Primary progressive aphasia : neuropsychological analysis and evolution

Tese de doutoramento, Ciências Biomédicas (Neurociências), Universidade de Lisboa, Faculdade de Medicina, 2015Frontotemporal lobar degeneration (FTLD) is the second leading cause of early-onset ( 2) revealed some clusters composed mostly by nonfluent or by semantic PPA cases. However, we could not evidence any group chiefly composed of logopenic PPA cases. Hence, findings obtained with the application of unsupervised data mining approaches do not clearly support a logopenic PPA. However further, supervised learning studies may indicate distinct results. Behaviour changes may occur early in PPA but the frequency of these symptoms across the three variants is still controversial. In the third study, 94 consecutive PPA patients (26 nonfluent, 36 semantic, 32 logopenic) underwent language and neuropsychological assessments. The presence of behavioural changes was ascertained by semi-structured informant-based interviews using the Blessed Dementia Rating Scale. Eighty-two percent of the cases endorsed at least one behaviour change. Nonfluent patients presented significantly more behaviour changes and scored more often (46.2%) the item “hobbies relinquished” when compared to logopenic patients. These differences in behaviour symptoms probably reflect distinct underlying neurodegenerative diseases. PPA is a neurodegenerative disorder with no effective pharmacological treatment. Cognition-based interventions are adequate alternatives, but their benefit has not been thoroughly explored. The aim of this last investigation was to study the effect of speech and language therapy (SLT) on naming ability in PPA. An open parallel prospective longitudinal study involving two centers was designed to compare patients with PPA submitted to SLT (1 h/week for 11 months, on average) with patients receiving no therapy. Twenty patients were enrolled and undertook baseline language and neuropsychological assessments; among them, 10 received SLT and 10 constituted an age- and education-matched historical control group. The primary outcome measure was the change in group mean performance on the Snodgrass and Vanderwart Naming Test between baseline and follow-up assessments. Intervention and control groups did not significantly differ on demographic and clinical variables at baseline. A mixed repeated measures ANOVA revealed a significant main effect of therapy (F(1,18) = 10.763; p = 0.005) on the performance on the Snodgrass and Vanderwart Naming Test. Although limited by a non-randomized open study design with a historical control group, the present study suggests that SLT may have a benefit in PPA, and it should prompt a randomized, controlled, rater-blind clinical trial. Conclusion: Despite the recent harmonization efforts, the delineation of certain PPA variants is still controversial. The present results show that neuropsychology is a key instrument not only for the clear definition of PPA subtypes but also for the study of the abnormal mechanisms and features underlying the main forms of PPA. Moreover, a neuropsychological approach to disease management seems to be feasible. Specifically, SLT emerges as an alternative and adequate approach to tackle the increasing language deficits experienced in all PPA phenotypes for some time. The emergence of promising disease-modifying therapies in the context of FTLD, in association with these cognitive-based interventions, will certainly be the future of PPA disease management

May subjective language complaints predict future language decline in community-dwelling subjects?

Subjective cognitive complaints are rather prevalent in the elderly population and are associated with an increased risk of cognitive impairment and dementia. However, the predictive role of specific types of cognitive complaints has been less systematically assessed. The aim of the present study is to examine the predictive value of language complaints for cognitive and language decline in a cohort of community-dwelling healthy older adults, followed longitudinally over a 5-year period. A total of 402 subjects were enrolled in a prospective longitudinal study on aging and cognition. Participants answered a cognitive complaints questionnaire including two questions directed to language and were classified at baseline as having “Language Complaints” (LC) or “No Language Complaints” (NLC). They also performed a neuropsychological assessment tackling attention/processing speed, memory, executive functioning, and language at baseline. From these, 275 (68.4%) participated in a follow-up evaluation 4.9 (±0.6) years later. At re-evaluation, subjects had a mean age of 70.4 (±8.3) years, 7.5 (±4.4) years of education, and 63.3% were female. Multivariate linear regression analysis was used to investigate whether language complaints at baseline predicted poorer language performance at follow-up or increased the risk of cognitive decline, with correction for sex, depressive symptoms, living status, baseline performance, and composite memory and executive performance. Results indicated that LC subjects had significantly worse performances than NLC subjects on semantic fluency 5 years later, but with a similar rate of decline overtime that was not associated with a follow-up outcome of cognitive decline/dementia. Language difficulties may represent a specific type of age-related cognitive complaints. Longer follow-ups are necessary to understand if they are associated with an increased risk of language or cognitive decline.info:eu-repo/semantics/publishedVersio

Avaliação da memória em portugueses com idade superior a 50 anos: Validação e dados normativos para o CVLT-9 e para os subtestes reprodução visual e faces da WMS – III

Dissertação de Mestrado apresentada ao Instituto Superior de Psicologia Aplicada para obtenção de grau de Mestre na especialidade de Psicologia Clínica.As queixas de memória são frequentes nas pessoas mais idosas, verificando-se declínio de memória episódica no envelhecimento normal, no defeito cognitivo ligeiro e na demência. Numerosos instrumentos procuram quantificar as alterações mnésicas neste âmbito, mas são poucos os que se encontram adaptados à nossa população. Procedemos à validação de um teste breve de memória verbal e dois de memória visual para a população portuguesa com idade igual ou superior a 50 anos. A 334 participantes saudáveis, sem lesão cerebral e autónomos nas actividades de vida diária, aplicaram-se o California Verbal Learning Test – versão reduzida (CVLT-9; Libon et al., 1996) e os subtestes Reprodução Visual e Faces da WMS – III (Wechsler, 1997), como parte de uma bateria desenvolvida para um estudo sobre envelhecimento. Os participantes apresentavam idades compreendidas entre os 50 e os 92 anos (65.64 + 8.4), com 6.9 anos de escolaridade em média (+ 4.2), sendo 63% do sexo feminino. Os testes apresentaram boa validade e consistência interna (entre .70 e .80). Os resultados evidenciaram um efeito de género, idade e escolaridade no desempenho dos três testes, revelando-se específicos para rastreio de lesão cerebral num grupo clínico, e demonstrando a sua utilidade na avaliação neuropsicológica de pessoas com queixas mnésicas ou com lesão cerebral.Memory complaints are common in the elderly, with decline in episodic memory in normal aging, mild cognitive impairment and dementia. There are many instruments which seek to quantify the memory changes in this group but there are few adapted to our population. The aim of our study was to validate a brief verbal memory and two visual memory tests in the Portuguese population aged 50 or older. 334 healthy participants without brain damage and independent on the activities of daily living undertook the California Verbal Learning Test – Short Version (CVLT-9; Libon et al., 1996) and Visual Reproduction and Faces subtests from WMS-III (Wechsler, 1997) as part of a battery developed for a study on aging. Participants age ranged from 50 to 92 yrs (65.64 + 8.4), with 6.9 yrs of literacy (+ 4.2), 63% female. The tests showed good validity and internal consistency (between .70 and .80). The results revealed an effect of gender, age and literacy in the performance of the three tests. The latter showed to be specific for detection of brain injury in a clinical sample, demonstrating its usefulness in neuropsychological assessment of individual with memory complaints and brain damage

The role of cognitive reserve in executive functioning and its relationship to cognitive decline and dementia

In this chapter, we explore how cognitive reserve is implicated in coping with the negative consequences of brain pathology and age-related cognitive decline. Individual differences in cognitive performance are based on different brain mechanisms (neural reserve and neural compensation), and reflect, among others, the effect of education, occupational attainment, leisure activities, and social involvement. These cognitive reserve proxies have been extensively associated with efficient executive functioning. We discuss and focus particularly on the compensation mechanisms related to the frontal lobe and its protective role, in maintaining cognitive performance in old age or even mitigating the clinical expression of dementia.info:eu-repo/semantics/publishedVersio

Locations of objects are better remembered than their identities in naturalistic scenes:An eye-tracking experiment in mild cognitive impairment

Objective: Retaining the identity or location of decontextualized objects in visual short-term working memory (VWM) is impaired by healthy and pathological ageing, but research remains inconclusive on whether these two features are equally impacted by it. Moreover, it is unclear whether similar impairments would manifest in naturalistic visual contexts. Method: 30 people with mild cognitive impairment (MCI) and 32 age-matched control participants (CPs) were eye-tracked within a change detection paradigm. They viewed 120 naturalistic scenes, and after a retention interval (1 s) asked whether a critical object in the scene had (or not) changed on either: identity (became a different object), location (same object but changed location), or both (changed in location and identity). Results: MCIs performed worse than CP but there was no interaction with the type of change. Changes in both were easiest while changes in identity alone were hardest. The latency to first fixation and first-pass duration to the critical object during successful recognition was not different between MCIs and CPs. Objects that changed in both features took longer to be fixated for the first time but required a shorter first pass compared to changes in identity alone which displayed the opposite pattern. Conclusions: Locations of objects are better remembered than their identities; memory for changes is best when involving both features. These mechanisms are spared by pathological ageing as indicated by the similarity between groups besides trivial differences in overall performance. These findings demonstrate that VWM mechanisms in the context of naturalistic scene information are preserved in people with MCI.info:eu-repo/semantics/acceptedVersio

Gender-related demographic, polysomnographic, cognitive and psychological factors in insomnia

info:eu-repo/semantics/publishedVersio

Cognitive performance along the migraine cycle: a negative exploratory study

Migraine patients frequently report cognitive difficulties in the proximity and during migraine attacks. We performed an exploratory comparison of executive functioning across the four stages of the migraine cycle. Consecutive patients with episodic migraine undertook cognitive tests for attention, processing speed, set-shifting, and inhibitory control. Performance was compared between patients in different migraine stages, controlling for attack frequency and prophylactic medication. One hundred forty-three patients (142 women, average age 36.2 ± 9.9 years) were included, 28 preictal (≤48 h before the attack), 21 ictal (during the attack), 18 postictal (≤24 h after attack), and 76 interictal. Test performance (age and literacy adjusted z-scores) was not significantly different across migraine phases, despite a tendency for a decline before the attack. This negative study shows that cognitive performance fluctuates as patients approach the attack. To control for individual variability, this comparison needs to be better characterized longitudinally with a within-patient design.info:eu-repo/semantics/publishedVersio

Cognitive aging in migraine sufferers is associated with more subjective complaints but similar age-related decline: a 5-year longitudinal study

Objectives and background: The effect of headache on cognitive performance is controversial, due to conflicting results obtained from studies in clinical or population settings. We aimed to understand if migraine and other headaches modify the rates of decline on different cognitive measures, during a 5-year interval. Design and method: A cohort of community dwelling adults (> 50 years) with migraine (MH), non-migraine headaches (NMH) and controls without headache (WoH), was assessed by a comprehensive neuropsychological battery with tests of memory, language and executive functions, repeated 5 years apart. Change in performance between baseline and reevaluation was compared between groups, and controlled for age, gender, literacy and depressive symptoms. Results: A total of 275 participants (78.5% WoH, 12.7% MH, 8.7% NMH) were reevaluated (average age 70.40 + 8.34 years, 64% females). Cognitive decline or dementia occurred in 11.4%, with a similar proportion among the three groups. Although MH participants had significantly more subjective cognitive complaints (p = 0.030, 95%CI:]-3.929,-0.014[), both MH and NMH subjects showed an age-associated decline identical to controls. Furthermore, migraine features (disease and attack duration, frequency and aura) were unrelated with cognitive performance. Conclusion: Migraine and non-migraine headache are not associated with increasing risk of dementia or cognitive decline at an older age although subjects with migraine have more cognitive complaints. Longer longitudinal studies are necessary to understand if this pattern persists for more than 5 years.info:eu-repo/semantics/publishedVersio

The Role of Cognitive Reserve in Executive Functioning and Its Relationship to Cognitive Decline and Dementia

In this chapter, we explore how cognitive reserve is implicated in coping with the negative consequences of brain pathology and age-related cognitive decline. Individual differences in cognitive performance are based on different brain mechanisms (neural reserve and neural compensation), and reflect, among others, the effect of education, occupational attainment, leisure activities, and social involvement. These cognitive reserve proxies have been extensively associated with efficient executive functioning. We discuss and focus particularly on the compensation mechanisms related to the frontal lobe and its protective role, in maintaining cognitive performance in old age or even mitigating the clinical expression of dementia

Iron Related Gene Expression and Biochemical Phenotype Support Iron Homeostasis Dysregulation in Alzheimer’s Disease

This research was supported by the Fundação para a Ciência e a Tecnologia (FCT) [SFRH/BPD/29354/2006 to MM, SFRH/BD/60718/2009 to BS, and SFRH/BD/48671/2008 to LM]; Fundação Astrazeneca (Research Grant awarded through the “Programme of Support to Research”); Instituto Nacional de Saúde Dr. Ricardo Jorge; Portuguese Ministry of Health (Research Grant 53/2007 of the “Comissão de Fomento da Investigação em Cuidados de Saúde”); Lundbeck Portugal, Lda (Research Grant)