{"id":{"repo_id":"utswmed","oai_identifier":"oai:utswmed-ir.tdl.org:2152.5/10463"},"canonical_url":"https://search.dev.ndltd.org/etd/utswmed/oai:utswmed-ir.tdl.org:2152.5/10463","repository":{"repo_id":"utswmed","name":"University of Texas Southwestern Medical Center","base_url":"https://utswmed-ir.tdl.org/server/oai/request"},"display":{"title":"HD-tDCS over Frontal Cortex and Neuropsychological Functioning in Cognitively Impaired Older Adults","abstract":"Alzheimer's Clinical Syndrome (ACS) is projected to triple in incidence over the next 30 years and is characterized by a gradual loss of cognitive and functional abilities. Mild cognitive impairment (MCI) is an earlier stage of cognitive impairment that often represents a prodromal stage of ACS. Individuals with MCI may have trouble completing complex instrumental activities of daily living such as managing medication regimens or multiple medical appointments, though they can maintain a level of independence with use of compensatory strategies. MCI and ACS commonly have an amnestic presentation (inability to learn and recall new information), though additional problems in executive functions, language, and/or visuospatial skills are typically present at the time of clinical diagnosis. As ACS progresses, the ability to function independently becomes compromised, and at this stage, assistance with complex activities of daily living (e.g., driving, financial management) is often necessary. Neuropsychiatric symptoms (NPS), such as depression, anxiety, and apathy, are common in MCI and ACS and are also associated with a faster rate of decline. Current treatments used to manage cognitive symptoms include acetylcholinesterase inhibitors (AChEIs) and NMDA-receptor blockers, while selective serotonin reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRI) are common first-line medications for NPS, though all demonstrate short-lived efficacy in symptom control. Lifestyle changes such as dietary interventions, physical exercise, and therapeutic approaches (e.g., reality orientation training, cognitive training, rehabilitation) aim to reduce symptoms and some may stave off decline, though all are unproven to be a restorative treatment for ACS. As such, there exists an urgent need for investigation of novel treatment approaches. Given the unmet treatment needs for MCI and ACS, it is important to evaluate new potential treatments that might provide symptom improvement. One line of possible treatment emerging in the literature is transcranial direct current stimulation (tDCS), which is a non-invasive brain stimulation technique aimed at altering neuronal activity in the brain. The frontal cortex serves as a brain circuitry hub connected to a variety of cortical and subcortical structures. Within the frontal cortex lies the dorsal anterior cingulate cortex (dACC) and pre-supplementary motor area (preSMA), which are differentially important areas for cognitive and emotional functioning. Some preliminary evidence also suggests that both areas are amenable to treatment in some patients with neurologic conditions. This investigation comprised two parts. Part One focused on understanding the current state of knowledge and findings of neuropsychological effects of tDCS over the frontal cortex in individuals with MCI and ACS through a comprehensive narrative review. This review revealed limited evidence to date (9 randomized controlled trials meeting criteria) for the utility of tDCS in treating cognitive deficits and NPS, likely due to a lack of thorough neuropsychological investigation and heterogeneity of study design and methods. However, the technology showed some early promise, as clinically meaningful change on global cognitive screeners was detected in a single trial with an MCI sample. Part Two of the investigation sought to add new knowledge and fill critical gaps currently in the literature by leveraging two mirrored randomized controlled clinical trials recently conducted at UT Southwestern Medical Center. The trials evaluated neuropsychological effects of High Definition tDCS over the dACC/preSMA in individuals with MCI and ACS before and after 10 treatments. Secondary analysis of the combined samples revealed no statistically significant treatment effects on a depressive symptom measure or on composite scores of episodic memory, executive function, language, and working memory. Individuals with MCI and ACS were also evaluated for clinically meaningful changes, and while this revealed several treatment responders across outcome measures in the MCI and ACS active treatment groups, no significant differences were detected between the proportion of responders to non-responders. The individual clinical improvements detected may suggest that certain characteristics (e.g., disease severity) in MCI and ACS may be associated with differential effects from this technology that are worth future investigation. Future studies would likely benefit from investigating different dosage parameters in these populations and use of innovative methods for targeted stimulation over cortical regions important for cognitive and emotional functioning (e.g., dACC/preSMA).","abstract_html":"Alzheimer's Clinical Syndrome (ACS) is projected to triple in incidence over the next 30 years and is characterized by a gradual loss of cognitive and functional abilities. Mild cognitive impairment (MCI) is an earlier stage of cognitive impairment that often represents a prodromal stage of ACS. Individuals with MCI may have trouble completing complex instrumental activities of daily living such as managing medication regimens or multiple medical appointments, though they can maintain a level of independence with use of compensatory strategies. MCI and ACS commonly have an amnestic presentation (inability to learn and recall new information), though additional problems in executive functions, language, and/or visuospatial skills are typically present at the time of clinical diagnosis. As ACS progresses, the ability to function independently becomes compromised, and at this stage, assistance with complex activities of daily living (e.g., driving, financial management) is often necessary. Neuropsychiatric symptoms (NPS), such as depression, anxiety, and apathy, are common in MCI and ACS and are also associated with a faster rate of decline. Current treatments used to manage cognitive symptoms include acetylcholinesterase inhibitors (AChEIs) and NMDA-receptor blockers, while selective serotonin reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRI) are common first-line medications for NPS, though all demonstrate short-lived efficacy in symptom control. Lifestyle changes such as dietary interventions, physical exercise, and therapeutic approaches (e.g., reality orientation training, cognitive training, rehabilitation) aim to reduce symptoms and some may stave off decline, though all are unproven to be a restorative treatment for ACS. As such, there exists an urgent need for investigation of novel treatment approaches. Given the unmet treatment needs for MCI and ACS, it is important to evaluate new potential treatments that might provide symptom improvement. One line of possible treatment emerging in the literature is transcranial direct current stimulation (tDCS), which is a non-invasive brain stimulation technique aimed at altering neuronal activity in the brain. The frontal cortex serves as a brain circuitry hub connected to a variety of cortical and subcortical structures. Within the frontal cortex lies the dorsal anterior cingulate cortex (dACC) and pre-supplementary motor area (preSMA), which are differentially important areas for cognitive and emotional functioning. Some preliminary evidence also suggests that both areas are amenable to treatment in some patients with neurologic conditions. This investigation comprised two parts. Part One focused on understanding the current state of knowledge and findings of neuropsychological effects of tDCS over the frontal cortex in individuals with MCI and ACS through a comprehensive narrative review. This review revealed limited evidence to date (9 randomized controlled trials meeting criteria) for the utility of tDCS in treating cognitive deficits and NPS, likely due to a lack of thorough neuropsychological investigation and heterogeneity of study design and methods. However, the technology showed some early promise, as clinically meaningful change on global cognitive screeners was detected in a single trial with an MCI sample. Part Two of the investigation sought to add new knowledge and fill critical gaps currently in the literature by leveraging two mirrored randomized controlled clinical trials recently conducted at UT Southwestern Medical Center. The trials evaluated neuropsychological effects of High Definition tDCS over the dACC/preSMA in individuals with MCI and ACS before and after 10 treatments. Secondary analysis of the combined samples revealed no statistically significant treatment effects on a depressive symptom measure or on composite scores of episodic memory, executive function, language, and working memory. Individuals with MCI and ACS were also evaluated for clinically meaningful changes, and while this revealed several treatment responders across outcome measures in the MCI and ACS active treatment groups, no significant differences were detected between the proportion of responders to non-responders. The individual clinical improvements detected may suggest that certain characteristics (e.g., disease severity) in MCI and ACS may be associated with differential effects from this technology that are worth future investigation. Future studies would likely benefit from investigating different dosage parameters in these populations and use of innovative methods for targeted stimulation over cortical regions important for cognitive and emotional functioning (e.g., dACC/preSMA).","abstract_has_math":false,"creators":["Helphrey, Jessica Helene"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["LoBue, Christian","Hart, John, Jr.","McClintock, Shawn Michael","Peters, Matthew E.","Thakkar, Vishal"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025-01-02T21:58:34Z","date_published":"2025-01-02T21:58:34Z","updated_at":"2026-07-24T05:52:34Z","subjects":["Alzheimer Disease","Cognitive Dysfunction","Outcome Assessment, Health Care","Transcranial Direct Current Stimulation","Treatment Outcome","Activities of Daily Living"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["1482732346"],"render_values":[{"text":"1482732346","href":null,"code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/2152.5/10463","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["LoBue, Christian","Hart, John, Jr.","McClintock, Shawn Michael","Peters, Matthew E.","Thakkar, Vishal"]},{"key":"dc:creator","label":"Author","values":["Helphrey, Jessica Helene"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2025-01-02T21:58:34Z","2024-12","December 2024"]},{"key":"dc:type","label":"Dc Type","values":["Thesis","text"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Alzheimer Disease","Cognitive Dysfunction","Outcome Assessment, Health Care","Transcranial Direct Current Stimulation","Treatment Outcome","Activities of Daily Living"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2152.5/10463","1482732346"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Alzheimer's Clinical Syndrome (ACS) is projected to triple in incidence over the next 30 years and is characterized by a gradual loss of cognitive and functional abilities. Mild cognitive impairment (MCI) is an earlier stage of cognitive impairment that often represents a prodromal stage of ACS. Individuals with MCI may have trouble completing complex instrumental activities of daily living such as managing medication regimens or multiple medical appointments, though they can maintain a level of independence with use of compensatory strategies. MCI and ACS commonly have an amnestic presentation (inability to learn and recall new information), though additional problems in executive functions, language, and/or visuospatial skills are typically present at the time of clinical diagnosis. As ACS progresses, the ability to function independently becomes compromised, and at this stage, assistance with complex activities of daily living (e.g., driving, financial management) is often necessary. Neuropsychiatric symptoms (NPS), such as depression, anxiety, and apathy, are common in MCI and ACS and are also associated with a faster rate of decline. Current treatments used to manage cognitive symptoms include acetylcholinesterase inhibitors (AChEIs) and NMDA-receptor blockers, while selective serotonin reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRI) are common first-line medications for NPS, though all demonstrate short-lived efficacy in symptom control. Lifestyle changes such as dietary interventions, physical exercise, and therapeutic approaches (e.g., reality orientation training, cognitive training, rehabilitation) aim to reduce symptoms and some may stave off decline, though all are unproven to be a restorative treatment for ACS. As such, there exists an urgent need for investigation of novel treatment approaches. Given the unmet treatment needs for MCI and ACS, it is important to evaluate new potential treatments that might provide symptom improvement. One line of possible treatment emerging in the literature is transcranial direct current stimulation (tDCS), which is a non-invasive brain stimulation technique aimed at altering neuronal activity in the brain. The frontal cortex serves as a brain circuitry hub connected to a variety of cortical and subcortical structures. Within the frontal cortex lies the dorsal anterior cingulate cortex (dACC) and pre-supplementary motor area (preSMA), which are differentially important areas for cognitive and emotional functioning. Some preliminary evidence also suggests that both areas are amenable to treatment in some patients with neurologic conditions. This investigation comprised two parts. Part One focused on understanding the current state of knowledge and findings of neuropsychological effects of tDCS over the frontal cortex in individuals with MCI and ACS through a comprehensive narrative review. This review revealed limited evidence to date (9 randomized controlled trials meeting criteria) for the utility of tDCS in treating cognitive deficits and NPS, likely due to a lack of thorough neuropsychological investigation and heterogeneity of study design and methods. However, the technology showed some early promise, as clinically meaningful change on global cognitive screeners was detected in a single trial with an MCI sample. Part Two of the investigation sought to add new knowledge and fill critical gaps currently in the literature by leveraging two mirrored randomized controlled clinical trials recently conducted at UT Southwestern Medical Center. The trials evaluated neuropsychological effects of High Definition tDCS over the dACC/preSMA in individuals with MCI and ACS before and after 10 treatments. Secondary analysis of the combined samples revealed no statistically significant treatment effects on a depressive symptom measure or on composite scores of episodic memory, executive function, language, and working memory. Individuals with MCI and ACS were also evaluated for clinically meaningful changes, and while this revealed several treatment responders across outcome measures in the MCI and ACS active treatment groups, no significant differences were detected between the proportion of responders to non-responders. The individual clinical improvements detected may suggest that certain characteristics (e.g., disease severity) in MCI and ACS may be associated with differential effects from this technology that are worth future investigation. Future studies would likely benefit from investigating different dosage parameters in these populations and use of innovative methods for targeted stimulation over cortical regions important for cognitive and emotional functioning (e.g., dACC/preSMA)."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["HD-tDCS over Frontal Cortex and Neuropsychological Functioning in Cognitively Impaired Older Adults"]}]}],"canonical_facts":{"dc:contributor":["LoBue, Christian","Hart, John, Jr.","McClintock, Shawn Michael","Peters, Matthew E.","Thakkar, Vishal"],"dc:creator":["Helphrey, Jessica Helene"],"dc:date":["2025-01-02T21:58:34Z","2024-12","December 2024"],"dc:description":["Alzheimer's Clinical Syndrome (ACS) is projected to triple in incidence over the next 30 years and is characterized by a gradual loss of cognitive and functional abilities. Mild cognitive impairment (MCI) is an earlier stage of cognitive impairment that often represents a prodromal stage of ACS. Individuals with MCI may have trouble completing complex instrumental activities of daily living such as managing medication regimens or multiple medical appointments, though they can maintain a level of independence with use of compensatory strategies. MCI and ACS commonly have an amnestic presentation (inability to learn and recall new information), though additional problems in executive functions, language, and/or visuospatial skills are typically present at the time of clinical diagnosis. As ACS progresses, the ability to function independently becomes compromised, and at this stage, assistance with complex activities of daily living (e.g., driving, financial management) is often necessary. Neuropsychiatric symptoms (NPS), such as depression, anxiety, and apathy, are common in MCI and ACS and are also associated with a faster rate of decline. Current treatments used to manage cognitive symptoms include acetylcholinesterase inhibitors (AChEIs) and NMDA-receptor blockers, while selective serotonin reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRI) are common first-line medications for NPS, though all demonstrate short-lived efficacy in symptom control. Lifestyle changes such as dietary interventions, physical exercise, and therapeutic approaches (e.g., reality orientation training, cognitive training, rehabilitation) aim to reduce symptoms and some may stave off decline, though all are unproven to be a restorative treatment for ACS. As such, there exists an urgent need for investigation of novel treatment approaches. Given the unmet treatment needs for MCI and ACS, it is important to evaluate new potential treatments that might provide symptom improvement. One line of possible treatment emerging in the literature is transcranial direct current stimulation (tDCS), which is a non-invasive brain stimulation technique aimed at altering neuronal activity in the brain. The frontal cortex serves as a brain circuitry hub connected to a variety of cortical and subcortical structures. Within the frontal cortex lies the dorsal anterior cingulate cortex (dACC) and pre-supplementary motor area (preSMA), which are differentially important areas for cognitive and emotional functioning. Some preliminary evidence also suggests that both areas are amenable to treatment in some patients with neurologic conditions. This investigation comprised two parts. Part One focused on understanding the current state of knowledge and findings of neuropsychological effects of tDCS over the frontal cortex in individuals with MCI and ACS through a comprehensive narrative review. This review revealed limited evidence to date (9 randomized controlled trials meeting criteria) for the utility of tDCS in treating cognitive deficits and NPS, likely due to a lack of thorough neuropsychological investigation and heterogeneity of study design and methods. However, the technology showed some early promise, as clinically meaningful change on global cognitive screeners was detected in a single trial with an MCI sample. Part Two of the investigation sought to add new knowledge and fill critical gaps currently in the literature by leveraging two mirrored randomized controlled clinical trials recently conducted at UT Southwestern Medical Center. The trials evaluated neuropsychological effects of High Definition tDCS over the dACC/preSMA in individuals with MCI and ACS before and after 10 treatments. Secondary analysis of the combined samples revealed no statistically significant treatment effects on a depressive symptom measure or on composite scores of episodic memory, executive function, language, and working memory. Individuals with MCI and ACS were also evaluated for clinically meaningful changes, and while this revealed several treatment responders across outcome measures in the MCI and ACS active treatment groups, no significant differences were detected between the proportion of responders to non-responders. The individual clinical improvements detected may suggest that certain characteristics (e.g., disease severity) in MCI and ACS may be associated with differential effects from this technology that are worth future investigation. Future studies would likely benefit from investigating different dosage parameters in these populations and use of innovative methods for targeted stimulation over cortical regions important for cognitive and emotional functioning (e.g., dACC/preSMA)."],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2152.5/10463","1482732346"],"dc:language":["en"],"dc:subject":["Alzheimer Disease","Cognitive Dysfunction","Outcome Assessment, Health Care","Transcranial Direct Current Stimulation","Treatment Outcome","Activities of Daily Living"],"dc:title":["HD-tDCS over Frontal Cortex and Neuropsychological Functioning in Cognitively Impaired Older Adults"],"dc:type":["Thesis","text"]},"updated_at":"2026-07-24T05:52:34Z"}