Ocular and systemic vascular dysfunction in neurodegenerative disease

The important role played by vascular factors in the pathogenesis of neurodegenerative disease has been increasingly realised over recent years. The nature and impact of ocular and systemic vascular dysfunction in the pathogenesis of comparable neurodegenerative diseases such as glaucoma and Alzheimer’s disease (AD) has however never been fully explored. The aim of this thesis was therefore to investigate the presence of macro- and micro-vascular alterations in both glaucoma and AD and to explore the relationships between these two chronic, slowly progressive neurodegenerative diseases. The principle sections and findings of this work were: 1. Is the eye a window to the brain? Retinal vascular dysfunction in Alzheimer’s disease · Mild newly diagnosed AD patients demonstrated ocular vascular dysfunction, in the form of an altered retinal vascular response to flicker light, which correlated with their degree of cognitive impairment. 2. Ocular and systemic vascular abnormalities in newly diagnosed normal tension glaucoma (NTG) patients · NTG patients demonstrated an altered retinal arterial constriction response to flicker light along with an increased systemic arterial stiffness and carotid artery intima-media thickness (IMT). These findings were not replicated by healthy age matched controls. 3. Ocular vascular dysregulation in AD compares to both POAG and NTG · AD patients demonstrated altered retinal arterial reactivity to flicker light which was comparable to that of POAG patients and altered baseline venous reactivity which was comparable to that of NTG patients. Neither alteration was replicated by healthy controls. 4. POAG and NTG: two separate diseases or one continuous entity? The vascular perspective · POAG and NTG patients demonstrated comparable alterations in nocturnal systolic blood pressure (SBP) variability, ocular perfusion pressure, retinal vascular reactivity, systemic arterial stiffness and carotid IMT. · Nocturnal SBP variability was found to correlate with both retinal artery baseline diameter fluctuation and carotid IMT across the glaucoma groups.

Retinal vascular dysfunction relates to cognitive impairment in Alzheimer's disease

Cerebral vascular dysregulation has been increasingly implicated as a risk factor in the development of Alzheimer disease (AD)1; however, because of the difficulties associated with assessing and visualizing the cerebral vasculature directly, the ability to detect such dysregulation, noninvasively, is currently limited.2 Consequently, one concept that is being increasingly explored is the possibility of using the eye as a "window to the brain"; this approach has reasonable scientific validity as the retinal and brain vessels share a large number of embryological, anatomic, and functional similarities.2 Indeed, previous research has demonstrated a correlation between cognition and the geometry of the retinal vessels in elderly people.3 The aim of this pilot study, therefore, was to explore whether microvascular functional anomalies are evident at the retinal level in mild AD patients and to determine whether these anomalies relate to the degree of concurrent cognitive deficit..