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Item Effects of Epigallcatechin-3-gallate in Novel Object Recognition of Ts65Dn Down Syndrome Mice(Office of the Vice Chancellor for Research, 2015-04-17) Minhas, Saniya; Abeysekera, Irushi; Delgado, Fatima; Dhillon, Hardeep; Goodlett, Charles R.; Roper, Randall J.Down syndrome (DS) is one of the most common genetic disorders and has an incidence of 1/700 births; which can lead to many impairments, both physically and mentally. All individuals with DS have cognitive impairments which results in learning and memory deficits. To study these deficits, we use the Ts65Dn mouse model that carries trisomy of approximately 50% of the genes found on human chromosome 21. DYRK1A, a gene found in three copies in both humans with DS and Ts65Dn mice has been shown to have increased expression in the brains of humans with DS. DYRK1A protein is involved in a number of critical pathways including CNS development. Epigallcatechin-3-gallate (EGCG), the main polyphenolic compound found in green tea, inhibits DYRK1A. We hypothesize that EGCG treatment help improve cognitive deficits in trisomic mice. After treatment, the mice were subjected to behavioral tasks, including the Novel Object Recognition (NOR) test. Our results indicate that there was a significant difference that existed due to trisomy in Ts65Dn mice; but there was no significant effect of a low dose EGCG treatment. Further studies are examining the effects of the NOR task after a higher dose EGCG treatment.Item Methylphenidate and Memory and Attention Adaptation Training for persistent cognitive symptoms after traumatic brain injury: a randomized, placebo-controlled trial(Nature, 2017) McDonald, Brenna C.; Flashman, Laura A.; Arciniegas, David B.; Ferguson, Robert J.; Xing, Li; Harezlak, Jaroslaw; Sprehn, Gwen C.; Hammond, Flora M.; Maerlender, Arthur C.; Kruck, Carrie L.; Gillock, Karen L.; Frey, Kim; Wall, Rachel N.; Saykin, Andrew J.; McAllister, Thomas W.; Department of Psychiatry, IU School of MedicineThe purpose of this multicenter, prospective, randomized, placebo-controlled study was to evaluate and compare the efficacy of two cognitive rehabilitation interventions (Memory and Attention Adaptation Training (MAAT) and Attention Builders Training (ABT)), with and without pharmacological enhancement (ie, with methylphenidate (MPH) or placebo), for treating persistent cognitive problems after traumatic brain injury (TBI). Adults with a history of TBI at least 4 months before study enrollment with either objective cognitive deficits or subjective cognitive complaints were randomized to receive MPH or placebo and MAAT or ABT, yielding four treatment combinations: MAAT/MPH (N=17), ABT/MPH (N=19), MAAT/placebo (N=17), and ABT/placebo (N=18). Assessments were conducted pre-treatment (baseline) and after 6 weeks of treatment (post treatment). Outcome measures included scores on neuropsychological measures and subjective rating scales. Statistical analyses used linear regression models to predict post-treatment scores for each outcome variable by treatment type, adjusting for relevant covariates. Statistically significant (P<0.05) treatment-related improvements in cognitive functioning were found for word-list learning (MAAT/placebo>ABT/placebo), nonverbal learning (MAAT/MPH>MAAT/placebo and MAAT/MPH>ABT/MPH), and auditory working memory and divided attention (MAAT/MPH>ABT/MPH). These results suggest that combined treatment with metacognitive rehabilitation (MAAT) and pharmacotherapy (MPH) can improve aspects of attention, episodic and working memory, and executive functioning after TBI.Item Type 1 Diabetes Mellitus and Cognitive Impairments: A Systematic Review(IOS, 2017) Li, Wei; Huang, Edgar; Gao, Sujuan; Physician Assistant Studies Program, School of Health and Rehabilitation SciencesType 1 diabetes mellitus (T1DM) is a major subtype of diabetes and is usually diagnosed at a young age with insulin deficiency. The life expectancy of T1DM patients has increased substantially in comparison with that three decades ago due to the availability of exogenous insulin, though it is still shorter than that of healthy people. However, the relation remains unclear between T1DM and dementia as an aging-related disease. We conducted a systematic review of existing literature on T1DM and cognition impairments by carrying out searches in electronic databases Medline, EMBASE, and Google Scholar. We restricted our review to studies involving only human subjects and excluded studies on type 2 diabetes mellitus or non-classified diabetes. A meta-analysis was first performed on the relationship between T1DM and cognitive changes in youths and adults respectively. Then the review focused on the cognitive complications of T1DM and their relation with the characteristics of T1DM, glycemic control, diabetic complications, comorbidities, and others. First, age at onset, disease duration, and glycemic dysregulation were delineated for their association with cognitive changes. Then diabetic ketoacidosis, angiopathy, and neuropathy were examined as diabetic complications for their involvement in cognitive impairments. Lastly, body mass index and blood pressure were discussed for their relations with the cognitive changes. Future studies are needed to elucidate the pathogenesis of T1DM-related cognitive impairments or dementia.