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5 LIfestyle for BRAin Health (LIBRA) Modifiable Factors Risk Score and Concussion History Associations with Cognition in Older Former National Football League Players.
- Benjamin L Brett, Neelum T Aggarwal, Avinash Chandran, Zachary Y Kerr, Samuel R Walton, J.D. DeFreese, Kevin M Guskiewicz, Ruben J Echemendia, William P Meehan III, Michael A McCrea, Rebekah Mannix
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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. 305-306
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Objective:
Traumatic brain injury is one of several recognized risk factors for cognitive decline and neurodegenerative disease. Currently, risk scores involving modifiable risk/protective factors for dementia have not incorporated head injury history as part of their overall weighted risk calculation. We investigated the association between the LIfestyle for BRAin Health (LIBRA) risk score with odds of mild cognitive impairment (MCI) diagnosis and cognitive function in older former National Football League (NFL) players, both with and without the influence of concussion history.
Participants and Methods:Former NFL players, ages ≥ 50 (N=1050; mean age=61.1±5.4-years), completed a general health survey including self-reported medical history and ratings of function across several domains. LIBRA factors (weighted value) included cardiovascular disease (+1.0), hypertension (+1.6), hyperlipidemia (+1.4), diabetes (+1.3), kidney disease (+1.1), cigarette use history (+1.5), obesity (+1.6), depression (+2.1), social/cognitive activity (-3.2), physical inactivity (+1.1), low/moderate alcohol use (-1.0), healthy diet (-1.7). Within Group 1 (n=761), logistic regression models assessed the association of LIBRA scores and independent contribution of concussion history with the odds of MCI diagnosis. A modified-LIBRA score incorporated concussion history at the level planned contrasts showed significant associations across concussion history groups (0, 1-2, 3-5, 6-9, 10+). The weighted value for concussion history (+1.9) within the modified-LIBRA score was based on its proportional contribution to dementia relative to other LIBRA risk factors, as proposed by the 2020 Lancet Commission Report on Dementia Prevention. Associations of the modified-LIBRA score with odds of MCI and cognitive function were assessed via logistic and linear regression, respectively, in a subset of the sample (Group 2; n=289) who also completed the Brief Test of Adult Cognition by Telephone (BTACT). Race was included as a covariate in all models.
Results:The median LIBRA score in the Group 1 was 1.6(IQR= -1, 3.6). Standard and modified-LIBRA median scores were 1.1(IQR= -1.3, 3.3) and 2(IQR= -0.4, 4.6), respectively, within Group 2. In Group 1, LIBRA score was significantly associated with odds of MCI diagnosis (odds ratio[95% confidence interval]=1.27[1.19, 1.28], p <.001). Concussion history provided additional information beyond LIBRA scores and was independently associated with odds of MCI; specifically, odds of MCI were higher among those with 6-9 (Odds Ratio[95% confidence interval]; OR=2.54[1.21, 5.32], p<.001), and 10+ (OR=4.55;[2.21, 9.36], p<.001) concussions, compared with those with no prior concussions. Within Group 2, the modified-LIBRA score was associated with higher odds of MCI (OR=1.61[1.15, 2.25]), and incrementally improved model information (0.04 increase in Nagelkerke R2) above standard LIBRA scores in the same model. Modified-LIBRA scores were inversely associated with BTACT Executive Function (B=-0.53[0.08], p=.002) and Episodic Memory scores (B=-0.53[0.08], p=.002).
Conclusions:Numerous modifiable risk/protective factors for dementia are reported in former professional football players, but incorporating concussion history may aid the multifactorial appraisal of cognitive decline risk and identification of areas for prevention and intervention. Integration of multi-modal biomarkers will advance this person-centered, holistic approach toward dementia reduction, detection, and intervention.
2 Contributions of Cardiovascular Disease Burden and Concussion History on Cognitive Function in Older Former National Football League Players.
- Benjamin L Brett, Alyssa Leitzke, Zachary Y Kerr, Neelum T Aggarwal, Avinash Chandran, Samuel R Walton, Rebekah Mannix, Landon B Lempke, J.D. DeFreese, Ruben J Echemendia, Kevin M Guskiewicz, William P Meehan III, Michael A McCrea
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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. 302-303
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Objective:
Traumatic brain injury and cardiovascular disease (CVD) are modifiable risk factors for cognitive decline and dementia. Greater concussion history can potentially increase risk for cerebrovascular changes associated with cognitive decline and may compound effects of CVD. We investigated the independent and dynamic effects of CVD/risk factor burden and concussion history on cognitive function and odds of mild cognitive impairment (MCI) diagnoses in older former National Football League (NFL) players.
Participants and Methods:Former NFL players, ages 50-70 (N=289; mean age=61.02±5.33 years), reported medical history and completed the Brief Test of Adult Cognition by Telephone (BTACT). CVD/risk factor burden was characterized as ordinal (0-3+) based on the sum of the following conditions: coronary artery disease/myocardial infarction, chronic obstructive pulmonary disease, hypertension, hyperlipidemia, sleep apnea, type-I and II diabetes. Cognitive outcomes included BTACT Executive Function and Episodic Memory Composite Z-scores (standardized on age- and education-based normative data), and the presence of physician diagnosed (self-reported) MCI. Concussion history was discretized into five groups: 0, 1-2, 3-5, 6-9, 10+. Linear and logistic regression models were fit to test independent and joint effects of concussion history and CVD burden on cognitive outcomes and odds of MCI. Race (dichotomized as White and Non-white due to sample distribution) was included in models as a covariate.
Results:Greater CVD burden (unstandardized beta [standard error]; B=-0.10[0.42], p=.013, and race (B=0.622[0.09], p<.001), were associated with lower executive functioning. Compared to those with 0 prior concussions, no significant differences were observed for those with 1-2, 3-5, 6-9, or 10+ prior concussions (ps >.05). Race (B=0.61[.13], p<.001), but not concussion history or CVD burden, was associated with episodic memory. There was a trend for lower episodic memory scores among those with 10+ prior concussion compared to those with no prior concussions (B=-0.49[.25], p=.052). There were no significant differences in episodic memory among those with 1-2, 3-5, or 6-9 prior concussions compared to those with 0 prior concussions (ps>.05). CVD burden (B=0.35[.13], p=.008), race (greater odds in Non-white group; B=0.82[.29], p=.005), and greater concussion history (higher odds of diagnosis in 10+ group compared to those with 0 prior concussions; B=2.19[0.78], p<.005) were associated with higher odds of MCI diagnosis. Significant interaction effects between concussion history and CVD burden were not observed for any outcome (ps >.05).
Conclusions:Lower executive functioning and higher odds of MCI diagnosis were associated with higher CVD burden and race. Very high concussion history (10+) was selectively associated with higher odds of MCI diagnosis. Reduction of these modifiable factors may mitigate adverse outcomes in older contact sport athletes. In former athletes, consideration of CVD burden is particularly pertinent when assessing executive dysfunction, considered to be a common cognitive feature of traumatic encephalopathy syndrome, as designated by the recent diagnostic criteria. Further research should investigate the social and structural determinants contributing to racial disparities in long-term health outcomes within former NFL players.
A dominance analysis of subjective cognitive complaint comorbidities in former professional football players with and without mild cognitive impairment
- Benjamin L. Brett, Zachary Yukio Kerr, Avinash Chandran, Samuel Walton, Neelum T. Aggarwal, Katherine Gifford, Rebekah Mannix, J. D. DeFreese, Ruben J. Echemendia, Kevin M. Guskiewicz, William P. Meehan III, Michael A. McCrea
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue 6 / July 2023
- Published online by Cambridge University Press:
- 30 August 2022, pp. 582-593
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Objectives:
Subjective cognitive difficulties (SCDs) are associated with factors commonly reported in older adults and former contact sport athletes, regardless of objective cognitive decline. We investigated the relative contribution of these factors to SCD in former National Football League (NFL)-players with and without a diagnosis of mild cognitive impairment (MCI).
Methods:Former NFL players (n = 907) aged ≥ 50 years (mean = 64.7 ± 8.9), with (n = 165) and without (n = 742) a diagnosis of MCI completed health questionnaires. Multivariable regression and dominance analyses determined the relative importance of SCD factors on SCD: 1) depression, 2) anxiety, 3) sleep disturbance, 4) pain interference, 5) ability to participate in social roles and activities, 6) stress-related events, 7) fatigue, 8) concussion history, and 9) education. SCD outcomes included Neuro-QoL Emotional-Behavioral Dyscontrol and the PROMIS Cognitive Function. Fisher’s z-transformation compared comorbid contributing factors to SCD across MCI and non-MCI groups.
Results:Complete dominance of anxiety was established over most comorbid factors across the MCI and non-MCI groups. Fatigue also exhibited complete dominance over most comorbid factors, though its influence in the MCI group was less robust (general dominance). Average contributions to variance accounted for by comorbid factors to ratings of SCD across MCI and non-MCI groups did not statistically differ (Z-statistics <1.96, ps>.05).
Conclusions:Anxiety and fatigue are the most robust factors associated with SCD in former professional football players across various combinations of clinical presentations (different combinations of comorbid factors), regardless of documented cognitive impairment. Self-reported deficits may be less reliable in detecting objective impairment in the presence of these factors, with multidimensional assessment being ideal.
Properties of the Cognitive Function Battery for the MIND Diet Intervention to Prevent Alzheimer’s Disease
- Kristin R. Krueger, Klodian Dhana, Neelum T. Aggarwal, Konstantinos Arfanakis, Vincent J. Carey, Frank M. Sacks, Lisa L. Barnes
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- Journal:
- Journal of the International Neuropsychological Society / Volume 28 / Issue 8 / September 2022
- Published online by Cambridge University Press:
- 06 October 2021, pp. 790-797
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Objective:
To evaluate the properties of the cognitive battery used in the MIND Diet Intervention to Prevent Alzheimer’s Disease. The MIND Diet Intervention is a randomized control trial to determine the relative effectiveness of the MIND diet in slowing cognitive decline and reducing brain atrophy in older adults at risk for Alzheimer’s dementia.
Methods:The MIND cognitive function battery was administered at baseline to 604 participants of an average age of 70 years, who agreed to participate in the diet intervention study, and was designed to measure change over time. The battery included 12 cognitive tests, measuring the 4 cognitive domains of executive function, perceptual speed, episodic memory, and semantic memory. We conducted a principal component analysis to examine the consistency between our theoretical domains and the statistical performance of participants in each domain. To further establish the validity of each domain, we regressed the domain scores against a late-life cognitive activity score, controlling for age, race, sex, and years of education.
Results:Four factors emerged in the principal component analyses that were similar to the theoretical domains. In regression equations, we found the expected associations with age, education, and late-life cognitive activity with each of the four cognitive domains.
Conclusions:These results indicate that the MIND cognitive battery is a comprehensive and valid battery of four separate domains of cognitive function that can be used in diet intervention trials for older adults.
Higher circulating α-carotene was associated with better cognitive function: an evaluation among the MIND trial participants
- Xiaoran Liu, Klodian Dhana, Jeremy D. Furtado, Puja Agarwal, Neelum T. Aggarwal, Christy Tangney, Nancy Laranjo, Vincent Carey, Lisa L. Barnes, Frank M. Sacks
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- Journal:
- Journal of Nutritional Science / Volume 10 / 2021
- Published online by Cambridge University Press:
- 16 August 2021, e64
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There is emerging evidence linking fruit and vegetable consumption and cognitive function. However, studies focusing on the nutrients underlying this relationship are lacking. We aim to examine the association between plasma nutrients and cognition in a population at risk for cognitive decline with a suboptimal diet. The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) trial is a randomized controlled intervention that examines the effects of the MIND diet to prevent cognitive decline. The primary outcome is global cognition. A multivariate linear model was used to investigate the association between blood nutrients and global and/or domain-specific cognition. The model was adjusted for age, sex, education, study site, smoking status, cognitive activities and physical activities. High plasma α-carotene was associated with better global cognition. Participants in the highest tertile of plasma α-carotene had a higher global cognition z score of 0⋅17 when compared with individuals in the lowest tertile (P 0⋅002). Circulating α-carotene levels were also associated with higher semantic memory scores (P for trend 0⋅007). Lutein and zeaxanthin (combined) was positively associated with higher semantic memory scores (P for trend 0⋅009). Our study demonstrated that higher α-carotene levels in blood were associated with higher global cognition scores in a US population at risk for cognitive decline. The higher α-carotene levels in blood reflected greater intakes of fruits, other types of vegetables and lesser intakes of butter and margarine and meat. The higher circulating levels of lutein plus zeaxanthin reflected a dietary pattern with high intakes of fruits, green leafy, other vegetables and cheese, and low consumption of fried foods. Objective nutrient markers in the blood can better characterize dietary intake, which may facilitate the implementation of a tailored dietary intervention for the prevention of cognitive decline.