Aging Brain: DTI, Subcortical Ischemia and Behavioral

Summary

Principal Investigator: Stephen P Salloway
Abstract: We will use diffusion-tensor imaging (DTI) to investigate the relationship between frontal white matter integrity and executive function and behavior in patients with subcortical ischemic vascular disease (SIVD). SIVD is characterized by lacunar infarcts and deep white matter changes and can cause cognitive impairment, accounts for approximately 50% of vascular dementia cases, and is associated with impairment in executive cognition and behavior presumably due to interruption of frontal-subcortical circuits. Executive and behavioral impairment leads to functional decline in the elderly and may hasten conversion to dementia. The aims of this proposal are (1) to demonstrate loss of white matter integrity in patients with SIVD vs. normal elderly controls using DTI, (2) to demonstrate an association between frontal white matter integrity measured with DTI and executive cognition and behavioral functioning in SIVD vs. normal elderly, and (3) to use innovative DTI tractography tools to identify specific white matter pathways and determine their association with cognition and behavior, j We will recruit a subgroup of subjects with CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarction and leukoencephalopathy) - a relatively pure form of SIVD - to serve as a "gold standard" comparison group to strengthen confidence that any significant associations are related to SIVD vs. other pathology. Our focus on behavior and the use of DTI tractography to explore associations in discrete fiber tracts is novel. The results of this study will contribute to our understanding of the impact of frontal systems disruption on cognition and behavior in SIVD and other disorders affecting white matter. The results could lead to the use of DTI as a predictor of susceptibility to cerebrovascular injury and of conversion to dementia, and help develop DTI as an outcome measure in treatment trails aimed at reducing cerebrovascular risk. Further, Aim 3 will produce innovative automated tractography methods that could lead to the development of a normative map of white matter connectivity across the lifespan which could be used to detect the earliest signs of white matter disease.
Funding Period: 2005-06-01 - 2008-04-30
more information: NIH RePORT

Top Publications

  1. ncbi Glial vascular degeneration in CADASIL
    Thea Brennan-Krohn
    Departments of Pathology Neuropathology, Neurology, Medicine, and Psychiatry and Human Behavior, Rhode Island Hospital, Butler Hospital, Veterans Affairs Medical Center, and Warren Alpert Medical School of Brown University, Providence, RI, USA
    J Alzheimers Dis 21:1393-402. 2010
  2. pmc Effectiveness and tolerability of high-dose (23 mg/d) versus standard-dose (10 mg/d) donepezil in moderate to severe Alzheimer's disease: A 24-week, randomized, double-blind study
    Martin R Farlow
    Department of Neurology, Indiana University School of Medicine, Indianapolis, 46202, USA
    Clin Ther 32:1234-51. 2010
  3. pmc A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease
    S Salloway
    Butler Hospital, The Warren Alpert Medical School of Brown University, 345 Blackstone Blvd, Providence, RI 02906, USA
    Neurology 73:2061-70. 2009

Scientific Experts

Detail Information

Publications3

  1. ncbi Glial vascular degeneration in CADASIL
    Thea Brennan-Krohn
    Departments of Pathology Neuropathology, Neurology, Medicine, and Psychiatry and Human Behavior, Rhode Island Hospital, Butler Hospital, Veterans Affairs Medical Center, and Warren Alpert Medical School of Brown University, Providence, RI, USA
    J Alzheimers Dis 21:1393-402. 2010
    ..These preliminary findings suggest that CADASIL is mediated by both glial and vascular degeneration with reduced expression of IGF receptors and AAH, which regulate Notch expression and function...
  2. pmc Effectiveness and tolerability of high-dose (23 mg/d) versus standard-dose (10 mg/d) donepezil in moderate to severe Alzheimer's disease: A 24-week, randomized, double-blind study
    Martin R Farlow
    Department of Neurology, Indiana University School of Medicine, Indianapolis, 46202, USA
    Clin Ther 32:1234-51. 2010
    ..We hypothesized that the loss of initial therapeutic benefit over time may be mitigated by higher doses of a cholinesterase inhibitor...
  3. pmc A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease
    S Salloway
    Butler Hospital, The Warren Alpert Medical School of Brown University, 345 Blackstone Blvd, Providence, RI 02906, USA
    Neurology 73:2061-70. 2009
    ..Bapineuzumab, a humanized anti-amyloid-beta (Abeta) monoclonal antibody for the potential treatment of Alzheimer disease (AD), was evaluated in a multiple ascending dose, safety, and efficacy study in mild to moderate AD...