Christian Ambler, Ph.D.

All Publications

• Brain Perfusion and Diffusion Abnormalities in Children Treated for Posterior Fossa Brain Tumors. journal of pediatrics Li, M. D., Forkert, N. D., Kundu, P., Ambler, C., Lober, R. M., Burns, T. C., Barnes, P. D., Gibbs, I. C., Grant, G. A., Fisher, P. G., Cheshier, S. H., Campen, C. J., Monje, M., Yeom, K. W. 2017

  Abstract

  To compare cerebral perfusion and diffusion in survivors of childhood posterior fossa brain tumor with neurologically normal controls and correlate differences with cognitive dysfunction.We analyzed retrospectively arterial spin-labeled cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) in 21 patients with medulloblastoma (MB), 18 patients with pilocytic astrocytoma (PA), and 64 neurologically normal children. We generated ANCOVA models to evaluate treatment effects on the cerebral cortex, thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala, nucleus accumbens, and cerebral white matter at time points an average of 5.7 years after original diagnosis. A retrospective review of patient charts identified 12 patients with neurocognitive data and in whom the relationship between IQ and magnetic resonance imaging variables was assessed for each brain structure.Patients with MB (all treated with surgery, chemotherapy, and radiation) had significantly lower global CBF relative to controls (10%-23% lower, varying by anatomic region, all adjusted P < .05), whereas patients with PA (all treated with surgery alone) had normal CBF. ADC was decreased specifically in the hippocampus and amygdala of patients with MB and within the amygdala of patients with PA but otherwise remained normal after therapy. In the patients with tumor previously evaluated for IQ, regional ADC, but not CBF, correlated with IQ (R(2) = 0.33-0.75).The treatment for MB, but not PA, was associated with globally reduced CBF. Treatment in both tumor types was associated with diffusion abnormalities of the mesial temporal lobe structures. Despite significant perfusion abnormalities in patients with MB, diffusion, but not perfusion, correlated with cognitive outcomes.

  View details for DOI 10.1016/j.jpeds.2017.01.019

  View details for PubMedID 28187964

• Longitudinal Evaluation of Cognitive Functioning in Young Children with Type 1 Diabetes over 18 Months. Journal of the International Neuropsychological Society Cato, M. A., Mauras, N., Mazaika, P., Kollman, C., Cheng, P., Aye, T., Ambrosino, J., Beck, R. W., Ruedy, K. J., Reiss, A. L., Tansey, M., White, N. H., Hershey, T. 2016; 22 (3): 293-302

  Abstract

  Decrements in cognitive function may already be evident in young children with type 1 diabetes (T1D). Here we report prospectively acquired cognitive results over 18 months in a large cohort of young children with and without T1D.A total of 144 children with T1D (mean HbA1c: 7.9%) and 70 age-matched healthy controls (mean age both groups 8.5 years; median diabetes duration 3.9 years; mean age of onset 4.1 years) underwent neuropsychological testing at baseline and after 18-months of follow-up. We hypothesized that group differences observed at baseline would be more pronounced after 18 months, particularly in those T1D patients with greatest exposure to glycemic extremes.Cognitive domain scores did not differ between groups at the 18 month testing session and did not change differently between groups over the follow-up period. However, within the T1D group, a history of diabetic ketoacidosis (DKA) was correlated with lower Verbal IQ and greater hyperglycemia exposure (HbA1c area under the curve) was inversely correlated to executive functions test performance. In addition, those with a history of both types of exposure performed most poorly on measures of executive function.The subtle cognitive differences between T1D children and nondiabetic controls observed at baseline were not observed 18 months later. Within the T1D group, as at baseline, relationships between cognition (Verbal IQ and executive functions) and glycemic variables (chronic hyperglycemia and DKA history) were evident. Continued longitudinal study of this T1D cohort and their carefully matched healthy comparison group is planned.

  View details for DOI 10.1017/S1355617715001289

  View details for PubMedID 26786245

• Longitudinal Assessment of Neuroanatomical and Cognitive Differences in Young Children With Type 1 Diabetes: Association With Hyperglycemia DIABETES Mauras, N., Mazaika, P., Buckingham, B., Weinzimer, S., White, N. H., Tsalikian, E., Hershey, T., Cato, A., Cheng, P., Kollman, C., Beck, R. W., Ruedy, K., Aye, T., Fox, L., Arbelaez, A. M., Wilson, D., Tansey, M., Tamborlane, W., Peng, D., Marzelli, M., Winer, K. K., Reiss, A. L. 2015; 64 (5): 1770-1779

  Abstract

  Significant regional differences in gray and white matter volume and subtle cognitive differences between young diabetic and nondiabetic children have been observed. Here, we assessed whether these differences change over time and the relation with dysglycemia. Children ages 4 to <10 years with (n = 144) and without (n = 72) type 1 diabetes (T1D) had high-resolution structural MRI and comprehensive neurocognitive tests at baseline and 18 months and continuous glucose monitoring and HbA1c performed quarterly for 18 months. There were no differences in cognitive and executive function scores between groups at 18 months. However, children with diabetes had slower total gray and white matter growth than control subjects. Gray matter regions (left precuneus, right temporal, frontal, and parietal lobes and right medial-frontal cortex) showed lesser growth in diabetes, as did white matter areas (splenium of the corpus callosum, bilateral superior-parietal lobe, bilateral anterior forceps, and inferior-frontal fasciculus). These changes were associated with higher cumulative hyperglycemia and glucose variability but not with hypoglycemia. Young children with T1D have significant differences in total and regional gray and white matter growth in brain regions involved in complex sensorimotor processing and cognition compared with age-matched control subjects over 18 months, suggesting that chronic hyperglycemia may be detrimental to the developing brain.

  View details for DOI 10.2337/db14-1445

  View details for PubMedID 25488901

• Feasibility of Conducting Long-Term Follow-Up of Children and Infants Treated for CNS Tumors on the Same Cooperative Group Clinical Trial Protocol JOURNAL OF CLINICAL PSYCHOLOGY IN MEDICAL SETTINGS Hoag, J., Kupst, M. J., Briere, M., Mabbott, D., Elkin, T. D., Trask, C. L., Isenberg, J., Holm, S., Ambler, C., Strother, D. R. 2014; 21 (2): 136-143

  Abstract

  Given the barriers to conducting long-term assessment of neurocognitive and psychosocial functioning of those treated in infancy for central nervous system (CNS) tumors, a multi-site feasibility study was conducted. The primary objective was to demonstrate that it is feasible to identify, locate and assess the functioning of children treated on the same protocol 10-years post-treatment. Six sites obtained institutional approval, identified and recruited subjects, and obtained comprehensive neurocognitive and psychosocial data. All feasibility objectives were met. Barriers to participation included length of time for Institutional Review Board submission and review, clinical demands, limited eligible participants at individual institutions, difficulty locating long-term subjects and stipend/reimbursement concerns. Results indicate that long-term studies are feasible and essential given the need to address long-term issues of children treated at a young age for CNS tumors, especially as they relate to later academic and vocational planning, but require significant coordination and commitment of cooperative group and institutional resources.

  View details for DOI 10.1007/s10880-014-9391-6

  View details for Web of Science ID 000336412200002

  View details for PubMedID 24668336

• White Matter Structural Differences in Young Children With Type 1 Diabetes: A Diffusion Tensor Imaging Study DIABETES CARE Aye, T., Barnea-Goraly, N., Ambler, C., Hoang, S., Schleifer, K., Park, Y., Drobny, J., Wilson, D. M., Reiss, A. L., Buckingham, B. A. 2012; 35 (11): 2167-2173

  Abstract

  To detect clinical correlates of cognitive abilities and white matter (WM) microstructural changes using diffusion tensor imaging (DTI) in young children with type 1 diabetes.Children, ages 3 to <10 years, with type 1 diabetes (n = 22) and age- and sex-matched healthy control subjects (n = 14) completed neurocognitive testing and DTI scans.Compared with healthy controls, children with type 1 diabetes had lower axial diffusivity (AD) values (P = 0.046) in the temporal and parietal lobe regions. There were no significant differences between groups in fractional anisotropy and radial diffusivity (RD). Within the diabetes group, there was a significant, positive correlation between time-weighted HbA(1c) and RD (P = 0.028). A higher, time-weighted HbA(1c) value was significantly correlated with lower overall intellectual functioning measured by the full-scale intelligence quotient (P = 0.03).Children with type 1 diabetes had significantly different WM structure (as measured by AD) when compared with controls. In addition, WM structural differences (as measured by RD) were significantly correlated with their HbA(1c) values. Additional studies are needed to determine if WM microstructural differences in young children with type 1 diabetes predict future neurocognitive outcome.

  View details for DOI 10.2337/dc12-0017

  View details for PubMedID 22966090

• An interview with Christian Ambler: Traumatic Brain Injury North American Journal of Psychology Shaughnessy, M. 2009; 11 (2)
• Change in indices of distress among Latino and Anglo female caregivers of elderly relatives with dementia: Site-specific results from the REACH national collaborative study GERONTOLOGIST Gallagher-Thompson, D., Coon, D. W., Solano, N., Ambler, C., Rabinowitz, Y., Thompson, L. W. 2003; 43 (4): 580-591

  Abstract

  Few empirical studies have compared the efficacy between psychoeducational (skill-building) approaches for reducing caregivers' psychological distress and interventions modeled after typical community-based support groups. We compare the impact of two distinct interventions on Anglo and Latino caregivers of elderly relatives with dementia.The change from preassessment to postassessment (baseline to 3 months) for 213 female caregivers (122 Anglo and 91 Latino) is presented. They were seen weekly for 10 weeks in either the Coping With Caregiving psychoeducational program (instruction and practice in small groups to learn specific cognitive and behavioral skills) or in the Enhanced Support Group condition (guided discussion and empathic listening to develop reciprocal support within the group). Both programs were tailored to be sensitive to the cultural concerns of Anglo and Latino caregivers, and they were delivered in either English or Spanish by trained interventionists.Overall, participants in the Coping With Caregiving condition reported a significant reduction in depressive symptoms, increased use of adaptive coping strategies, and a trend toward decreased use of negative coping strategies when compared with those in the Enhanced Support Group condition. Results were similar for both ethnic groups: there were no main effects for ethnicity, and no significant ethnicity by treatment interaction effects.This study provides empirical support that female caregivers benefit more from a skill-building approach to managing their distress than from support group membership alone. We find it very encouraging that the Latino caregivers responded well on key outcome variables, suggesting that Latinos will participate in clinical research and will benefit from their involvement when services are provided to meet their specific needs.

  View details for Web of Science ID 000184967700014

  View details for PubMedID 12937336

• Treatment options for improving well being in dementia family caregivers The Gerontologisr Gallagher-Thompson, D. 2003; 43