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Involvement of the Cortical Cholinergic Receptor System in Symptoms of Cognitive Aging in HIV-Associated Neurocognitive Disorders (HAND)

dc.creatorKamkwalala, Asante Rochelle
dc.date.accessioned2020-08-22T20:33:43Z
dc.date.available2019-07-24
dc.date.issued2019-07-24
dc.identifier.urihttps://etd.library.vanderbilt.edu/etd-07232019-090733
dc.identifier.urihttp://hdl.handle.net/1803/13504
dc.description.abstractAs 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.
dc.format.mimetypeapplication/pdf
dc.subjectMuscarinic
dc.subjectNeurovirology
dc.subjectNicotinic
dc.subjectHIV-1
dc.subjectCognition
dc.subjectNeuroscience
dc.titleInvolvement of the Cortical Cholinergic Receptor System in Symptoms of Cognitive Aging in HIV-Associated Neurocognitive Disorders (HAND)
dc.typedissertation
dc.contributor.committeeMemberTodd Hulgan, MD
dc.contributor.committeeMemberPaul A Newhouse, MD
dc.contributor.committeeMemberCarrie Jones, PhD
dc.type.materialtext
thesis.degree.namePHD
thesis.degree.leveldissertation
thesis.degree.disciplineNeuroscience
thesis.degree.grantorVanderbilt University
local.embargo.terms2019-07-24
local.embargo.lift2019-07-24
dc.contributor.committeeChairDavid Zald, PhD


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