Hearts and Minds: Emotion Recognition and Mentalizing in Parkinson's Disease and Progressive Supranuclear Palsy.

OBJECTIVE: There are scarce data comparing Parkinson's disease (PD) and Progressive Supranuclear Palsy (PSP) in social cognition (SC). We aimed to compare patients with PSP and PD in SC. METHODS: We included three groups: PD (n = 18), PSP (n = 20) and controls (n = 23). Participants underwent neuropsychological exams, including the mini-version of the Social and Emotional Assessment, which is composed of the facial emotion recognition test (FERT) and the modified faux-pas (mFP) test, which assesses Theory of Mind (ToM). RESULTS: Patients with PD scored lower than controls in the FERT, but not in the mFP test. Patients with PSP performed worse than controls in both the mFP and FERT. PD and PSP groups did not differ in the FERT, but PSP performed worse than PD in the mFP test. The mFP test distinguished PSP from PD with 89% accuracy. CONCLUSION: The assessment of ToM may contribute to the differentiation between PD and PSP.

Cognitive impairment in hoarding disorder: a systematic review.

OBJECTIVE: In the present study, we aimed to perform a systematic review evaluating the cognitive performance of patients with hoarding disorder (HD) compared with controls. We hypothesized that HD patients would present greater cognitive impairment than controls. METHODS: A systematic search of the literature using the electronic databases MEDLINE, SCOPUS, and LILACS was conducted on May 2020, with no date limit. The search terms were "hoarding disorder," "cognition," "neuropsychology," "cognitive impairment," and "cognitive deficit." We included original studies assessing cognitive functioning in patients with HD. RESULTS: We retrieved 197 studies initially. Of those, 22 studies were included in the present study. We evaluated 1757 patients who were 41 to 72 years old. All selected studies comprised case-control studies and presented fair quality. Contrary to our hypothesis, HD patients showed impairment only in categorization skills in comparison with controls, particularly at confidence to complete categorization tasks. Regarding attention, episodic memory, working memory, information-processing speed, planning, decision-making, inhibitory control, mental flexibility, language, and visuospatial ability, HD patients did not show impairment when compared with controls. There is a paucity of studies on social cognition in HD patients, although they may show deficits. The impact of emotion in cognition is also understudied in HD patients. CONCLUSION: Except for categorization skills, the cognitive performance in HD patients does not seem to be impaired when compared with that in controls. Further work is needed to explore social cognition and the impact of emotion in cognitive performance in HD patients.

Irisin levels are correlated with inflammatory markers in frontotemporal dementia.

Irisin is a recently discovered adipomyokine involved in the regulation of glucose and lipid, which also exhibits anti-inflammatory and neuroprotective properties. Here we aimed to compare irisin peripheral levels between individuals with behavioral variant frontotemporal dementia (bvFTD) and cognitively healthy matched controls, in addition to investigating whether there is a correlation between irisin and pro-inflammatory cytokines (IL-6 and TNF) concentrations. Twenty-nine individuals participated in this study, being 18 patients with probable bvFTD and 11 controls. Irisin, IL-6 and TNF levels were measured in EDTA plasma through ELISA. There was no difference of the levels of irisin between the groups (p = 0.964). However, in the bvFTD, but not in control group, the levels of irisin were positively correlated with the concentration of IL-6 (r = 0.637, p = 0.006) and TNF (r = 0.517, p = 0.034). The results suggest that the production of irisin in bvFTD could be related to chronic inflammatory and neurodegenerative states in these patients.

Pro-inflammatory interleukin-6 signaling links cognitive impairments and peripheral metabolic alterations in Alzheimer's disease.

Alzheimer's disease (AD) is associated with memory impairment and altered peripheral metabolism. Mounting evidence indicates that abnormal signaling in a brain-periphery metabolic axis plays a role in AD pathophysiology. The activation of pro-inflammatory pathways in the brain, including the interleukin-6 (IL-6) pathway, comprises a potential point of convergence between memory dysfunction and metabolic alterations in AD that remains to be better explored. Using T2-weighted magnetic resonance imaging (MRI), we observed signs of probable inflammation in the hypothalamus and in the hippocampus of AD patients when compared to cognitively healthy control subjects. Pathological examination of post-mortem AD hypothalamus revealed the presence of hyperphosphorylated tau and tangle-like structures, as well as parenchymal and vascular amyloid deposits surrounded by astrocytes. T2 hyperintensities on MRI positively correlated with plasma IL-6, and both correlated inversely with cognitive performance and hypothalamic/hippocampal volumes in AD patients. Increased IL-6 and suppressor of cytokine signaling 3 (SOCS3) were observed in post-mortem AD brains. Moreover, activation of the IL-6 pathway was observed in the hypothalamus and hippocampus of AD mice. Neutralization of IL-6 and inhibition of the signal transducer and activator of transcription 3 (STAT3) signaling in the brains of AD mouse models alleviated memory impairment and peripheral glucose intolerance, and normalized plasma IL-6 levels. Collectively, these results point to IL-6 as a link between cognitive impairment and peripheral metabolic alterations in AD. Targeting pro-inflammatory IL-6 signaling may be a strategy to alleviate memory impairment and metabolic alterations in the disease.

The Timed Inspiratory Effort Index as a Weaning Predictor: Analysis of Intra- and Interobserver Reproducibility.

BACKGROUND: Prolonged ventilatory weaning may expose patients to unnecessary discomfort, increase the risk of complications, and raise the costs of hospital treatment. In this scenario, indexes that reliably predict successful liberation can be helpful. OBJECTIVE: To evaluate the intra- and interobserver reproducibility of the timed inspiratory effort index as a weaning predictor. METHODS: This prospective observational study included subjects judged as able to start liberation from mechanical ventilation. For the intra-observer analysis, the same investigator performed 2 measurements in each selected patient with an interval of 30 min a rest. For interobserver analysis, 2 measurements were obtained in another sample of subjects, also with an interval of 30 min rest, but each of one performed by a different investigator. The Bland-Altman diagram, the coefficient concordance of kappa, and the Pearson correlation coefficient were used to compare the measurements. The performance of the timed inspiratory effort index was assessed by receiver operating characteristic curves. Values of P < .05 were considered significant. RESULTS: We selected 113 subjects (43 males; mean ± SD age, 77 ± 14 y). Fifty-six (49.6%) achieved successful liberation, and 33 (29%) died in the ICU. The mean ± SD duration of mechanical ventilation was 14.4 ± 6.7 d. The Bland-Altman diagrams that addressed intra- and interobservers agreement showed low variability between measurements. Values of the concordance coefficients of kappa were 0.82 (0.68-0.95) and 0.80 (0.65-0.94), and of the linear correlation coefficients, 0.86 (0.77-0.91) and 0.89 (0.82-0.93) for the intra- and interobservers measurements, respectively. The mean ± SD values for the area under the curve for each pair of the intra- and interobserver measurements were 0.96 ± 0.07 versus 0.94 ± 0.07 (P = .41) and 0.94 ± 0.05 versus 0.90 ± 0.07 (P = .14), respectively. CONCLUSIONS: The variability of the measurement of the timed inspiratory effort index by intra- and interobservers showed very high reproducibility, which reinforced the index as a sensible, accurate, and reliable outcome predictor of liberation from mechanical ventilation.

Disinhibition in Frontotemporal Dementia and Alzheimer's Disease: A Neuropsychological and Behavioural Investigation.

OBJECTIVE: Cognitive tests of inhibitory control show variable results for the differential diagnosis between behavioural variant of Frontotemporal Dementia (bvFTD) and Alzheimer's disease (AD). We compared the diagnostic accuracies of tests of inhibitory control and of a behavioural questionnaire, to distinguish bvFTD from AD. METHODS: Three groups of participants were enrolled: 27 bvFTD patients, 25 AD patients, and 24 healthy controls. Groups were matched for gender, education, and socio-economic level. Participants underwent a comprehensive neuropsychological assessment of inhibitory control, including Hayling Test, Stroop, the Five Digits Test (FDT) and the Delay Discounting Task (DDT). Caregivers completed the Barratt Impulsiveness Scale 11th version (BIS-11). RESULTS: bvFTD and AD groups showed no difference in the tasks of inhibitory control, while the caregiver questionnaire revealed that bvFTD patients were significantly more impulsive (BIS-11: bvFTD 76.1+9.5, AD 62.9+13, p < .001). CONCLUSIONS: Neuropsychological tests of inhibitory control failed to distinguish bvFTD from AD. On the contrary, impulsivity caregiver-completed questionnaire provided good distinction between bvFTD and AD. These results highlight the current limits of cognitive measures of inhibitory control for the differential diagnosis between bvFTD and AD, whereas questionnaire information appears more reliable and in line with clinical diagnostics.

Microparticles are related to cognitive and functional status from normal aging to dementia.

Recently, we have shown that microparticles (MPs) levels derived from leukocytes (LMPs), endothelium (EMPs), neurons (NMPs) and those expressing tissue factor (TFMPs) were higher in Alzheimer's Disease (AD) patients when compared to cognitively healthy subjects. Therefore, in this study we proposed to investigate the correlation between MPs levels, cognitive performance and functional status in a sample of elderly individuals. We evaluated MPs derived from platelets (PMPs), LMPs, EMPs, NMPs and TFMPs in 43 participants, of whom 12 with probable dementia due to AD, 16 with mild cognitive impairment (MCI) and 15 with no objective cognitive or functional impairment. PMPs, LMPs and TFMPs, were associated with cognitive impairment in this population. LMPs and NMP, were associated to lower functional performance in the elderly sample. These results suggest that MPs may be involved in the pathophysiology of neurodegenerative disorders.

BsmI polymorphism in the vitamin D receptor gene is associated with 25-hydroxy vitamin D levels in individuals with cognitive decline.

OBJECTIVE: Elderly people are at a high risk of developing vitamin D (VitD) deficiency due to both decreased intake and cutaneous synthesis. Most of the biological actions of VitD are mediated by the vitamin D receptor (VDR), which is present in neurons and glial cells of the hippocampus, and in the cortex and subcortical nuclei, essential areas for cognition. It is known that VDR gene polymorphisms may decrease the VDR affinity for VitD. Objective: The present study aimed to investigate the influence of VitD levels on cognitive decline in patients with dementia due to Alzheimer's disease (AD, n = 32) and mild cognitive impairment (MCI, n = 15) compared to cognitively healthy elderly (n = 24). METHODS: We also evaluated the association of VDR gene polymorphisms with cognitive disturbance. Methods: Four polymorphisms on the VDR gene were studied, namely, BsmI, ApaI, FokI and TaqI, by polymerase chain reaction-restriction fragment length polymorphism. Serum levels of 25-hydroxy vitamin D (25(OH)D) were determined by high performance liquid chromatography. RESULTS: Results: No significant difference in 25(OH)D levels or genotypic/allelic frequencies was observed between the groups. Deficiency of 25(OH)D was more frequently observed in women. The AA/AG genotypes of the BsmI polymorphism was associated with sufficient 25(OH)D levels, while the GG genotype of this same polymorphism was associated to insufficient levels in the cognitively-impaired group (individuals with AD or MCI). CONCLUSIONS: Conclusions: The data obtained do not confirm the relationship between reductions of VitD levels, polymorphisms in the VDR gene, and altered cognitive function in this sample. However, the data indicate that BsmI polymorphism in the VDR gene is associated with the VitD levels in individuals with cognitive decline.

Leptin, hsCRP, TNF-α and IL-6 levels from normal aging to dementia: Relationship with cognitive and functional status.

Cognitive impairment, including mild cognitive impairment (MCI) and dementia, compromises the patients' cognitive abilities and, to different extents, to carry out daily activities, accompanied by personality and behavioral changes. Studies suggest that leptin, an adipokine, has a neuroprotective role against Alzheimer's disease (AD) and that cytokines are associated with inflammatory processes and dementia. This study aimed to evaluate serum leptin, hsCRP, IL-6 and TNF-α levels in a cognitive continuum group from normal to demential status, and to assess whether they correlates to Mini-Mental State Examination (MMSE) and Functional Assessment Staging (FAST) scores. Forty-three participants were included, of whom 12 with probable AD, 18 with MCI and 13 with no objective cognitive decline. Serum leptin and hsCRP levels were evaluated by immunoturbidimetric method, and IL-6 and TNF-α by ELISA. Higher TNF-α levels were found in individuals with FAST stages 1/2 and normal scores evaluated by MMSE. hsCRP levels were inversely correlated with FAST stages. No association with function or global cognition was observed for leptin and IL-6 levels. However, women presented higher leptin serum levels than men while lower leptin and IL-6 levels were observed in individuals aged ≥59 years. Our results suggest that TNF-α is associated with cognitive and functional decline and that inflammation could be a substrate of cognitive impairment at early clinical stages of dementia.

Cerebrospinal Fluid Levels of Angiotensin-Converting Enzyme Are Associated with Amyloid-ß42 Burden in Alzheimer's Disease.

This study was designed to determine whether the levels of renin-angiotensin system (RAS) components are associated with Alzheimer's disease (AD) pathology. Cerebrospinal fluid levels of Angiotensin (Ang) II, Ang-(1-7), angiotensin-converting enzyme (ACE), ACE2, Amyloid-ß (Aß)40, Aß42, total tau (hTau), and phospho-tau (pTau) were measured in 18 patients with AD and 10 controls. Patients with AD presented decreased levels of ACE when compared with controls. We found a significant positive correlation between ACE and Aß42 levels among patients. Our results strengthen the hypothesis that ACE is associated with Aß pathology in AD.

Validity and Reliability of the Frontotemporal Dementia Rating Scale (FTD-FRS) for the Progression and Staging of Dementia in Brazilian Patients.

INTRODUCTION: Few studies on instruments for staging frontotemporal dementia (FTD) have been conducted. OBJECTIVE: The objective of this study was to analyze the factor structure, internal consistency, reliability, and convergent validity of the Brazilian version of the Frontotemporal Dementia Rating Scale (FTD-FRS). METHODS: A total of 97 individuals aged 40 years and above with >2 years' education took part in the study, 31 patients diagnosed with behavioral variant FTD (bvFTD), 8 patients with primary progressive aphasia, 28 with Alzheimer disease, 8 with mild cognitive impairment, and a control group of 22 healthy subjects. The FTD-FRS was completed by family members or caregivers, and Neurologists completed the 8-item Clinical Dementia Rating for Frontotemporal Lobar Degeneration (CDR-FTLD) scale (6 original domains plus Language and Behavior). The Alzheimer disease and FTD patients had equivalent disease severity level. RESULTS: The internal consistency of the FTD-FRS, estimated by Cronbach α, was 0.975 whereas test-retest reliability was 0.977. Scree plot and exploratory factor (Varimax rotation) analyses revealed the existence of 4 factors, with eigenvalues >1, which together explained 77.13% of the total variance with values of 1.28 to 17.52. The domains of the Brazilian version of the FTD-FRS scale correlated with the domains of the CDR-FTLD. CONCLUSIONS: The present study is the first to document the factorial structure of the FTD-FRS and its convergent validity with the CDR-FTLD. These tools are key to determine dementia severity in FTD. The Brazilian FTD-FRS demonstrated adequate psychometric properties for use in Brazil. This instrument may contribute to disease staging in FTD and may help to document intervention-related changes.

Frontal lobe neurology and the creative mind.

Concepts from cognitive neuroscience strongly suggest that the prefrontal cortex (PFC) plays a crucial role in the cognitive functions necessary for creative thinking. Functional imaging studies have repeatedly demonstrated the involvement of PFC in creativity tasks. Patient studies have demonstrated that frontal damage due to focal lesions or neurodegenerative diseases are associated with impairments in various creativity tasks. However, against all odds, a series of clinical observations has reported the facilitation of artistic production in patients with neurodegenerative diseases affecting PFC, such as frontotemporal dementia (FTD). An exacerbation of creativity in frontal diseases would challenge neuroimaging findings in controls and patients, as well as the theoretical role of prefrontal functions in creativity processes. To explore this paradox, we reported the history of a FTD patient who exhibited the emergence of visual artistic productions during the course of the disease. The patient produced a large amount of drawings, which have been evaluated by a group of professional artists who were blind to the diagnosis. We also reviewed the published clinical cases reporting a change in the artistic abilities in patients with neurological diseases. We attempted to reconcile these clinical observations to previous experimental findings by addressing several questions raised by our review. For instance, to what extent can the cognitive, conative, and affective changes following frontal damage explain changes in artistic abilities? Does artistic exacerbation truly reflect increased creative capacities? These considerations could help to clarify the place of creativity-as it has been defined and explored by cognitive neuroscience-in artistic creation and may provide leads for future lesion studies.