IMPORTANCE: Microglia, the resident immune cells of the central nervous system, play an important role in the brain’s response to injury and neurodegenerative processes. It has been proposed that ...prolonged microglial activation occurs after single and repeated traumatic brain injury, possibly through sports-related concussive and subconcussive injuries. Limited in vivo brain imaging studies months to years after individuals experience a single moderate to severe traumatic brain injury suggest widespread persistent microglial activation, but there has been little study of persistent glial cell activity in brains of athletes with sports-related traumatic brain injury. OBJECTIVE: To measure translocator protein 18 kDa (TSPO), a marker of activated glial cell response, in a cohort of National Football League (NFL) players and control participants, and to report measures of white matter integrity. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional, case-control study included young active (n = 4) or former (n = 10) NFL players recruited from across the United States, and 16 age-, sex-, highest educational level–, and body mass index–matched control participants. This study was conducted at an academic research institution in Baltimore, Maryland, from January 29, 2015, to February 18, 2016. MAIN OUTCOMES AND MEASURES: Positron emission tomography–based regional measures of TSPO using 11CDPA-713, diffusion tensor imaging measures of regional white matter integrity, regional volumes on structural magnetic resonance imaging, and neuropsychological performance. RESULTS: The mean (SD) ages of the 14 NFL participants and 16 control participants were 31.3 (6.1) years and 27.6 (4.9) years, respectively. Players reported a mean (SD) of 7.0 (6.4) years (range, 1-21 years) since the last self-reported concussion. Using 11CDPA-713 positron emission tomographic data from 12 active or former NFL players and 11 matched control participants, the NFL players showed higher total distribution volume in 8 of the 12 brain regions examined (P < .004). We also observed limited change in white matter fractional anisotropy and mean diffusivity in 13 players compared with 15 control participants. In contrast, these young players did not differ from control participants in regional brain volumes or in neuropsychological performance. CONCLUSIONS AND RELEVANCE: The results suggest that localized brain injury and repair, indicated by higher TSPO signal and white matter changes, may be associated with NFL play. Further study is needed to confirm these findings and to determine whether TSPO signal and white matter changes in young NFL athletes are related to later onset of neuropsychiatric symptoms.
Abstract
Objective
Because stress is a risk factor for Alzheimer’s disease (ad), characterizing individual differences in the stress response could help identify those who might be targeted in ...risk-prevention efforts. Studies measuring the stress response in individuals with mild cognitive impairment (MCI), however, are lacking, in part due to concerns that doing so would be too distressing to these individuals. In this study, we aimed to characterize the subjective response to an acute stressor in individuals with mild cognitive impairment (MCI).
Method
This study consisted of 20 community-dwelling individuals (9 with MCI and 11 cognitively normal individuals; 11 women) 60 years and older (Mean = 70.1, SD = 5.6) who underwent the Trier Social Stress Test (TSST). Subjects rated their subjective distress using a standardized visual analog scale at prespecified intervals 3 points prior to, and 6 points following, the TSST. Data were subjected to repeated measures analysis with sex as a covariate.
Results
Subjects with MCI rated the TSST as less stressful than their cognitively normal peers (p = 0.04), due to group differences in both post-TSST ratings of subjective distress (p = 0.013) and an increase from pre-TSST to post-TSST ratings of subjective distress (p = 0.04). No individuals withdrew from the study while participating in the TSST.
Conclusion(s)
Our finding that individuals with MCI reported experiencing lower distress than their cognitively normal peers in response to a laboratory-based stressor may help alleviate concerns regarding the risks of studying stress in this population. Future research with larger samples will be valuable in studying other determinants of the stress response in these individuals.
Introduction
The reasons why women are at higher risk than men for developing dementia are unclear. Although studies implicate sex differences in the effect of stress on cognitive functioning, ...whether stressful life events are associated with subsequent cognitive decline has received scant research attention.
Methods
In Wave 3 (1993–1996) of the Baltimore Epidemiologic Catchment Area study, 337 men and 572 women (mean age = 47 years) reported recent (within the last year) and remote (from 1981 until 1 year ago) traumatic events (eg, combat) and stressful life events (eg, divorce/separation). At Waves 3 and 4 (2004–2005), they completed the Mini Mental State Examination (MMSE) and a word‐list memory test. Multivariable models were used to examine the association between traumatic and stressful life events at Wave 3 and cognitive change by Wave 4.
Results
A greater number of recent stressful life events at Wave 3, but not of more remote stressful events, was associated with greater verbal memory decline by Wave 4 in women but not in men. Stressful events were not associated with change in MMSE, and there were no associations between traumatic events occurring at any time and subsequent memory or MMSE decline in either sex.
Conclusions
Unlike men, middle‐aged women with a greater number of recent stressful life events demonstrate memory decline over a decade later. Sex differences in cognitive vulnerability to stressful life events may underlie women's increased risk of memory impairment in late life, suggesting that stress reduction interventions may help prevent cognitive decline in women.
Multiple exposures to gadolinium-based contrast agents (GBCAs) is known to be associated with gadolinium deposition in the brain in certain patients. Such deposition has been correlated with specific ...brain MRI findings, although most available data is in patients with underlying neurologic disorders. We aim to prospectively evaluate brain MRI signal changes as well as neurologic and neuropsychologic testing results in women undergoing screening breast MRI.
In this IRB-approved, HIPAA-compliant prospective study, 9 women with 5 or more exposures to linear and/or macrocyclic GBCA due to screening breast MRI underwent noncontrast brain MRI, neurologic exam and neuropsychologic testing. Women with underlying neurologic, psychologic, hepatic or renal disorders were excluded.
The mean total number of GBCA exposures was 8 (standard deviation 2.7), with 63/72 (87%) of the exposures being linear agents. There was no association between brain MRI signal changes and abnormalities on neurologic or neuropsychologic examination. There was no association between total number of GBCA exposures and abnormalities on neurologic or neuropsychologic examination.
In this prospective exploratory study of 9 women with 5 or more GBCA exposures due to screening breast MRI, there was no association between brain MRI signal changes and clinical abnormalities on neurologic or neuropsychologic examination. While larger studies are needed in this patient population, the lack of clinical impact of multiple GBCA exposures in this study is reassuring.
•GBCA exposures and brain MRI signal changes showed no association in 9 healthy women with multiple GBCA exposures•In this study, there was no association between GBCA exposures and neurologic or neuropsychologic exam•Although this is reassuring for women undergoing annual breast cancer screening with MRI, larger studies are needed
Alzheimer's disease (AD) is a disabling, common cause of dementia, and agitation is one of the most common and distressing symptoms for patients with AD. Escitalopram for agitation in Alzheimer's ...disease (S-CitAD) tests a novel, clinically derived therapeutic approach to treat agitation in patients with AD.
S-CitAD is a NIH-funded, investigator-initiated, randomized, multicenter clinical trial. Participants receive a structured psychosocial intervention (PSI) as standard of care. Participants without sufficient response to PSI are randomized to receive 15 mg escitalopram/day or a matching placebo in addition to PSI. Primary outcome is the Modified Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (mADCS-CGIC).
S-CitAD will provide information about a practical, immediately available approach to treating agitation in patients with AD. S-CitAD may become a model of how to evaluate and predict treatment response in patients with AD and agitation as a neuropsychiatric symptom (ClinicalTrials.gov Identifier: NCT03108846).
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