History of traumatic brain injury interferes with accurate diagnosis of Alzheimer’s dementia: a nation-wide case-control study

Abstract

Background: Traumatic brain injury (TBI) and Alzheimer's disease (AD) bear a complex relationship, potentially increasing risk of one another reciprocally. However, recent evidence suggests post-TBI dementia exists as a distinct neurodegenerative syndrome, confounding AD diagnostic accuracy in clinical settings. This investigation sought to evaluate TBI's impact on the accuracy of clinician-diagnosed AD using gold standard neuropathological criteria. Methods:In this preliminary analysis, data was acquired from the National Alzheimer's Coordinating Center (NACC), which aggregates clinical and neuropathologic information from Alzheimer's Disease Centers across the United States. Modified National Institute on Aging-Reagan criteria were applied to confirm AD by neuropathology.Results: Among participants with clinician-diagnosed AD, TBI history was associated with misdiagnosis (false positives) (OR = 1.351 (95% CI: 1.091 -1.674), p = 0.006). Among participants without clinician-diagnosed AD, TBI history was not associated with false negatives.Discussion: TBI moderates AD diagnostic accuracy. Possible AD misdiagnosis can mislead patients, influence treatment decisions, and confound research study designs. Further work examining the influence of TBI on dementia diagnosis is warranted.

Head injury and 25‐year risk of dementia

“…In addition, we were able to investigate the impact of head injury severity in the subset of hospitalized cases using standardized criteria 31 . It is also important to consider the impact of a head injury diagnosis on a dementia diagnosis 37 as well as the timing of dementia diagnosis after head injury diagnosis, as head injury‐related symptoms may be misdiagnosed as dementia, particularly in the time following the head injury. We addressed this by performing 1‐ and 2‐year wash‐out analyses in which associations were somewhat attenuated, but remained significant, which suggests that part of the association between head injury and dementia may be driven by dementia diagnoses occurring close to the time of head injury.…”

Traumatic brain injury alters neuropsychiatric symptomatology in all‐cause dementia

“…Center Uniform Data Set (NACC-UDS), showed that TBI history was associated with clinician misdiagnosis of Alzheimer's disease (increased false-positives evaluated using gold-standard autopsy neuropathology). 7 Despite extensive investigation into connections between (1) TBI and dementia or (2) NPS with cognitive decline in dementia, there is little research into the influence of TBI on NPS in the course of dementia development. NPS occurring after TBI are often transient; however, in a portion of the population, symptoms persist permanently and cause a significant decrease in quality of life, independent of associated dementia onset.…”

Brain Injury and Dementia in Pakistan: Current Perspectives

“…Recent evidence further clarifies the molecular mechanisms underlying TBI that trigger amyloid precursor protein (APP) and Tau cleavage mediating AD pathology in animals (68). Additionally, the relationship of TBI and AD has shown to be quite complex and the presence of TBI leads to misdiagnoses of AD, interferes with treatment plans and makes research studies difficult to interpret (69). However, Pakistan lacks state-of-the-art diagnostic assessment of dementia and its risk factors, including neuroimaging of brain injury and aging that are extremely limited in Pakistan due to the inadequate infrastructure and limited training of clinicians (63).…”