Abstract
Traumatic brain injury (TBI), seizures, and dementia increase with age. There is a gap in understanding the associations of TBI, seizures, and medications such as antiseizure and antipsychotics with the progression of cognitive impairment across racial and ethnic groups.ImportanceTraumatic brain injury (TBI), seizures, and dementia increase with age. There is a gap in understanding the associations of TBI, seizures, and medications such as antiseizure and antipsychotics with the progression of cognitive impairment across racial and ethnic groups.To investigate the association of TBI and seizures with the risk of cognitive impairment among cognitively normal older adults and the role of medications in moderating the association.ObjectiveTo investigate the association of TBI and seizures with the risk of cognitive impairment among cognitively normal older adults and the role of medications in moderating the association.This multicenter cohort study was a secondary analysis of the Uniform Data Set collected between June 1, 2005, and June 30, 2020, from the National Alzheimer's Coordination Center. Statistical analysis was performed from February 1 to April 3, 2024. Data were collected from participants from 36 Alzheimer's Disease Research Centers in the US who were 65 years or older at baseline, cognitively normal at baseline (Clinical Dementia Rating of 0 and no impairment based on a presumptive etiologic diagnosis of AD), and had complete information on race and ethnicity, age, sex, educational level, and apolipoprotein E genotype.Design, Setting, and ParticipantsThis multicenter cohort study was a secondary analysis of the Uniform Data Set collected between June 1, 2005, and June 30, 2020, from the National Alzheimer's Coordination Center. Statistical analysis was performed from February 1 to April 3, 2024. Data were collected from participants from 36 Alzheimer's Disease Research Centers in the US who were 65 years or older at baseline, cognitively normal at baseline (Clinical Dementia Rating of 0 and no impairment based on a presumptive etiologic diagnosis of AD), and had complete information on race and ethnicity, age, sex, educational level, and apolipoprotein E genotype.Health history of TBI, seizures, or both conditions.ExposureHealth history of TBI, seizures, or both conditions.Progression to cognitive impairment measured by a Clinical Dementia Rating greater than 0.Main Outcomes and MeasuresProgression to cognitive impairment measured by a Clinical Dementia Rating greater than 0.Among the cohort of 7180 older adults (median age, 74 years [range, 65-102 years]; 4729 women [65.9%]), 1036 were African American or Black (14.4%), 21 were American Indian or Alaska Native (0.3%), 143 were Asian (2.0%), 332 were Hispanic (4.6%), and 5648 were non-Hispanic White (78.7%); the median educational level was 16.0 years (range, 1.0-29.0 years). After adjustment for selection basis using propensity score weighting, seizure was associated with a 40% higher risk of cognitive impairment (hazard ratio [HR], 1.40; 95% CI, 1.19-1.65), TBI with a 25% higher risk of cognitive impairment (HR, 1.25; 95% CI, 1.17-1.34), and both seizure and TBI were associated with a 57% higher risk (HR, 1.57; 95% CI, 1.23-2.01). The interaction models indicated that Hispanic participants with TBI and seizures had a higher risk of cognitive impairment compared with other racial and ethnic groups. The use of antiseizure medications (HR, 1.23; 95% CI, 0.99-1.53), antidepressants (HR, 1.32; 95% CI, 1.17-1.50), and antipsychotics (HR, 2.15; 95% CI, 1.18-3.89) was associated with a higher risk of cognitive impairment, while anxiolytic, sedative, or hypnotic use (HR, 0.88; 95% CI, 0.83-0.94) was associated with a lower risk.ResultsAmong the cohort of 7180 older adults (median age, 74 years [range, 65-102 years]; 4729 women [65.9%]), 1036 were African American or Black (14.4%), 21 were American Indian or Alaska Native (0.3%), 143 were Asian (2.0%), 332 were Hispanic (4.6%), and 5648 were non-Hispanic White (78.7%); the median educational level was 16.0 years (range, 1.0-29.0 years). After adjustment for selection basis using propensity score weighting, seizure was associated with a 40% higher risk of cognitive impairment (hazard ratio [HR], 1.40; 95% CI, 1.19-1.65), TBI with a 25% higher risk of cognitive impairment (HR, 1.25; 95% CI, 1.17-1.34), and both seizure and TBI were associated with a 57% higher risk (HR, 1.57; 95% CI, 1.23-2.01). The interaction models indicated that Hispanic participants with TBI and seizures had a higher risk of cognitive impairment compared with other racial and ethnic groups. The use of antiseizure medications (HR, 1.23; 95% CI, 0.99-1.53), antidepressants (HR, 1.32; 95% CI, 1.17-1.50), and antipsychotics (HR, 2.15; 95% CI, 1.18-3.89) was associated with a higher risk of cognitive impairment, while anxiolytic, sedative, or hypnotic use (HR, 0.88; 95% CI, 0.83-0.94) was associated with a lower risk.This study highlights the importance of addressing TBI and seizures as risk factors for cognitive impairment among older adults. Addressing the broader social determinants of health and bridging the health divide across various racial and ethnic groups are essential for the comprehensive management and prevention of dementia.Conclusions and RelevanceThis study highlights the importance of addressing TBI and seizures as risk factors for cognitive impairment among older adults. Addressing the broader social determinants of health and bridging the health divide across various racial and ethnic groups are essential for the comprehensive management and prevention of dementia.