Antonina Pereira

Abnormal expression of cerebrospinal fluid cation chloride cotransporters in patients with Rett syndrome.

Objective Rett Syndrome is a progressive neurodevelopmental disorder caused mainly by mutations in the gene encoding methyl-CpG-binding protein 2. The relevance of MeCP2 for GABAergic function was previously documented in animal models. In these models, animals show deficits in brain-derived neurotrophic factor, which is thought to contribute to the pathogenesis of this disease. Neuronal Cation Chloride Cotransporters (CCCs) play a key role in GABAergic neuronal maturation, and brain-derived neurotrophic factor is implicated in the regulation of CCCs expression during development. Our aim was to analyse the expression of two relevant CCCs, NKCC1 and KCC2, in the cerebrospinal fluid of Rett syndrome patients and compare it with a normal control group. Methods The presence of bumetanide sensitive NKCC1 and KCC2 was analysed in cerebrospinal fluid samples from a control pediatric population (1 day to 14 years of life) and from Rett syndrome patients (2 to 19 years of life), by immunoblot analysis. Results Both proteins were detected in the cerebrospinal fluid and their levels are higher in the early postnatal period. However, Rett syndrome patients showed significantly reduced levels of KCC2 and KCC2/NKCC1 ratio when compared to the control group. Conclusions Reduced KCC2/NKCC1 ratio in the cerebrospinal fluid of Rett Syndrome patients suggests a disturbed process of GABAergic neuronal maturation and open up a new therapeutic perspective.

Enhancing prospective memory in mild cognitive impairment: The role of enactment

Introduction: Prospective memory (PM) is a fundamental requirement for independent living which might be prematurely compromised in the neurodegenerative process, namely in mild cognitive impairment (MCI), a typical prodromal Alzheimer’s disease (AD) phase. Most encoding manipulations that typically enhance learning in healthy adults are of minimal benefit to AD patients. However, there is some indication that these can display a recall advantage when encoding is accompanied by the physical enactment of the material. The aim of this study was to explore the potential benefits of enactment at encoding and cue-action relatedness on memory for intentions in MCI patients and healthy controls using a behavioral PM experimental paradigm. Method: We report findings examining the influence of enactment at encoding for PM performance in MCI patients and age- and education-matched controls using a laboratory-based PM task with a factorial independent design. Results: PM performance was consistently superior when physical enactment was used at encoding and when target–action pairs were strongly associated. Importantly, these beneficial effects were cumulative and observable across both a healthy and a cognitively impaired lifespan as well as evident in the perceived subjective difficulty in performing the task. Conclusions: The identified beneficial effects of enacted encoding and semantic relatedness have unveiled the potential contribution of this encoding technique to optimize attentional demands through an adaptive allocation of strategic resources. We discuss our findings with respect to their potential impact on developing strategies to improve PM in AD sufferers.

The effects of age, enactment, and cue-action relatedness on memory for intentions in the Virtual Week task

ABSTRACT The current study investigated the influence of encoding modality and cue-action relatedness on prospective memory (PM) performance in young and older adults using a modified version of the Virtual Week task. Participants encoded regular and irregular intentions either verbally or by physically performing the action during encoding. For half of the intentions there was a close semantic relation between the retrieval cue and the intended action, while for the remaining intentions the cue and action were semantically unrelated. For irregular tasks, both age groups showed superior PM for related intentions compared to unrelated intentions in both encoding conditions. While older adults retrieved fewer irregular intentions than young adults after verbal encoding, there was no age difference following enactment. Possible mechanisms of enactment and relatedness effects are discussed in the context of current theories of event-based PM.

A comparison of laboratory, clinical, and self-report measures of prospective memory in healthy adults and individuals with brain injury

ABSTRACT Individuals with traumatic brain injury (TBI) have demonstrated deficits in prospective memory (PM) functioning when compared to healthy adults. These deficits have been measured using laboratory measures, clinical measures, and self-report questionnaires. However, PM has been shown to involve multiple cognitive processes and have a variety of stages. Thus, it is not known whether these measures all assess the same aspects of PM. Thus, this study was designed to measure the convergent validity of the three types of PM measures in both healthy adults and individuals with TBI. We aimed to investigate the convergent validity of the three types of tasks in two ways. First, we sought to investigate whether the PM deficits experienced by people with TBI are consistent across tasks. Second, we sought to examine the relationship between the three types of tasks. Results demonstrated that while all three types of measures were sensitive to PM deficits in TBI, there were differences in the aspects/processes of PM being measured. Data from the laboratory measure suggested a specific difficulty with detecting the correct cue. Data from the clinical measure suggested that TBI has a greater effect on time-based cues than event-based cues and that the primary deficit is a prospective intention retrieval deficit rather than the retrospective memory component. In addition, those with TBI did not differ from healthy adults when the time delay was short enough, suggesting that PM is not universally impaired. Data from the self-report questionnaire suggested that those with TBI are more sensitive to difficulties with basic activities of daily living rather than instrumental activities on daily living. These results are discussed in terms of rehabilitation techniques that could focus first on cue detection and use basic activities of daily living as outcome measures.

Sustaining Prospective Memory Functioning in Amnestic Mild Cognitive Impairment: a Lifespan Approach to the Critical Role of Encoding

Objective: Prospective memory (PM), the ability to remember to perform future activities, is a fundamental requirement for independent living. PM tasks pervade our daily lives, and PM failures represent one of the most prominent memory concerns across the entire life span. This study aimed to address this issue by exploring the potential benefits of specific encoding strategies on memory for intentions across healthy adulthood and in the early stages of cognitive impairment. Method: PM performance was explored through an experimental paradigm in 96 participants: 32 amnestic mild cognitively impaired patients aged 64–87 years (M = 6.75, SD = 5.88), 32 healthy older adults aged 62–84 years (M = 76.06, SD = 6.03), and 32 younger adults 18–22 years (M = 19.75, SD = 1.16). The potential benefit of the use of enactment (i.e., physically simulating the intended action) at encoding to support an autonomous performance despite neuronal degeneration was assessed. Results: PM was consistently identified as a sensitive and specific indicator of cognitive impairment. Importantly, enacted encoding was consistently beneficial for PM performance of all the participants, but especially so in the case of healthy and cognitively impaired older adults. These positive results have unveiled the potential of this encoding technique to optimize attentional demands through an adaptive allocation of strategic resources across both healthy and cognitively impaired samples. Theoretical implications of this work are discussed as well as the considerable translational potential to improve social well-being. Conclusions: A better understanding of the strategies that can enhance PM offers the potential for cost-effective and widely applicable tools which may support independent living across the adult life span.

Memory complaints in amnestic Mild Cognitive Impairment: more prospective or retrospective?

Patients with amnestic Mild Cognitive Impairment (aMCI), usually considered an early stage of Alzheimers disease, have deficits not only in retrospective memory (RM), that is, recalling of past events, words or people, but also on prospective memory (PM), the cognitive ability of remembering to execute delayed intentions in the future. This study investigated whether patients with aMCI refer more PM complaints as compared with RM complaints, and whether this might depend upon short‐term vs long‐term items or time‐based vs event‐based tasks.

Piloting a brief relational operant training program: analyses of response latencies and intelligence test performance

ABSTRACT Previous research suggests that training relational operant responding using the SMART (Strengthening Mental Abilities with Relational Training) program over several months can result in improved performance on cognitive intelligence tests. This study aimed to investigate whether engaging in a 3-week relational training program would improve (i) scores and (ii) reaction times on a standardised intelligence test, and (iii) to pilot a new multiple exemplar training procedure targeting complex analogical operant responding (SMARTA; SMART for Analogy). We administered the Kaufman Brief Intelligence Test (KBIT-2) to eight adults across four time points. Control: Time 1–4: No intervention. Experimental: Time 1–2: No intervention. Time 2–3: SMART relational operant training. Time 3–4: SMARTA analogical relational operant training. Experimental participants demonstrated greater improvements in terms of both (i) response latencies and (ii) response fluencies on the Verbal Knowledge subscale of the KBIT-2.

Behavioural changes in dementia and their impact on professional caregivers: A grounded theory approach

Aim The present study aimed to explore the impact that changes in behavioural symptoms of people living with dementia have on professional caregiver and resident relationships. Method A total of 21 interviews were carried out with professional caregivers of people living with dementia. A grounded theory approach was used to investigate everyday experiences of provision of professional care in dementia settings, focussing specifically on the effect of behavioural change on such relationships. Results A core category emerged from this analysis: ‘Developing behaviour in dementia impacts relationships on a personal and professional level’. Discussion Professionals have recognized as part of their everyday practice an eventual deterioration in relationships between themselves as professional caregivers and the residents, but also between the residents and their family members and among residents themselves. Importantly, understanding patients’ behaviour and behavioural change was identified as a crucial factor to achieve and sustain good relationships between professionals and residents suffering with dementia.

TREADING THE PATH BETWEEN INTENTIONS AND ACTIONS: A COMPLEX HIERARCHICAL MODEL OF PROSPECTIVE MEMORY

Background:Middle-life hypertension (HTN) increases the risk of late-life Alzheimer’s disease (AD). However, whether HTN causes ADor is a distinct disease that increases the prevalencewith age (comorbidity) remains unclear. This study aims to test if there is a causal relationship between HTN and AD. Methods: Two animal models were used to test the role of HTN in AD pathogenesis. First, 3xTg AD model mice at the ages of 2, 5 and 7 months were subjected to “two-kidney-one-clip” (2K1C) surgery to induce HTN. One and three months after the surgery, the blood pressures, hippocampus-dependent learning and memory, and AD-related pathologies, including Ab production and deposition and Tau phosphorylation, were evaluated. Second, Lanyu-miniature-pigs, at the age of 7 months, were subjected to abdominal aortic constriction (AAC) to induce HTN. The blood pressures and AD-related pathologies were determined 1, 2 and 3 months after the surgery. Results:The 3xTg mouse study: In all three ages of mice, the blood pressures were increased 7 days after the 2K1C surgery and last at least 1 month. One month after the surgery, the hippocampusdependent memories were impaired. The levels of Ab, amyloid precursor protein, pS412-Tau in the ventral hippocampi were elevated, while the levels of Tau protein kinase, GSK3b, were not affected. Furthermore, 7-month-old mice subjected to 2K1C for three months showed higher amyloid plaque loads in the hippocampi than the Sham controls. The pig study: Three months after the AAC surgery, the blood pressures of pigs were increased. The levels of Ab, amyloid precursor protein, pT212-Tau, pS412Tau, activated GSK3b and RAGE were increased, while the levels of LRP1 and pAKT were unchanged in the ventral hippocampi. The activities of another GSK3b upstream inhibition kinase, PKC, were decreased by AAC surgery. Immunohistochemistry revealed that the expression levels of pS412-Tau in the mossy fiber of hippocampi were increased. Conclusions:HTN aggravates the AD-related pathologies, including impairment of hippocampusdependent learning and memory, accumulation and deposition of Ab and increases of Tau phosphorylation. Control of blood pressure during middle-life may delay the onset of AD.

Acting is the Key: New directions for the stimulation of prospective memory in mild cognitive impairment

Background: The fulfillment of delayed intended actions (e.g. taking medication or attending an appointment) is described in the literature as prospective memory (PM), and is often pointed out as a fairly common concern for healthy adults in everyday life constituting a fundamental requirement for independent living across the lifespan. PM may be compromised in the course of healthy aging and may be particularly disrupted very early in the neurodegenerative process, namely at the stage of Mild Cognitive Impairment (MCI), which usually represents an initial phase of Alzheimer’s disease (AD), severely affecting a self-sufficient life-style and causing immense apprehension to caregivers. Methods: We have addressed this issue by investigating whether enactment at encoding could improve PM performance and whether these potential benefits were dependent of the relationship between the retrieval cue and its associated action. We report findings that explored this hypothesis in 64 young adults aged 18-39 years (M ¼ 20.41, SD ¼ 3.553) and 64 educationally matched older adults aged 58-90 years (M ¼ 71.17, SD ¼ 7.204) using a behavioral PM testing paradigm with a 2 X 2 X 2 between-subject factorial design. Results: Older adults’ PM performance (like that of their younger counterparts) benefited from enactment at encoding and from a strong semantic cue-action relation. Furthermore, there were no reliable effects of encoding modality or cue-action relatedness on performance accuracy or speed, despite a generalized slowness associated with age. Importantly, these beneficial effects were maintained across the lifespan, and even under high attentional demands. Figure 1. Mean proportion of PM cues eliciting a correct response at the appropriate moment in each Method of Encoding X Cue-Action Relatedness X Age