deficits — overlooked cognitive marker for preclinical Alzheimer disease? Nat. Rev. Neurol. 14, 496–506 (2018).

    Article  PubMed  Google Scholar 

  139. Babulal, G. M. et al. A naturalistic study of driving behavior in older adults and preclinical Alzheimer disease: a pilot study. J. Appl. Gerontol. 38, 277–289 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  140. Lichtenberg, P. A. Financial exploitation, financial capacity, and Alzheimer’s disease. Am. Psychol. 71, 312 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  141. Richards, M. & Brayne, C. What do we mean by Alzheimer’s disease? BMJ 341, c4670 (2010).

    Article  PubMed  Google Scholar 

  142. Pampuscenko, K. et al. Extracellular tau induces microglial phagocytosis of living neurons in cell cultures. J. Neurochem. 154, 316–329 (2020).

    Article  CAS  PubMed  Google Scholar 

  143. Reimand, J. et al. PET and CSF amyloid-β status are differently predicted by patient features: information from discordant cases. Alzheimers Res. Ther. 11, 100 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Lowe, V. J. et al. Widespread brain tau and its association with ageing, Braak stage and Alzheimer’s dementia. Brain 141, 271–287 (2017).

    Article  PubMed Central  Google Scholar 

  145. Therriault, J. et al. Topographic distribution of amyloid-β, tau, and atrophy in patients with behavioral/dysexecutive Alzheimer disease. Neurology 96, e81–e92 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Weigand, A. J. et al. Is tau in the absence of amyloid on the Alzheimer’s continuum?: A study of discordant PET positivity. Brain Commun. 2, fcz046 (2020).

    Article  PubMed  Google Scholar 

  147. Abe, K. et al. A new serum biomarker set to detect mild cognitive impairment and Alzheimer’s disease by peptidome technology. J. Alzheimers Dis. 73, 217–227 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Bogoslovsky, T. et al. Increases of plasma levels of glial fibrillary acidic protein, tau, and amyloid beta up to 90 days after traumatic brain injury. J. Neurotrauma 34, 66–73 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  149. Fossati, S. et al. Differential value of plasma tau as a biomarker for Alzheimer’s disease and chronic traumatic brain injury. Alzheimers Dement. 13, P1307 (2017).

    Article  Google Scholar 

  150. Mattsson, N. et al. Plasma tau in Alzheimer disease. Neurology 87, 1827–1835 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Pase, M. et al. Plasma tau corresponds to preclinical Alzheimer’s disease and is a strong predictor of future dementia. Neurology 90(Suppl. 15), S48.001 (2018).

    Google Scholar 

  152. Thijssen, E. H. et al. Diagnostic value of plasma phosphorylated tau181 in Alzheimer’s disease and frontotemporal lobar degeneration. Nat. Med. 26, 387–397 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Janelidze, S. et al. Plasma p-tau181 in Alzheimer’s disease: relationship to other biomarkers, differential diagnosis, neuropathology and longitudinal progression to Alzheimer’s dementia. Nat. Med. 26, 379–386 (2020).

    Article  CAS  PubMed  Google Scholar 

  154. Barthélemy, N. R., Horie, K., Sato, C. & Bateman, R. J. Blood plasma phosphorylated-tau isoforms track CNS change in Alzheimer’s disease. J. Exp. Med. 217, e20200861 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  155. Mielke, M. M. et al. Plasma phospho-tau181 increases with Alzheimer’s disease clinical severity and is associated with tau- and amyloid-positron emission tomography. Alzheimers Dement. 14, 989–997 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  156. Kritikos, M. et al. Pathway analysis for plasma β-amyloid, tau and neurofilament light (ATN) in World Trade Center responders at midlife. Neurol. Ther. 9, 159–171 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  157. Savjani, R. R., Taylor, B. A., Acion, L., Wilde, E. A. & Jorge, R. E. Accelerated changes in cortical thickness measurements with age in military service members with traumatic brain injury. J. Neurotrauma 34, 3107–3116 (2017).

    Article  PubMed  Google Scholar 

  158. Whitwell, J. L. et al. Patterns of atrophy differ among specific subtypes of mild cognitive impairment. Arch. Neurol. 64, 1130–1138 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  159. O’Donnell, L. J. & Westin, C. F. An introduction to diffusion tensor image analysis. Neurosurg. Clin. N. Am. 22, 185–196 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  160. Faria Dde, P., Copray, S., Buchpiguel, C., Dierckx, R. & de Vries, E. PET imaging in multiple sclerosis. J. Neuroimmune Pharmacol. 9, 468–482 (2014).

    Article  PubMed  Google Scholar 

  161. Ciccarelli, O. et al. Pathogenesis of multiple sclerosis: insights from molecular and metabolic imaging. Lancet Neurol. 13, 807–822 (2014).

    Article  CAS  PubMed  Google Scholar 

  162. Mielke, M. M. et al. Plasma and CSF neurofilament light. Relat. Longitud. Neuroimaging Cogn. Measures 93, e252–e260 (2019).

    CAS  Google Scholar 

  163. Boyle, P. A. et al. Much of late life cognitive decline is not due to common neurodegenerative pathologies. Ann. Neurol. 74, 478–489 (2013).

    Article  PubMed  Google Scholar 

  164. Wilson, R. S. et al. Neural reserve, neuronal density in the locus ceruleus, and cognitive decline. Neurology 80, 1202–1208 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  165. Honer, W. et al. Cognitive reserve, presynaptic proteins and dementia in the elderly. Transl. Psychiat. 2, e114–e114 (2012).

    Article  CAS  Google Scholar 

  166. Eisenstein, M. Genetics: finding risk factors. Nature 475, S20–S22 (2011).

    Article  CAS  PubMed  Google Scholar 

  167. Montagne, A. et al. APOE4 leads to blood–brain barrier dysfunction predicting cognitive decline. Nature 581, 71–76 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Kritikos, M., Gandy, S. E., Meliker, J. R., Luft, B. J. & Clouston, S. A. P. Acute versus chronic exposures to inhaled particulate matter and neurocognitive dysfunction: pathways to Alzheimer’s disease or a related dementia. J. Alzheimers Dis. 78, 871–886 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Plassman, B. L. et al. Intelligence and education as predictors of cognitive state in late life: a 50-year follow-up. Neurology 45, 1446–1450 (1995).

    Article  CAS  PubMed  Google Scholar 

  170. Deary, I. J., Whalley, L. J., Lemmon, H., Crawford, J. R. & Starr, J. M. The stability of individual differences in mental ability from childhood to old age: follow-up of the 1932 Scottish Mental Survey. Intelligence 28, 49–55 (2000).

    Article  Google Scholar 

  171. Snowdon, D. A. et al. Linguistic ability in early life and cognitive function and Alzheimer’s disease in late life: findings from the Nun Study. JAMA 275, 528–532 (1996).

    Article  CAS  PubMed  Google Scholar 

  172. Clouston, S. A. P. et al. Benefits of educational attainment on adult fluid cognition: international evidence from three birth cohorts. Int. J. Epidemiol. 41, 1729–1736 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  173. Vňuková, M., Richards, M. & Cadar, D. How do our decisions to smoke and drink in midlife affect our cognitive performance in later life? Findings from the 1946 British Birth Cohort. J. Aging Geriatr. Med. 1, 2 (2017).

    Google Scholar 

  174. Rawle, M. J. et al. Apolipoprotein-E (APOE) ε4 and cognitive decline over the adult life course. Transl. Psychiat. 8, 1–8 (2018).

    Article  CAS  Google Scholar 

  175. Yu, J.-T. et al. Evidence-based prevention of Alzheimer’s disease: systematic review and meta-analysis of 243 observational prospective studies and 153 randomised controlled trials. J. Neurol. Neurosurg. Psychiat. 91, 1201–1209 (2020).

    Article  PubMed  Google Scholar 

  176. The SPRINT MIND Investigators for the SPRINT Research Group. Effect of intensive vs standard blood pressure control on probable dementia: a randomized clinical trial. JAMA 321, 553–561 (2019).

    Article  PubMed Central  Google Scholar 

  177. Mintun, M. A. et al. Donanemab in early Alzheimer’s disease. N. Engl. J. Med. 384, 1691–1704 (2021).

    Article  CAS  PubMed  Google Scholar 

  178. Xu, H. et al. Long term effects of cholinesterase inhibitors on cognitive decline and mortality. Neurology 96, e2220–e22230 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Richards, M. et al. Identifying the lifetime cognitive and socioeconomic antecedents of cognitive state: seven decades of follow-up in a British birth cohort study. BMJ Open 9, e024404 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Northey, J. M., Cherbuin, N., Pumpa, K. L., Smee, D. J. & Rattray, B. Exercise interventions for cognitive function in adults older than 50: a systematic review with meta-analysis. Br. J. Sports Med. 52, 154–160 (2018).

    Article  PubMed  Google Scholar 

  181. Stern, Y. et al. Effect of aerobic exercise on cognition in younger adults: a randomized clinical trial. Neurology 92, e905–e916 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  182. Sloan, R. P. et al. Aerobic exercise training and inducible inflammation: results of a randomized controlled trial in healthy, young adults. J. Am. Heart Assoc. 7, e010201 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  183. Berg, A. et al. Treatment of PTSD: An Assessment of the Evidence (National Academies Press, 2007).

  184. Hoskins, M. et al. Pharmacotherapy for post-traumatic stress disorder: systematic review and meta-analysis. Br. J. Psychiat. 206, 93–100 (2015).

    Article  Google Scholar 

  185. Berger, W. et al. Pharmacologic alternatives to antidepressants in posttraumatic stress disorder: a systematic review. Prog. Neuropsychopharmacol. Biol. Psychiat. 33, 169–180 (2009).

    Article  CAS  Google Scholar 

  186. Feder, A. et al. Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: a randomized clinical trial. JAMA Psychiat. 71, 681–688 (2014).

    Article  CAS  Google Scholar 

  187. Kelmendi, B. et al. PTSD: from neurobiology to pharmacological treatments. Eur. J. Psychotraumatol. 7, 31858 (2016).

    Article  PubMed  Google Scholar 

  188. Raskind, M. A. et al. A parallel group placebo controlled study of prazosin for trauma nightmares and sleep disturbance in combat veterans with post-traumatic stress disorder. Biol. Psychiat. 61, 928–934 (2007).

    Article  CAS  PubMed  Google Scholar 

  189. Peskind, E. R., Bonner, L. T., Hoff, D. J. & Raskind, M. A. Prazosin reduces trauma-related nightmares in older men with chronic posttraumatic stress disorder. J. Geriatr. Psychiat. Neurol. 16, 165–171 (2003).

    Article  Google Scholar 

  190. Ahmadpanah, M. et al. Comparing the effect of prazosin and hydroxyzine on sleep quality in patients suffering from posttraumatic stress disorder. Neuropsychobiology 69, 235–242 (2014).

    Article  CAS  PubMed  Google Scholar 

  191. Germain, A. et al. Placebo-controlled comparison of prazosin and cognitive-behavioral treatments for sleep disturbances in US military veterans. J. Psychosom. Res. 72, 89–96 (2012).

    Article  PubMed  Google Scholar 

  192. Taylor, F. B. et al. Prazosin effects on objective sleep measures and clinical symptoms in civilian trauma posttraumatic stress disorder: a placebo-controlled study. Biol. Psychiat. 63, 629–632 (2008).

    Article  CAS  PubMed  Google Scholar 

  193. Raskind, M. A. et al. Trial of prazosin for post-traumatic stress disorder in military veterans. N. Engl. J. Med. 378, 507–517 (2018).

    Article  CAS  PubMed  Google Scholar 

  194. Raskind, M. A. et al. A trial of prazosin for combat trauma PTSD with nightmares in active-duty soldiers returned from Iraq and Afghanistan. Am. J. Psychiat. 170, 1003–1010 (2013).

    Article  PubMed  Google Scholar 

  195. Raskind, M. A. et al. Reduction of nightmares and other PTSD symptoms in combat veterans by prazosin: a placebo-controlled study. Am. J. Psychiat. 160, 371–373 (2003).

    Article  PubMed  Google Scholar 

  196. Monson, C. M. & Shnaider, P. Treating PTSD With Cognitive–Behavioral Therapies Interventions That Work (American Psychological Association, 2014).

  197. Difede, J. & Eskra, D. Cognitive processing therapy for PTSD in a survivor of the World Trade Center bombing. J. Trauma. Pract. 1, 155–165 (2002).

    Article  Google Scholar 

  198. Wachen, J. S. et al. Implementing cognitive processing therapy for posttraumatic stress disorder with active duty U.S. military personnel: special considerations and case examples. Cogn. Behav. Pract. 23, 133–147 (2016).

    Article  Google Scholar 

  199. Waltman, S. H. Functional analysis in differential diagnosis: using cognitive processing therapy to treat PTSD. Clin. Case Stud. 14, 422–433 (2015).

    Article  Google Scholar 

  200. Ehlers, A. & Clark, D. M. A cognitive model of posttraumatic stress disorder. Behav. Res. Ther. 38, 319–345 (2000).

    Article  CAS  PubMed  Google Scholar 

  201. Ehlers, A. et al. A randomized controlled trial of 7-day intensive and standard weekly cognitive therapy for PTSD and emotion-focused supportive therapy. Am. J. Psychiat. 171, 294–304 (2014).

    Article  PubMed  Google Scholar 

  202. Foa, E., Hembree, E. A., Rothbaum, B. O. & Rauch, S. Prolonged Exposure Therapy for PTSD — Therapist Guide: Emotional Processing of Traumatic Experiences (Oxford University Press, 2019).

  203. Bahar-Fuchs, A., Clare, L. & Woods, B. Cognitive training and cognitive rehabilitation for mild to moderate Alzheimer’s disease and vascular dementia. Cochrane Database Syst. Rev. 2013, CD003260 (2013).

    PubMed Central  Google Scholar 

  204. Mowszowski, L., Batchelor, J. & Naismith, S. L. Early intervention for cognitive decline: can cognitive training be used as a selective prevention technique? Int. Psychogeriatr. 22, 537–548 (2010).

    Article  PubMed  Google Scholar 

  205. Bahar-Fuchs, A., Martyr, A., Goh, A. M., Sabates, J. & Clare, L. Cognitive training for people with mild to moderate dementia. Cochrane Database Syst. Rev. 3, CD013069 (2019).

    PubMed  Google Scholar 

  206. Belleville, S., Mellah, S., de Boysson, C., Demonet, J. F. & Bier, B. The pattern and loci of training-induced brain changes in healthy older adults are predicted by the nature of the intervention. PLoS ONE 9, e102710 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  207. Belleville, S. et al. Training-related brain plasticity in subjects at risk of developing Alzheimer’s disease. Brain 134, 1623–1634 (2011).

    Article  PubMed  Google Scholar 

  208. Hampstead, B. M. et al. Activation and effective connectivity changes following explicit-memory training for face–name pairs in patients with mild cognitive impairment: a pilot study. Neurorehabil Neural Repair. 25, 210–222 (2011).

    Article  PubMed  Google Scholar 

  209. Edwards, J. D., Fausto, B. A., Tetlow, A. M., Corona, R. T. & Valdés, E. G. Systematic review and meta-analyses of useful field of view cognitive training. Neurosci. Biobehav. Rev. 84, 72–91 (2018).

    Article  PubMed  Google Scholar 

  210. Edwards, J. D. et al. Speed of processing training results in lower risk of dementia. Alzheimers Dement. Transl. Res. Clin. Interv. 3, 603–611 (2017).

    Article  Google Scholar 

  211. Vasterling, J. J., Verfaellie, M. & Sullivan, K. D. Mild traumatic brain injury and posttraumatic stress disorder in returning veterans: perspectives from cognitive neuroscience. Clin. Psychol. Rev. 29, 674–684 (2009).

    Article  PubMed  Google Scholar 

  212. H.R.847 – James Zadroga 9/11 Health and Compensation Act of 2010. Report 111-560 (House of Representatives, 2010).

  213. World Trade Center Health Effects program at a glance. https://www.cdc.gov/wtc/ataglance.html (NIOSH, Centers for Disease Control and Prevention, 2021).

  214. Farfel, M. et al. An overview of 9/11 experiences and respiratory and mental health conditions among World Trade Center Health Registry enrollees. J. Urban. Health 85, 880–909 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank R. D. Daniels, T. Kubale and D. Reismann for their assistance in planning and participating in the meeting that led to this Perspective. We would also like to acknowledge funding from the National Institute for Occupational Safety and Health (CDC/NIOSH: 200-2011-39361; U01 OH011314; U01 OH010718), and from the National Institute on Aging (NIH/NIA: R01 AG049953; P50 AG005138).

Review criteria

A comprehensive literature review was completed in advance of the 2019 US National Institute for Occupational Safety and Health (NIOSH) meeting using a database of papers published about World Trade Center (WTC) exposures and outcomes maintained by the NIOSH programme. Speakers were invited by two WTC researchers and asked to provide two representative papers of their own work to be briefly discussed during the meeting to educate audience members about their research. In preparation for this Perspective, a scoping literature search was also conducted using PubMed, including articles published in the areas of cognition, ageing, neurobiology, neuroimaging or neurodegeneration in survivor and responder populations affected by WTC attacks from 11 September 2001 to 1 May 2021 (search terms: “World Trade Center” AND (cogniti* OR aging OR neurobiology OR neuroimage* OR neurodegener*). The search resulted in 70 non-overlapping citations; relevant studies were retained and cited in this Perspective and studies specific to the topics of interest in this Perspective were highlighted. Attendees were also asked to discuss the relevance of MCI in this cohort and highlight important aspects that merited further investigation. The meeting was recorded and transcribed. Each presenter was asked to review transcripts for errors and for clarity, and all presenters were asked to review this manuscript for accuracy and to ensure final agreement with these materials. A writing team was tasked with capturing meeting materials and relevant background in this paper, and all authors were provided with opportunities to edit, modify and update sections in the final manuscript.

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Authors and Affiliations

  1. Program in Public Health, Department of Family, Population, and Preventive Medicine, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA

    Sean A. P. Clouston, Minos Kritikos & Erica D. Diminich

  2. Saul R. Korey Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA

    Charles B. Hall

  3. Rush Alzheimer’s Disease Center, Department of Neurological Sciences, Rush Medical College, Rush University, Chicago, IL, USA

    David A. Bennett

  4. Evelyn F. and William L. McKnight Brain Institute and Florida Alzheimer’s Disease Research Center, Department of Neurology and Neuroscience, University of Florida, Gainesville, FL, USA

    Steven DeKosky

  5. Department of Psychiatry and Behavioral Neuroscience, Morsani College of Medicine, University of South Florida, Tampa, FL, USA

    Jerri Edwards

  6. Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA

    Caleb Finch

  7. Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Department of Neurology, Columbia University, New York, NY, USA

    William C. Kreisl

  8. Specialized Center of Research Excellence on Sex Differences, Department of Neurology, Department of Epidemiology, Mayo Clinic, Rochester, MN, USA

    Michelle Mielke

  9. Veteran’s Association VISN 20 Northwest Mental Illness Research, Education, and Clinical Center, Veteran’s Affairs Puget Sound Health Care System, Seattle, WA, USA

    Elaine R. Peskind & Murray Raskind

  10. Medical Research Council Unit for Lifelong Health and Ageing, Population Health Sciences, University College London, London, UK

    Marcus Richards

  11. Department of Psychiatry, Columbia University Irving Medical Center, New York, NY, USA

    Richard P. Sloan

  12. Department of Epidemiology, School of Public Health, Boston University, Boston, MA, USA

    Avron Spiro III

  13. Azrieli Centre for Neuro-Radiochemistry, Brain Health Imaging Center, Center for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, ON, Canada

    Neil Vasdev

  14. World Trade Center Health Registry, New York Department of Health and Mental Hygiene, New York, NY, USA

    Robert Brackbill, Mark Farfel & Kacie Seil

  15. Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Megan Horton

  16. The World Trade Center Mental Health Program, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Sandra Lowe

  17. Department of Environmental Health Sciences, Robert Stempel College of Public Health and Social Work, Florida International University, Miami, FL, USA

    Roberto G. Lucchini

  18. World Trade Center Health Program, Fire Department of the City of New York, Brooklyn, NY, USA

    David Prezant & Rachel Zeig-Owens

  19. Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA

    Charles B. Hall, David Prezant & Rachel Zeig-Owens

  20. Department of Environmental Medicine, New York University Langone Health, New York, NY, USA

    Joan Reibman

  21. World Trade Center Environmental Health Center, Department of Psychiatry, New York University, New York, NY, USA

    Rebecca Rosen

  22. Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), Department of Veterans Affairs Boston Healthcare System, Boston, MA, USA

    Avron Spiro III

  23. Research and Development Service, James J. Peters Department of Veterans Affairs Medical Center, Bronx, NY, USA

    Sam Gandy & Mary Sano

  24. Alzheimer’s Disease Research Center, Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, USA

    Elaine R. Peskind & Murray Raskind

  25. Department of Medicine, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, USA

    Yael Deri & Benjamin J. Luft

  26. Center for Molecular & Behavioral Neuroscience, Rutgers, The State University of New Jersey, Newark, NJ, USA

    Bernadette A. Fausto

  27. Mount Sinai Alzheimer’s Disease Research Center and Ronald M. Loeb Center for Alzheimer’s Disease, Department of Psychiatry, Icahn School of Medicine, Mount Sinai, New York, NY, USA

    Sam Gandy & Mary Sano

  28. Department of Psychiatry, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, USA

    Yael Deri & Evelyn J. Bromet

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  1. Sean A. P. Clouston
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  2. Charles B. Hall
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  15. Neil Vasdev
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  18. Megan Horton
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  19. Sandra Lowe
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Contributions

S.A.P.C., M.K. and Y.D. researched data for the article, made substantial contributions to discussion of content, wrote the article, and reviewed and edited the manuscript before submission. C.B.H., C.F., E.R.P., A.S. and E.D.D. made substantial contributions to discussion of content, wrote the article, and reviewed and edited the manuscript before submission. J.E. wrote the article, and reviewed and edited the manuscript before submission. All other authors made substantial contributions to discussion of content, and reviewed and edited the manuscript before submission.

Corresponding author

Correspondence to Sean A. P. Clouston.

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The authors declare no competing interests.

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Nature Reviews Neurology thanks B. Snitz, who co-reviewed with B. Shaaban; D. Cory-Sletcha and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Glossary

Cognitive reserve theory

The theory that individual differences in the cognitive processes or neural networks underlying task performance enable some individuals to cope better with brain damage than other individuals

Healthy worker effect

The tendency for those who are working to be healthier, on average, than those who were unemployed or who do not participate in the workforce, leading to a consistent under-estimation of the impact of occupational exposures

Re-experiencing symptoms

Having sudden and unwanted traumatic memories that intrude into or even seem to replace what is happening in the current moment

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Clouston, S.A.P., Hall, C.B., Kritikos, M. et al. Cognitive impairment and World Trade Centre-related exposures. Nat Rev Neurol 18, 103–116 (2022). https://doi.org/10.1038/s41582-021-00576-8

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