A network approach to brain aging through multimodal neuroimaging

Tese de Doutoramento em Ciências da Saúde.

The choroid plexus transcriptome reveals changes in type I and II interferon responses in a mouse model of Alzheimer's disease

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a marked decline in cognition and memory function. Increasing evidence highlights the essential role of neuroinflammatory and immune-related molecules, including those produced at the brain barriers, on brain immune surveillance, cellular dysfunction and amyloid beta (Aß) pathology in AD. Therefore, understanding the response at the brain barriers may unravel novel pathways of relevance for the pathophysiology of AD. Herein, we focused on the study of the choroid plexus (CP), which constitutes the blood-cerebrospinal fluid barrier, in aging and in AD. Specifically, we used the PDGFB-APPSwInd (J20) transgenic mouse model of AD, which presents early memory decline and progressive Aß accumulation, and littermate age-matched wild-type (WT) mice, to characterize the CP transcriptome at 3, 5-6 and 11-12months of age. The most striking observation was that the CP of J20 mice displayed an overall overexpression of type I interferon (IFN) response genes at all ages. Moreover, J20 mice presented a high expression of type II IFN genes in the CP at 3months, which became lower than WT at 5-6 and 11-12months. Importantly, along with a marked memory impairment and increased glial activation, J20 mice also presented a similar overexpression of type I IFN genes in the dorsal hippocampus at 3months. Altogether, these findings provide new insights on a possible interplay between type I and II IFN responses in AD and point to IFNs as targets for modulation in cognitive decline.

Cognitive stimulation for portuguese older adults with cognitive impairment: a randomized controlled trial of efficacy, comparative duration, feasibility and experiential relevance

Although some studies point to cognitive stimulation as a beneficial therapy for older adults with cognitive impairments, this area of research and practice is still lacking dissemination and is underrepresented in many countries. Moreover, the comparative effects of different intervention durations remain to be established and, besides cognitive effects, pragmatic parameters, such as cost-effectiveness and experiential relevance to participants, are seldom explored. In this work, we present a randomized con- trolled wait-list trial evaluating 2 different intervention durations (standard 1⁄4 17 vs brief 1⁄4 11 sessions) of a cognitive stimulation program developed for older adults with cognitive impairments with or without dementia. 20 participants were randomly assigned to the standard duration intervention program (17 sessions, 1.5 months) or to a wait-list group. At postintervention of the standard intervention group, the wait-list group crossed over to receive the brief intervention program (11 sessions, 1 month). Changes in neuropsychological, functionality, quality of life, and caregiver outcomes were evaluated. Experience during intervention and costs and feasibility were also evaluated. The current cognitive stimulation programs (ie, standard and brief) showed high values of experiential relevance for both intervention durations. High adherence, completion rates, and reasonable costs were found for both formats. Further studies are needed to definitively establish the potential efficacy, optimal duration, cost-effectiveness, and experiential relevance for participants of cognitive intervention approaches.

Neurocognitive profile and cognitive intervention in Alzheimer's disease

Tese de Doutoramento em Psicologia (Especialidade de Psicologia Clínica)

"Virar a Sala de Aula”: centrar a aprendizagem no aluno recorrendo a ferramentas cognitivas

Relatório de projeto de mestrado em Ensino de Informática

Ensino, aprendizagem e avaliação no Ensino Superior: Perspetivas e práticas

Tese de Doutoramento em Ciências da Educação - Especialidade de Desenvolvimento Curricular

Changes in institutional governance and management of higher education in Laos: National University of Laos

PhD thesis in Educational Sciences (specialization in Politics of Education).

Aging and Alzheimer's disease: Searching for novel molecular cues

Tese de Doutoramento em Ciências da Saúde

Acontecimentos significativos em terapia cognitivo-comportamental: a perspetiva do cliente e do terapeuta

Dissertação de mestrado em Psicologia Aplicada

Momentos de inovação e mudança na terapia cognitivo comportamental para a bulimia nervosa

Dissertação de mestrado em Psicologia Aplicada

Self-narrative reconstruction after dilemma-focused therapy for depression: a comparison of good and poor outcome cases

Objective: The aim of this study is to improve the understanding of self-changes after an intervention for depression focused on implicative dilemmas, a type of cognitive conflict related to identity. As recent research has highlighted the relevance of identity-related dilemmas in clients with depression, we sought to assess the way in which clients resolve such inner conflicts after a tailored dilemma-focused intervention and how this is reflected in the clients’ self-narratives. Method: We used three instruments to observe differences between good (n = 5) and poor (n = 5) outcome cases: (i) the Repertory Grid Technique to track the resolution of dilemmas, (ii) the Change Interview to compile clients’ accounts of changes at posttreatment, and (iii) the Innovative Moments Coding System to examine the emergence of clients’ novelties at the Change Interview. Results: Groups did not differ in terms of the number and relevance of client-identified significantly helpful events. However, between-group differences were found for the resolution of dilemmas and for the proportion of high-level innovative moment (IM) types. Furthermore, a greater self-narrative reconstruction was associated with higher levels of symptom improvement. Conclusions: Good outcome cases seem to be associated with the resolution of conflicts and high-level IMs.

Corrigendum to “Short-term changes in light distortion in orthokeratology subjects"

Artigo completo publicado na revista "BioMed Research International, (2015), 1-7" e disponível no RepositóriUM em: http://hdl.handle.net/1822/33375

Short-term corneal changes with gas-permeable contact lens wear in keratoconus subjects: a comparison of two fitting approaches

Purpose: To evaluate changes in anterior corneal topography and higher-order aberrations (HOA) after 14-days of rigid gas-permeable (RGP) contact lens (CL) wear in keratoconus subjects comparing two different fitting approaches. Methods: Thirty-one keratoconus subjects (50 eyes) without previous history of CL wear were recruited for the study. Subjects were randomly fitted to either an apical-touch or three-pointtouch fitting approach. The lens’ back optic zone radius (BOZR) was 0.4 mm and 0.1 mm flatter than the first definite apical clearance lens, respectively. Differences between the baseline and post-CL wear for steepest, flattest and average corneal power (ACP) readings, central corneal astigmatism (CCA), maximum tangential curvature (KTag), anterior corneal surface asphericity, anterior corneal surface HOA and thinnest corneal thickness measured with Pentacam were compared. Results: A statistically significant flattening was found over time on the flattest and steepest simulated keratometry and ACP in apical-touch group (all p < 0.01). A statistically significant reduction in KTag was found in both groups after contact lens wear (all p < 0.05). Significant reduction was found over time in CCA (p = 0.001) and anterior corneal asphericity in both groups (p < 0.001). Thickness at the thinnest corneal point increased significantly after CL wear (p < 0.0001). Coma-like and total HOA root mean square (RMS) error were significantly reduced following CL wearing in both fitting approaches (all p < 0.05). Conclusion: Short-term rigid gas-permeable CL wear flattens the anterior cornea, increases the thinnest corneal thickness and reduces anterior surface HOA in keratoconus subjects. Apicaltouch was associated with greater corneal flattening in comparison to three-point-touch lens wear.

Changes in peripheral refractive profile after orthokeratology for different degrees of myopia

Purpose: The purpose of this study was to evaluate the effect of orthokeratology for different degrees of myopia correction in the relative location of tangential (FT) and sagittal (FS) power errors across the central 70 of the visual field in the horizontal meridian. Methods: Thirty-four right eyes of 34 patients with a mean age of 25.2 ± 6.4 years were fitted with Paragon CRT (Mesa, AZ) rigid gas permeable contact lenses to treat myopia (2.15 ± 1.26D, range: 0.88 to 5.25D). Axial and peripheral refraction were measured along the central 70 of the horizontal visual field with the Grand Seiko WAM5500 open-field auto-refractor. Spherical equivalent (M), as well as tangential (FT) and sagittal power errors (FS) were obtained. Analysis was stratified in three groups according to baseline spherical equivalent: Group 1 [MBaseline = 0.88 to 1.50D; n = 11], Group 2 [MBaseline = 1.51 to 2.49D; n = 11], and Group 3 [MBaseline = 2.50 to 5.25D; n = 12]. Results: Spherical equivalent was significantly more myopic after treatment beyond the central 40 of the visual field (p50.001). FT became significantly more myopic for all groups in the nasal and temporal retina with 25 (p 0.017), 30 (p 0.007) and 35 (p 0.004) of eye rotation. Myopic change in FS was less consistent, achieving only statistical significance for all groups at 35 in the nasal and temporal retina (p 0.045). Conclusions: Orthokeratology changes significantly FT in the myopic direction beyond the central 40 of the visual field for all degrees of myopia. Changes induced by orthokeratology in relative peripheral M, FT and FS with 35 of eye rotation were significantly correlated with axial myopia at baseline. Keywords: Field

Effector memory CD4+ T cells are associated with cognitive performance in a senior population

Objective: Immunosenescence and cognitive decline are common markers of the aging process. Taking into consideration the heterogeneity observed in aging processes and the recently described link between lymphocytes and cognition, we herein explored the possibility of an association between alterations in lymphocytic populations and cognitive performance. Methods: In a cohort of cognitively healthy adults (n = 114), previously characterized by diverse neurocognitive/psychological performance patterns, detailed peripheral blood immunophenotyping of both the innate and adaptive immune systems was performed by flow cytometry. Results: Better cognitive performance was associated with lower numbers of effector memory CD4(+) T cells and higher numbers of naive CD8(+) T cells and B cells. Furthermore, effector memory CD4(+) T cells were found to be predictors of general and executive function and memory, even when factors known to influence cognitive performance in older individuals (e.g., age, sex, education, and mood) were taken into account. Conclusions: This is the first study in humans associating specific phenotypes of the immune system with distinct cognitive performance in healthy aging.