Dataset Information

Sex-specific incident dementia in patients with central nervous system trauma.

ABSTRACT:

Introduction

Despite evidence that central nervous system (CNS) trauma, including traumatic brain injury and spinal cord injury, can cause sustained neurocognitive impairment, it remains unclear whether trauma-related variables are associated with incident dementia independently of other known risk factors.

Methods

All adults without dementia entering the health-care system with diagnoses of CNS trauma were examined for occurrence of dementia. All trauma-related variables were examined as predictors in sex-specific Cox regression models, controlling for other known risk factors.

Results

Over a median follow-up of 52 months, 32,834 of 712,708 patients (4.6%) developed dementia. Traumatic brain injury severity and spinal cord injury interacted with age to influence dementia onset; women were at a greater risk of developing dementia earlier than men, all other factors being equal.

Discussion

Risk stratification of patients with CNS trauma by sex is vital in identifying those most likely to develop dementia and in understanding the course and modifying factors.

SUBMITTER: Mollayeva T

PROVIDER: S-EPMC6495080 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Sex-specific incident dementia in patients with central nervous system trauma.

Mollayeva Tatyana T Hurst Mackenzie M Escobar Michael M Colantonio Angela A

Alzheimer's & dementia (Amsterdam, Netherlands) 20190429

<h4>Introduction</h4>Despite evidence that central nervous system (CNS) trauma, including traumatic brain injury and spinal cord injury, can cause sustained neurocognitive impairment, it remains unclear whether trauma-related variables are associated with incident dementia independently of other known risk factors.<h4>Methods</h4>All adults without dementia entering the health-care system with diagnoses of CNS trauma were examined for occurrence of dementia. All trauma-related variables were exa ...[more]

PMID: 31065582

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Project description:Vitamin D3 (VitD) insufficiency is postulated to represent a major modifiable risk factor for multiple sclerosis (MS). While low VitD levels strongly correlate with higher MS risk in white populations, this is not the case for other ethnic groups, suggesting the existence of a genetic component. Moreover, VitD supplementation studies in MS so far have not shown a consistent benefit. We sought to determine whether direct manipulation of VitD levels modulates central nervous system autoimmune disease in a sex-by-genotype-dependent manner. To this end, we used a dietary model of VitD modulation, together with the autoimmune animal model of MS, experimental autoimmune encephalomyelitis (EAE). To assess the impact of genotype-by-VitD interactions on EAE susceptibility, we utilized a chromosome substitution (consomic) mouse model that incorporates the genetic diversity of wild-derived PWD/PhJ mice. High VitD was protective in EAE in female, but not male C57BL/6J (B6) mice, and had no effect in EAE-resistant PWD/PhJ (PWD) mice. EAE protection was accompanied by sex- and genotype-specific suppression of proinflammatory transcriptional programs in CD4 T effector cells, but not CD4 regulatory T cells. Decreased expression of proinflammatory genes was observed with high VitD in female CD4 T effector cells, specifically implicating a key role of MHC class II genes, interferon gamma, and Th1 cell-mediated neuroinflammation. In consomic strains, effects of VitD on EAE were also sex- and genotype dependent, whereby high VitD: (1) was protective, (2) had no effect, and (3) unexpectedly had disease-exacerbating effects. Systemic levels of 25(OH)D differed across consomic strains, with higher levels associated with EAE protection only in females. Analysis of expression of key known VitD metabolism genes between B6 and PWD mice revealed that their expression is genetically determined and sex specific and implicated Cyp27b1 and Vdr as candidate genes responsible for differential EAE responses to VitD modulation. Taken together, our results support the observation that the association between VitD status and MS susceptibility is genotype dependent and suggest that the outcome of VitD status in MS is determined by gene-by-sex interactions.

Dataset Information

Sex-specific incident dementia in patients with central nervous system trauma.

Introduction

Methods

Results

Discussion

Publications

Sex-specific incident dementia in patients with central nervous system trauma.

Similar Datasets

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