Effects of APOE ε4, age, and HIV on glial metabolites and cognitive deficits.
Objective: We aimed to evaluate the combined effects of HIV and APOE ε4 allele(s) on glial metabolite levels, and on known cognitive deficits associated with either condition, across the ages.Methods: One hundred seventy-seven participants, primarily of white and mixed race (97 seronegative subjects...
| Publicado en: | Neurology Vol. 82; no. 24; pp. 2213 - 2223 |
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| Autores principales: | , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
Lippincott Williams & Wilkins
6/17/2014
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=107859450&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 107859450 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00283878 NRO jtl: Neurology issn: 00283878 maglogo: N pubinfo: dt: 6/17/2014 vid: 82 iid: 24 pid: 433 pub: Lippincott Williams & Wilkins place: Baltimore, Maryland artinfo: ui: 107859450 107859450 NLM24850492 2012629469 10.1212/WNL.0000000000000526 NLM24850492 PMC4113464 107859450 ppf: 2213 ppct: 10 formats: tig: atl: Effects of APOE ε4, age, and HIV on glial metabolites and cognitive deficits. aug: au: Chang, Linda Jiang, Caroline Cunningham, Eric Buchthal, Steven Douet, Vanessa Andres, Marilou Ernst, Thomas affil: From the Department of Medicine, Division of Neurology, John A. Burns School of Medicine (L.C., C.J., E.C., S.B., V.D., T.E.), and Pacific Biosciences Research Center (M.A.), University of Hawai'i at Manoa, and The Queen's Medical Center, Honolulu, HI. lchang@hawaii.edu. sug: subj: Aging Apolipoproteins Cognition Disorders HIV Seropositivity Physiopathology Cells Metabolism Adult Choline Cross Sectional Studies Female Frontal Lobe Metabolism Frontal Lobe Pathology Human Image Processing, Computer Assisted Inositol Magnetic Resonance Imaging Magnetic Resonance Spectroscopy Male Middle Age Neuropsychological Tests Adult: 19-44 years Middle Aged: 45-64 years Female Male ab: Objective: We aimed to evaluate the combined effects of HIV and APOE ε4 allele(s) on glial metabolite levels, and on known cognitive deficits associated with either condition, across the ages.Methods: One hundred seventy-seven participants, primarily of white and mixed race (97 seronegative subjects: aged 44.7 ± 1.3 years, 85 [87.6%] men, 28 [28.9%] APOE ε4+; 80 HIV+ subjects: aged 47.3 ± 1.1 years, 73 [91.3%] men, 23 [28.8%] APOE ε4+), were assessed cross-sectionally for metabolite concentrations using proton magnetic resonance spectroscopy in 4 brain regions and for neuropsychological performance.Results: Frontal white matter myo-inositol was elevated in subjects with HIV across the age span but showed age-dependent increase in seronegative subjects, especially in APOE ε4+ carriers. In contrast, only seronegative APOE ε4+ subjects showed elevated myo-inositol in parietal cortex. All APOE ε4+ subjects had lower total creatine in basal ganglia. While all HIV subjects showed greater cognitive deficits, HIV+ APOE ε4+ subjects had the poorest executive function, fluency memory, and attention/working memory. Higher myo-inositol levels were associated with poorer fine motor function across all subjects, slower speed of information processing in APOE ε4+ subjects, and worse fluency in HIV+ APOE ε4+ subjects.Conclusions: In frontal white matter of subjects with HIV, the persistent elevation and lack of normal age-dependent increase in myo-inositol suggest that persistent glial activation attenuated the typical antagonistic pleiotropic effects of APOE ε4 on neuroinflammation. APOE ε4 negatively affects energy metabolism in brain regions rich in dopaminergic synapses. The combined effects of HIV infection and APOE ε4 may lead to greater cognitive deficits, especially in those with greater neuroinflammation. APOE ε4 allele(s) may be a useful genetic marker to identify white and mixed-race HIV subjects at risk for cognitive decline. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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