Differential Contribution of Right and Left Temporo-Occipital and Anterior Temporal Lesions to Face Recognition Disorders

In the study of prosopagnosia, several issues (such as the specific or non-specific manifestations of prosopagnosia, the unitary or non-unitary nature of this syndrome and the mechanisms underlying face recognition disorders) are still controversial. Two main sources of variance partially accounting for these controversies could be the qualitative differences between the face recognition disorders observed in patients with prevalent lesions of the right or left hemisphere and in those with lesions encroaching upon the temporo-occipital (TO) or the (right) anterior temporal cortex. Results of our review seem to confirm these suggestions. Indeed, they show that (a) the most specific forms of prosopagnosia are due to lesions of a right posterior network including the occipital face area and the fusiform face area, whereas (b) the face identification defects observed in patients with left TO lesions seem due to a semantic defect impeding access to person-specific semantic information from the visual modality. Furthermore, face recognition defects resulting from right anterior temporal lesions can usually be considered as part of a multimodal people recognition disorder. The implications of our review are, therefore, the following: (1) to consider the components of visual agnosia often observed in prosopagnosic patients with bilateral TO lesions as part of a semantic defect, resulting from left-sided lesions (and not from prosopagnosia proper); (2) to systematically investigate voice recognition disorders in patients with right anterior temporal lesions to determine whether the face recognition defect should be considered a form of “associative prosopagnosia” or a form of the “multimodal people recognition disorder.

Different Apathy Profile in Behavioral Variant of Frontotemporal Dementia and Alzheimer's Disease: A Preliminary Investigation

Apathy is one of the most common behavioral symptoms of dementia; it is one of the salient features of behavioral variant of frontotemporal dementia (bvFTD) but is also very frequent in Alzheimer's disease. This preliminary investigation was aimed at assessing the type of apathy-related symptoms in a population of bvFTD and AD subjects showing comparable apathy severity. Each patient underwent a comprehensive neuropsychological assessment; behavioral changes were investigated by the neuropsychiatric inventory (NPI), using the NPI-apathy subscale to detect apathetic symptoms. At univariate analysis, bvFTD subjects showed lack of initiation (χ2 = 4.602, p = 0.032), reduced emotional output (χ2 = 6.493, p = 0.008), and reduced interest toward friends and family members (χ2 = 4.898, p = 0.027), more frequently than AD subjects. BvFTD displayed higher scores than AD on NPI total score (p = 0.005) and on subscales assessing agitation (p = 0.004), disinhibition (p = 0.007) and sleep disturbances (p = 0.025); conversely, AD subjects were more impaired on memory, constructional abilities, and attention. On multivariate logistic regression, reduced emotional output was highly predictive of bvFTD (OR = 18.266; p = 0.008). Our preliminary findings support the hypothesis that apathy is a complex phenomenon, whose clinical expression is conditioned by the site of anatomical damage. Furthermore, apathy profile may help in differentiating bvFTD from AD

“Gestão de Interfaces”: a evolução do controle para o apoio à execução

Atualmente, as referências mais utilizadas para gerenciamento de projetos são o PMBOK e o PRINCE2, inclusive no âmbito da Administração Pública. Nas versões mais recentes desses guias, têm se observado uma crescente preocupação com o impacto dos stakeholders nos resultados dos projetos. Dessa forma, com base no framework atualizado dessas duas metodologias – que possui uma visão para o exterior do empreendimento -, foi desenvolvido na Administração Pública mineira um método para gerenciamento das questões que, a priori, eram tidas como componentes que não faziam parte dos empreendimentos de maneira direta. Trata-se da administração daquelas ações desencadeadas principalmente por atores externos que geram impacto considerável nos resultados alcançados pelos projetos. Esse método foi desenvolvido a partir das experiências do Escritório de Projeto da Secretaria de Estado de Transporte e Obras Públicas do governo do estado de Minas Gerais. As etapas para implementação e operacionalização dessa metodologia são os seguintes: (i) o plano do gerenciamento por exceções; (ii) identificação e sistematização dos stakeholders; (iii) comunicação eficiente com todos os stakeholders; (iv) a organização das informações referentes às interfaces do projeto; (v) a gestão de riscos referentes às interfaces e (vi) sistema de avaliação e monitoramento. Cada uma dessas etapas está detalhada no texto a seguir

Treating depression in clinical practice: new insights on the multidisciplinary use of trazodone

Depression is estimated to be a leading contributor to the global mental health-related burden. The determinants of this huge prevalence lie in the fact that depressive symptoms may be comorbid in a wide variety of disorders, thus complicating and exacerbating their clinical framework. This makes the treatment of depressive symptoms difficult, since many pharmacological interactions should be considered by physicians planning therapy. Hence, depression still represents a challenge for both psychiatrists and other clinicians, in terms of its high rates of relapse and resistance despite well-established protocols. It is also complicated by the well-known latency in its complete response to current antidepressant treatments. In this context, the search for new strategies regarding antidepressant treatment is mandatory. Revising the use of “old” pharmacotherapies by considering their specific features may help to perfecting the treatment of depression, both in its standalone psychiatric manifestation and in the framework of other clinical conditions. Using a nominal group technique approach, the results of a consensus of expert physicians regarding the possible use of trazodone as a valuable strategy for addressing the “real world” unmet needs of depression treatment in different fields (psychiatry, primary care, neurology and geriatrics) is herein provided. This idea is based on the unique characteristics of this drug which delivers a more rapid antidepressant action as compared to other selective serotonin reuptake inhibitors. It also has pharmacodynamic malleability (i.e., the possibility of exerting different effects on depressive symptoms at different dosages) and pharmacokinetic tolerability (i.e., the possibility of being used as an add-on to other antidepressants with scarce interaction and achieving complimentary effects) when used in the milieu of other drugs in treating comorbid depressive symptoms. Moreover, the large number of formulations available permits finite dosage adjustments, and the use of trazodone for specific pathologies, such as dysphagia. Therefore, although additional studies exploring the real-world conditions of antidepressant treatment are warranted, experts agree on the idea that depressive disorder, in both its standalone and its comorbid manifestations, may surely take advantage of the particular characteristics of trazodone, thus attempting to reach the greatest effectiveness in different contexts

Cerebellar white matter disruption in Alzheimer’s Disease patients: a Diffusion Tensor Imaging study

The cognitive role of the cerebellum has recently gained much attention, and its pivotal role in Alzheimer’s disease (AD) has now been widely recognized. Diffusion tensor imaging (DTI) has been used to evaluate the disruption of the microstructural milieu in AD, and though several white matter (WM) tracts such as corpus callosum, inferior and superior longitudinal fasciculus, cingulum, fornix, and uncinate fasciculus have been evaluated in AD, data on cerebellar WM tracts are currently lacking. We performed a tractography-based DTI reconstruction of the middle cerebellar peduncle (MCP), and the left and right superior cerebellar peduncles separately (SCPL and SCPR) and addressed the differences in fractional anisotropy (FA), axial diffusivity (Dax), radial diffusivity (RD), and mean diffusivity (MD) in the three tracts between 50 patients with AD and 25 healthy subjects. We found that AD patients showed a lower FA and a higher RD compared to healthy subjects in MCP, SCPL, and SCPR. Moreover, a higher MD was found in SCPR and SCPL and a higher Dax in SCPL. This result is important as it challenges the traditional view that WM bundles in the cerebellum are unaffected in AD and might identify new targets for therapeutic interventions

In vivo mapping of brainstem nuclei functional connectivity disruption in Alzheimer's disease

We assessed here functional connectivity changes in the locus coeruleus (LC) and ventral tegmental area (VTA) of patients with Alzheimer's disease (AD). We recruited 169 patients with either AD or amnestic mild cognitive impairment due to AD and 37 elderly controls who underwent cognitive and neuropsychiatric assessments and resting-state functional magnetic resonance imaging at 3T. Connectivity was assessed between LC and VTA and the rest of the brain. In amnestic mild cognitive impairment patients, VTA disconnection was predominant with parietal regions, while in AD patients, it involved the posterior nodes of the default-mode network. We also looked at the association between neuropsychiatric symptoms (assessed by the neuropsychiatric inventory) and VTA connectivity. Symptoms such as agitation, irritability, and disinhibition were associated with VTA connectivity with the parahippocampal gyrus and cerebellar vermis, while sleep and eating disorders were associated with VTA connectivity to the striatum and the insular cortex. This suggests a contribution of VTA degeneration to AD pathophysiology and to the occurrence of neuropsychiatric symptoms. We did not find evidence of LC disconnection, but this could be explained by the size of this nucleus, which makes it difficult to isolate. These results are consistent with animal findings and have potential implications for AD prognosis and therapies

Patterns of cerebellar gray matter atrophy across Alzheimer's disease progression

The role of the cerebellum in cognitive function has been broadly investigated in the last decades from an anatomical, clinical, and functional point of view and new evidence points toward a significant contribution of the posterior lobes of the cerebellum in cognition in Alzheimer's disease (AD). In the present work we used SUIT-VBM (spatially unbiased infratentorial template, voxel-based morphometry) to perform an analysis of the pattern of cerebellar gray matter (GM) atrophy in amnestic mild cognitive impairment (a-MCI) and AD dementia patients compared to healthy subjects (HS), in order to follow the changes of non-motor features of cerebellar degeneration throughout disease progression. This template has been validated to guarantee a significant improvement in voxel-to-voxel alignment of the individual fissures and the deep cerebellar nuclei compared to Montreal Neurological Institute (MNI) whole-brain template. Our analysis shows a progression of cerebellar GM volume changes throughout a continuous spectrum from early to late clinical stages of AD. In particular vermis and paravermian areas of the anterior (I-V) and posterior (VI) lobes are involved since the a-MCI stage, with a later involvement of the hemispheric part of the posterior lobes (VI lobule) and Crus I in AD dementia patients only. These findings support the role of the cerebellum in higher-level functions, and whilst confirming previous data on the involvement of Crus I in AD dementia, provide new evidence of an involvement of the vermis in the early stages of the disease

In search of sleep biomarkers of Alzheimer's disease: K-Complexes do not discriminate between patients with mild cognitive impairment and healthy controls

The K-complex (KC) is one of the hallmarks of Non-Rapid Eye Movement (NREM) sleep. Recent observations point to a drastic decrease of spontaneous KCs in Alzheimer's disease (AD). However, no study has investigated when, in the development of AD, this phenomenon starts. The assessment of KC density in mild cognitive impairment (MCI), a clinical condition considered a possible transitional stage between normal cognitive function and probable AD, is still lacking. The aim of the present study was to compare KC density in AD/ MCI patients and healthy controls (HCs), also assessing the relationship between KC density and cognitive decline. Twenty amnesic MCI patients underwent a polysomnographic recording of a nocturnal sleep. Their data were compared to those of previously recorded 20 HCs and 20 AD patients. KCs during stage 2 NREM sleep were visually identified and KC densities of the three groups were compared. AD patients showed a significant KC density decrease compared with MCI patients and HCs, while no differences were observed between MCI patients and HCs. KC density was positively correlated with Mini-Mental State Examination (MMSE) scores. Our results point to the existence of an alteration of KC density only in a full-blown phase of AD, which was not observable in the early stage of the pathology (MCI), but linked with cognitive deterioratio

EEG alterations during wake and sleep in mild cognitive impairment and Alzheimer's disease

Patients with Alzheimer’s disease (AD) undergo a slowing of waking electroencephalographic (EEG) rhythms since prodromal stages, which could be ascribed to poor sleep quality. We examined the relationship between wake and sleep alterations by assessing EEG activity during sleep and (pre-sleep/post-sleep) wakefulness in AD, mild cognitive impairment (MCI) and healthy controls. AD and MCI show high sleep latency and less slow-wave sleep. Reduced sigma activity characterizes non-rapid eyemovement (NREM) sleep, reflecting sleep spindles loss. The EEG slowing characterizes REM sleep and wakefulness of AD and MCI, with strong correlations among the two phenomena suggesting common neuropathological mechanisms. Evening-to-morning variations in waking EEG revealed the gradual disappearance in MCI and AD of overnight changes in delta activity, indicating a progressive decay of sleep restorative functions on diurnal activity that correlates with the impairment of sleep high-frequency activity in AD. Our findings support a linkage between wake and sleep alterations, and the importance of sleep-related processes in Alzheimer’s disease progression