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1 Sex Differences in Associations Between APOE ε2 and Longitudinal Cognitive Decline
- Madeline Wood, Lisa Xiong, Yuen Yan Wong, Rachel F Buckley, Walter Swardfager, Mario Masellis, Andrew Lim, Emma Nichols, Renaud La Joie, Kaitlin Casaletto, Raj Kumar, Kristen Dams-O’Connor, Priya Palta, Kristen George, Claudia Satizabal, Lisa L Barnes, Julie A Schneider, Judy Pa, Adam Brickman, Sandra Black, Jennifer Rabin
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 405-406
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Objective:
Women have a greater lifetime risk of developing Alzheimer’s disease (AD) dementia than men, a sex/gender disparity that cannot be explained by female longevity alone. There is substantial evidence for sex differences in the effects of APOE £4 on risk for AD. While APOE e4 increases AD risk in both sexes, women who carry APOE e4 are disproportionately vulnerable to cognitive impairment and AD compared to their counterpart men. In contrast to APOE e4, APOE £2 is associated with slower cognitive decline and a lower risk of AD. Although a less robust literature, APOE e2 may also have sex-specific effects. Because APOE e2 is the rarest major APOE allele, well-powered studies are needed to examine sex-specific effects. The objective of the present study was to examine sex-specific associations of APOE e2 carriage with longitudinal cognitive decline in a large cohort of clinically unimpaired adults.
Participants and Methods:We used observational data from two sources: the National Alzheimer’s Coordinating Center (NACC) and the Rush Alzheimer’s Disease Center (ROS/MAP/MARS) studies. We included data from clinically unimpaired adults who were >50 years old at baseline who self-identified as non-Hispanic White (NHW) or non-Hispanic Black (NHB). Participants were categorized as APOE £2, £4, or £3/e3 carriers. APOE e2/e4 carriers were excluded. The same battery of neuropsychological tests was used to assess global cognition in participants from both data sources. Linear mixed models examined interactive associations of genotype (£2 or £4 vs. £3/£3), sex, and time on longitudinal cognition in NHW and NHB participants separately. Analyses were first performed in a pooled sample of NACC and ROS/MAP/MARS participants and if significant they were repeated separately in each data source.
Results:Across both data sources, 9,766 NHW (mean (SD) age=73.0(9.00) years, mean (SD) education=16.3(2.83) years, n(%) women=6,344(65.0)) and 2,010 NHB participants (mean(SD) age=71.3(7.59) years, mean(SD) education=14.9(3.10) years, n(%) women=1,583(78.8)) met inclusion criteria. Sex modified the association between APOE £2 and cognitive decline in NHW (ß=0.097, 95% CI: 0.023-0.172, pint=.01) but not NHB participants (ß=-0.011, 95% CI: -0.153-0.131, pint=.9). In sex-stratified analyses of NHW participants, APOE £2 (vs. £3/£3) carriage was associated with attenuated cognitive decline in men (ß=0.096, 95% CI: 0.037-0.155, p=.001), but not women (ß=-0.001, 95% CI: -0.044-0.043, p=.97). In analyses comparing men and women APOE £2 carriers, men exhibited slower cognitive decline than women (ß=0.120, 95% CI: 0.051-0.190, p=.001). Analyses performed separately in NACC and ROS/MAP revealed the same pattern of male-specific APOE £2 protection in NHW participants in both data sources.
Conclusions:In light of the longstanding view that APOE £2 protects against AD and dementia, our results provide evidence that APOE £2 is associated with attenuated cognitive decline in men but not women among NHW adults. This male-specific protection may contribute to sex differences in AD-related cognitive decline. Our findings have important implications for understanding the biological drivers of sex differences in AD risk, which is crucial for developing sex-specific strategies to prevent and treat AD dementia.
Neuropsychological Characteristics of the Confusional State Following Traumatic Brain Injury
- Rachel E. Keelan, Elaine J. Mahoney, Mark Sherer, Tessa Hart, Joseph Giacino, Yelena G. Bodien, Risa Nakase-Richardson, Kristen Dams-O’Connor, Thomas A. Novack, Rodney D. Vanderploeg
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- Journal:
- Journal of the International Neuropsychological Society / Volume 25 / Issue 3 / March 2019
- Published online by Cambridge University Press:
- 25 January 2019, pp. 302-313
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Objectives: Individuals with moderate–severe traumatic brain injury (TBI) experience a transitory state of impaired consciousness and confusion often called posttraumatic confusional state (PTCS). This study examined the neuropsychological profile of PTCS. Methods: Neuropsychometric profiles of 349 individuals in the TBI Model Systems National Database were examined 4 weeks post-TBI (±2 weeks). The PTCS group was subdivided into Low (n=46) and High Performing PTCS (n=45) via median split on an orientation/amnesia measure, and compared to participants who had emerged from PTCS (n=258). Neuropsychological patterns were examined using multivariate analyses of variance and mixed model analyses of covariance. Results: All groups were globally impaired, but severity differed across groups (F(40,506)=3.44; p<.001; ŋp2 =.206). Rate of forgetting (memory consolidation) was impaired in all groups, but failed to differentiate them (F(4,684)=0.46; p=.762). In contrast, executive memory control was significantly more impaired in PTCS groups than the emerged group: Intrusion errors: F(2,343)=8.78; p<.001; ŋp2=.049; False positive recognition errors: F(2,343)=3.70; p<.05; ŋp2=.021. However, non-memory executive control and other executive memory processes did not differentiate those in versus emerged from PTCS. Conclusions: Executive memory control deficits in the context of globally impaired cognition characterize PTCS. This pattern differentiates individuals in and emerged from PTCS during the acute recovery period following TBI. (JINS, 2019, 25, 302–313)
Integrating Interventions after Traumatic Brain Injury: A Synergistic Approach to Neurorehabilitation
- Kristen Dams-O'Connor, Wayne A. Gordon
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- Journal:
- Brain Impairment / Volume 14 / Issue 1 / May 2013
- Published online by Cambridge University Press:
- 03 May 2013, pp. 51-62
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Deficits in attention, processing speed and executive functioning are among the most commonly reported and functionally limiting cognitive impairments among individuals with TBI. Changes in mood can exacerbate cognitive deficits and reduce life quality. Contemporary hierarchical models of cognitive functioning suggest that attention/arousal processes underlie and support higher-order functions. Building on decades of clinical research, a synergistic, integrative approach to neurorehabilitation is described, which combines bottom-up and top-town cognitive interventions in addition to psychotherapeutic interventions for mood. This approach is intended to address directly impairments in both foundational (i.e., attention) and higher-order (i.e., executive functions) processes. Executive dysfunction is addressed in a top-down fashion through the application of a series of problem-solving and emotional regulation modules that teach and integrate strategies that can be generalised across situations with practice. Attention, arousal and information processing are necessary prerequisites of successful higher-order thinking, attention skills, and are addressed in a bottom-up fashion through intensive individualised attention and processing training tasks. Combining top-down and bottom-up approaches within a comprehensive day-treatment programme can effect a synergistic improvement of overall functioning.