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

Abstract

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. In this preliminary analysis, data were acquired from the National Alzheimer’s Coordinating Centre (NACC), which aggregates clinical and neuropathologic information from Alzheimer’s disease centres across the United States. Modified National Institute on Aging-Reagan criteria were applied to confirm AD by neuropathology. 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. 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.

Keywords:

• Traumatic brain injury
• Alzheimer’s disease
• dementia
• chronic traumatic encephalopathy
• diagnostic accuracy
• neuropathology
• neurodegeneration
• acquired brain injury
• neurology

Acknowledgements

NACC data are contributed by the NIA funded ADCs: P30 AG019610 (PI Eric Reiman, MD), P30 AG013846 (PI Neil Kowall, MD), P50 AG008702 (PI Scott Small, MD), P50 AG025688 (PI Allan Levey, MD, PhD), P50 AG047266 (PI Todd Golde, MD, PhD), P30 AG010133 (PI Andrew Saykin, PsyD), P50 AG005146 (PI Marilyn Albert, PhD), P50 AG005134 (PI Bradley Hyman, MD, PhD), P50 AG016574 (PI Ronald Petersen, MD, PhD), P50 AG005138 (PI Mary Sano, PhD), P30 AG008051 (PI Thomas Wisniewski, MD), P30 AG013854 (PI M. Marsel Mesulam, MD), P30 AG008017 (PI Jeffrey Kaye, MD), P30 AG010161 (PI David Bennett, MD), P50 AG047366 (PI Victor Henderson, MD, MS), P30 AG010129 (PI Charles DeCarli, MD), P50 AG016573 (PI Frank LaFerla, PhD), P50 AG005131 (PI James Brewer, MD, PhD), P50 AG023501 (PI Bruce Miller, MD), P30 AG035982 (PI Russell Swerdlow, MD), P30 AG028383 (PI Linda Van Eldik, PhD), P30 AG053760 (PI Henry Paulson, MD, PhD), P30 AG010124 (PI John Trojanowski, MD, PhD), P50 AG005133 (PI Oscar Lopez, MD), P50 AG005142 (PI Helena Chui, MD), P30 AG012300 (PI Roger Rosenberg, MD), P30 AG049638 (PI Suzanne Craft, PhD), P50 AG005136 (PI Thomas Grabowski, MD), P50 AG033514 (PI Sanjay Asthana, MD, FRCP), P50 AG005681 (PI John Morris, MD), P50 AG047270 (PI Stephen Strittmatter, MD, PhD).

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The NACC database is funded by National Institute on Aging, U.S. National Institutes of Health Grant [U01 AG016976].