Persistent immune activation is one of the suspected causes of HIV-associated neurocognitive disorders (HAND) in cART era. The CD4/CD8 ratio has been recently showed as a marker of immune activation and HAND. Our aim was to analyze if a decrease in the CD4/CD8 ratio over time could have an impact on neurocognitive deterioration. Randomly selected HIV-infected patients were followed for neuropsychological (NP) testing during a period of almost 2 years. Tests were adjusted for age, gender, and education. Patients were divided into 5 groups: normal tests (NT), neuropsychological deficit (ND, one impaired cognitive domain), asymptomatic neurocognitive disorders (ANI), mild neurocognitive disorders (MND), and HIV-associated dementia (HAD). Risk factors for neurocognitive deterioration were analyzed. Two hundred fifty-six patients underwent NP tests and 94 participated in the follow-up. The groups were comparable. Upon neuropsychological re-testing, six patients showed clinical improvement, 30 had worsened, and 58 were stable, resulting in 42 patients presenting with HAND (45 %). The majority of HAND cases consisted of ANI (26 %) and MND (16 %). In patients whose NP performance worsened, CPE 2010 score was lower at inclusion (7.13 vs 8.00, p = 0.003) and CD4/CD8 decrease more frequent (60 vs 31 %, p = 0.008) than in those who were stable or improved. Multivariate analysis confirmed these results. A decreasing CD4/CD8 ratio during a longitudinal follow-up of randomly selected HIV-infected patients and lower CSF-penetrating regimens were independently associated with cognitive decline. Monitoring trends in CD4/CD8 ratio could contribute to identifying patients at higher risk of neurocognitive deterioration.

IntroductionCognitive impairment in multiple sclerosis (MS) is common even in the early stages of the disease. Our objective was to improve early detection of cognitive impairment in MS.MethodsSeventy-five patients with relapsing remitting (RR) MS and 20 controls were enrolled. Two RRMS groups were defined according to their results at the Paced Auditory Serial Addition Test (PASAT). Patients with a z score below two standard deviations were considered impaired. We quantified T2 and T1 lesion volumes, and cerebral white and grey matter volumes on a conventional brain magnetic resonance imaging (MRI) scan. Global brain atrophy was evaluated using the third ventricle (V3) width (in mm). An average brain model was built based on controls and compared with the patient’s MRI to quantify regional volumetric changes.ResultsSixteen (21.3%) patients with RRMS had low PASAT performance. They had a higher Expanded Disability Status Scale (EDSS) score (P = 0.019). T2 and T1 lesion volumes, and grey and white matter volumes were the same in both groups. An enlargement of the V3 width was observed in the low performer group (P = 0.044) and V3 width was correlated with the PASAT score (r = −0.271; P = 0.021). A composite score, named HV3, was obtained by adding the EDSS and V3 width (in mm) and correlated with the PASAT (r = −0.325; P = 0.006). A cutoff HV3 score of over 5.5 identified patients with low PASAT performance, with a positive predictive value of 92.5% and an accuracy of 70.1%. Focal atrophy was detected in the supplementary motor area, the cingulate gyrus, the right thalamus, and the inferior parietal lobules of patients with lower PASAT performance.ConclusionSpecific brain morphological changes, including an enlargement of the V3 width, are associated with low PASAT performance in patients with RRMS. The HV3 score is an additional and complementary tool, accessible in clinical practice, to suspect easily cognitive impairment in patients with RRMS and to better identify patients requiring a complete cognitive assessment.Electronic supplementary materialThe online version of this article (doi:10.1007/s40120-014-0021-x) contains supplementary material, which is available to authorized users.

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