Family history of dementia and APOE e4 status predict neurocognitive trajectories among persons with HIV

痴呆家族史和 APOE e4 状态可预测 HIV 感染者的神经认知轨迹

• 批准号: 10533760
• 负责人: Maulika Kohli
• 金额: $ 4.06万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10533760
• 关键词: Acquired Immunodeficiency Syndrome; Address; Adult; Age; Aging; Alcohol consumption; Alleles; Alzheimer' s Disease; Alzheimer' s disease risk; Amyloid deposition; Attention; Cerebrum; Characteristics; Chronic; Clinical; Cognitive; Cognitive deficits; Data; Dementia; Development; Diagnosis; Disease; Disease Progression; Elderly; Employment; Family history of; Genetic; Genetic Markers; Genotype; Goals; HIV; HIV antiretroviral; HIV-associated neurocognitive disorder; Hepatitis C; Highly Active Antiretroviral Therapy; Impaired cognition; Inherited; Intervention; Lead; Lewy Body Dementia; Link; Medial; Medical; Memory; Mental Depression; Nerve Degeneration; Neurocognition; Neurocognitive; Neurocognitive Deficit; Neurodegenerative Disorders; Older Population; Outcome; Patient Self-Report; Performance; Persons; Predisposition; Proxy; Quality of life; Research; Risk; Risk Factors; Sampling; Second Degree Relative; Senile Plaques; Temporal Lobe; Therapeutic Intervention; Time; Traumatic Brain Injury; United States; Viral Load result; Vulnerable Populations; age effect; age related; aged; antiretroviral therapy; apolipoprotein E-4; archive data; archived data; brain health; comorbidity; daily functioning; executive function; expectation; follow-up; high risk; longitudinal analysis; middle age; neuroAIDS; neurocognitive disorder; neuropsychiatry; neurotoxicity; normal aging; preventive intervention; programs; resilience; secondary analysis; sex; substance use; tau Proteins; working group

PROJECT SUMMARY/ABSTRACT With the introduction of highly-active antiretroviral therapy, people with HIV (PWH) are living longer and the proportion of middle-older age PWH continues to rise. Advancing age is associated with an increased risk of age-related neurogenerative diseases including Alzheimer’s disease. Both chronic HIV and aging are associated with cognitive deficits beyond the expectations of normal aging. Comorbidities are also elevated in older PWH which may additionally increase risk for neurodegenerative diseases. As such, it is imperative to focus research efforts on investigating pre-determined risk factors of neurocognitive impairment among PWH. Neurodegenerative diseases are considered to be partially inherited. In fact, the apolipoprotein e4 (APOE e4) allele increases the risk of neurodegenerative diseases such as Alzheimer’s disease and is associated with poorer neurocognitive outcomes. Furthermore, HIV-uninfected (HIV-) adults with a family history of dementia (FHD), considered a proxy for genetic markers of dementia, are at a higher risk for developing dementia and long-term cognitive decline compared to those without FHD. We have shown that FHD may be a risk factor for HIV-associated neurocognitive disorders as persons with FHD have significantly worse global neurocognitive function compared to those without FHD. Nevertheless, these cross-sectional data do not address the potential additive effect of FHD and APOE e4 on rate of global and domain-specific neurocognitive decline among older PWH. Assessing the relationships between FHD, APOE e4 and neurocognitive decline is critical toward identifying risk and neuroprotective factors among the vulnerable population of older PWH. Accordingly, the proposed F31 project will follow-up on the initial cross-sectional examination of FHD and neurocognition in order to: 1) determine whether FHD among first- and second-degree relatives and APOE e4 status are associated with worse global- and domain-specific neurocognition in middle-to-older age PWH; 2) determine whether FHD and APOE e4 status predict neurocognitive trajectories; and 3) explore potential effects of demographic, neuropsychiatric, substance use, daily functioning, comorbidities, and HIV disease characteristics on neurocognitive trajectories by FHD and APOE-e4 status. The proposed research will use cross-sectional and longitudinal archival data of middle-to-older PWH from the Multi-Dimensional Successful Aging Among HIV-Infected Adults and CNS HIV Antiretroviral Therapy Effects Research programs. The opportunities afforded via this F31 mechanism will facilitate the applicant’s professional development toward becoming an independent academic neuropsychologist dedicated to promoting neurocognitive resilience among older PWH.

项目总结/文摘