Contributo para o desenvolvimento de um Instrumento de Investigação Neuropsicológica

Tese apresentada à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Doutor em Ciências Sociais, especialidade em Psicologia

Established cardiovascular disease and CVD risk factors in a primary care population of middle-aged Irish men and women

Contemporary Irish data on the prevalence of major cardiovascular disease (CVD) risk factors are sparse. The primary aims of this study were (1) to estimate the prevalence of major cardiovascular disease risk factors, including Type 2 Diabetes Mellitus, in the general population of men and women between the ages of 50 and 69 years; and (2) to estimate the proportion of individuals in this age group at high absolute risk of cardiovascular disease events on the basis of pre-existing cardiovascular disease or as defined by the Framingham equation. Participants were drawn from the practice lists of 17 general practices in Cork and Kerry using stratified random sampling. A total of 1018 people attended for screening (490 men, 48%) from 1473 who were invited, a response rate of 69.1%. Cardiovascular disease risk factors and glucose intolerance are common in the population of men and women aged between 50 and 69 years. Almost half the participants were overweight and a further quarter met current international criteria for obesity, one of the highest recorded prevalence rates for obesity in a European population sample. Forty per cent of the population reported minimal levels of physical activity and 19% were current cigarette smokers. Approximately half the sample had blood pressure readings consistent with international criteria for the diagnosis of hypertension, but only 38% of these individuals were known to be hypertensive. Eighty per cent of the population sample had a cholesterol concentration in excess of 5 mmol/l. Almost 4% of the population had Type 2 Diabetes Mellitus, of whom 30% were previously undiagnosed. A total of 137 participants (13.5%) had a history or ECG findings consistent with established cardiovascular disease. Of the remaining 881 individuals in the primary prevention population, a total of 20 high-risk individuals (19 male) had a risk of a coronary heart disease event 30% over ten years according to the Framingham risk equation, giving an overall population prevalence of 2.0% (95% CI 1.3 - 3.0). At a risk level 20% over ten years, an additional 91 individuals (8.9%) were identified. Thus a total of 24.4% of the population were at risk either through pre-existing CVD (13.5%) or an estimated 10-year risk exceeding 20% according to the Framingham risk equation (10.9%). Thus a substantial proportion of middle-aged men are at high risk of CVD. The findings emphasise the scale of the CVD epidemic in Ireland and the need for ongoing monitoring of risk factors at the population level and the need to develop preventive strategies at both the clinical and societal level.

Victimisation of street children in Addis Ababa: factors of resilience and susceptibility

Cross-cultural variations in conceptions of childhood are discussed, particularly with regard to child abuse and child labour. Regardless of cultural background, a universal minimum standard of child rearing is required. The street child literature is reviewed, culminating in an analysis of Ethiopian street children. Theoretically this work is informed by victimology. Concepts shared by victimology and rational choice perspective are discussed, after Fattah (1993a). Victim surveys are described, highlighting their accuracy of crime estimates. Juvenile prostitution, runaways and rape are examined, particularly with regard to their relevance in Addis Ababa. Fifty five male and 135 female street children were interviewed. Interviews with boys focused on delinquency. An age-related pattern emerged, with younger boys less likely to drink, chew khat, steal or be sexually active. Interviews with street girls focused on the differences between girls living on the streets (girls of the street), girls working on the streets (girls on the street) and a sample of homebased girls. Girls of the street come to the street come to the streets for many reasons. Conflicts with a parent or guardian account for almost 50%. They are highly vulnerable to sexual assaults, particularly those 43% who have worked as prostitutes. Girls on the street experience considerably less victimisation. Urban poor girls live in socio-economic circumstances akin to girls on the street but enjoy almost universal protection from victimisation because they do not spend time on the streets. Unprotected by the stability which a family provides, girls of the street experience high victimisation levels. Such victimisation is often the result of reliance on types of work, such as prostitution, which brings the girls into contact with exploitative adults. Resistance to such victimisation is provided by a secure place to sleep, companions, and relatively safe types of work. Such protective factors are more readily available to family based children as compared to those living independently.

Defining metabolically healthy obesity: role of dietary and lifestyle factors

Background: There is a current lack of consensus on defining metabolically healthy obesity (MHO). Limited data on dietary and lifestyle factors and MHO exist. The aim of this study is to compare the prevalence, dietary factors and lifestyle behaviours of metabolically healthy and unhealthy obese and non-obese subjects according to different metabolic health criteria. Method: Cross-sectional sample of 1,008 men and 1,039 women aged 45-74 years participated in the study. Participants were classified as obese (BMI ≥30kg/m2) and non-obese (BMI <30kg/m2). Metabolic health status was defined using five existing MH definitions based on a range of cardiometabolic abnormalities. Dietary composition and quality, food pyramid servings, physical activity, alcohol and smoking behaviours were examined. Results: The prevalence of MHO varied considerably between definitions (2.2% to 11.9%), was higher among females and generally increased with age. Agreement between MHO classifications was poor. Among the obese, prevalence of MH was 6.8% to 36.6%. Among the non-obese, prevalence of metabolically unhealthy subjects was 21.8% to 87%. Calorie intake, dietary macronutrient composition, physical activity, alcohol and smoking behaviours were similar between the metabolically healthy and unhealthy regardless of BMI. Greater compliance with food pyramid recommendations and higher dietary quality were positively associated with metabolic health in obese (OR 1.45-1.53 unadjusted model) and non-obese subjects (OR 1.37-1.39 unadjusted model), respectively. Physical activity was associated with MHO defined by insulin resistance (OR 1.87, 95% CI 1.19-2.92, p = 0.006).

Health of the older worker in Ireland - occupational physical and psychosocial factors in the autumn of work life

Introduction: Worldwide, governments are striving to keep people in work to an older age. However, little is known about the effects of work on an older workforce. This thesis aims to investigate the importance of job characteristics to the antecedents and evolution of cardiovascular disease and functional limitations for the older worker (50+ years). Methods: Three studies were used in this thesis. The 5C (Cork Coronary Care Case- Control) Study investigated the association between job strain and a coronary event in males (n=208) 35-74 years old. The Mitchelstown Study examined the association between job characteristics and positive lifestyle behaviours and further, job characteristics and blood pressure for males and females 50-69 years (n=2,047). Finally, the Cork & Kerry Study investigated the physical effects of manual work and reported functional limitations/disabilities in a sample of 60-80 year olds (n=362). Results: Results from the 5C Study show a clear difference between younger (<50 years) and older (≥50 years) workers, with older workers who had a coronary event more likely to have high job strain and low job control. Data from the Mitchelstown Study showed workers with intermediate possibility for development or high quantitative demands (versus low) at work significantly more likely to have co-occurrence of positive lifestyle behaviours. Further, those who had high possibility for development were more likely to have high systolic blood pressure with no indication of recovery from this activation at night. Physically demanding work as reported by the participants of the Cork & Kerry Study was associated with functional limitations and activities of daily living disability for both the paid and unpaid worker. Discussion: The findings from this piece of work highlight the necessity to examine job characteristics and health outcomes in isolation for the over fifties. The challenge is to get this information into the workplace.

Akt signal transduction dysfunction in the 3xTg-AD mouse model of Alzheimer's disease

Alzheimer’s disease (AD) is an incurable neurodegenerative disorder, accounting for over 60% of all cases of dementia. The primary risk factor for AD is age, however several genetic and environmental factors are also involved. The pathological characteristics of AD include extracellular deposition of the beta-amyloid peptide (Aβ) and intraneuronal accumulation of neurofibrillary tangles (NFTs) made of aggregated paired helical filaments (PHFs) of the hyperphosphorylated tau protein, along with synaptic loss and neuronal death. There are numerous biochemical mechanisms involved in AD pathogenesis, however the reigning hypothesis points to toxic oligomeric Aβ species as the primary causative factor in a cascade of events leading to neuronal stress and dyshomeostasis that initiate abnormal regulation of tau. The insulin and IGF-1 receptors (IR, IGF-1R) are the primary activators of PI3- K/Akt through which they regulate cell growth, development, glucose metabolism, and learning and memory. Work in our lab and others shows increased Akt activity and phosphorylation of its downstream targets in AD brain, along with insulin and insulin-like growth factor-1 signalling (IIS) dysfunction. This is supported by studies of AD models in vivo and in vitro. Our group and others hypothesise that Aβ activates Akt through IIS to initiate a negative feedback mechanism that desensitises neurons to insulin/IGF-1, and sustains activation of Akt. In this study the functions of endogenous Akt, IR, and the insulin receptor substrate (IRS-1) were examined in relationship to Aβ and tau pathology in the 3xTg-AD mouse model, which contains three mutant human transgenes associated with familial AD or dementia. The 3xTg-AD mouse develops Aβ and tau pathology in a spatiotemporal manner that best recapitulates the progression of AD in human brain. Western blotting and immunofluorescent microscopy techniques were utilised in vivo and in vitro, to examine the relationship between IIS, Akt, and AD pathology. I first characterised in detail AD pathology in 3xTg-AD mice, where an age-related accumulation of intraneuronal Aβ and tau was observed in the hippocampal formation, amygdala, and entorhinal cortex, and at late stages (18 months), extracellular amyloid plaques and NFTs, primarily in the subiculum and the CA1 layer of the hippocampal formation. Increased activity of Akt, detected with antibody to phosphoSer473-Akt, was increased in 3xTg-AD mice compared to age-matched non-transgenic mice (non-Tg), and in direct correlation to the accumulation of Aβ and tau in neuronal somatodendritic compartments. Akt phosphorylates tau at residue Ser214 within a highly specific consensus sequence for Akt phosphorylation, and phosphoSer214-tau strongly decreases microtubule (MT) stabilisation by preventing tau-MT binding. PhosphoSer214-tau increased concomitantly with this in the same age-related and region-specific fashion. Polarisation of tau phosphorylation was observed, where PHF-1 (tauSer396/404) and phosphoSer214-tau both appeared early in 3xTg-AD mice in distinct neuronal compartments: PHF-1 in axons, and phosphoSer214-tau in neuronal soma and dendrites. At 18 months, phosphoSer214-tau strongly colocalised with NFTs positive for the PHF- 1 and AT8 (tauSer202/Thr205) phosphoepitopes. IR was decreased with age in 3xTg-AD brain and in comparison to age-matched non-Tg, and this was specific for brain regions containing Aβ, tau, and hyperactive Akt. IRS-1 was similarly decreased, and both proteins showed altered subcellular distribution. Phosphorylation of IRS-1Ser312 is a strong indicator of IIS dysfunction and insulin resistance, and was increased in 3xTg-AD mice with age and in relation to pathology. Of particular note was our observation that abberant IIS and Akt signalling in 3xTg-AD brain related to Aβ and tau pathology on a gross anatomical level, and specifically localised to the brain regions and circuitry of the perforant path. Finally, I conducted a preliminary study of the effects of synthetic Aβ oligomers on embryonic rat hippocampus neuronal cultures to support these results and those in the literature. Taken together, these novel findings provide evidence for IIS and Akt signal transduction dysfunction as the missing link between Aβ and tau pathogenesis, and contribute to the overall understanding of the biochemical mechanisms of AD.

Aging African American Women and the Impact of Positive Psychological Factors on Quality of Life

Aging African-American women are disproportionately affected by negative health outcomes and mortality. Life stress has strong associations with these health outcomes. The purpose of this research was to understand how aging African American women manage stress. Specifically, the effects of coping, optimism, resilience, and religiousness as it relates to quality of life were examined. This cross-sectional exploratory study used a self-administered questionnaire and examined quality of life in 182 African-American women who were 65 years of age or older living in senior residential centers in Baltimore using convenience sampling. The age range for these women was 65 to 94 years with a mean of 71.8 years (SD = 5.6). The majority (53.1%) of participants completed high school, with 23 percent (N = 42) obtaining college degrees and 19 percent (N = 35) holding advanced degrees. Nearly 58 percent of participants were widowed and 81 percent were retired. In addition to demographics, the questionnaire included the following reliable and valid survey instruments: The Brief Cope Scale (Carver, Scheier, & Weintraub, 1989), Optimism Questionnaire (Scheier, Carver, & Bridges, 1994), Resilience Survey (Wagnild & Young, 1987), Religiousness Assessment (Koenig, 1997), and Quality of Life Questionnaire (Cummins, 1996). Results revealed that the positive psychological factors examined were positively associated with and significant predictors of quality of life. The bivariate correlations indicated that of the six coping dimensions measured in this study, planning (r=.68) was the most positively associated with quality of life. Optimism (r=.33), resilience (=.48), and religiousness (r=.30) were also significantly correlated with quality of life. In the linear regression model, again the coping dimension of planning was the best predictor of quality of life (beta = .75, p <.001). Optimism (beta = .31, p <.001), resilience (beta = .34, p, .001) and religiousness (beta = .17, p <.01) were also significant predictors of quality of life. It appears as if positive psychology plays an important role in improving quality of life among aging African-American women.

Walking in old age and development of metabolic syndrome: the health, aging, and body composition study.

BACKGROUND: The specific health benefits of meeting physical activity guidelines are unclear in older adults. We examined the association between meeting, not meeting, or change in status of meeting physical activity guidelines through walking and the 5-year incidence of metabolic syndrome in older adults. METHODS: A total of 1,863 Health, Aging, and Body Composition (Health ABC) Study participants aged 70-79 were followed for 5 years (1997-1998 to 2002-2003). Four walking groups were created based on self-report during years 1 and 6: Sustained low (Year 1, <150 min/week, and year 6, <150 min/week), decreased (year 1, >150 min/week, and year 6, <150 min/week), increased (year 1, <150 min/week, and year 6, >150 min/week), and sustained high (year 1, >150 min/week, and year 6, >150 min/week). Based on the Adult Treatment Panel III (ATP III) panel guidelines, the metabolic syndrome criterion was having three of five factors: Large waist circumference, elevated blood pressure, triglycerides, blood glucose, and low high-density lipoprotein (HDL) levels. RESULTS: Compared to the sustained low group, the sustained high group had a 39% reduction in odds of incident metabolic syndrome [adjusted odds ratio (OR) = 0.61; 95% confidence interval (CI), 0.40-0.93], and a significantly lower likelihood of developing the number of metabolic syndrome risk factors that the sustained low group developed over 5 years (beta = -0.16, P = 0.04). CONCLUSIONS: Meeting or exceeding the physical activity guidelines via walking significantly reduced the odds of incident metabolic syndrome and onset of new metabolic syndrome components in older adults. This protective association was found only in individuals who sustained high levels of walking for physical activity.

Risk factors for and estimated incidence of community-associated Clostridium difficile infection, North Carolina, USA.

We determined estimated incidence of and risk factors for community-associated Clostridium difficile infection (CA-CDI) among patients treated at 6 North Carolina hospitals. CA-CDI case-patients were defined as adults (>18 years of age) with a positive stool test result for C. difficile toxin and no hospitalization within the prior 8 weeks. CA-CDI incidence was 21 and 46 per 100,000 person-years in Veterans Affairs (VA) outpatients and Durham County populations, respectively. VA case-patients were more likely than controls to have received antimicrobial drugs (adjusted odds ratio [aOR] 17.8, 95% confidence interval [CI] 6.6-48] and to have had a recent outpatient visit (aOR 5.1, 95% CI 1.5-17.9). County case-patients were more likely than controls to have received antimicrobial drugs (aOR 9.1, 95% CI 2.9-28.9), to have gastroesophageal reflux disease (aOR 11.2, 95% CI 1.9-64.2), and to have cardiac failure (aOR 3.8, 95% CI 1.1-13.7). Risk factors for CA-CDI overlap with those for healthcare-associated infection.

Effects of task instruction on autobiographical memory specificity in young and older adults

Older adults tend to retrieve autobiographical information that is overly general (i.e., not restricted to a single event, termed the overgenerality effect) relative to young adults' specific memories. A vast majority of studies that have reported overgenerality effects explicitly instruct participants to retrieve specific memories, thereby requiring participants to maintain task goals, inhibit inappropriate responses, and control their memory search. Since these processes are impaired in healthy ageing, it is important to determine whether such task instructions influence the magnitude of the overgenerality effect in older adults. In the current study participants retrieved autobiographical memories during presentation of musical clips. Task instructions were manipulated to separate age-related differences in the specificity of underlying memory representations from age-related differences in following task instructions. Whereas young adults modulated memory specificity based on task demands, older adults did not. These findings suggest that reported rates of overgenerality in older adults' memories might include age-related differences in memory representation, as well as differences in task compliance. Such findings provide a better understanding of the underlying cognitive mechanisms involved in age-related changes in autobiographical memory and may also be valuable for future research examining effects of overgeneral memory on general well-being. © 2013 Taylor & Francis.

Effects of task instruction on autobiographical memory specificity in young and older adults.

Older adults tend to retrieve autobiographical information that is overly general (i.e., not restricted to a single event, termed the overgenerality effect) relative to young adults' specific memories. A vast majority of studies that have reported overgenerality effects explicitly instruct participants to retrieve specific memories, thereby requiring participants to maintain task goals, inhibit inappropriate responses, and control their memory search. Since these processes are impaired in healthy ageing, it is important to determine whether such task instructions influence the magnitude of the overgenerality effect in older adults. In the current study participants retrieved autobiographical memories during presentation of musical clips. Task instructions were manipulated to separate age-related differences in the specificity of underlying memory representations from age-related differences in following task instructions. Whereas young adults modulated memory specificity based on task demands, older adults did not. These findings suggest that reported rates of overgenerality in older adults' memories might include age-related differences in memory representation, as well as differences in task compliance. Such findings provide a better understanding of the underlying cognitive mechanisms involved in age-related changes in autobiographical memory and may also be valuable for future research examining effects of overgeneral memory on general well-being.

A memory-based model of posttraumatic stress disorder: evaluating basic assumptions underlying the PTSD diagnosis.

In the mnemonic model of posttraumatic stress disorder (PTSD), the current memory of a negative event, not the event itself, determines symptoms. The model is an alternative to the current event-based etiology of PTSD represented in the Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; American Psychiatric Association, 2000). The model accounts for important and reliable findings that are often inconsistent with the current diagnostic view and that have been neglected by theoretical accounts of the disorder, including the following observations. The diagnosis needs objective information about the trauma and peritraumatic emotions but uses retrospective memory reports that can have substantial biases. Negative events and emotions that do not satisfy the current diagnostic criteria for a trauma can be followed by symptoms that would otherwise qualify for PTSD. Predisposing factors that affect the current memory have large effects on symptoms. The inability-to-recall-an-important-aspect-of-the-trauma symptom does not correlate with other symptoms. Loss or enhancement of the trauma memory affects PTSD symptoms in predictable ways. Special mechanisms that apply only to traumatic memories are not needed, increasing parsimony and the knowledge that can be applied to understanding PTSD.

The short and long of it: neural correlates of temporal-order memory for autobiographical events.

Previous functional neuroimaging studies of temporal-order memory have investigated memory for laboratory stimuli that are causally unrelated and poor in sensory detail. In contrast, the present functional magnetic resonance imaging (fMRI) study investigated temporal-order memory for autobiographical events that were causally interconnected and rich in sensory detail. Participants took photographs at many campus locations over a period of several hours, and the following day they were scanned while making temporal-order judgments to pairs of photographs from different locations. By manipulating the temporal lag between the two locations in each trial, we compared the neural correlates associated with reconstruction processes, which we hypothesized depended on recollection and contribute mainly to short lags, and distance processes, which we hypothesized to depend on familiarity and contribute mainly to longer lags. Consistent with our hypotheses, parametric fMRI analyses linked shorter lags to activations in regions previously associated with recollection (left prefrontal, parahippocampal, precuneus, and visual cortices), and longer lags with regions previously associated with familiarity (right prefrontal cortex). The hemispheric asymmetry in prefrontal cortex activity fits very well with evidence and theories regarding the contributions of the left versus right prefrontal cortex to memory (recollection vs. familiarity processes) and cognition (systematic vs. heuristic processes). In sum, using a novel photo-paradigm, this study provided the first evidence regarding the neural correlates of temporal-order for autobiographical events.

Cultural life scripts structure recall from autobiographical memory.

Three classes of evidence demonstrate the existence of life scripts, or culturally shared representations of the timing of major transitional life events. First, a reanalysis of earlier studies on age norms shows an increase in the number of transitional events between the ages of 15 and 30 years, and these events are associated with narrower age ranges and more positive emotion than events outside this period. Second, 1,485 Danes estimated how old hypothetical centenarians were when they had been happiest, saddest, most afraid, most in love, and had their most important and most traumatic experiences. Only the number of positive events showed an increase between the ages of 15 and 30 years. Third, undergraduates generated seven important events that were likely to occur in the life of a newborn. Pleasantness and whether events were expected to occur between the ages of 15 and 30 years predicted how frequently events were recorded. Life scripts provide an alternative explanation of the reminiscence bump. Emphasis is on culture, not individuals.

The spacing effect depends on an encoding deficit, retrieval, and time in working memory: evidence from once-presented words.

The spacing effect in list learning occurs because identical massed items suffer encoding deficits and because spaced items benefit from retrieval and increased time in working memory. Requiring the retrieval of identical items produced a spacing effect for recall and recognition, both for intentional and incidental learning. Not requiring retrieval produced spacing only for intentional learning because intentional learning encourages retrieval. Once-presented words provided baselines for these effects. Next, massed and spaced word pairs were judged for matches on their first three letters, forcing retrieval. The words were not identical, so there was no encoding deficit. Retrieval could and did cause spacing only for the first word of each pair; time in working memory, only for the second.