This retrospective study used data from the National Alzheimer's Coordinating Center (NACC) database and compared neuropathologic, neuropsychiatric, motor, and neuropsychological features between those with and without chronic traumatic encephalopathy neuropathologic change (CTE-NC). Data were obtained from the NACC database from 2014 to December 2024, with the only inclusion criterion being evaluation for CTE-NC. Participants with CTE-NC were identified and matched approximately 1:4 to those without CTE-NC on demographics (age, education, sex) and staging of Alzheimer and Lewy body neuropathology. Chi-square tests and analyses of covariance (covarying for cognitive symptom duration, time to death, and cognitive diagnosis) compared neuropathologic features, history of traumatic brain injury (TBI), neuropsychiatric symptoms, parkinsonism features, and neuropsychological scores between groups. CTE-NC was present in 0.8% of participants (29/3,845) since 2014. Matching on a 1:4 ratio was achieved for 22 individuals and 1:3 for an additional 3, yielding a total comparison sample of 25 with CTE-NC and 97 without. All but 1 individual with CTE-NC were male with a mean age of 74.7 years (SD = 8.0). Moderate-to-severe Alzheimer neuropathology (54.0%) was common in those with CTE-NC while comorbid cortical or limbic Lewy inclusions were less frequent (8.0%). Compared with those without CTE-NC, those with CTE-NC had higher rates of hippocampal sclerosis (40.0% vs 9.6%; p < 0.001, V = 0.338), progressive supranuclear palsy (16.0% vs 3.1%; p = 0.013, V = 0.224), argyrophilic grain disease (28.0% vs 10,3%; p = 0.023, V = 0.206), other 4R tauopathies (16.7% vs 3.1%; p = 0.011, V = 0.231), other 3R + 4R tauopathies (8.3% vs 1.0%; p = 0.039, V = 0.187), aging-related tau astrogliopathy (33.0% vs 8.9%; p < 0.001, V = 0.313), and transactive response DNA binding protein 43 (TDP-43) inclusions (24.0% vs 7.0%; p = 0.017, V = 0.228). Those with CTE-NC had higher rates of TBI (45.8%) compared with those without CTE-NC (21.9%, p = 0.018, V = 0.217). Neuropsychological scores, neuropsychiatric symptoms, and parkinsonism symptoms did not differ between groups. CTE-NC was rare in NACC since 2014. Those with CTE-NC did not differ in clinical symptoms but had higher rates of hippocampal sclerosis, other tauopathies, and TDP-43 inclusions. In this clinicopathologic investigation using in vivo clinical data, although NACC lacks CTE-NC severity/distribution and repetitive head impact data for sensitivity analyses. Larger in vivo clinicopathologic studies are greatly needed to correlate CTE-NC with clinical features.
Schaffert et al. (Fri,) studied this question.