A population‐based study of head injury, cognitive function and pathological markers

Abstract

Objective To assess associations between head injury (HI) with loss of consciousness (LOC), ageing and markers of later‐life cerebral pathology; and to explore whether those effects may help explain subtle cognitive deficits in dementia‐free individuals. Methods Participants (n = 502, age = 69–71) from the 1946 British Birth Cohort underwent cognitive testing (subtests of Preclinical Alzheimer Cognitive Composite), 18F‐florbetapir Aβ‐PET and MR imaging. Measures include Aβ‐PET status, brain, hippocampal and white matter hyperintensity (WMH) volumes, normal appearing white matter (NAWM) microstructure, Alzheimer’s disease (AD)‐related cortical thickness, and serum neurofilament light chain (NFL). LOC HI metrics include HI occurring: (i) >15 years prior to the scan (ii) anytime up to age 71. Results Compared to those with no evidence of an LOC HI, only those reporting an LOC HI>15 years prior (16%, n = 80) performed worse on cognitive tests at age 69–71, taking into account premorbid cognition, particularly on the digit‐symbol substitution test (DSST). Smaller brain volume (BV) and adverse NAWM microstructural integrity explained 30% and 16% of the relationship between HI and DSST, respectively. We found no evidence that LOC HI was associated with Aβ load, hippocampal volume, WMH volume, AD‐related cortical thickness or NFL (all p > 0.01). Interpretation Having a LOC HI aged 50’s and younger was linked with lower later‐life cognitive function at age ~70 than expected. This may reflect a damaging but small impact of HI; explained in part by smaller BV and different microstructure pathways but not via pathology related to AD (amyloid, hippocampal volume, AD cortical thickness) or ongoing neurodegeneration (serum NFL).

The 2022 Lady Estelle Wolfson lectureship on neurofilaments

“…Regarding sport‐related concussion research on Nf included American football, soccer, ice‐hockey, rugby and contact sports (Joseph et al, 2019; Pattinson et al, 2020). The evidence is however not yet conclusive at population level (James et al, 2021) or targeted at top professional football players (Cornali et al, 2022). A word of caution also comes from post‐mortem data which highlight the likelihood of multiple neuropathologies as source for increased body fluid Nf levels (Asken et al, 2022).…”

Traumatic brain injury and Alzheimer’s Disease biomarkers: A systematic review of findings from amyloid and tau positron emission tomography (PET)

“…85 James and colleagues (2021) also observed no associations between TBI with loss of consciousness (LOC) and amyloid status; however, TBI with LOC was associated with lower cognitive function on the digit symbol substitution test (DSST). 86 Evidence of a link between TBI with LOC and cognitive changes, but no association with amyloid deposition on PET, is somewhat contrary to the study by Asken and colleagues (2021) which found no evidence of an impact of TBI on either cognition or amyloid. 86 However, that study examined only mTBI subjects, which suggests LOC may be a better predictor of dementia-related cognitive changes than simply the presence or absence of a TBI.…”

“…These ROIs included measures of global amyloid status and/or burden, as well as the frontal, parietal, temporal, and occipital lobes, the corpus callosum and/or fornix, the anterior and the posterior cingulate, and the cuneus or precuneus (Table 4). [74][75][76][77][78][79][80][85][86][87][88][89][90][91][92][93][94][95] Global amyloid status and/or burden Schneider and colleagues (2019) found history of TBI to be associated with increased global cortical Florbetapir SUVRs in cognitively normal individuals. 89 Mielke and colleagues (2014) similarly observed no association between TBI and amyloid deposition in cognitively normal individuals via [ 11 C]-PiB, but amongst individuals with mild cognitive impairment (MCI), those with TBI had ~18% higher global amyloid and 5-fold higher odds of increased amyloid compared to those without TBI.…”

Clinical Efficacy and Safety of Eculizumab for Treating Myasthenia Gravis

“…Notably, two recently published retrospective analyses closely simulated clinical practice. James et al reported the analysis of 98 patients with gMG with a mean follow-up period of 2.7 years (42). All patients were subjected to eculizumab therapy and had undergone prior therapy (cholinesterase inhibitors, oral corticosteroids, or other immunosuppressive treatments) at the initiation of treatment.…”

“…The participants were divided into an eculizumab group and a control group. Remission was achieved in most patients, and the disease was controlled to a certain extent in each patient by week 12 of eculizumab treatment, according to the MG-ADL and quantitative myasthenia gravis (QMG) scores ( 42 ). Renato et al.…”