Cognitive Trajectory Phenotypes in Human Immunodeficiency Virus-Infected Patients.

TitleCognitive Trajectory Phenotypes in Human Immunodeficiency Virus-Infected Patients.
Publication TypeJournal Article
Year of Publication2019
AuthorsDastgheyb, RM, Sacktor, N, Franklin, D, Letendre, S, Marcotte, T, Heaton, R, Grant, I, McArthur, JC, Rubin, LH, Haughey, NJ
JournalJ Acquir Immune Defic Syndr
Date Published2019 09 01
KeywordsAdult, Antirheumatic Agents, CHARTER, Cognition, Cognitive Dysfunction, Cohort Studies, Electronic Data Processing, Executive function, Female, HIV Infections, Humans, Internal, Learning, Male, Memory, Short-Term, Mental Recall, Middle Aged, Neuropsychological Tests, Phenotype, Prevalence, Speech Disorders, Verbal Learning

OBJECTIVE: The presentation of cognitive impairments in HIV-infected individuals has transformed since the introduction of antiretroviral therapies. Although the overall prevalence of cognitive impairments has not changed considerably, frank dementia is now infrequent, and milder forms of cognitive impairments predominate. Mechanistic insights to the underlying causes of these residual cognitive impairments have been elusive, in part due to the heterogenous etiology of cognitive dysfunction in this population. Here, we sought to categorize longitudinal change in HIV-infected patients based on the performance in specific cognitive domains.DESIGN: This study consisted of 193 participants from the CHARTER cohort with detailed demographic, clinical, and neuropsychological testing data obtained from 2 study visits interspersed by ∼6 months. Cognitive testing assessed executive function, learning and delayed recall, working memory, verbal fluency, speed of information processing, and motor skills. Change scores were calculated for each domain between the 2 study visits. Dimension reduction and clustering was accomplished by principal component analysis of change scores and k-means clustering to identify cognitive domains that group together and groups of subjects with similar patterns of change.RESULTS: We identified 4 distinct cognitive change phenotypes that included declines in: (1) verbal fluency, (2) executive function (3) learning and recall, and (4) motor function, with approximately equal numbers of participants in each phenotype.CONCLUSIONS: Each of the 4 cognitive change phenotypes identify deficits that imply perturbations in specific neural networks. Future studies will need to validate if cognitive change phenotypes are associated with alterations in associated neural pathways.

Alternate JournalJ Acquir Immune Defic Syndr
PubMed ID31107302
PubMed Central IDPMC6692206
Grant ListR01 AG057420 / AG / NIA NIH HHS / United States
P30 MH075673 / MH / NIMH NIH HHS / United States
R01 MH110246 / MH / NIMH NIH HHS / United States
R01 MH096636 / MH / NIMH NIH HHS / United States
P01 MH105280 / MH / NIMH NIH HHS / United States
N01MH22005 / MH / NIMH NIH HHS / United States
HHSN271201000036C / MH / NIMH NIH HHS / United States
HHSN271201000030C / MH / NIMH NIH HHS / United States