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Incidence and nature of cognitive decline over 1 year among HIV-infected former plasma donors in China.

ABSTRACT: To quantify and characterize the nature of cognitive change over 1 year in a cohort of HIV-positive former plasma donors in rural China.The present study is an observational cohort study.One hundred and ninety-two HIV-positive and 101 demographically comparable HIV-negative individuals, all former plasma donors, who lived in a rural part of China, received comprehensive medical and neuropsychological examinations. At study entry, 56% of HIV-positive group was on combination antiretroviral treatment and 60.9% at follow-up. Multiple regression change score approach was used with the HIV-negative sample to develop norms for change that would be then applied to the HIV-positive participants. Follow-up test scores adjusted for the control group practice effect.Fifty-three HIV-positive individuals (27%) developed significant cognitive decline as compared with five (5%) HIV-negative individuals. Cognitive decline was predicted at baseline by AIDS status, lower nadir CD4, and worse processing speed; at follow-up, it was associated with lower current CD4 cell count and failure of viral suppression on combination antiretroviral treatment. Neuropsychological decline also was associated with decreased independence in activities of daily living. Using neuropsychological impairment scores that were corrected for 'practice' on repeated testing, we found that among the decliners, 41.5% (N = 22) had incident impairment, whereas 38% (N = 20) declined within the impaired range and another 20.7% (N = 11) declined within the normal range.The present study demonstrates that despite ongoing combination antiretroviral treatment, cognitive decline in HIV-positive people is common over a 1-year follow-up. Regression-based norms for change on western neuropsychological tests can be used to detect disease-related cognitive decline in a developing country.

SUBMITTER: Cysique LA

PROVIDER: S-EPMC2898923 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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Incidence and nature of cognitive decline over 1 year among HIV-infected former plasma donors in China.

Cysique Lucette A LA Letendre Scott L SL Ake Christopher C Jin Hua H Franklin Donald R DR Gupta Saurabh S Shi Chuan C Yu Xin X Wu Zunyou Z Abramson Ian S IS Grant Igor I Heaton Robert K RK

AIDS (London, England) 20100401 7

<h4>Objective</h4>To quantify and characterize the nature of cognitive change over 1 year in a cohort of HIV-positive former plasma donors in rural China.<h4>Design</h4>The present study is an observational cohort study.<h4>Methods</h4>One hundred and ninety-two HIV-positive and 101 demographically comparable HIV-negative individuals, all former plasma donors, who lived in a rural part of China, received comprehensive medical and neuropsychological examinations. At study entry, 56% of HIV-positi ...[more]

PMID: 20299964

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Project description:BackgroundHere, we address a pivotal factor in Alzheimer's prevention-identifying those at risk early, when dementia can still be avoided. Recent research highlights an accelerated forgetting phenotype as a risk factor for Alzheimer's disease. We hypothesized that delayed recall over 4 weeks would predict cognitive decline over 1 year better than 30-min delayed recall, the current gold standard for detecting episodic memory problems which could be an early clinical manifestation of incipient Alzheimer's disease. We also expected hippocampal subfield volumes to improve predictive accuracy.MethodsForty-six cognitively healthy older people (mean age 70.7 ± 7.97, 21/46 female), recruited from databases such as Join Dementia Research, or a local database of volunteers, performed 3 memory tasks on which delayed recall was tested after 30 min and 4 weeks, as well as Addenbrooke's Cognitive Examination III (ACE-III) and CANTAB Paired Associates Learning. Medial temporal lobe subregion volumes were automatically measured using high-resolution 3T MRI. The ACE-III was repeated after 12 months to assess the change in cognitive ability. We used univariate linear regressions and ROC curves to assess the ability of tests of delayed recall to predict cognitive decline on ACE-III over the 12 months.ResultsFifteen of the 46 participants declined over the year (≥ 3 points lost on ACE-III). Four-week verbal memory predicted cognitive decline in healthy older people better than clinical gold standard memory tests and hippocampal MRI. The best single-test predictor of cognitive decline was the 4-week delayed recall on the world list (R2 = .123, p = .018, β = .418). Combined with hippocampal subfield volumetry, 4-week verbal recall identifies those at risk of cognitive decline with 93% sensitivity and 86% specificity (AUC = .918, p < .0001).ConclusionsWe show that a test of accelerated long-term forgetting over 4 weeks can predict cognitive decline in healthy older people where traditional tests of delayed recall cannot. Accelerated long-term forgetting is a sensitive, easy-to-test predictor of cognitive decline in healthy older people. Used alone or with hippocampal MRI, accelerated forgetting probes functionally relevant Alzheimer's-related change. Accelerated forgetting will identify early-stage impairment, helping to target more invasive and expensive molecular biomarker testing.

Project description:BACKGROUND: HIV-1 subtype B' isolates have been predominantly circulating in China. Their intra- and inter-subtype neutralization sensitivity to autologous and heterologous plasmas has not been well studied. RESULTS: Twelve HIV-1 B' clinical isolates obtained from patients were tested for their intra- and inter-subtype neutralization sensitivity to the neutralization antibodies in the plasmas from patients infected by HIV-1 B' and CRF07_BC subtypes, respectively. We found that the plasmas from the HIV-1 B'-infected patients could potently neutralize heterologous viruses of subtype B' with mean ID50 titer (1/x) of about 67, but they were not effective in neutralizing autologous viruses of subtype B' with mean ID50 titer (1/x) of about 8. The plasmas from HIV-1 CRF07_BC-infected patients exhibited weak inter-subtype neutralization activity against subtype B' viruses with ID50 titer (1/x) is about 22. The neutralization sensitivity of HIV-1 B' isolates was inversely correlated with the neutralizing activity of plasmas from HIV-1 B'-infected patients (Spearman's r = -0.657, P = 0.020), and with the number of potential N-glycosylation site (PNGS) in V1-V5 region (Spearman's r = -0.493, P = 0.034), but positively correlated with the viral load (Spearman's r = 0.629, P = 0.028). It had no correlation with the length of V1-V5 regions or the CD4+ T cell count. Virus AH259V has low intra-subtype neutralization sensitivity, it can be neutralized by 17b (IC50: 10?g/ml) and 447-52D (IC50: 1.6?g/ml), and the neutralizing antibodies (nAbs) in plasma AH259P are effective in neutralizing infection by the primary HIV-1 isolates with different subtypes with ID50 titers (1/x) in the range of 32-396. CONCLUSIONS: These findings suggest that the HIV-1 subtype B' viruses may mutate under the immune pressure, thus becoming resistant to the autologous nAbs, possibly by changing the number of PNGS in the V1-V5 region of the viral gp120. Some of primary HIV-1 isolates are able to induce both intra- and inter-subtype cross-neutralizing antibody responses.

Dataset Information

Incidence and nature of cognitive decline over 1 year among HIV-infected former plasma donors in China.

Publications

Incidence and nature of cognitive decline over 1 year among HIV-infected former plasma donors in China.

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