Date of Award
2008
Degree Type
Thesis
Degree Name
Doctor of Philosophy
Program
Medical Biophysics
Supervisor
Dr. Ting-Yim Lee
Abstract
An association between motor neuron disease (MND) and dementia was first realized in the late 1800s, yet substantiating research and a description of dementia as part of the clinical syndrome would not appear until the 1990s. In the last two decades, medical imaging has investigated cerebral blood flow changes in the motor and non motor cortex to correlate with motor dysfunction and clinical dementia, respectively. The aim of this thesis is to describe early cerebral hemodynamic disturbances with the goal to determine a marker for cognitive decline in MND.
Chapter 2 describes the relationship between changes in cerebral hemodynamics and cognition in primary lateral sclerosis (PLS) patients compared to normal controls. Neuropsychological testing revealed subtle frontotemporal changes characterized by executive dysfunction that were associated with global increases in mean transit time (MTT) in grey and white matter, and increased cerebral blood volume (CBV) in the frontotemporal grey matter.
Chapter 3 présents a longitudinal clinical study of early cerebral hemodynamic changes in amyotrophie lateral sclerosis (ALS) patients without evidence of cognitive impairment at study onset. This Chapter characterized the relationship between duration ofdiseaseandMTTinthecorticalgreymatter. MTTwasfoundtobethemostsensitive indicator of early cerebral hemodynamic change accompanying disease progression in ALS. Furthermore,thesefindingscorroboratethetrendofincreasedMTTintheabsence of cognitive impairment found in PLS patients in Chapter 2, and may further indicate that hemodynamic changes may occur before the onset of cognitive impairment.
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The aim of Chapter 4 was to elucidate a biological mechanism for increased MTT described in the previous Chapters 2 and 3. A rabbit model of global hypotension was used to demonstrate that MTT is an indicator of cerebral perfusion pressure (CPP).
A spectrum of cognitive dysfunction has now been described in MND. The use of sensitive neuropsychological testing has enabled us to identify patients with mild changes in cognitive function from those who are cognitively intact. With the help of this stratification, we were able to show that changes in MTT was associated with disease progression and cognitive impairment. The experimental data presented in this thesis suggest that vascular factors may contribute to cognitive dysfunction in MND.
Recommended Citation
Murphy, Matthew J., "Cerebral Hemodynamic Disturbances in Motor Neuron Disease" (2008). Digitized Theses. 4616.
https://ir.lib.uwo.ca/digitizedtheses/4616