Head trauma and in vivo measures of amyloid and neurodegeneration in a population-based study
ABSTRACT We determined whether head trauma was associated with amyloid deposition and neurodegeneration among individuals who were cognitively normal (CN) or had mild cognitive impairment (MCI).
Participants included 448 CN individuals and 141 individuals with MCI from the Mayo Clinic Study of Aging who underwent Pittsburgh compound B (PiB)-PET, fluorodeoxyglucose-PET, and MRI. Head trauma was defined as a self-reported brain injury with at least momentary loss of consciousness or memory. Regression models examined whether head trauma was associated with each neuroimaging variable (assessed as continuous and dichotomous measures) in both CN and MCI participants, controlling for age and sex.
Among 448 CN individuals, 74 (17%) self-reported a head trauma. There was no difference in any neuroimaging measure between CN subjects with and without head trauma. Of 141 participants with MCI, 25 (18%) self-reported a head trauma. MCI participants with a head trauma had higher amyloid levels (by an average 0.36 standardized uptake value ratio units, p = 0.002).
Among individuals with MCI, but not CN individuals, self-reported head trauma with at least momentary loss of consciousness or memory was associated with greater amyloid deposition, suggesting that head trauma may be associated with Alzheimer disease-related neuropathology. Differences between CN individuals and individuals with MCI raise questions about the relevance of head injury-PET abnormality findings in those with MCI.
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- "No difference in any neuroimaging measure between cognitive normal subjects with and without head trauma was found. However, of 141 participants with mild cognitive impairment (MCI), participants with a head trauma had higher amyloid levels (by an average 0.36 standardized uptake value ratio units, p ¼ 0.002), suggesting that head trauma may be associated with Alzheimer's disease-related neuropathology (Mielke et al., 2014). However, a smaller study found amyloid-b deposition with PET scan in 3 of 12 subjects with posttraumatic neuropsychological impairment (Kawai et al., 2013). "
ABSTRACT: A number of small studies and anecdotal reports have been suggested that sports involving repeated head trauma may have long-term risks of neurodegenerative disease. There are now plausible mechanisms for these effects, and a recognition that these problems do not just occur in former boxers, but in a variety of sports involving repeated concussions, and possibly also in sports in which low-level head trauma is common. These neurodegenerative effects potentially include increased risks of impaired cognitive function and dementia, Parkinson's disease, and amyotrophic lateral sclerosis. Many would argue for taking a precautionary approach and immediately banning or restricting sports such as boxing. However, there are important public health issues in terms of how wide the net should be cast in terms of other sports, and what remedial measures could be taken? This in turn requires a major research effort involving both clinical and basic research to understand the underlying mechanisms, leading from head trauma to neurodegenerative disease and epidemiologic studies to assess the long-term consequences. Copyright © 2015 Elsevier Inc. All rights reserved.Neurobiology of Aging 03/2015; 36(3). DOI:10.1016/j.neurobiolaging.2014.12.024 · 5.01 Impact Factor
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- "MMSE might be not adequately sensitive enough to detect extremely mild cognitive impairment, especially for people with prior high cognitive function. However, this finding could be comparable with previous studies, either in case–control studies or cohort studies on health care database analysis . Although the clinical manifestations were similar among the mTBI − D and mTBI + D groups, the ILOC appears to be a risk factor for the subsequent development of dementia in mTBI patients (5/6 vs. "
ABSTRACT: Recent epidemiology studies have indicated that traumatic brain injury (TBI) can increase the risk of developing neurodegenerative diseases such as Alzheimer's disease (AD). Amyloid-β (Aβ) plaques and neurofibrillary tangles are pathological indicators of AD. The accumulation of Aβ is considered the first step of AD pathophysiology. Compelling studies have supported the hypothesis that TBI accelerates the formation and accumulation of Aβ. These findings could link TBI with AD, although the research that reported these findings had limitations, particularly regarding mild TBI (mTBI) patients. The effects of mTBI on Aβ accumulation remain uncertain because of a lack of mTBI pathology data. Using amyloid-positron emission tomography (amyloid-PET), researchers can help to determine whether mTBI increases the accumulation of Aβ, which might be involved in the pathophysiological mechanisms of mTBI in AD, and could be a target for the treatment of neurodegenerative diseases associated with TBI. In this study, we recruited 27 mTBI patients with mTBI in mean 6years before this study (21 mTBI patients without cognitive impairment, 6 mTBI patients with cognitive impairment,) and 10 controls. All of them underwent mini-mental state examination, apolipoprotein E (APOE) genotyping, and amyloid-PET. The results show an increase of amyloid accumulation and allele frequency of APOE4 in the mTBI patients with cognitive impairment. These findings indicate that amyloid accumulation is an important indicator of cognitive impairment, and amyloid-PET should be a safe and useful tool for diagnosing amyloid-related cognitive impairment. APOE allele might play a role in the occurrence of cognitive impairment after mTBI. The contribution of mTBI to the amyloid accumulation requires further study, and mTBI patients should be recruited for longitudinal research with repeated amyloid-PET studies. Copyright © 2014 Elsevier B.V. All rights reserved.Journal of the Neurological Sciences 12/2014; 349(1-2). DOI:10.1016/j.jns.2014.12.032 · 2.47 Impact Factor
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ABSTRACT: Epidemiological studies reveal growing evidence that most cases of Alzheimer`s Disease (AD) likely involve a combination of genetic and environmental risk factors. Identifying and validating these risk factors remains one of the most critical scientific challenges. Several diseases appear to have strong implications for neurodegeneration leading to dementia. This risk encompasses different forms of cardiovascular disease, carotid atherosclerosis, history of hypertension or high cholesterol, Type II diabetes, stroke or transient ischemic attack and brain trauma. However, the molecular pathways that are common and central in the progression of these diseases and AD are not yet elucidated. Unveiling these critical mechanisms at the molecular level is necessary for the development of therapeutic strategies aimed at preventing AD progression. The Receptor for Advanced Glycation Endproducts (RAGE) plays a key role in all the diseases that represent a risk for AD. RAGE-mediated signaling also contributes to neurodegeneration in AD, suggesting that it may mediate the effect of risk factors in promoting AD. We will summarize the current knowledge on the role of RAGE in pathologies promoting AD and in AD progression. We will also provide evidence showing the relevance of RAGE-induced inflammation as a risk pathway that is implicated in AD pathophysiology.Histology and histopathology 07/2014; 30(2). · 2.10 Impact Factor