UC San Diego

Dementia with Lewy bodies (DLB) is a neurodegenerative disorder characterized pathologically by cell loss and the deposition of alpha-synuclein-positive, eosinophilic inclusions (i.e., Lewy bodies) in brainstem, limbic, and neocortical regions. Clinical features of DLB include progressive dementia, spontaneous Parkinsonism, well- formed and recurrent visual hallucinations, and fluctuations in consciousness and cognition. The symptoms of DLB overlap considerably with those of Alzheimer's disease (AD), and it is often difficult to clinically distinguish between the two disorders. However, retrospective studies of autopsy-confirmed cases indicate that DLB patients may have early and disproportionately severe deficits in visual cognition compared to equally demented patients with AD. The studies in this dissertation aimed to further characterize the nature and extent of deficits in visual cognition in DLB and related disorders. Study 1 examined the ability of DLB patients to discriminate simple horizontal motion. Patients with DLB were markedly impaired with greater deficits than patients with AD. The effect was sustained in a small subset of the AD and DLB patients with autopsy-confirmed diagnoses. Study 2 assessed the integrity of single-feature and dual- feature visual search in patients with DLB or AD. Patients with DLB were generally slow in performing search, but showed a normal pattern of performance in both tasks. Patients with AD, in contrast, were impaired in performing dual-feature search, perhaps due to a breakdown in cortico -cortical connectivity that attenuates the ability to integrate visual features. To better understand the role of Lewy body pathology per se in disruption of visual cognition, Study 3 examined higher order visual cognition in non-demented patients with Parkinson's disease (PD). Patients with PD have Lewy body pathology in brainstem nuclei (e.g., substantia nigra) and a disruption of basal ganglia and certain cortical functions due to the loss of dopaminergic projections from these nuclei. They do not have significant cortical Lewy bodies or concomitant AD pathology that often occurs in DLB. The results of Study 3 showed that PD patients had no deficits in either search efficiency for subtle differences in shape or speed of motion stimuli, or visual search that required the integration of color and motion information. However, patients with PD were impaired on a task that required integration of motion and luminance information. Because both luminance and motion are processed through the dorsal visual processing stream, this task may have taxed the dorsal visual processing stream, allowing subtle impairment to be revealed. Thus, Lewy body pathology may be associated with specific impairments in information processing carried out in the dorsal visual processing stream