Julie E Gretler, Madeline D.W. Noland, Laura Lazzeroni, Arthur Noda, Jerome A Yesavage, Lisa M Kinoshita
{"title":"1 APOzA 和 BDNF val66met 对患有创伤后应激障碍的老年退伍军人执行功能的影响","authors":"Julie E Gretler, Madeline D.W. Noland, Laura Lazzeroni, Arthur Noda, Jerome A Yesavage, Lisa M Kinoshita","doi":"10.1017/s1355617723006720","DOIUrl":null,"url":null,"abstract":"Objective:Both <jats:italic>Apolipoprotein</jats:italic> z4 (APOz4) and <jats:italic>Brain-Derived Neurotropic Factor</jats:italic> val66met (BDNF-met) have been implicated as cognitive risk polymorphisms and may signal a more rapid trajectory of cognitive decline (Boots et al., 2017; Lim et al., 2015). The presence of both risk alleles may additively result in greater cognitive difficulties (Cechova et al., 2020), specifically executive functioning (Sapkota et al., 2017). As executive functioning difficulties can be associated with Posttraumatic Stress Disorder (PTSD; Woon et al., 2017), individuals with PTSD who carry these polymorphisms may be at higher risk for decline in executive functioning. In this study, we examined the cross-sectional and longitudinal impact of these alleles on executive functioning performance in Veterans with PTSD.Participants and Methods:Seventy community-dwelling male Veterans were enrolled as part of a larger study at VAPAHCS and consented to genetic analysis. A current or lifetime history of PTSD (score > 40 on the CAPS-IV; Blake et al., 1995) was required for study participation. Trail Making Test B (TMT-B; Army Individual Test Battery, 1994) was used to assess executive functioning. TMT-B was part of a comprehensive neuropsychological battery administered at baseline and yearly over the following three years. Mean age and education were 61 years old (SD = 4.5; range = 55-78) and 14 years (SD = 2.3; range = 8-20), respectively.The majority of the sample was White (71%) and were from the Korean and Vietnam War eras.Results:<jats:italic>APO</jats:italic>z4 and <jats:italic>BDNF</jats:italic>-met were present in 29% and 27% of the sample, respectively; both were present in six participants. Regression models were fitted separately for TMT-B raw time-to-complete and number of errors, both cross-sectionally at screening and then longitudinally. The presence of BDNF-met was a significant predictor of TMT-B time and number of errors in both models (Time: <jats:italic>ß</jats:italic> = 0.09, p = 0.03 and <jats:italic>ß</jats:italic> = 0.11, p < 0.01; Errors: IRR = 2.4, p = 0.01 and IRR = 1.9, p = 0.01), while APOz4 only predicted errors longitudinally (IRR = 1.8, p = 0.03). There was no significant allelic interaction; however, the presence of both alleles additively multiplied TMT-B errors by approximately 3.7 times at screening (IRR = 3.7; p = 0.01) and 3.3 times longitudinally (IRR = 3.3; p < 0.01).Conclusions:Altogether, these results are suggestive of an adverse, additive, effect of the <jats:italic>APO</jats:italic>z4 and <jats:italic>BDNF</jats:italic>-met polymorphisms on executive functioning, in particular error-proneness, with their combined presence tripling the errors made on TMT-B cross-sectionally and longitudinally. Consistent with previous research, the TMT-B error analysis increases detection of cognitive impairment, similar to other clinical samples (Varjacic et al., 2018). While TMT-B errors are typically interpreted qualitatively, the strong effect of these established risk alleles on error rates further support this metric as a clinically useful indicator of executive dysfunction in a PTSD population. In keeping with the Boston Process approach, these findings support the importance of error analysis in clinical interpretation of neuropsychological performance.","PeriodicalId":49995,"journal":{"name":"Journal of the International Neuropsychological Society","volume":null,"pages":null},"PeriodicalIF":2.6000,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"1 The Impact of APOzA and BDNF val66met on Executive Function in Older Veterans with Post-traumatic Stress Disorder\",\"authors\":\"Julie E Gretler, Madeline D.W. Noland, Laura Lazzeroni, Arthur Noda, Jerome A Yesavage, Lisa M Kinoshita\",\"doi\":\"10.1017/s1355617723006720\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Objective:Both <jats:italic>Apolipoprotein</jats:italic> z4 (APOz4) and <jats:italic>Brain-Derived Neurotropic Factor</jats:italic> val66met (BDNF-met) have been implicated as cognitive risk polymorphisms and may signal a more rapid trajectory of cognitive decline (Boots et al., 2017; Lim et al., 2015). The presence of both risk alleles may additively result in greater cognitive difficulties (Cechova et al., 2020), specifically executive functioning (Sapkota et al., 2017). As executive functioning difficulties can be associated with Posttraumatic Stress Disorder (PTSD; Woon et al., 2017), individuals with PTSD who carry these polymorphisms may be at higher risk for decline in executive functioning. In this study, we examined the cross-sectional and longitudinal impact of these alleles on executive functioning performance in Veterans with PTSD.Participants and Methods:Seventy community-dwelling male Veterans were enrolled as part of a larger study at VAPAHCS and consented to genetic analysis. A current or lifetime history of PTSD (score > 40 on the CAPS-IV; Blake et al., 1995) was required for study participation. Trail Making Test B (TMT-B; Army Individual Test Battery, 1994) was used to assess executive functioning. TMT-B was part of a comprehensive neuropsychological battery administered at baseline and yearly over the following three years. Mean age and education were 61 years old (SD = 4.5; range = 55-78) and 14 years (SD = 2.3; range = 8-20), respectively.The majority of the sample was White (71%) and were from the Korean and Vietnam War eras.Results:<jats:italic>APO</jats:italic>z4 and <jats:italic>BDNF</jats:italic>-met were present in 29% and 27% of the sample, respectively; both were present in six participants. Regression models were fitted separately for TMT-B raw time-to-complete and number of errors, both cross-sectionally at screening and then longitudinally. The presence of BDNF-met was a significant predictor of TMT-B time and number of errors in both models (Time: <jats:italic>ß</jats:italic> = 0.09, p = 0.03 and <jats:italic>ß</jats:italic> = 0.11, p < 0.01; Errors: IRR = 2.4, p = 0.01 and IRR = 1.9, p = 0.01), while APOz4 only predicted errors longitudinally (IRR = 1.8, p = 0.03). There was no significant allelic interaction; however, the presence of both alleles additively multiplied TMT-B errors by approximately 3.7 times at screening (IRR = 3.7; p = 0.01) and 3.3 times longitudinally (IRR = 3.3; p < 0.01).Conclusions:Altogether, these results are suggestive of an adverse, additive, effect of the <jats:italic>APO</jats:italic>z4 and <jats:italic>BDNF</jats:italic>-met polymorphisms on executive functioning, in particular error-proneness, with their combined presence tripling the errors made on TMT-B cross-sectionally and longitudinally. Consistent with previous research, the TMT-B error analysis increases detection of cognitive impairment, similar to other clinical samples (Varjacic et al., 2018). While TMT-B errors are typically interpreted qualitatively, the strong effect of these established risk alleles on error rates further support this metric as a clinically useful indicator of executive dysfunction in a PTSD population. In keeping with the Boston Process approach, these findings support the importance of error analysis in clinical interpretation of neuropsychological performance.\",\"PeriodicalId\":49995,\"journal\":{\"name\":\"Journal of the International Neuropsychological Society\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2023-12-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of the International Neuropsychological Society\",\"FirstCategoryId\":\"102\",\"ListUrlMain\":\"https://doi.org/10.1017/s1355617723006720\",\"RegionNum\":4,\"RegionCategory\":\"心理学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the International Neuropsychological Society","FirstCategoryId":"102","ListUrlMain":"https://doi.org/10.1017/s1355617723006720","RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
1 The Impact of APOzA and BDNF val66met on Executive Function in Older Veterans with Post-traumatic Stress Disorder
Objective:Both Apolipoprotein z4 (APOz4) and Brain-Derived Neurotropic Factor val66met (BDNF-met) have been implicated as cognitive risk polymorphisms and may signal a more rapid trajectory of cognitive decline (Boots et al., 2017; Lim et al., 2015). The presence of both risk alleles may additively result in greater cognitive difficulties (Cechova et al., 2020), specifically executive functioning (Sapkota et al., 2017). As executive functioning difficulties can be associated with Posttraumatic Stress Disorder (PTSD; Woon et al., 2017), individuals with PTSD who carry these polymorphisms may be at higher risk for decline in executive functioning. In this study, we examined the cross-sectional and longitudinal impact of these alleles on executive functioning performance in Veterans with PTSD.Participants and Methods:Seventy community-dwelling male Veterans were enrolled as part of a larger study at VAPAHCS and consented to genetic analysis. A current or lifetime history of PTSD (score > 40 on the CAPS-IV; Blake et al., 1995) was required for study participation. Trail Making Test B (TMT-B; Army Individual Test Battery, 1994) was used to assess executive functioning. TMT-B was part of a comprehensive neuropsychological battery administered at baseline and yearly over the following three years. Mean age and education were 61 years old (SD = 4.5; range = 55-78) and 14 years (SD = 2.3; range = 8-20), respectively.The majority of the sample was White (71%) and were from the Korean and Vietnam War eras.Results:APOz4 and BDNF-met were present in 29% and 27% of the sample, respectively; both were present in six participants. Regression models were fitted separately for TMT-B raw time-to-complete and number of errors, both cross-sectionally at screening and then longitudinally. The presence of BDNF-met was a significant predictor of TMT-B time and number of errors in both models (Time: ß = 0.09, p = 0.03 and ß = 0.11, p < 0.01; Errors: IRR = 2.4, p = 0.01 and IRR = 1.9, p = 0.01), while APOz4 only predicted errors longitudinally (IRR = 1.8, p = 0.03). There was no significant allelic interaction; however, the presence of both alleles additively multiplied TMT-B errors by approximately 3.7 times at screening (IRR = 3.7; p = 0.01) and 3.3 times longitudinally (IRR = 3.3; p < 0.01).Conclusions:Altogether, these results are suggestive of an adverse, additive, effect of the APOz4 and BDNF-met polymorphisms on executive functioning, in particular error-proneness, with their combined presence tripling the errors made on TMT-B cross-sectionally and longitudinally. Consistent with previous research, the TMT-B error analysis increases detection of cognitive impairment, similar to other clinical samples (Varjacic et al., 2018). While TMT-B errors are typically interpreted qualitatively, the strong effect of these established risk alleles on error rates further support this metric as a clinically useful indicator of executive dysfunction in a PTSD population. In keeping with the Boston Process approach, these findings support the importance of error analysis in clinical interpretation of neuropsychological performance.
期刊介绍:
The Journal of the International Neuropsychological Society is the official journal of the International Neuropsychological Society, an organization of over 4,500 international members from a variety of disciplines. The Journal of the International Neuropsychological Society welcomes original, creative, high quality research papers covering all areas of neuropsychology. The focus of articles may be primarily experimental, applied, or clinical. Contributions will broadly reflect the interest of all areas of neuropsychology, including but not limited to: development of cognitive processes, brain-behavior relationships, adult and pediatric neuropsychology, neurobehavioral syndromes (such as aphasia or apraxia), and the interfaces of neuropsychology with related areas such as behavioral neurology, neuropsychiatry, genetics, and cognitive neuroscience. Papers that utilize behavioral, neuroimaging, and electrophysiological measures are appropriate.
To assure maximum flexibility and to promote diverse mechanisms of scholarly communication, the following formats are available in addition to a Regular Research Article: Brief Communication is a shorter research article; Rapid Communication is intended for "fast breaking" new work that does not yet justify a full length article and is placed on a fast review track; Case Report is a theoretically important and unique case study; Critical Review and Short Review are thoughtful considerations of topics of importance to neuropsychology and include meta-analyses; Dialogue provides a forum for publishing two distinct positions on controversial issues in a point-counterpoint format; Special Issue and Special Section consist of several articles linked thematically; Letter to the Editor responds to recent articles published in the Journal of the International Neuropsychological Society; and Book Review, which is considered but is no longer solicited.