BLOG: TBI linked to earlier onset of neurodegenerative disease
There is increasingly strong evidence that traumatic brain injuries raise the risk for future Alzheimer’s disease.
While research has most heavily focused on Alzheimer’s disease (AD), emerging evidence also suggests that traumatic brain injury (TBI) may be a risk factor for many forms of proteinopathic neurodegenerative diseases, including Parkinson’s disease (PD), Lewy body dementia, amyotrophic lateral sclerosis and others.
It can be challenging to determine whether an increased incidence or prevalence of TBI in certain individuals, particularly those with neurodegenerative movement disorders such as PD, represents greater risk or simply reverse causality. In other words, it is possible that in the early stages of the disorder, even before PD has been diagnosed, patients have subtle motor changes and are therefore more likely to fall and sustain a head injury.
To avoid this problem, my colleagues and I evaluated the age of diagnosis of PD as well as the age of onset of cognitive symptoms in two other neurodegenerative disorders, progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). We felt that the risk of presymptomatic falls shouldn’t vary, regardless of whether the patient became symptomatic at age 50 or 70.
For this research, which was presented at the 2021 Alzheimer’s Association International Conference (Spiegel et al.), we retrospectively analyzed data from the National Alzheimer’s Coordinating Centers (NACC) database, which collects and pools demographic, clinical and neuropathological (autopsy) data from 32 AD research centers around the country. Some of these centers also do research on PD and other neurodegenerative disorders, so the data set includes primary PD cases, patients who had both AD and PD, and those who were normal controls when they first signed up, but went on to develop PD. All in all, we analyzed data from 423 PD patients, including 53 with a history of TBI.
We found that TBI was associated with a significantly earlier age of onset in PD, PSP and CBD. For example, patients with a history of TBI had a 4.9-year earlier age of PD onset, and those who reported having a TBI with loss of consciousness for more than 5 minutes had a 9.9-year earlier age of PD onset.
In addition to looking at age at onset, we also reviewed the autopsy data. We found that despite the earlier onset of PD, there was no significant difference in the age of death between those who had a prior TBI and those who didn’t. Even more importantly, a prior TBI was not associated with greater nerve cell loss in the substantia nigra region of the brain that is implicated in PD. This is an intriguing finding. If the TBI isn’t worsening the underlying nerve damage, why would those patients experience symptoms earlier?
One theory is that TBI accelerates many pathological processes in the brain in ways that are too small for us to detect with current science. Perhaps it is some combination of affected pathways that leads to earlier symptoms. Another possibility is that the TBI lowers the threshold for later life neurodegenerative brain changes to become symptomatic. In other words, even when the underlying nerve cell damage or protein accumulation is exactly the same, the TBI has depleted the brain’s reserves or made it less resilient to future injury, making the patient become symptomatic earlier in the course of the disease.
These are preliminary findings. There is much more we could learn in the future with better data or longitudinal studies that follow patients with known TBI. For example, it would be great to have clinical reports or standardized measures of TBI severity, rather than just self-reported data that is more subject to error. We’d also like to know whether the age at TBI, years since TBI, severity of TBI, where they hit their head or any post-TBI interventions affect the onset of PD or other neurodegenerative disease symptoms.
One thing is certain: Combining data on TBI with data on neurodegenerative disorders like AD and PD diseases holds great potential for better understanding the ways in which brain function can go awry and identifying strategies for prevention or treatment.
Reference:
- Spiegel J, et al. Alzheimer’s Dement. 2021;doi.org/10.1002/alz.051517.
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Jonathan Spiegel double majored in neuroscience and philosophy during his undergraduate years at Brown University and is now in his third year at the Warren Alpert School of Medicine at Brown University, with plans to go into neurology. His research with the Brain Health Imaging Institute at Weill Cornell focuses on the relationship between traumatic brain injury and neurodegenerative diseases.
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