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Title page for ETD etd-07232019-090733


Type of Document Dissertation
Author Kamkwalala, Asante Rochelle
Author's Email Address asante.kamkwalala@gmail.com
URN etd-07232019-090733
Title Involvement of the Cortical Cholinergic Receptor System in Symptoms of Cognitive Aging in HIV-Associated Neurocognitive Disorders (HAND)
Degree PhD
Department Neuroscience
Advisory Committee
Advisor Name Title
David Zald, PhD Committee Chair
Carrie Jones, PhD Committee Member
Paul A Newhouse, MD Committee Member
Todd Hulgan, MD Committee Member
Keywords
  • Muscarinic
  • Neurovirology
  • Nicotinic
  • HIV-1
  • Cognition
  • Neuroscience
Date of Defense 2019-07-10
Availability unrestricted
Abstract
As of the year 2016, an estimated 50% of the United States’ population living with the Human Immunodeficiency Virus (HIV-1) is at least 50 years or older, due to the success of Anti-Retroviral Therapy (ART) steadily increasing the life-expectancy of those living with the disease. Long-term survival with HIV interacts with numerous treatment and lifestyle factors over the lifespan which may increase the risk of developing HIV-Associated Neurocognitive Disorders (HAND), a collection of cognitive impairments involving memory, attention, executive functioning deficits, often in spite of successful ART keeping peripheral viral markers controlled or undetectable. This pattern of cognitive symptoms in HAND closely overlaps those seen in the process of Cognitive Aging in seronegative healthy older adults, which is associated with the decrease in integrity of the Neuronal Acetylcholinergic Receptor System. To understand the degree to which these separate processes interact, we investigated the relative contribution of acetylcholinergic system tone to the cognitive phenotype of HAND, using a comprehensive cognitive test battery after administration of a double-blinded, placebo-controlled anti-cholinergic drug challenge. We found that both the nicotinic and muscarinic agonists showed heightened physiological and cognitive effects on the HIV-positive participants, relative to the HIV-negative participants, particularly on measures of speed, attention, and memory functioning. The differential responsivity to cholinergic antagonists between serostatus groups indicates a relative deficit of cholinergic neurotransmitter system functioning in the HIV-positive brain, and for these cognitive domains, may suggest an accentuated pattern of cognitive aging, subsequent to HIV-diagnosis.
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