Cognitive impairment and cardiovascular disease related to alexithymia in a well-controlled HIV-infected population.

Both cognitive diseases and alexithymia may be associated with HIV. Moreover, alexithymia has been linked to cardiovascular (CV) diseases. Our aim was to explore the prevalence of alexithymia and its associations with neurocognitive disorders (HAND) and CV risk factors in a well-controlled HIV-positive population. We consecutively enrolled 140 HIV-positive individuals on antiretroviral therapy and 35 healthy subjects matched for age, education and gender. In all participants alexithymia was explored by the 20-item Toronto Alexithymia Scale. For HIV-positive subjects also data about CV risk factors were collected, and a comprehensive neuropsychological examination was administered; HAND was defined according to Frascati criteria. Patients and controls did not differ in the proportion of alexithymic status (10% vs. 11%; p=0.761). Among HIV-positive patients, alexithymic participants presented a higher prevalence of diabetes (21% vs. 3%, p=0.035) and hypertension (36% vs. 13%, p= 0.037) compared to non-alexithymic. About 30% (n=41) of HIV-positive patients met criteria for asymptomatic HAND. Alexithymia was not independently associated with a higher risk of HAND (p=0.189). Analyzing each cognitive domain, alexithymia showed an independent association with an abnormal performance (OR 1.08; p=0.037) only in psychomotor speed. In conclusion, in the context of a well-controlled HIV infection, we found a low prevalence of alexithymia comparable to healthy controls. Alexithymia was linked to higher risk of CV disease in the HIV-positive population, but with a rate similar to that previously estimated in the HIV-negative alexithymic. Finally, alexithymia was clearly associated to cognitive impairment only in the psychomotor speed domain, suggesting a common fronto-striatal system dysregulation.

Verbal list learning and memory profiles in HIV-infected adults, Alzheimer's disease, and Parkinson's disease: An evaluation of the "cortical hypothesis" of NeuroAIDS.

HIV+ population is getting older because of progress in treatments. Yet, there are concerns that Older HIV+ individuals (OHIV+) may be more vulnerable for developing a "cortical" dementia such as Alzheimer Disease (AD). Our aim was to explore the hypothesis that the cognitive deficit extends to ''cortical'' functions in OHIV+ by comparing serial position effects (SPE) in different groups of participants affected by "cortical" or "subcortical" damage. We enrolled a total of 122 subjects: 22 OHIV+ (≥60 years of age), 31 Younger HIV+ (YHIV+) (<60 years of age), 18 participants with AD, 23 subjects with Parkinson Disease (PD), and 28 healthy subjects. All subjects performed verbal learning tasks (VLT) to explore SPE. Factorial analysis of covariance showed a significant effect of "group" (p < 0.001) and "task" (Primacy vs Recency) (p < 0.001), but no significant group*task (p = 0.257) interaction. Compared with healthy subjects (p = 0.003), AD had the most severe reduction of Primacy, confirming a primary "encoding deficit," while PD confirmed a "frontal pattern." OHIV+ showed a memory profile similar to that of PD with a worsening of the cognitive performance in comparison with YHIV+. In conclusion, we did not confirm the "cortical" hypothesis in OHIV+, at least in terms of learning and memory functions.

Neuropsychological screening tools in Italian HIV+ patients: a comparison of Montreal Cognitive Assessment (MoCA) and Mini Mental State Examination (MMSE).

OBJECTIVE: Despite the progress in HIV treatments, mild forms of cognitive impairment still persist. Brief and sensitive screening tools are needed. We evaluated the accuracy of the Montreal Cognitive Assessment (MoCA) compared to the Mini Mental State Examination (MMSE) to detect cognitive impairment in HIV-infected participants. METHOD: HIV-infected patients were consecutively enrolled during routine outpatient visits at a single institution. The MoCA, the MMSE, and a comprehensive neuropsychological battery were administered. Patients were considered as affected by cognitive impairment if they showed decreased cognitive function in at least two ability domains based on age and education adjusted Italian normative cut-offs. RESULTS: Ninety-three HIV-infected participants (75% males, median age 47, all on antiretroviral therapy; 90% HIV-RNA <50copies/mL, median CD4 644 cells/µL) were enrolled. Thirteen participants (14%) were diagnosed as cognitively compromised via a comprehensive neuropsychological examination. The area under the curve of the adjusted MMSE and MoCA scores to detect cognitive impairment were .51 (95% CI = .31-.72, p = .877) and .70 (95% CI = .53-.86, p = .025), respectively. A MoCA score <22 was able to predict the cognitive impairment with 62% of sensitivity and 76% of specificity. CONCLUSIONS: Our findings suggested that the prognostic performance of the MoCA to detect cognitive impairment among mildly impaired HIV-infected participants was only moderate. Further investigations are needed to identify optimal cognitive tests to screen HIV-infected individuals or to explore whether a combination of cognitive tests might represent a viable alternative to a single screening tool.

Baseline CD4(+) T-cell count and cardiovascular risk factors predict the evolution of cognitive performance during 2-year follow-up in HIV-infected patients.

BACKGROUND: The aim of our study was to better understand the dynamics between cardiovascular risk factors and immunological parameters in the evolution of cognitive performance in HIV+ patients. METHODS: We conducted a prospective longitudinal study, consecutively enrolling asymptomatic HIV+ subjects during routine outpatient visits at two clinical centres. At baseline and after 2 years, all patients underwent a comprehensive neuropsychological battery. Common carotid intima-media thickness (cIMT) was also measured. RESULTS: A total of 150 patients completed the study (77% males, median age 46 years, 20% with past AIDS-defining events, 95% on cART, 88% with HIV-RNA<50 copies/ml). After a 2-year follow-up, there was no difference in the proportion of patients with cognitive impairment (32% versus 33% at baseline; P=1.00). However, a significantly worse memory performance was observed (z score mean change -0.51, sd 1.05; P=0.001). At multivariate analysis, baseline dyslipidaemia (OR 2.7, 95% CI 1.1, 7.1; P=0.037) showed a significant association with a higher risk of memory impairment at 2-year follow-up, while higher baseline CD4(+) T-cell count (OR 0.80 per 100 cells/µl higher; 95% CI 0.66, 0.97; P=0.026) was found to be a protective factor, adjusting for the presence of a memory impairment at baseline. When the analysis was restricted to patients who did not change antiretroviral therapy during the study period (n=109), baseline cIMT (OR 14.6 per 0.1 mm higher; 95% CI 1.1, 189.9; P=0.041) also emerged as an independent risk factor for memory impairment at 2-year follow-up. CONCLUSIONS: Immunological parameters and cardiovascular risk factors are independently associated with the evolution of cognitive status in HIV+ patients.

Antiretroviral neuropenetration scores better correlate with cognitive performance of HIV-infected patients after accounting for drug susceptibility.

BACKGROUND: The aim of the study was to explore how viral resistance and antiretroviral central nervous system (CNS) penetration could impact on cognitive performance of HIV-infected patients. METHODS: We performed a multicentre cross-sectional study enrolling HIV-infected patients undergoing neuropsychological testing, with a previous genotypic resistance test on plasma samples. CNS penetration-effectiveness (CPE) scores and genotypic susceptibility scores (GSS) were calculated for each regimen. A composite score (CPE-GSS) was then constructed. Factors associated with cognitive impairment were investigated by logistic regression analysis. RESULTS: A total of 215 patients were included. Mean CPE was 7.1 (95% CI 6.9, 7.3) with 206 (95.8%) patients showing a CPE≥6. GSS correction decreased the CPE value in 21.4% (mean 6.5, 95% CI 6.3, 6.7), 26.5% (mean 6.4, 95% CI 6.1, 6.6) and 24.2% (mean 6.4, 95% CI 6.2, 6.6) of subjects using ANRS, HIVDB and REGA rules, respectively. Overall, 66 (30.7%) patients were considered cognitively impaired. No significant association could be demonstrated between CPE and cognitive impairment. However, higher GSS-CPE was associated with a lower risk of cognitive impairment (CPE-GSSANRS odds ratio 0.75, P=0.022; CPE-GSSHIVDB odds ratio 0.77, P=0.038; CPE-GSSREGA odds ratio 0.78, P=0.038). Overall, a cutoff of CPE-GSS≥5 seemed the most discriminatory according to each different interpretation system. CONCLUSIONS: GSS-corrected CPE score showed a better correlation with neurocognitive performance than the standard CPE score. These results suggest that antiretroviral drug susceptibility, besides drug CNS penetration, can play a role in the control of HIV-associated neurocognitive disorders.

Posterior AD-type pathology: cognitive subtypes emerging from a cluster analysis.

BACKGROUND: "Posterior shift" of the neuropathological changes of Alzheimer's disease (AD) produces a syndrome (posterior cortical atrophy) (PCA) dominated by high-level visual deficits. OBJECTIVE: To explore in patients with AD-type pathology whether a data-driven analysis (cluster analysis) based on neuropsychological findings resulted in the emergence of different subgroups of patients; in particular to find out whether it was possible to identify patients with visuospatial deficits consistent with the hypothesis that PCA is a "dorsal stream" syndrome or, rather, whether there were subgroups of patients with different types of impairment within the high-level visual domain. METHODS: 23 PCA and 16 DAT patients were studied. By a principal component analysis performed on a wide range of neuropsychological tasks, 15 variables were obtained that loaded onto five main factors (memory, language, perceptual, visuospatial, and calculation) which entered a hierarchical cluster analysis. RESULTS: Four clusters of cognitive impairment emerged: visuospatial/perceptual, memory, perceptual/calculation, and language. Only in the first cluster a visuospatial deficit clearly emerged. conclusions: AD pathology produces not only variants dominated by memory (DAT) and, to a lesser extent, visuospatial deficit (PCA), but also other distinct syndromic subtypes with disorders in visual perception and language which reflect a different vulnerability of specific functional networks.

Visual short-term store can compensate for a defective phonological short-term store in patients with apraxia of speech.

OBJECTIVE: The aim of the study was to investigate whether, within the phonological short-term memory (STM) system, speech articulation disorders primarily due to cortical damage are associated with deficits in the phonological recoding of visual-verbal material, and whether the visual short-term store (STS) can compensate for inefficient access to the phonological STS, as suggested in previous reports. METHOD: Two patients (AE and TM) with apraxia of speech due to atrophic cerebral damage were administered a battery of tasks devised to explore the organization of the phonological STM. RESULTS: AE's span was normal and TM's span was markedly reduced. Phonological similarity and word-length effects: Both patients showed the effects in visual presentation; the effect was less evident in verbal presentation. This suggests a phonological STS disorder and preserved rehearsal/phonological recoding, consistently with involvement of the left parietal regions, which was documented by the MRI in both patients. Unexpectedly, TM had a longer span for similar than for dissimilar words in visually presented stimuli. Silent phonology (on written material): At variance with controls, stress assignment improved during unattended speech both in AE and TM, while in both patients and controls a detrimental effect of unattended speech was documented in the initial sound task. CONCLUSIONS: To account for this unusual pattern of results, we hypothesized that whenever possible, AE and TM adopt the strategy that takes advantage of the visual STM store to compensate for a defective phonological STS.

Neuropsychological features of patients with Parkinson's disease and impulse control disorders.

Impulse control disorders (ICDs) are frequent in Parkinson's disease (PD). Aim of the present study was to investigate cognition and behaviour in PD patients with and without ICDs, in order to identify potential early clinical features which might be associated to the development of ICDs. We recruited 17 PD patients with ICDs and 17 without ICDs, matched for several clinical variables, without clinically significant cognitive deficits. Assessments included behavioural scales and a neuropsychological battery, including the Iowa Gambling Task (IGT). In patients with ICDs, the total score of the BIS and the Motor Impulsivity subscore were significantly higher than in patients without ICDs. In patients with ICDs, we observed only statistical trends towards a worse performance on neuropsychological tasks (go-no-go subtest of the Frontal Assessment Battery, oral verb naming task, copying of drawings with landmarks) sensitive to frontal lobe dysfunction (FLD) and on the IGT (loss of a greater amount of money, more risky choices). As compared to patients without ICDs, they reported a more than threefold number of errors on the interference subtest of Stroop test, which is also sensitive to FLD. Although this study did not show any significant difference between PD patients presenting ICDs as compared with patients without ICDs on neuropsychological variables, some preliminary evidence was detected suggesting a trend toward a worse performance of the PD-ICD group on few neuropsychological tasks which are at least partially sensitive to frontal lobe dysfunction, including tasks sensitive to dysfunction of ventral fronto-striatal loops.

Evaluation of emotion processing in HIV-infected patients and correlation with cognitive performance.

BACKGROUND: Facial emotion recognition depends on cortical and subcortical networks. HIV infection of the central nervous system can damage these networks, leading to impaired facial emotion recognition. METHODS: We performed a cross-sectional single cohort study consecutively enrolling HIV + subjects during routine outpatient visits. Age, gender and education-matched HIV-negative healthy individuals were also selected. Subjects were submitted to a Facial Emotion Recognition Test, which assesses the ability to recognize six basic emotions (disgust, anger, fear, happiness, surprise, sadness). The score for each emotion and a global score (obtained by summing scores for each emotion) were analyzed. General cognitive status of patients was also assessed. RESULTS: A total of 49 HIV + and 20 HIV - subjects were enrolled. On the Facial Emotion Recognition Test, ANOVA revealed a significantly lower performance of HIV + subjects than healthy controls in recognizing fear. Moreover, fear facial emotion recognition was directly correlated with Immediate Recall of Rey Words. The lower the patients' neurocognitive performance the less accurate they were in recognizing happiness. AIDS-defining events were negatively related to the correct recognition of happiness. CONCLUSIONS: Fear recognition deficit in HIV + patients might be related to the impaired function of neural networks in the frontostriatal system. AIDS events, including non-neurological ones, may have a negative effect on this system. Inclusion of an emotion recognition test in the neuropsychological test battery could help clinicians during the long term management of HIV-infected patients, to better understand the cognitive mechanisms involved in the reduction of emotion recognition ability and the impact of this impairment on daily life.

Effect of aging and human immunodeficiency virus infection on cognitive abilities.

OBJECTIVES: To explore the combined effects of aging and human immunodeficiency virus (HIV) infection on cognitive decay. DESIGN: Cross-sectional, single-cohort study. SETTING: Institute of Clinical Infectious Diseases, Catholic University of the Sacred Heart, Rome, Italy. PARTICIPANTS: One hundred fifty-three asymptomatic HIV-positive (HIV+) outpatients (20% aged ≥ 60) and an age- and education-matched control population of 39 HIV-negative individuals. MEASUREMENTS: A neuropsychological investigation was conducted to compare four groups of participants classified on the basis of HIV serostatus and age (<60 vs ≥ 60). The effects of age and HIV infection on neuropsychological performance were analyzed using a two-by-two factorial analysis of variance. Demographic and clinical variables associated with neuropsychological performance were identified using linear regression analysis in the HIV+ population. RESULTS: HIV infection and aging had significant negative effects on cognitive performance, but no significant interaction was observed between these two factors. Although older HIV+ participants had worse cognitive performance, they showed no distinct cognitive pattern from younger HIV+ participants. Moreover, younger HIV+ participants' performance on memory tasks was qualitatively and quantitatively comparable with that of older HIV- participants, despite the dramatic age difference. CONCLUSION: Aging and HIV might be additive factors in the expression of cognitive decline. As the HIV+ population ages, routine neuropsychological examinations could help clinicians better understand and manage the expression of cognitive impairment.

Effects of stimulation of the subthalamic nucleus on naming and reading nouns and verbs in Parkinson's disease.

UNLABELLED: An impairment for verbs has been described in patients with Parkinson's disease (PD), suggesting that a disruption of frontal-subcortical circuits may result in dysfunction of the neural systems involved in action-verb processing. A previous study suggested that deep brain stimulation (DBS) of the subthalamic nucleus (STN) during verb generation may affect the ability to select from many competing lexical alternatives. In this study, 12 PD patients who had undergone bilateral STN DBS and completed an 8-year follow-up and 14 matched normal controls were administered action and object naming tasks and verb and noun reading tasks. Their responses were recorded using a microphone, resulting in a signal that marked the onset of the verbal response and allowed to measure response times (RTs). Accuracy was scored manually. RESULTS: Overall performance in naming (independently of stimulation): In naming task controls were faster and more accurate than PD patients. In both groups, performance (accuracy and RTs) was worse on action naming than object naming. PD patients were significantly slower than controls in naming actions. Effect of stimulation: Compared with the OFF stimulation condition, in ON stimulation condition PD patients showed improved performance on object and action naming tasks (increased accuracy, faster RTs), with a decreased number of semantic errors. Some evidence also emerged that action naming in the ON stimulation condition improved more than object naming. On noun and verb reading tasks, although accuracy was at ceiling in both groups and no significant difference was observed in RTs for nouns and verbs, PD patients were slower than controls. CONCLUSIONS: Our findings suggest that STN DBS may improve lexical search in PD patients. We hypothesize that STN stimulation may facilitate the motor components involved in naming and reading tasks (increased speed of speech onset), resulting in shorter RTs in both naming and reading and, to some extent, in increased accuracy in naming due to fewer omissions (no response within the 7500 ms time limit). However, to account for greater accuracy in naming due to decreased number of semantic errors in the ON stimulation condition, we hypothesize that STN stimulation restores the activity of the corticostriatal circuits involved in selection processes of a target word among different alternatives.