Apolipoprotein E epsilon 4 (APOE-ε4) genotype is associated with decreased 6-month verbal memory performance after mild traumatic brain injury

the TRACK-TBI Investigators

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Introduction: The apolipoprotein E (APOE) ε4 allele associates with memory impairment in neurodegenerative diseases. Its association with memory after mild traumatic brain injury (mTBI) is unclear. Methods: mTBI patients (Glasgow Coma Scale score 13–15, no neurosurgical intervention, extracranial Abbreviated Injury Scale score ≤1) aged ≥18 years with APOE genotyping results were extracted from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study. Cohorts determined by APOE-ε4(+/−) were assessed for associations with 6-month verbal memory, measured by California Verbal Learning Test, Second Edition (CVLT-II) subscales: Immediate Recall Trials 1–5 (IRT), Short-Delay Free Recall (SDFR), Short-Delay Cued Recall (SDCR), Long-Delay Free Recall (LDFR), and Long-Delay Cued Recall (LDCR). Multivariable regression controlled for demographic factors, seizure history, loss of consciousness, posttraumatic amnesia, and acute intracranial pathology on computed tomography (CT). Results: In 114 mTBI patients (APOE-ε4(−)=79; APOE-ε4(+)=35), ApoE-ε4(+) was associated with long-delay verbal memory deficits (LDFR: B = −1.17 points, 95% CI [−2.33, −0.01], p =.049; LDCR: B = −1.58 [−2.63, −0.52], p =.004), and a marginal decrease on SDCR (B = −1.02 [−2.05, 0.00], p =.050). CT pathology was the strongest predictor of decreased verbal memory (IRT: B = −8.49, SDFR: B = −2.50, SDCR: B = −1.85, LDFR: B = −2.61, LDCR: B = −2.60; p <.001). Seizure history was associated with decreased short-term memory (SDFR: B = −1.32, p =.037; SDCR: B = −1.44, p =.038). Conclusion: The APOE-ε4 allele may confer an increased risk of impairment of 6-month verbal memory for patients suffering mTBI, with implications for heightened surveillance and targeted therapies. Acute intracranial pathology remains the driver of decreased verbal memory performance at 6 months after mTBI.

Original languageEnglish (US)
Article numbere00791
JournalBrain and Behavior
Volume7
Issue number9
DOIs
StatePublished - Sep 2017

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Brain Concussion
Apolipoprotein E4
Genotype
Short-Term Memory
Apolipoproteins E
Pathology
Seizures
Alleles
Tomography
Abbreviated Injury Scale
Verbal Learning
Glasgow Coma Scale
Amnesia
Unconsciousness
Memory Disorders
Neurodegenerative Diseases
Demography
Research

Keywords

  • apolipoprotein E
  • genetic factors
  • human studies
  • outcome measures
  • traumatic brain injury
  • verbal memory

Cite this

Apolipoprotein E epsilon 4 (APOE-ε4) genotype is associated with decreased 6-month verbal memory performance after mild traumatic brain injury. / the TRACK-TBI Investigators.

In: Brain and Behavior, Vol. 7, No. 9, e00791, 09.2017.

Research output: Contribution to journalArticle

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title = "Apolipoprotein E epsilon 4 (APOE-ε4) genotype is associated with decreased 6-month verbal memory performance after mild traumatic brain injury",
abstract = "Introduction: The apolipoprotein E (APOE) ε4 allele associates with memory impairment in neurodegenerative diseases. Its association with memory after mild traumatic brain injury (mTBI) is unclear. Methods: mTBI patients (Glasgow Coma Scale score 13–15, no neurosurgical intervention, extracranial Abbreviated Injury Scale score ≤1) aged ≥18 years with APOE genotyping results were extracted from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study. Cohorts determined by APOE-ε4(+/−) were assessed for associations with 6-month verbal memory, measured by California Verbal Learning Test, Second Edition (CVLT-II) subscales: Immediate Recall Trials 1–5 (IRT), Short-Delay Free Recall (SDFR), Short-Delay Cued Recall (SDCR), Long-Delay Free Recall (LDFR), and Long-Delay Cued Recall (LDCR). Multivariable regression controlled for demographic factors, seizure history, loss of consciousness, posttraumatic amnesia, and acute intracranial pathology on computed tomography (CT). Results: In 114 mTBI patients (APOE-ε4(−)=79; APOE-ε4(+)=35), ApoE-ε4(+) was associated with long-delay verbal memory deficits (LDFR: B = −1.17 points, 95{\%} CI [−2.33, −0.01], p =.049; LDCR: B = −1.58 [−2.63, −0.52], p =.004), and a marginal decrease on SDCR (B = −1.02 [−2.05, 0.00], p =.050). CT pathology was the strongest predictor of decreased verbal memory (IRT: B = −8.49, SDFR: B = −2.50, SDCR: B = −1.85, LDFR: B = −2.61, LDCR: B = −2.60; p <.001). Seizure history was associated with decreased short-term memory (SDFR: B = −1.32, p =.037; SDCR: B = −1.44, p =.038). Conclusion: The APOE-ε4 allele may confer an increased risk of impairment of 6-month verbal memory for patients suffering mTBI, with implications for heightened surveillance and targeted therapies. Acute intracranial pathology remains the driver of decreased verbal memory performance at 6 months after mTBI.",
keywords = "apolipoprotein E, genetic factors, human studies, outcome measures, traumatic brain injury, verbal memory",
author = "{the TRACK-TBI Investigators} and Yue, {John K.} and Robinson, {Caitlin K.} and Burke, {John F.} and Winkler, {Ethan A.} and Hansen Deng and Cnossen, {Maryse C.} and Lingsma, {Hester F.} and Ferguson, {Adam R.} and McAllister, {Thomas W.} and Jonathan Rosand and Burchard, {Esteban G.} and Sorani, {Marco D.} and Sourabh Sharma and Nielson, {Jessica L.} and Satris, {Gabriela G.} and Talbott, {Jason F.} and Tarapore, {Phiroz E.} and Korley, {Frederick K.} and Wang, {Kevin K.W.} and Yuh, {Esther L.} and Pratik Mukherjee and Ramon Diaz-Arrastia and Valadka, {Alex B.} and Okonkwo, {David O.} and Manley, {Geoffrey T.}",
year = "2017",
month = "9",
doi = "10.1002/brb3.791",
language = "English (US)",
volume = "7",
journal = "Brain and Behavior",
issn = "2157-9032",
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T1 - Apolipoprotein E epsilon 4 (APOE-ε4) genotype is associated with decreased 6-month verbal memory performance after mild traumatic brain injury

AU - the TRACK-TBI Investigators

AU - Yue, John K.

AU - Robinson, Caitlin K.

AU - Burke, John F.

AU - Winkler, Ethan A.

AU - Deng, Hansen

AU - Cnossen, Maryse C.

AU - Lingsma, Hester F.

AU - Ferguson, Adam R.

AU - McAllister, Thomas W.

AU - Rosand, Jonathan

AU - Burchard, Esteban G.

AU - Sorani, Marco D.

AU - Sharma, Sourabh

AU - Nielson, Jessica L.

AU - Satris, Gabriela G.

AU - Talbott, Jason F.

AU - Tarapore, Phiroz E.

AU - Korley, Frederick K.

AU - Wang, Kevin K.W.

AU - Yuh, Esther L.

AU - Mukherjee, Pratik

AU - Diaz-Arrastia, Ramon

AU - Valadka, Alex B.

AU - Okonkwo, David O.

AU - Manley, Geoffrey T.

PY - 2017/9

Y1 - 2017/9

N2 - Introduction: The apolipoprotein E (APOE) ε4 allele associates with memory impairment in neurodegenerative diseases. Its association with memory after mild traumatic brain injury (mTBI) is unclear. Methods: mTBI patients (Glasgow Coma Scale score 13–15, no neurosurgical intervention, extracranial Abbreviated Injury Scale score ≤1) aged ≥18 years with APOE genotyping results were extracted from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study. Cohorts determined by APOE-ε4(+/−) were assessed for associations with 6-month verbal memory, measured by California Verbal Learning Test, Second Edition (CVLT-II) subscales: Immediate Recall Trials 1–5 (IRT), Short-Delay Free Recall (SDFR), Short-Delay Cued Recall (SDCR), Long-Delay Free Recall (LDFR), and Long-Delay Cued Recall (LDCR). Multivariable regression controlled for demographic factors, seizure history, loss of consciousness, posttraumatic amnesia, and acute intracranial pathology on computed tomography (CT). Results: In 114 mTBI patients (APOE-ε4(−)=79; APOE-ε4(+)=35), ApoE-ε4(+) was associated with long-delay verbal memory deficits (LDFR: B = −1.17 points, 95% CI [−2.33, −0.01], p =.049; LDCR: B = −1.58 [−2.63, −0.52], p =.004), and a marginal decrease on SDCR (B = −1.02 [−2.05, 0.00], p =.050). CT pathology was the strongest predictor of decreased verbal memory (IRT: B = −8.49, SDFR: B = −2.50, SDCR: B = −1.85, LDFR: B = −2.61, LDCR: B = −2.60; p <.001). Seizure history was associated with decreased short-term memory (SDFR: B = −1.32, p =.037; SDCR: B = −1.44, p =.038). Conclusion: The APOE-ε4 allele may confer an increased risk of impairment of 6-month verbal memory for patients suffering mTBI, with implications for heightened surveillance and targeted therapies. Acute intracranial pathology remains the driver of decreased verbal memory performance at 6 months after mTBI.

AB - Introduction: The apolipoprotein E (APOE) ε4 allele associates with memory impairment in neurodegenerative diseases. Its association with memory after mild traumatic brain injury (mTBI) is unclear. Methods: mTBI patients (Glasgow Coma Scale score 13–15, no neurosurgical intervention, extracranial Abbreviated Injury Scale score ≤1) aged ≥18 years with APOE genotyping results were extracted from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study. Cohorts determined by APOE-ε4(+/−) were assessed for associations with 6-month verbal memory, measured by California Verbal Learning Test, Second Edition (CVLT-II) subscales: Immediate Recall Trials 1–5 (IRT), Short-Delay Free Recall (SDFR), Short-Delay Cued Recall (SDCR), Long-Delay Free Recall (LDFR), and Long-Delay Cued Recall (LDCR). Multivariable regression controlled for demographic factors, seizure history, loss of consciousness, posttraumatic amnesia, and acute intracranial pathology on computed tomography (CT). Results: In 114 mTBI patients (APOE-ε4(−)=79; APOE-ε4(+)=35), ApoE-ε4(+) was associated with long-delay verbal memory deficits (LDFR: B = −1.17 points, 95% CI [−2.33, −0.01], p =.049; LDCR: B = −1.58 [−2.63, −0.52], p =.004), and a marginal decrease on SDCR (B = −1.02 [−2.05, 0.00], p =.050). CT pathology was the strongest predictor of decreased verbal memory (IRT: B = −8.49, SDFR: B = −2.50, SDCR: B = −1.85, LDFR: B = −2.61, LDCR: B = −2.60; p <.001). Seizure history was associated with decreased short-term memory (SDFR: B = −1.32, p =.037; SDCR: B = −1.44, p =.038). Conclusion: The APOE-ε4 allele may confer an increased risk of impairment of 6-month verbal memory for patients suffering mTBI, with implications for heightened surveillance and targeted therapies. Acute intracranial pathology remains the driver of decreased verbal memory performance at 6 months after mTBI.

KW - apolipoprotein E

KW - genetic factors

KW - human studies

KW - outcome measures

KW - traumatic brain injury

KW - verbal memory

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