Clinical Features of Patients with Alzheimer’s Disease and a History of Traumatic Brain Injury

Abstract

Introduction Traumatic brain injury (TBI) has been associated with a greater risk of developing Alzheimer's disease (AD). Less is known about the clinical features of AD patients with TBI history. The objective of this study was to examine whether a history of TBI and specific injury characteristics are associated with differences in age of disease onset, cognitive features, and neuropsychiatric symptoms (NPSs) in AD patients. Methods Biomarker-proven AD patients (CSF or amyloid PET) were selected from the Amsterdam Dementia Cohort. TBI events were classified by age at injury (TBI <25 or ≥25 years) and TBI severity (loss of consciousness, multiple events). Cognitive composite scores were calculated from results of a neuropsychological test battery. NPSs were assessed with the Neuropsychiatric Inventory Questionnaire (NPI-Q). Linear regression analyses were utilized to examine associations between TBI, TBI characteristics, and clinical outcome measures. Results Among the 1,755 selected AD patients (mean age = 65.2 years), 166 (9.5%) had documented ≥1 TBI in their medical history. Overall, TBI history was not related to differences in age of disease onset, but age at injury <25 years old was associated with 2.3 years earlier age at symptom onset ( B = −2.34, p = 0.031). No significant associations were found between TBI history or TBI characteristics and differences in cognition or NPSs. Conclusion Our results underscore previous findings on the vulnerability of the brain during critical maturation phases and suggest that an early TBI may contribute to lower resilience to neurodegenerative changes.

Blunt Traumatic Brain Injury and Alzheimer Pathology

“…In other series, the follow-up between TBI and AD was a mean of 7.8 years [19] or up to 18 years after TBI [69]. This and another recent clinical study showing a lower percentage of APOE ε4 genotype in AD patients with a TBI history [70], like ours indicated that closed head injury is a factor in the development of AD among subjects lacking APOE ε4 alleles, whereas experimental studies showed that transgenic mice expressing human APOE ε4 are more susceptible than those express-ing APOE ε3 to closed head injury, probably related to a preventive function of APOE ε3 and an APOE ε4-related pathological function [71]. Thus, the role of the APOE genotype in the development of AD following TBI remains inconclusive and ambiguous [72].…”