Early detection of dementia is critical for intervention and care planning, but remains difficult. This study evaluated a computerized cognitive testing battery (BrainCheck) for its diagnostic accuracy and ability to distinguish the severity of cognitive impairment. 99 participants diagnosed with Dementia, Mild Cognitive Impairment (MCI), or Normal Cognition (NC) completed the BrainCheck battery. Statistical analyses compared participant’s performance on BrainCheck based on their diagnosis group BrainCheck battery performance showed significant differences between the NC, MCI, and Dementia groups, achieving ≥88% sensitivity/specificity for separating NC from Dementia, and ≥77% sensitivity/specificity in separating the MCI group from NC/Dementia groups. Three-group-classification found true positive rates ≥80% for the NC and Dementia groups and ≥60% for the MCI group. BrainCheck was able to distinguish between diagnoses of Dementia, MCI, and NC, providing a potentially reliable tool for early detection of cognitive impairment.
In non–small cell lung cancer (NSCLC), concurrent mutations in the oncogene KRAS and the tumor suppressor STK11 encoding the kinase LKB1 result in aggressive tumors prone to metastasis but with liabilities arising from reprogrammed metabolism. We previously demonstrated perturbed nitrogen metabolism and addiction to an unconventional pathway of pyrimidine synthesis in KRAS/LKB1 co-mutant (KL) cancer cells. To gain broader insight into metabolic reprogramming in NSCLC, we analyzed tumor metabolomes in a series of genetically engineered mouse models with oncogenic KRAS combined with mutations in LKB1 or p53. Metabolomics and gene expression profiling pointed towards an activation of the hexosamine biosynthesis pathway (HBP), another nitrogen-related metabolic pathway, in both mouse and human KL mutant tumors. KL cells contain high levels of HBP metabolites, higher flux through the HBP pathway and elevated dependence on the HBP enzyme Glutamine-Fructose-6-Phosphate Transaminase 2 (GFPT2). GFPT2 inhibition selectively reduced KL cell growth in culture and xenografts. Our results define a new metabolic vulnerability in KL tumors and provide a rationale for targeting GFPT2 in this aggressive NSCLC subtype.
Traditional pen and paper based neuropsychological tests (NPT) for cognition assessment have several challenges limiting their use. They are time consuming, expensive, and require highly trained specialists to administer. This leads to testing being available to only a small portion of the population and often with wait times of several months. In clinical practice, we have found results tend not to be integrated effectively into assessment and plans of the ordering provider. Here we compared several tests using BrainCheck (BC), a computer-based NPT battery, to traditional paper-based NPT, by evaluating individual tests as well as comparing composite scores to scores on traditional screening tools. 26 volunteers took both paper-based tests and BC. We found scores of four assessments (Ravens Matrix, Digit Symbol Modulation, Stroop Color Word Test and Trails Making A&B Test) were highly correlated. The Balance Examination and Immediate/Delayed Hopkins Verbal Learning, however, were not correlated. The BC composite score was correlated to results of the Saint Louis University Mental Status (SLUMS) exam [1], the Mini-Mental State Examination (MMSE) [2], and the Montreal Cognitive Assessment (MoCA). Our results suggest BC may offer a computer-based avenue to address the gap between basic screening and formal neuropsychological testing.
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