Medical and Psychiatric Risk Factors for Dementia in Veterans with and without Traumatic Brain Injury (TBI): A Nationwide Cohort Study.

BACKGROUND: Traumatic brain injury (TBI) is a risk factor for dementia and is common, especially among Veterans. It is unknown whether TBI exposure moderates the effect of other common medical/psychiatric comorbidities that are also risk factors for dementia. If treatable or preventable risk factors have a different impact on TBI-exposed Veterans, then this may have important public health implications for dementia prevention. OBJECTIVES: Determine prevalence of common medical/psychiatric comorbidities and associated risk of dementia in Veterans with versus without TBI. DESIGN: Observational cohort. SETTING: Nationwide Veterans Health Administrative data 2001-2019. PARTICIPANTS: After excluding baseline dementia, Veterans age ≥55 years with TBI (N=95,139) were age/sex/race-matched 1:2 with Veterans without TBI (N=190,278). MEASUREMENTS: We compared prevalence of hypertension, coronary artery disease (CAD), diabetes, cerebrovascular disease (CVD), epilepsy, depression, and post-traumatic stress disorder (PTSD) among Veterans with and without TBI. We calculated risk of incident dementia associated with each comorbidity using multivariable hazard ratios (HR) with Fine-Grey competing risk of death adjusted for baseline demographics. We estimated population attributable fraction (PAF) of dementia due to each comorbidity among Veterans with versus without TBI. RESULTS: Prevalence of all comorbidities were significantly more prevalent (5.7% to 21.5% higher) among Veterans compared to those without TBI. All comorbidities were associated with increased risk of dementia in both groups. There were significant interactions between comorbidities and TBI in which HRs were slightly lower among Veterans with TBI (adjusted HRs 1.08-1.37) compared to those without TBI (adjusted HRs 1.12-2.13). Nevertheless, PAFs for dementia due to depression, hypertension, CAD, CVD, and epilepsy were slightly higher in Veterans with TBI due to their high prevalence in this group. CONCLUSIONS: Targeting depression, hypertension, CAD, CVD, and epilepsy may be especially important for dementia risk reduction among Veterans with TBI.

Distinct categories of immunologic changes in frail elderly.

Immune changes and their relationships in a frail elderly population (N=116, age 70-103, median 86 years) were defined in comparison to a healthy younger group. Previous immune studies in the elderly have generally focused on one or few parameters without correlation analyses. Furthermore, the study populations have been active elderly in relatively small numbers. A total of 33 immune parameters representing many aspects of the immune system were quantified. Most changes in the frail elderly were parallel to those reported in active elderly. A classification tree analysis revealed that increased plasma activation markers (neopterin and sTNF-R) and increased CD28 expression on CD8 T cells and proliferative response separated the aged and control populations. Statistical procedures utilizing principal components analyses, partial correlations and exploratory factor analyses all indicated that immunologic parameters in frail elderly are grouped in three major clusters of immunologic results. These involved (a) increased plasma levels of neopterin and sTNF receptor indicating elevated IFNgamma and TNF cytokine activity; (b) increased proportion of mature (CD45RO) versus naïve (CD45RA) T cells; and (c) a diverse group of related changes including impaired proliferative response, reduced T cells, CD28 and CD25 expression, B cell percentage and lower CD4:CD8 ratios and increased HLA-DR expression. These findings emphasize that several different groups of immune parameters but not 33 independent immune changes, occurred in the aged population.

Human intradiscal levels with cefazolin.

The administration of prophylactic antibiotics for the prevention of discitis is common in the field of spinal surgery. The purpose of this study was to determine 1) whether cefazolin administered intravenously would result in detectable intradiscal levels; and 2) if so, what the proper timing of the antibiotic bolus should be to achieve optimal intradiscal concentrations. Forty human lumbar discs were obtained during the study period. All subjects received a preoperative bolus infusion of 2 g of cefazolin during a 3-5 minute period. Serum and intradiscal samples were obtained at intervals ranging from 6 to 220 minutes after the antibiotic infusion. The respective intradiscal concentrations of cefazolin were then determined, and the findings were as follows: 1) cefazolin does diffuse into the human disc in detectable concentrations; and 2) a critical time relationship exists (15-80 minutes after a bolus administration of cefazolin) for the optimal level of intradiscal antibiotics to be achieved.

Dermatomal somatosensory evoked potentials: their use in lumbar radiculopathy.

The accurate diagnosis of lumbar radiculopathy secondary to intervertebral disc herniation or spinal stenosis remains a significant problem. Studies have stressed that misdiagnosis of root entrapment significantly contributes to the incidence of failed back syndrome. In an attempt to aid the proper selection of surgical candidates, dermatomal somatosensory evoked potentials ( DSSEP ) have been used in conjunction with standard diagnostic techniques to evaluate our patients. The advantage of this technique lies in the root specificity. The authors studied the DSSEP using two methods. In Method 1, using myelograms as the standard, the accuracy was 85.7%. In Method II, using surgical outcome as the standard, the accuracy was 87.5%. As a result, the authors have found the noninvasive, relatively inexpensive DSSEP to be a useful adjunct in the selection of patients undergoing lumbar spine surgery.

The biomechanics of head-first versus feet-first sliding.

The two basic sliding techniques, head-first and feet-first, were analyzed kinematically with high speed cinematography. Four phases were identified with each technique: sprint, attainment of sliding position, airborne, and landing. The velocity and displacement of the center of gravity were measured with each technique. The study was primarily descriptive but demonstrated potential for injury with each technique. Further studies are needed to determine which technique is safer and faster.

Cytokine gene expression occurs more rapidly in stimulated peripheral blood mononuclear cells from human immunodeficiency virus-infected persons.

Evaluation of cytokine gene expression following in vitro stimulation is one means of examining the dysregulation of the immune system in human immunodeficiency virus (HIV) infection. We have assessed differences in the immune status of non-HIV-infected (HIV-) and HIV-infected (HIV+) individuals by evaluating the kinetics of the expression of cytokine genes. We compared detailed time courses of cytokine mRNA expression in HIV- and HIV+ peripheral blood mononuclear cells (PBMC) and found that there is a significant shift (P<0.01) for all cytokines examined (interleukin 2 [IL-2], IL-6, IL-10, gamma interferon, and tumor necrosis factor alpha [TNF-alpha]) to an earlier time of mean peak mRNA expression by HIV+ PBMC (between 4 and 8 h) compared to HIV- PBMC (8 h) in response to either phytohemagglutinin (PHA) or anti-CD3 stimulation. Additional studies showed that although PHA-stimulated HIV+ PBMC showed decreased median IL-2, IL-4, and TNF-alpha mRNA levels, they typically demonstrated more rapid kinetics (increased mean 4-h/24-h cytokine mRNA ratios), with significant differences for IL-4 (P<0.05) and TNF-alpha (P<0.005), compared to HIV- PBMC. The use of fresh or frozen cells gave comparable cytokine mRNA data; however, the secretion of some cytokine proteins (IL-2 receptor, IL-10, and TNF-alpha) appeared to be reduced in HIV+ PBMC that had been frozen and thawed. Our studies demonstrate that the kinetics of cytokine gene expression can reveal additional dysregulation of the immune system in HIV infection, suggesting that PBMC of HIV-infected persons exist in an activated state in vivo that permits them to express cytokine genes more rapidly than a normal PBMC.