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Impaired brain metabolism and neurocognitive function in childhood leukemia survivors despite complete hormone supplementation in adulthood

Follin, Cecilia LU ; Erfurth, Eva Marie LU ; Johansson, Aki; Lätt, Jimmy LU ; Sundgren, Pia C. LU ; Österberg, Kai LU ; Spulber, Gabriella; Mannfolk, Peter LU and Björkman-Burtscher, Isabella M. LU (2016) In Psychoneuroendocrinology 73. p.157-165
Abstract

Cranial radiotherapy is a known risk factor for neurocognitive impairment in survivors of childhood acute lymphoblastic leukemia (ALL). Understanding the nature of cognitive dysfunction during adulthood in ALL survivors is important as it has an impact on major life situations. Thirty-eight (21 women) ALL survivors were investigated 34 years after diagnosis. Median-age was 38 (27–46) years. All were treated with a CRT dose of 24 Gy and 11 years (3–13) of complete hormone supplementation. Comparisons were made to 29 matched controls. Assessments of magnetic resonance spectroscopy (white and grey matter metabolic alterations), brain volume and neuropsychological tests were performed. ALL survivors demonstrate a generally lower performance... (More)

Cranial radiotherapy is a known risk factor for neurocognitive impairment in survivors of childhood acute lymphoblastic leukemia (ALL). Understanding the nature of cognitive dysfunction during adulthood in ALL survivors is important as it has an impact on major life situations. Thirty-eight (21 women) ALL survivors were investigated 34 years after diagnosis. Median-age was 38 (27–46) years. All were treated with a CRT dose of 24 Gy and 11 years (3–13) of complete hormone supplementation. Comparisons were made to 29 matched controls. Assessments of magnetic resonance spectroscopy (white and grey matter metabolic alterations), brain volume and neuropsychological tests were performed. ALL survivors demonstrate a generally lower performance in neuropsychological tests. ALL survivors scored lower than controls in vocabulary (p < 0.001), memory (p < 0.001), learning capacity (p < 0.001), spatial ability (p < 0.001), executive functions and attention (p < 0.001) 34 years after ALL treatment. Compared to controls ALL survivors had reduced white matter (WM) (492 vs 536 cm3, p < 0.001) and grey matter (GM) volumes (525 vs 555 cm3, p = 0.001). ALL survivors had lower levels of WM N-acetyl aspartate/creatin (NAA/Cr) (1.48 vs 1.63, p = 0.004), WM NAA + NAAG (N-acetylaspartylglutamate)/Cr (1.61 vs 1.85, p < 0.001) and lower levels of GM NAA/Cr (1.18 vs 1.30, p = 0.001) and GM NAA + NAAG/Cr (1.28 vs 1.34, p = 0.01) compared to controls. ALL survivors had higher levels in WM MI (Myoinositol)/NAA (0.65 vs 0.56, p = 0.01) concentrations compared to controls. There was a significantly negative correlation of years since ALL diagnosis to WM NAA + NAAG/Cr (r = −0.4, p = 0.04) in ALL survivors. The present study shows impaired brain metabolism detected by MRS, reduced brain volumes and neurocognitive impairment in childhood ALL survivors treated with cranial radiotherapy and chemotherapy, despite complete hormone substitution. We also report an impairment of metabolites correlated to time since treatment and a progressive impairment in sustained attention, suggesting an accelerated aging in the irradiated brain. Following these survivors many decades, or throughout life, after treatment with cranial radiotherapy and chemotherapy is highly warranted for a broader understanding of long-term outcome in this patient group.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Acute lymphoblastic leukemia, Brain metabolism, Childhood leukemia, Cranial radiotherapy, Magnetic resonance spectroscopy, MR-spectroscopy, Neurocognitive function, Neuropsychology
in
Psychoneuroendocrinology
volume
73
pages
9 pages
publisher
Elsevier
external identifiers
  • Scopus:84980340090
ISSN
0306-4530
DOI
10.1016/j.psyneuen.2016.07.222
language
English
LU publication?
yes
id
d7021d73-383a-421e-91cd-5299a3d3b265
date added to LUP
2016-10-13 09:45:03
date last changed
2016-11-14 09:43:06
@misc{d7021d73-383a-421e-91cd-5299a3d3b265,
  abstract     = {<p>Cranial radiotherapy is a known risk factor for neurocognitive impairment in survivors of childhood acute lymphoblastic leukemia (ALL). Understanding the nature of cognitive dysfunction during adulthood in ALL survivors is important as it has an impact on major life situations. Thirty-eight (21 women) ALL survivors were investigated 34 years after diagnosis. Median-age was 38 (27–46) years. All were treated with a CRT dose of 24 Gy and 11 years (3–13) of complete hormone supplementation. Comparisons were made to 29 matched controls. Assessments of magnetic resonance spectroscopy (white and grey matter metabolic alterations), brain volume and neuropsychological tests were performed. ALL survivors demonstrate a generally lower performance in neuropsychological tests. ALL survivors scored lower than controls in vocabulary (p &lt; 0.001), memory (p &lt; 0.001), learning capacity (p &lt; 0.001), spatial ability (p &lt; 0.001), executive functions and attention (p &lt; 0.001) 34 years after ALL treatment. Compared to controls ALL survivors had reduced white matter (WM) (492 vs 536 cm<sup>3</sup>, p &lt; 0.001) and grey matter (GM) volumes (525 vs 555 cm<sup>3</sup>, p = 0.001). ALL survivors had lower levels of WM N-acetyl aspartate/creatin (NAA/Cr) (1.48 vs 1.63, p = 0.004), WM NAA + NAAG (N-acetylaspartylglutamate)/Cr (1.61 vs 1.85, p &lt; 0.001) and lower levels of GM NAA/Cr (1.18 vs 1.30, p = 0.001) and GM NAA + NAAG/Cr (1.28 vs 1.34, p = 0.01) compared to controls. ALL survivors had higher levels in WM MI (Myoinositol)/NAA (0.65 vs 0.56, p = 0.01) concentrations compared to controls. There was a significantly negative correlation of years since ALL diagnosis to WM NAA + NAAG/Cr (r = −0.4, p = 0.04) in ALL survivors. The present study shows impaired brain metabolism detected by MRS, reduced brain volumes and neurocognitive impairment in childhood ALL survivors treated with cranial radiotherapy and chemotherapy, despite complete hormone substitution. We also report an impairment of metabolites correlated to time since treatment and a progressive impairment in sustained attention, suggesting an accelerated aging in the irradiated brain. Following these survivors many decades, or throughout life, after treatment with cranial radiotherapy and chemotherapy is highly warranted for a broader understanding of long-term outcome in this patient group.</p>},
  author       = {Follin, Cecilia and Erfurth, Eva Marie and Johansson, Aki and Lätt, Jimmy and Sundgren, Pia C. and Österberg, Kai and Spulber, Gabriella and Mannfolk, Peter and Björkman-Burtscher, Isabella M.},
  issn         = {0306-4530},
  keyword      = {Acute lymphoblastic leukemia,Brain metabolism,Childhood leukemia,Cranial radiotherapy,Magnetic resonance spectroscopy,MR-spectroscopy,Neurocognitive function,Neuropsychology},
  language     = {eng},
  month        = {11},
  pages        = {157--165},
  publisher    = {ARRAY(0xd818358)},
  series       = {Psychoneuroendocrinology},
  title        = {Impaired brain metabolism and neurocognitive function in childhood leukemia survivors despite complete hormone supplementation in adulthood},
  url          = {http://dx.doi.org/10.1016/j.psyneuen.2016.07.222},
  volume       = {73},
  year         = {2016},
}