• Specific memory complaints and the identification of preclinical Alzheimer's disease years before conversion to Mild Cognitive Impairment.

      Adler, Claudia; The University of Arizona College of Medicine - Phoenix; Baxter, Leslie (The University of Arizona., 2014-04)
      Early detection of cognitive decline will become increasingly important as preventative therapies for Alzheimer’s disease (AD) become available. While new imaging techniques and biomarkers have shown evidence of neuropathology in the preclinical stages of AD, most clinicians must rely on the subjective report of symptoms to identify the onset of cognitive decline. Patients often present to primary care physicians with complaints from self or family members about confusion, memory loss or personality changes. However, discriminating complaints associated with normal from abnormal aging is difficult. The identification of patient-generated specific complaints indicating prodromal or Mild Cognitive Impairment (MCI) could lead to more prompt and effective intervention strategies for future dementia patients, and could improve prognosis. This study investigated how specific subjective complaints may be related to subsequent conversion to MCI in a cohort of cognitively normal elderly subjects who have a familial and/or genetic risk for AD. Subjects included cognitively intact participants and their informants (spouse, sibling, adult child) from a large longitudinal study of cognition in individuals with a family history of AD. Participants were further characterized by their APOE ε4 allele status. Both subjects and their informants were administered the Multidimensional Assessment of Neurodegenerative Symptoms (MANS), a questionnaire that assesses subjective changes in memory, personality, motor, vision, and speech. Of 85 subjects who were cognitively normal at the initial MANS administration, 12 converted to MCI within 25-167 months. The participants who later converted to MCI had greater memory complaints at baseline compared to nonconverters (2 = 5.65, p <0.05). There were no significant differences in other MANS domains. In regards to specific memory complaints, converters were significantly more likely to endorse symptoms of “losing or misplacing things” (2 = 13.99, p<0.001), having an “inability to keep events or tasks in right order,” (2 =12.06, p<0.001), "forgetting names of familiar people" (2 = 4.59, p < 0.05), and "forgetting things or events from long ago," (2 = 6.62, p < 0.05). Nonconverters also endorsed some memory complaints, but no complaint or group of complaints was endorsed more than others. The APOE ε4 allele was observed in 83% of the participants who converted to MCI compared to 52% of those who remained cognitively intact over the course of the assessment period. In cognitively normal subjects with a family history of AD, specific memory complaints about losing or misplacing items, forgetting the order of tasks or events, forgetting names of familiar people and forgetting things or events from long ago may be useful clinical tools for identifying Preclinical AD up to eight years before conversion to MCI.
    • SIRT3: Molecular Signaling in Insulin Resistance

      Barber, Collin; The University of Arizona College of Medicine - Phoenix; Mandarino, Lawrence (The University of Arizona., 2014-04)
      Post-translational modification of intracellular proteins through acetylation is recognized as an important regulatory mechanism of cellular energy homeostasis. Specific proteins called sirtuins deacetylate other mitochondrial proteins involved in glucose and lipid metabolism, activating them in metabolic processes. SIRT3 is a sirtuin of particular interest as it is found exclusively in mitochondria and has been shown to affect a variety of cellular metabolic processes. The activity of this enzyme is related to cellular insulin sensitivity. This study attempted to identify the relationship between insulin sensitivity and change in amount of SIRT3 following a bout of exercise in non-diabetic individuals. We find a moderate inverse correlation between insulin sensitivity and increase in SIRT3 abundance following exercise. This suggests that this protein may not be involved directly in cells’ ability to regulate energy homeostasis or that it may act through another mechanism not investigated in this study.
    • Pediatric Out‐of‐Hospital Cardiac Arrest in the State of Arizona

      Tully, Jeffrey; The University of Arizona College of Medicine - Phoenix; Buttram, Sandra (The University of Arizona., 2014-04)
      Comprehensive databases which collect data on out of hospital cardiac arrests have been useful in identifying markers of outcome in adults, but this data is limited in children. The Arizona Department of Health Services’ Save Hearts in Arizona Registry and Education (SHARE) database contains data on pediatric cardiac arrests in the field and offers a unique opportunity to examine outcome measures and pre-hospital care. We retrospectively analyzed 312 children (1-215 months) from the SHARE database between 2004-2010. Variables assessed included: bystander cardiopulmonary resuscitation (CPR) administration, transport times and impact of Pediatric Intensive Care Unit (PICU) availability on outcome to hospital discharge. Data were analyzed by t-test and Fisher’s exact test. Of 312 children with out of hospital cardiac arrest, 11 (3.6%) survived to hospital discharge. The low survival rates in this review make statistical comparisons difficult, though potential trends were noted that, with additional numbers to increase power, may provide insight into factors affecting survival from pediatric OHCA that have not been assessed on a wide scale in this vulnerable population.