Evaluation of memory impairment in aging adult survivors of childhood acute lymphoblastic leukemia treated with cranial radiotherapy

Gregory T. Armstrong, Wilburn E. Reddick, Ronald Carl Petersen, Aimee Santucci, Nan Zhang, Deokumar Srivastava, Robert J. Ogg, Claudia M. Hillenbrand, Noah Sabin, Matthew J. Krasin, Larry Kun, Ching Hon Pui, Melissa M. Hudson, Leslie L. Robison, Kevin R. Krull

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Abstract

Background Cranial radiotherapy (CRT) is a known risk factor for neurocognitive impairment in survivors of childhood cancer and may increase risk for mild cognitive impairment and dementia in adulthood. Methods We performed a cross-sectional evaluation of survivors of childhood acute lymphoblastic leukemia (ALL) treated with 18 Gy (n = 127) or 24 Gy (n = 138) CRT. Impairment (age-adjusted score >1 standard deviation below expected mean, two-sided exact binomial test) on the Wechsler Memory Scale IV (WMS-IV) was measured. A subset of survivors (n = 85) completed structural and functional neuroimaging. Results Survivors who received 24 Gy, but not 18 Gy, CRT had impairment in immediate (impairment rate = 33.8%, 95% confidence interval [CI] = 25.9% to 42.4%; P < .001) and delayed memory (impairment rate = 30.2%, 95% CI = 22.6% to 38.6%; P < .001). The mean score for long-term narrative memory among survivors who received 24 Gy CRT was equivalent to that for individuals older than 69 years. Impaired immediate memory was associated with smaller right (P = .02) and left (P = .008) temporal lobe volumes, and impaired delayed memory was associated with thinner parietal and frontal cortices. Lower hippocampal volumes and increased functional magnetic resonance imaging activation were observed with memory impairment. Reduced cognitive status (Brief Cognitive Status Exam from the WMS-IV) was identified after 24 Gy (18.5%, 95% CI = 12.4% to 26.1%; P < .001), but not 18 Gy (8.7%, 95% CI = 4.4% to 15.0%; P = .11), CRT, suggesting a dose-response effect. Employment rates were equivalent (63.8% for 24 Gy CRT and 63.0% for 18 Gy CRT). Conclusions Adult survivors who received 24 Gy CRT had reduced cognitive status and memory, with reduced integrity in neuroanatomical regions essential in memory formation, consistent with early onset mild cognitive impairment.

Original languageEnglish (US)
Pages (from-to)899-907
Number of pages9
JournalJournal of the National Cancer Institute
Volume105
Issue number12
DOIs
StatePublished - Jun 19 2013

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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Radiotherapy
Survivors
Repression (Psychology)
Confidence Intervals
Wechsler Scales
Parietal Lobe
Functional Neuroimaging
Long-Term Memory
Frontal Lobe
Temporal Lobe
Short-Term Memory
Dementia
Magnetic Resonance Imaging
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Evaluation of memory impairment in aging adult survivors of childhood acute lymphoblastic leukemia treated with cranial radiotherapy. / Armstrong, Gregory T.; Reddick, Wilburn E.; Petersen, Ronald Carl; Santucci, Aimee; Zhang, Nan; Srivastava, Deokumar; Ogg, Robert J.; Hillenbrand, Claudia M.; Sabin, Noah; Krasin, Matthew J.; Kun, Larry; Pui, Ching Hon; Hudson, Melissa M.; Robison, Leslie L.; Krull, Kevin R.

In: Journal of the National Cancer Institute, Vol. 105, No. 12, 19.06.2013, p. 899-907.

Research output: Contribution to journalArticle

Armstrong, GT, Reddick, WE, Petersen, RC, Santucci, A, Zhang, N, Srivastava, D, Ogg, RJ, Hillenbrand, CM, Sabin, N, Krasin, MJ, Kun, L, Pui, CH, Hudson, MM, Robison, LL & Krull, KR 2013, 'Evaluation of memory impairment in aging adult survivors of childhood acute lymphoblastic leukemia treated with cranial radiotherapy', Journal of the National Cancer Institute, vol. 105, no. 12, pp. 899-907. https://doi.org/10.1093/jnci/djs539
Armstrong, Gregory T. ; Reddick, Wilburn E. ; Petersen, Ronald Carl ; Santucci, Aimee ; Zhang, Nan ; Srivastava, Deokumar ; Ogg, Robert J. ; Hillenbrand, Claudia M. ; Sabin, Noah ; Krasin, Matthew J. ; Kun, Larry ; Pui, Ching Hon ; Hudson, Melissa M. ; Robison, Leslie L. ; Krull, Kevin R. / Evaluation of memory impairment in aging adult survivors of childhood acute lymphoblastic leukemia treated with cranial radiotherapy. In: Journal of the National Cancer Institute. 2013 ; Vol. 105, No. 12. pp. 899-907.
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title = "Evaluation of memory impairment in aging adult survivors of childhood acute lymphoblastic leukemia treated with cranial radiotherapy",
abstract = "Background Cranial radiotherapy (CRT) is a known risk factor for neurocognitive impairment in survivors of childhood cancer and may increase risk for mild cognitive impairment and dementia in adulthood. Methods We performed a cross-sectional evaluation of survivors of childhood acute lymphoblastic leukemia (ALL) treated with 18 Gy (n = 127) or 24 Gy (n = 138) CRT. Impairment (age-adjusted score >1 standard deviation below expected mean, two-sided exact binomial test) on the Wechsler Memory Scale IV (WMS-IV) was measured. A subset of survivors (n = 85) completed structural and functional neuroimaging. Results Survivors who received 24 Gy, but not 18 Gy, CRT had impairment in immediate (impairment rate = 33.8{\%}, 95{\%} confidence interval [CI] = 25.9{\%} to 42.4{\%}; P < .001) and delayed memory (impairment rate = 30.2{\%}, 95{\%} CI = 22.6{\%} to 38.6{\%}; P < .001). The mean score for long-term narrative memory among survivors who received 24 Gy CRT was equivalent to that for individuals older than 69 years. Impaired immediate memory was associated with smaller right (P = .02) and left (P = .008) temporal lobe volumes, and impaired delayed memory was associated with thinner parietal and frontal cortices. Lower hippocampal volumes and increased functional magnetic resonance imaging activation were observed with memory impairment. Reduced cognitive status (Brief Cognitive Status Exam from the WMS-IV) was identified after 24 Gy (18.5{\%}, 95{\%} CI = 12.4{\%} to 26.1{\%}; P < .001), but not 18 Gy (8.7{\%}, 95{\%} CI = 4.4{\%} to 15.0{\%}; P = .11), CRT, suggesting a dose-response effect. Employment rates were equivalent (63.8{\%} for 24 Gy CRT and 63.0{\%} for 18 Gy CRT). Conclusions Adult survivors who received 24 Gy CRT had reduced cognitive status and memory, with reduced integrity in neuroanatomical regions essential in memory formation, consistent with early onset mild cognitive impairment.",
author = "Armstrong, {Gregory T.} and Reddick, {Wilburn E.} and Petersen, {Ronald Carl} and Aimee Santucci and Nan Zhang and Deokumar Srivastava and Ogg, {Robert J.} and Hillenbrand, {Claudia M.} and Noah Sabin and Krasin, {Matthew J.} and Larry Kun and Pui, {Ching Hon} and Hudson, {Melissa M.} and Robison, {Leslie L.} and Krull, {Kevin R.}",
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T1 - Evaluation of memory impairment in aging adult survivors of childhood acute lymphoblastic leukemia treated with cranial radiotherapy

AU - Armstrong, Gregory T.

AU - Reddick, Wilburn E.

AU - Petersen, Ronald Carl

AU - Santucci, Aimee

AU - Zhang, Nan

AU - Srivastava, Deokumar

AU - Ogg, Robert J.

AU - Hillenbrand, Claudia M.

AU - Sabin, Noah

AU - Krasin, Matthew J.

AU - Kun, Larry

AU - Pui, Ching Hon

AU - Hudson, Melissa M.

AU - Robison, Leslie L.

AU - Krull, Kevin R.

PY - 2013/6/19

Y1 - 2013/6/19

N2 - Background Cranial radiotherapy (CRT) is a known risk factor for neurocognitive impairment in survivors of childhood cancer and may increase risk for mild cognitive impairment and dementia in adulthood. Methods We performed a cross-sectional evaluation of survivors of childhood acute lymphoblastic leukemia (ALL) treated with 18 Gy (n = 127) or 24 Gy (n = 138) CRT. Impairment (age-adjusted score >1 standard deviation below expected mean, two-sided exact binomial test) on the Wechsler Memory Scale IV (WMS-IV) was measured. A subset of survivors (n = 85) completed structural and functional neuroimaging. Results Survivors who received 24 Gy, but not 18 Gy, CRT had impairment in immediate (impairment rate = 33.8%, 95% confidence interval [CI] = 25.9% to 42.4%; P < .001) and delayed memory (impairment rate = 30.2%, 95% CI = 22.6% to 38.6%; P < .001). The mean score for long-term narrative memory among survivors who received 24 Gy CRT was equivalent to that for individuals older than 69 years. Impaired immediate memory was associated with smaller right (P = .02) and left (P = .008) temporal lobe volumes, and impaired delayed memory was associated with thinner parietal and frontal cortices. Lower hippocampal volumes and increased functional magnetic resonance imaging activation were observed with memory impairment. Reduced cognitive status (Brief Cognitive Status Exam from the WMS-IV) was identified after 24 Gy (18.5%, 95% CI = 12.4% to 26.1%; P < .001), but not 18 Gy (8.7%, 95% CI = 4.4% to 15.0%; P = .11), CRT, suggesting a dose-response effect. Employment rates were equivalent (63.8% for 24 Gy CRT and 63.0% for 18 Gy CRT). Conclusions Adult survivors who received 24 Gy CRT had reduced cognitive status and memory, with reduced integrity in neuroanatomical regions essential in memory formation, consistent with early onset mild cognitive impairment.

AB - Background Cranial radiotherapy (CRT) is a known risk factor for neurocognitive impairment in survivors of childhood cancer and may increase risk for mild cognitive impairment and dementia in adulthood. Methods We performed a cross-sectional evaluation of survivors of childhood acute lymphoblastic leukemia (ALL) treated with 18 Gy (n = 127) or 24 Gy (n = 138) CRT. Impairment (age-adjusted score >1 standard deviation below expected mean, two-sided exact binomial test) on the Wechsler Memory Scale IV (WMS-IV) was measured. A subset of survivors (n = 85) completed structural and functional neuroimaging. Results Survivors who received 24 Gy, but not 18 Gy, CRT had impairment in immediate (impairment rate = 33.8%, 95% confidence interval [CI] = 25.9% to 42.4%; P < .001) and delayed memory (impairment rate = 30.2%, 95% CI = 22.6% to 38.6%; P < .001). The mean score for long-term narrative memory among survivors who received 24 Gy CRT was equivalent to that for individuals older than 69 years. Impaired immediate memory was associated with smaller right (P = .02) and left (P = .008) temporal lobe volumes, and impaired delayed memory was associated with thinner parietal and frontal cortices. Lower hippocampal volumes and increased functional magnetic resonance imaging activation were observed with memory impairment. Reduced cognitive status (Brief Cognitive Status Exam from the WMS-IV) was identified after 24 Gy (18.5%, 95% CI = 12.4% to 26.1%; P < .001), but not 18 Gy (8.7%, 95% CI = 4.4% to 15.0%; P = .11), CRT, suggesting a dose-response effect. Employment rates were equivalent (63.8% for 24 Gy CRT and 63.0% for 18 Gy CRT). Conclusions Adult survivors who received 24 Gy CRT had reduced cognitive status and memory, with reduced integrity in neuroanatomical regions essential in memory formation, consistent with early onset mild cognitive impairment.

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