Specificity of Embedded Performance Validity Tests in Elderly Veterans with Mild and Major Neurocognitive Disorder.

OBJECTIVE: This study explored the specificity of four embedded performance validity tests (PVTs) derived from common neuropsychological tasks in a sample of older veterans with verified cognitive decline and whose performance was deemed valid by licensed psychologists. METHOD: Participants were 180 veterans who underwent comprehensive neuropsychological evaluation, were determined to have valid performance following profile analysis/conceptualization, and were diagnosed with mild neurocognitive disorder (i.e., MCI; n = 64) or major neurocognitive disorder (i.e., Dementia; n = 116). All participants completed at least one of four embedded PVTs: Reliable Digit Span (RDS), California Verbal Learning Test-2nd ed. Short Form (CVLT-II SF) Forced choice, Trails B:A, and Delis-Kaplan Executive Function System (DKEFS) Letter and Category Fluency. RESULTS: Adequate specificity (i.e., ≥90%) was achieved at modified cut-scores for all embedded PVTs across MCI and Dementia groups. Trails B:A demonstrated near perfect specificity at its traditional cut-score (Trails B:A < 1.5). RDS ≤ 5 and CVLT-II SF Forced Choice ≤7 led to <10% false positive classification errors across MCI and dementia groups. DKEFS Letter and Category Fluency achieved 90% specificity at extremely low normative cut-scores. CONCLUSIONS: RDS, Trails B:A, and CVLT-II SF Forced Choice reflect promising embedded PVTs in the context of dementia evaluations. DKEFS Letter and Category Fluency appear too sensitive to genuine neurocognitive decline and, therefore, are inappropriate PVTs in adults with MCI or dementia. Additional research into embedded PVT sensitivity (via known-groups or analogue designs) in MCI and dementia is needed.

Comparing Detection of Alzheimer's and Vascular Disease-Related Cognitive Impairment With Brief Cognitive Screens.

Objectives: The study compared the accuracy of the Mini-Mental State Examination (MMSE) with its modified version (3MS) in distinguishing healthy older adults from adults with cognitive impairment due to suspected Alzheimer's disease (AD) or vascular disease (VaD). Method: Participants were 98 veterans who underwent comprehensive neuropsychological evaluation due to concern for cognitive decline. Participants were selected via retrospective chart review on the basis of diagnosis. They had diagnoses of mild or major neurocognitive disorder due to suspected AD (N=20), mild or major neurocognitive disorder due to suspected VaD (N=44), or no neurocognitive diagnosis (i.e., healthy adult comparisons; HC, N=34). Results: The 3MS demonstrated superior detection of cognitive impairment. The extent of this enhanced detection was influenced by the suspected etiology of cognitive impairment. The 3MS and MMSE had comparable discrimination of AD and HC. With respect to VaD, the 3MS showed superior discriminability compared to the MMSE. Conclusions: Overall, results support the adoption of the 3MS over that of the MMSE. The 3MS is a superior (and free) tool for detecting cognitive impairment in geriatric populations. Its use is recommended for first-line screening of cognitive symptoms in older adult populations, especially those with concern for VaD.

The effect of Aspergillus fumigatus infection on vitamin D receptor expression in cystic fibrosis.

RATIONALE: Aspergillus fumigatus (A. fumigatus) in cystic fibrosis (CF) is increasingly recognized. Although allergic bronchopulmonary aspergillosis (ABPA) leads to deterioration of pulmonary function, the effect of A. fumigatus colonization in the absence of ABPA remains unclear. OBJECTIVES: To address this, we examined individuals with CF with A. fumigatus who were ABPA negative to identify the effects of itraconazole therapy on Aspergillus-induced lung inflammation. METHODS: The effect of A. fumigatus on nuclear vitamin D receptor (VDR) expression was investigated using qRT-PCR and Western blotting. IL-5 and IL-13 levels were quantified by ELISA. The effect of itraconazole was assessed by a combination of high-resolution computed tomography, lung function test, and microbiological analysis. MEASUREMENTS AND MAIN RESULTS: We demonstrate that A. fumigatus down-regulates VDR in macrophages and airway epithelial cells and that the fungal metabolite gliotoxin (Gt) is the main causative agent. Gt overcame the positive effect of 1,25-OH vitamin D(3) on VDR expression in vitro, resulting in increased IL-5 and IL-13 production. In vivo, A. fumigatus positivity was associated with increased Gt in CF bronchoalveolar lavage fluid and increased bronchoalveolar lavage fluid levels of IL-5 and IL-13. After airway eradication of A. fumigatus with itraconazole, we observed decreased Gt, IL-5 and IL-13, improved respiratory symptoms, and diminished high-resolution computed tomography mosaic pattern consistent with sustained pulmonary function. CONCLUSIONS: This study provides a rationale for the therapeutic effect of itraconazole and implied that the therapeutic potential of vitamin D supplementation in preventing ABPA is only feasible with concurrent elimination of A. fumigatus to permit VDR expression and its positive functional consequences.