Menú Cerrar

The Developmental Trajectory of Cancer-Related Cognitive Impairment in Breast Cancer Patients: A Systematic Review of Longitudinal Neuroimaging Studies

Helena Sousa 1 2Susana Almeida 2 3João Bessa 2 4 5M Graça Pereira 6 7

Neuropsychol Rev doi: 10.1007/s11065-020-09441-9. 

Abstract

This systematic review explored the neurobiological mechanisms underlying the clinical time course of cancer-related cognitive impairment (CRCI) in breast cancer patients through the review of longitudinal neuroimaging studies. Before chemotherapy, results reported no evidence for neuropsychological, structural (gray matter) and brain perfusion changes. However, functional brain alterations were evident and revealed a frontoparietal hyperactivation during working memory tasks. Fatigue and number of days since surgery were the two suggested confounding factors. Acutely after chemotherapy, this review found no evidence for neuropsychological changes while suggesting a pattern of frontal structural, perfusion and functional brain abnormalities. These findings seemed to be dependent on age, menopausal status at baseline, and fMRI task performed. Years after chemotherapy, results revealed evidence of partial neuropsychological, structural, and functional brain recovery. Regarding brain abnormality, this review suggested that it may begin quite early in the disease course, be more prominent shortly after chemotherapy and partially recover over time. Several hypotheses underlying these changes were discussed. The present review also provided important information for developing a time-specific treatment and prevention strategies and for the consideration of functional neuroimaging as a relevant tool for CRCI diagnosis, clinical monitoring, and intervention studies. The findings also suggested the need to implement studies with longitudinal designs, including a pre-treatment assessment, since cross-sectional studies were not able to detect this pattern of recovery over time, supporting only the theory of brain abnormalities, in breast cancer survivors.

Conclusion

This review found no evidence for neuropsychological, gray matter structural and perfusion changes before chemotherapy treatment. Functional changes were evident and demonstrated a frontoparietal hyperactivation during working memory tasks, suggestive of higher fMRI sensitivity to detect lower task performance and cognitive impairment at this early stage of the disease process. Fatigue and number of days since surgery were the two confounding factors proposed to mediate these findings, suggesting a direct effect of cancer on the brain via mechanisms such as neuroinflammation (Kesler et al., 2017a). Acutely, after chemotherapy, the present review suggested that a pattern of frontal structural, perfusion and functional changes could be found in a subset of breast cancer patients.

Working memory was the most predominant cognitive domain across studies, showing correlations with structural changes in frontal GMV (Lepage et al., 2014) and WMintegrity (Billiet et al., 2018; Deprez et al., 2012). Findings of frontal hyper and hypo-activity seem to be dependent on age, menopausal status at baseline and domain targeted by a specific fMRI task, although requiring further investigation. Years after chemotherapy, the present review showed evidence of a partial neuropsychological, structural, and functional recovery. This evidence was already present in GMD and VBM studies one year after chemotherapy ended. Depending on the post-chemotherapy interval, some regions (such as inferior frontal regions and hippocampus) remained affected chronically by adjuvant treatments, suggesting that some abnormalities might still persist over time and never entirely normalize.

This review found converging evidence fromstructural and functional studies that show a particular vulnerability of frontal lobes to CRCI, known to be critical for working memory (Wefel & Schagen, 2012). Possible CRCI neuromarkers were also discussed. Since working memory is the most reportedly affected cognitive domain in these studies, the present review can also point to a specific vulnerability of working memory due to chemotherapy treatment and a later improvement. However, most of the included studies focused on the consequences of chemotherapy for patients’ working memory and, therefore, future research with magnetic resonance imaging should focus on other cognitive domains such as learning ability, executive function, attention, decision-making, language, and processing speed.

In conclusion, the present review suggests that brain abnormalities (especially compensatory frontal hyperactivation) may begin quite early in the disease course, being more prominent shortly after chemotherapy with a partial recovery over time (Kesler et al., 2017a). The developmental trajectory of CRCI confirms the need to implement longitudinal designs including a pre-surgery assessment, since cross-sectional studies were not able to detect this pattern of recovery over time, supporting only the theory of brain abnormality in breast cancer survivors.

Delegaciones y Núcleos de Trabajo

Juntas Directivas

Delegaciones

Edo. Bolívar

Presidente: Dr. Guillermo Herrera (Ginecólogo)

Secretario: Dra. Falva Acosta (Gineco-Obstetra)

Tesorero: Dra. Ximena Madrid (Cardiología)

Vocal: Dra. Wilmania Bouchard Dra. Mercedes Santomauro (Endocrinología)

Edo. Mérida

Presidente: Dra. María Eugenia Noguera  (Ginecobstetra)

Secretario: Dra. Nazira Monsalve (Ginecobstetra)

Tesorero: Dra. Juleida Askul (Endocrinóloga)

Vocal: Dra. Lelis Quintero (Ginecobstetra)

Vocal: Dra. Maira Useche (Cardióloga)

Edo. Táchira

Presidente: Dr. Álvaro Padilla  (Ginecología y Obstetricia)

Secretario: Dra. Raiza Bontemps (Ginecología y Obstetricia)

Tesorero: Dr. Luis Ernesto Jaimes (Endocrinología)

Vocal: Dra. Maria Hercilia Esteva (Reumatología)

Vocal: Dr. Renny Cárdenas  (Traumatología)

Núcleos de Trabajo

Edo. Falcón

Presidente: Dra. Ma. Auxiliadora Curiel  (Gineco-Obstetra)

Secretario: Dr. Arnaldo Acosta (Endocrinólogo).

Tesorero: Dra. Lourdes Aldama (Gineco-Obstetra)

Edo. Sucre

Presidente: Dra. Haydee Rodríguez de Sánchez  (Ginecología)

Secretario: Dra. Esmely Salazar  (Ginecología y Obstetricia)

Tesorero: Dr. Luis Diaz (Cardiología)

Miembros Fundadores

Miembros Fundadores ( Sociedad Venezolana de Osteoporosis)

  1. Ada Perdomo
  2. Adolfo Melendez
  3. Alberto Zuloaga
  4. Alfonso Jacir
  5. Alfonso Vergara
  6. Alfredo Guariguata
  7. Alfredo Posada
  8. Anabela San Vicente
  9. Andrés M.Amaya Angulo
  10. Andrés Mendoza
  11. Andrés Monterola
  12. Antonio De Santolo
  13. Antonio Tarrazzi Salazar
  14. Bernardo Birnbaum
  15. Carlos Sandrea
  16. Carlos Soto Rivera
  17. Carmen Afonzo De Hernández
  18. Daniela Jakubowicz
  19. Douglas Ponce
  20. Douglas Urbina Oteiza
  21. Eddie Kaswan
  22. Eddy Alberto Salazar
  23. Eduardo Coll García
  24. Eladio R. Diaz Camero
  25. Elías Salazar Aboud
  26. Elie Nehme
  27. Elio Antonio Romero S.
  28. Eva Essenfeld De Sekler
  29. Eva Mariela Salazar
  30. Ezequiel Bellorin Font
  31. Ezequiel Hidalgo
  32. Florencio Quintero Rojo
  33. Francisco Carelli F
  34. Francisco Pinto
  35. Francisco Tapanes
  36. Frank Gorrochotegui
  37. Froino Gartner K.
  38. Gary Sterba
  39. Guillermo Bajares
  40. Gustavo Galué
  41. Haydeé Ríos De Vielma
  42. Héctor Marcano
  43. Humberto Acosta
  44. Ibrahim Pazos
  45. Ildemar Moncada
  46. Imperia Brajkovich
  47. Isidoro Brosnstein
  48. Israel Montes De Oca
  49. Ivan Stekman
  50. Jonny Engler
  51. José A. Zurita
  52. José Delgado
  53. José R García Cervén
  54. José Quijada Palacios
  55. José Rafael Roura
  56. José Weissinger
  57. Juan Antonio Yabur
  58. Juan Bautista Zambrano
  59. Juan F. Duque Pernía
  60. Julieta V. De Bello
  61. Jusés Mazzei Berti
  62. Leopoldo Baptista
  63. Leslie Sánchez
  64. Lilia Pérez De Rivero
  65. Luis A. Hernández
  66. Luis Alberto Blanco Acevedo
  67. Luis Alejandro Rodriguez
  68. Luis Alfredo Rodriguez
  69. Luis E. Rodriguez Mora
  70. Luis J. González Leon
  71. Mariá Eugenia De D´Empaire
  72. Marcos Troccoli
  73. María Carmen Cordido
  74. Maria Cristina Angelino De Blanco
  75. Maria Luisa Cumaná De López
  76. María Maiello De Betancourt
  77. María Zoraida Pacheco
  78. Mario Ogni
  79. Miguel Padilla
  80. Miriam Alvarado
  81. Moisés R.Attias
  82. Nancy Negrín De Moreno
  83. Nujem Szomsteim
  84. Oscar J. Solís
  85. Oswaldo Pbregón
  86. Pablo Amair M
  87. Pedro Armas
  88. Pedro Jose Vicentelli
  89. Pedro Monsalve
  90. Pedro Teppa
  91. Rafael Rodríguez Cedeño
  92. Ramón Castro
  93. Ramón Francisco Soto Sánchez
  94. Ramón Franco
  95. Raúl J. Fernández Barboza
  96. Raúl Veitia
  97. Régulo Millán
  98. Rodrigo Infante
  99. Ronal Paredes
  100. Rosa Hernández Gandolfi
  101. Rubén Jaén
  102. Ruben Quintero Monasterios
  103. Rufino Rengifo
  104. Salvador Rivas
  105. Samuel Abbo
  106. Sergio Tovar
  107. Vicente Franco De Lugo
  108. Virgilio Paz Martínez
  109. Xabier Arozena
  110. Yolanda Díaz De Perdomo
  111. Yolanda Salazar
  112. Zoraida Paz

 

Miembros Fundadores ( SOVEMO)

  1. Alfredo Guariguata
  2. Anabella San Vicente
  3. Andrés Mendoza
  4. Antonio De Santolo
  5. Antonio Tarrazzi
  6. Bernardo Birbaum
  7. Carlos Soto Rivera
  8. Desiderio Rincón Pacheco
  9. Douglas Ponce
  10. Douglas Urbina
  11. Edgar Nieto
  12. Eduardo Coll García
  13. Eladio Díaz Camero
  14. Elias Salazar
  15. Elie Nehme
  16. Eva Mariela Salazar
  17. Farid Atías
  18. Florencio Quintero Rojo
  19. Francisco Tapanes
  20. Frank Gorrochotegui
  21. Froino Gartner
  22. Gary Sterba
  23. Gregorio Riera
  24. Guillermo Bajares
  25. Gunter Lentz
  26. Humberto Acosta
  27. Ibrahim Pazos
  28. Isidoro Bronstein
  29. Jonny Engler
  30. Jorge Cedeño
  31. José Delgado
  32. José R. García
  33. Juan Antonio Yabur
  34. Julieta De Bello
  35. Leopoldo Baptista
  36. Leslie Sánchez
  37. Luis González León
  38. María C. Maiello De Betancourt
  39. María Carmen Cordido
  40. María Cristina Angelino De Blanco
  41. María Eugenia De D’empaire
  42. Mariela Bajares De Lilue
  43. Miriam Alvarado
  44. Moisés Atias
  45. Nujem Szomstein
  46. Pablo Amair
  47. Pedro Armas
  48. Pedro Vicentelli
  49. Ramón González Cerruti
  50. Raúl Fernández
  51. Raúl Veitía
  52. Rosa Hernández
  53. Rubén Quintero
  54. Rufino Rengifo
  55. Sergio Tovar
  56. Valmore Quintero