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Peripheral errors in writing, that is errors produced download the spelling, have been occasionally described in primary progressive aphasia (PPA), but the possibility that these errors might be a marker of parkinsonism associated to some subtypes of PPA has not been explored. We investigated whether errors of peripheral nature characterize the writing disorder in PPA when associated with parkinsonian signs (PSs). Subgroups of PPA without PSs and with PSs were studied. The proportion of the central and peripheral errors in writing words and pseudowords was calculated in each group. In writing words, central errors significantly exceeded peripheral errors in subgroups without PSs. The higher the number of peripheral errors, the higher the probability of presenting PSs. No relation emerged between any error and the Unified Parkinson's Disease Rating Scale, but both types of errors correlated with measures of cognitive ability. Peripheral errors emerge when PSs are associated with PPA and may be linked to a decay of the cognitive control on movement, possibly involving the right hemisphere. Peripheral errors have clinical relevance in PPA, to the extent that they may assume the significance of a marker of specific subtypes and can help to outline the specific clinical picture of individual patients.

We explored the association between cognitive reserve (CR) and Parkinson' s disease (PD) related cognitive deterioration.Forty PD patients and 12 matchedhealthy controls (HC) were enrolled. The PD group was balanced for the presence/absence of cognitive impairment All participants underwent MOCA. CR was measured by the Brief Intelligence Test, and a new comprehensive tool, named Cognitive Reserve Test (CoRe-T), including sections on leisure activities and creativity.Participants with higher CR obtained a better MOCA score irrespective of the group they belonged to. At the same time, irrespective of the CR level, the performance of the HC group was always better in comparison to the PD group. Within the PD group, a higher frequency of leisure activities was associated to be cognitively unimpaired, independently by the severity of motor symptoms and age .CR could help to cope with PD-related cognitive decline. Its multidimensional nature could have important applications in prevention and rehabilitation interventions.

Based on the available literature, women living with HIV (WLWH) seem to show greater cognitive and emotional disadvantages than men living with HIV (MLWH). Our aim was to compare the cognitive performance of MLWH and WLWH in an Italian cohort of People Living With HIV (PLWH) and to analyse factors potentially contributing to sex differences in cognitive function. We ran a retrospective, cross-sectional analysis of a monocentric dataset of PLWH who were administered a standardized neuropsychological test battery (SNB) during routine clinical care. We enrolled 161 Italian PLWH who are on combined antiretroviral therapy (cART): 114 (70.8%) MLWH and 47 (29.2%) WLWH. Global cognitive performance (composite z score) (GCP) was significantly higher in MLWH than WLWH [mean 0.19 (SD 0.85) vs − 0.13 (SD 0.96); p = 0.039]. Moreover, WLWH obtained significantly higher scores on the Zung Depression Scale than MLWH [mean 41.8 (SD 10.9) vs 36.7 (SD 9.2); p = 0.003]. However, there was no statistically significant direct effect between male sex and better GCP (p = 0.692) in the context of a mediation model. On the contrary, the associations between male sex and better GCP were mediated by higher level of education (a*b = + 0.15, Bootstrap CI95 = 0.05 and 0.27) and a lower Zung depression score (a*b = + 0.10, Bootstrap CI95 = 0.02 and 0.21). In conclusion, the global cognitive performance of WLWH is lower than that of MLWH. However, other demographic and clinical factors besides sex might help explain differences in their neurocognitive functions and make it possible for us to monitor them and identify those patients most in need.

Objective: We explored the relationship between a visual scanning strategy and a facial emotion recognition deficit in Parkinson's disease (PD). Method: Thirty nondemented PD patients (balanced for symptom side at onset) and 20 age, education and gender-matched healthy controls (HC) were enrolled. The PD group underwent a comprehensive neuropsychological battery also exploring the executive functions. In both groups, eye movements were recorded while subjects categorized facial emotion from Ekman's 60-faces test. We were particularly interested in the location of fixations on facial pictures (top vs. bottom) and in emotional valence (positive vs. negative). We also compared performance of the two groups on a verbal emotion attribution task. Results: Compared to HC, PD patients performed worse on visual recognition of negative emotions such as anger, fear, and sadness (where the upper part of the face is more informative than the lower part); the two groups did not differ on the verbal emotion attribution task. HC modified their visual scanning strategy (both number and overall time duration of fixations) according to the valence of the emotion; by contrast, PD showed the same pattern regardless of the valence. In the PD group, accuracy in the visual recognition of negative emotions and fixation pattern correlated with performance on tasks exploring executive functions; however, no associations were observed with severity of motor state. Conclusions: Our results suggest that visual scanning strategy contributes significantly to the facial emotion recognition deficit of PD patients, especially at a "high level" related to cognitive control of eye movements.

The care engagement of people living with HIV (PLWH) measured with the patient health engagement (PHE) model and its association with HIV-related internalized stigma are not well established. Indeed, currently there are no data yet about the engagement of PLWH measured with the PHE model. This study aimed to evaluate the effects of HIV-related internalized stigma on care engagement and mental health and to fill the lack of data on PHE model applied to PLWH. We found that the internalized stigma score was significantly higher for PLWH (n=82) in worse care engagement phase and both higher internalized stigma scores and worse engagement were associated to major depression symptoms.In conclusion, our findings describe for the first time the engagement in care of PLWH measured with PHE and highlight the importance of PLWH support to find strategies to cope stigma-related stress and optimize their care engagement.

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Objectives: Cognitive screening is not widely used in acute stroke patients, and usually is based on tests developed for dementia. Our aim was to explore the feasibility of a new tool designed for stroke survivors, as the Oxford Cognitive Screen (OCS). Materials: 3–10 days after stroke, patients underwent the OCS, providing a five domain-specific cognitive profile: attention and executive function, language, memory, number processing and praxis. Pre-morbid functional and cognitive status was evaluated by caregiver interview. The National Institute of Health and Stroke Scale (NIHSS) estimated the stroke severity. Method: This cross-sectional study consecutively enrolled stroke patients (both ischemic and hemorrhagic). Exclusion criteria: Pre-morbid cognitive decay, difficulties with the Italian language, visual impairment or other preexisting conditions affecting cognitive status. OCS was considered non-applicable when patients failed the preliminary subtest. Ischemic brain lesions were classified according to the Bamford criteria: Total Anterior Circulation Stroke (TACS), Partial Anterior Circulation Stroke (PACS), Posterior Circulation Syndrome (POCS), Lacunar Syndrome (LACS). Results: Between October and December 2019, 45 out of 62 patients admitted to the Stroke Unit of Poliambulanza Foundation of Brescia were enrolled. Eight patients were non-eligible, 2 died, and 7 did not fit the time window inclusion criteria. Characteristics of the sample were: 43 (95.6%) Italian born, 33 (73.3%) male, 37 (82.2%) with ischemic stroke, mean age (years) 68.00 (DS 15.45), mean initial NIHSS score 7.02 (DS 7.67). Overall, 25 (55.6%) patients had a left sided brain lesion, 13/37 (35%) were affected by TACS, 19 (42.2%) were discharged at home without any cognitive follow-up indications, and 9 (20%) were transferred to neurologic rehabilitation. OCS was applicable in 37/45 (82.2%) patients. Twenty-eight (75.7%) patients showed at least one impaired cognitive domain. At multivariate

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.

We explored the association between cognitive reserve (CR) and Parkinson' s disease (PD) related cognitive deterioration. Forty PD patients and 12 matchedhealthy controls (HC) were enrolled. The PD group was balanced for the presence/absence of cognitive impairment All participants underwent MOCA. CR was measured by the Brief Intelligence Test, and a new comprehensive tool, named Cognitive Reserve Test (CoRe-T), including sections on leisure activities and creativity. Participants with higher CR obtained a better MOCA score irrespective of the group they belonged to. At the same time, irrespective of the CR level, the performance of the HC group was always better in comparison to the PD group. Within the PD group, a higher frequency of leisure activities was associated to be cognitively unimpaired, independently by the severity of motor symptoms and age. CR could help to cope with PD-related cognitive decline. Its multidimensional nature could have important applications in prevention and rehabilitation interventions.

The aim of this study was to explore the psychological impact of the initial stage of the 2019 coronavirus (CO-VID-19) pandemic on people living with HIV (PLWH), a population at increased risk of psychological distress. PLWH participated in an online survey exploring demographic and clinical data, physical symptoms, con-tact history, knowledge and concerns, precautionary measures and additional information about COVID-19 during the first phase of the pandemic in Italy. The Impact of Event Scale-Revised (IES-R) (identifying the COVID-19 pandemic as a specific traumatic life event) and the Depression, Anxiety and Stress Scale (DASS-21) also formed part of the survey. Out of 98 participants, 45% revealed from mild to severe psychological impact from COVID-19 according to IES-R. A lower percentage, instead, complained of significant levels of depression (14%), anxiety (11%) or stress (6%) according to DASS-21. Higher education, being unemployed, number of perceived COVID-19 physical symptoms, concerns about risk of contracting COVID-19 and the pandemic situation in Italy, and needing additional information to prevent COVID-19 infection were positively associated to a higher risk of negative psychological impact. More-over, among the participants, female gender, age, fewer years from HIV diagnosis and not being aware of their own viremia were associated to a higher risk of negative psychological outcomes. Almost half of our PLWH sample experienced significant levels of distress related to the COVID-19 pandemic. Women, elderly patients and those with recent HIV diagnosis appear to be the more psychologically fragile subgroups. Our findings could help identify patients most in need of psychological interventions to improve the wellbeing of PLWH.

Objectives: Vascular and degenerative damage are so different brain pathologies that the impact on cognition cannot be expected to be the same. The present study aims to identify possible markers able to distinguish vascular and neurodegenerative aphasias. Materials: 18 logopenic variant/mixed primary progressive aphasias (lv-mPPA) and 11 fluent post-stroke aphasics (psA) of comparable severity, and 12 matched healthy controls (HC) were enrolled. All participants underwent a comprehensive neuropsychological battery, and the examination of macro and microlinguistic aspects of language. Methods: A Principal Component Analysis (PCA) was performed (after z-transformation of the scores) to identify factors explaining the overall performance on patient groups only; factor scores were entered into a cluster analysis by fixing 2-groups solution in order to verify if lv-mPPA and psA were assigned to different clusters. Results: The PCA extracted two factors, “global cognition/lexical semantic factor” and “morphosyntactic factor”, accounting for 42.9% of variability, and two factors loading macrolinguistic variables (accounting for 22.7% of variability). A two-step cluster analysis, exclusively based on behavioural data, allowed to some extent the re-emergence of the two etiologies: a first cluster composed of 18 subjects (78% lv-mPPA and 22% PSA), a second cluster composed of 11 subjects (64% PSA and 36%lvPPA patients). Subjects of the first cluster were more impaired both in global cognition/lexical semantic and morphosyntactic factors. Macrolinguistic factors did not differentiate instead, the two clusters. Lv-mPPA that fell in the first cluster showed widespread cortical thinning in both the cerebral hemispheres (with left prevalence) including the temporal poles; atrophy was confined in the left hemisphere, and the temporal pole was relatively spared in lv-mPPA of the second cluster. The ischemic area was distributed in the posterior regions of the left middle cerebral a

Objectives: To investigate the long-term safety and efficacy of a treatment switch to dual ART with atazanavir/ritonavir + lamivudine versus continuing a standard regimen with atazanavir/ritonavir + 2NRTI in virologically suppressed patients. Methods: ATLAS-M is a 96 week open-label, randomized, non-inferiority (margin -12%) trial enrolling HIV-infected adults on atazanavir/ritonavir + 2NRTI, with stable HIV-RNA <50 copies/mL and CD4 counts >200 cells/mm3. At baseline, patients were randomized 1:1 to switch to atazanavir/ritonavir + lamivudine or to continue the previous regimen. Here, we report the 96 week efficacy and safety data. The study was registered with ClinicalTrials.gov, number NCT01599364. Results: Overall, 266 subjects were enrolled (133 in each arm). At 96 weeks, in the ITT population, patients free of treatment failure totalled 103 (77.4%) with atazanavir/ritonavir + lamivudine and 87 (65.4%) with triple therapy (difference +12.0%, 95% CI +1.2/+22.8, P = 0.030), demonstrating the superiority of dual therapy. Two (1.5%) and 9 (6.8%) virological failures occurred in the dual-therapy arm and the triple-therapy arm, respectively, without development of resistance to any study drug. Clinical adverse events occurred at similar rates in both arms. A higher frequency of grade 3-4 hyperbilirubinemia (66.9% versus 50.4%, P = 0.006) and hypertriglyceridaemia (6.8% versus 1.5%, P = 0.031) occurred with dual therapy, although this never led to treatment discontinuation. A significant improvement in renal function and lumbar spine bone mineral density occurred in the dual-therapy arm. The evolution of CD4, HIV-DNA levels and neurocognitive performance was similar in both arms. Conclusions: In this randomized study, a treatment switch to atazanavir/ritonavir + lamivudine was superior over the continuation of atazanavir/ritonavir + 2NRTI in virologically suppressed patients, with a sustained benefit in terms of improved renal function and bone mineral density.

Parkinson’s disease (PD) typically occurs in elderly people and some degree of cognitive impairment is usually present. Cognitive reserve (CR) theory was proposed to explain the discrepancy between the degree of brain pathologies and clinical manifestations. We administered a comprehensive neuropsychological battery to 35 non-demented participants affected by PD. All participants underwent also the Cognitive Reserve Index questionnaire and the Brief Intelligence Test as proxies for CR. Relationships between CR and cognitive performance were investigated by linear regression analyses, adjusting for significant confounding factors. At linear regression analyses, higher CR scores were independently associated with a better performance on Word Fluency (p ≤ 0.04) and Digit Span (backward) (p ≤ 0.02); no associations were observed between CR and other cognitive tests. Our data provide empirical support to the relation between CR and cognitive impairment in PD. In particular, this study suggests that CR may have greater effects on the cognitive areas mostly affected in PD as executive functions.

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Background: Neuropsychiatric symptoms (NPs) have been reported with dolutegravir use. We hypothesized that increasing dolutegravir trough concentrations (Ctrough) and/or polymorphism in the SLC22A2 gene, encoding the organic cation transporter-2 (OCT2), which is involved in monoamine clearance in the CNS and is inhibited by dolutegravir, might be associated with NPs. Methods: A cross-sectional cohort of HIV-positive patients treated with a dolutegravir-containing regimen underwent determination of allelic discrimination for SLC22A2 808 C → A polymorphism and dolutegravir Ctrough. The Symptom Checklist-90-R [investigating 10 psychiatric dimensions and reporting a general severity index (GSI)], a self-reported questionnaire and the Mini-International Neuropsychiatric Interview were offered to investigate current NPs. The effects of dolutegravir Ctrough and the SLC22A2 gene variant on NPs were explored by multivariable logistic regression. Results: A cohort of 203 patients was analysed: 71.4% were male, with median age 51 years and 11 years of ART exposure. Median time on dolutegravir was 18 months. Dolutegravir was associated with different antiretroviral combinations (mainly lamivudine, 38.9%, and abacavir/lamivudine, 35.5%). SLC22A2 CA genotype was independently associated with an abnormal GSI [adjusted OR (aOR) 2.43; P = 0.072], anxiety (aOR 2.61; P = 0.044), hostility (aOR 3.76; P = 0.012) and with moderate to severe headache (aOR 5.55; P = 0.037), and dolutegravir Ctrough was associated with hostility (fourth versus first quartile aOR 6.70; P = 0.007) and psychoticism (fourth versus first quartile aOR 19.01; P = 0.008). Other NPs were not associated with SLC22A2 polymorphism or dolutegravir Ctrough. Conclusions: A variant of the OCT2-encoding gene, in addition to or in synergy with higher dolutegravir Ctrough, is associated with a set of NPs observed during dolutegravir therapy.

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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.