Interactive Effects of Racial Identity and Repetitive Head Impacts on Cognitive Function, Structural MRI-Derived Volumetric Measures, and Cerebrospinal Fluid Tau and Aβ

Background and Objectives:Late neuropathologies of repetitive head impacts from contact sports can include chronic traumatic encephalopathy (CTE) and white matter degeneration. White matter hyperintensities (WMH) on fluid attenuated inversion recovery (FLAIR) MRI scans are often viewed as microvascular disease from vascular risk, but might have unique underlying pathologies and risk factors in the setting of repetitive head impacts. We investigated the neuropathological correlates of antemortem WMH in brain donors exposed to repetitive head impacts. The association between WMH, and repetitive head impact exposure and informant-reported cognitive and daily function were tested.Methods:This imaging-pathological correlation study included symptomatic deceased men exposed to repetitive head impacts. Donors had antemortem FLAIR scans from medical records and were without evidence of CNS neoplasm, large vessel infarcts, hemorrhage, and/or encephalomalacia. WMH were quantified using log-transformed values for total lesion volume (TLV), calculated using the lesion prediction algorithm from the Lesion Segmentation Toolbox. Neuropathological assessments included semi-quantitative ratings of white matter rarefaction, cerebrovascular disease, p-tau severity (CTE stage, dorsolateral frontal cortex), and Aβ. Among football players, years of play was a proxy for repetitive head impact exposure. Retrospective informant-reported cognitive and daily function were assessed using the Cognitive Difficulties Scale (CDS) and Functional Activities Questionnaire (FAQ). Regression models controlled for demographics, diabetes, hypertension, and MRI resolution. Statistical significance was defined as p<0.05.Results:The sample included 75 donors: 67 football players and 8 non-football contact sport athletes and/or military veterans. Dementia was the most common MRI indication (64%). Fifty-three (70.7%) had CTE at autopsy. Log-TLV was associated with white matter rarefaction (OR=2.32, 95% CI=1.03,5.24, p=0.04), arteriolosclerosis (OR=2.38, 95% CI=1.02,5.52, p=0.04), CTE stage (OR=2.58, 95% CI=1.17,5.71, p=0.02), and dorsolateral frontal p-tau severity (OR=3.03, 95% CI=1.32,6.97, p=0.01). There was no association with Aβ. More years of football play was associated with log-TLV (b=0.04, 95% CI=0.01,0.06, p=0.01). Greater log-TLV correlated with higher FAQ (unstandardized beta=4.94, 95% CI=0.42,8.57, p=0.03) and CDS scores (unstandardized beta=15.35, 95% CI=-0.27,30.97, p=0.05).Discussion:WMH might capture long-term white matter pathologies from repetitive head impacts, including those from white matter rarefaction and p-tau, in addition to microvascular disease. Prospective imaging-pathological correlation studies are needed.Classification of Evidence:This study provides Class IV evidence of associations between FLAIR white matter hyperintensities, and neuropathological changes (white matter rarefaction, arteriolosclerosis, p-tau accumulation), years of American football play, and reported cognitive symptoms in symptomatic brain donors exposed to repetitive head impacts.

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Late contributions of repetitive head impacts and TBI to depression symptoms and cognition

Neurology ◽

10.1212/wnl.0000000000010040 ◽

2020 ◽

Vol 95 (7) ◽

pp. e793-e804 ◽

Cited By ~ 1

Author(s):

Michael L. Alosco ◽

Yorghos Tripodis ◽

Zachary H. Baucom ◽

Jesse Mez ◽

Thor D. Stein ◽

...

Keyword(s):

Geriatric Depression Scale ◽

Depression Scale ◽

Later Life ◽

Depression Symptoms ◽

Neurocognitive Performance ◽

Contact Sport ◽

Cross Sectional ◽

Head Impacts ◽

Repetitive Head Impacts ◽

History Of

ObjectiveTo test the hypothesis that repetitive head impacts (RHIs), like those from contact sport play and traumatic brain injury (TBI) have long-term neuropsychiatric and cognitive consequences, we compared middle-age and older adult participants who reported a history of RHI and/or TBI with those without this history on measures of depression and cognition.MethodsThis cross-sectional study included 13,323 individuals (mean age, 61.95; 72.5% female) from the Brain Health Registry who completed online assessments, including the Ohio State University TBI Identification Method, the Geriatric Depression Scale (GDS-15), and the CogState Brief Battery and Lumos Labs NeuroCognitive Performance Tests. Inverse propensity-weighted linear regressions accounting for age, sex, race/ethnicity, and education tested the effects of RHI and TBI compared to a non-RHI/TBI group.ResultsA total of 725 participants reported RHI exposure (mostly contact sport play and abuse) and 7,277 reported TBI (n = 2,604 with loss of consciousness [LOC]). RHI (β, 1.24; 95% CI, 0.36–2.12), TBI without LOC (β, 0.43; 95% CI, 0.31–0.54), and TBI with LOC (β, 0.75; 95% CI, 0.59–0.91) corresponded to higher GDS-15 scores. While TBI with LOC had the most neuropsychological associations, TBI without LOC had a negative effect on CogState Identification (β, 0.004; 95% CI, 0.001–0.01) and CogState One Back Test (β, 0.004; 95% CI, 0.0002–0.01). RHI predicted worse CogState One Back Test scores (β, 0.02; 95% CI, −0.01 to 0.05). There were RHI × TBI interaction effects on several neuropsychological subtests, and participants who had a history of both RHI and TBI with LOC had the greatest depression symptoms and worse cognition.ConclusionsRHI and TBI independently contributed to worse mid- to later-life neuropsychiatric and cognitive functioning.

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