Determinants of vascular cognitive impairment : White matter lesions, brain atrophy and their neuropsychological correlates

The concept of vascular cognitive impairment (VCI) covers a wide spectrum of cognitive dysfunctions related to cerebrovascular disease. Among the pathophysiological determinants of VCI are cerebral stroke, white matter lesions and brain atrophy, which are known to be important risk factors for dementia. However, the specific mechanisms behind the brain abnormalities and cognitive decline are still poorly understood. The present study investigated the neuropsychological correlates of particular magnetic resonance imaging (MRI) findings, namely, medial temporal lobe atrophy (MTA), white matter hyperintensities (WMH), general cortical atrophy and corpus callosum (CC) atrophy in subjects with cerebrovascular disease. Furthermore, the cognitive profile of subcortical ischaemic vascular disease (SIVD) was examined. This study was conducted as part of two large multidisciplinary study projects, the Helsinki Stroke Aging Memory (SAM) Study and the multinational Leukoaraiosis and Disability (LADIS) Study. The SAM cohort consisted of 486 patients, between 55 and 85 years old, with ischaemic stroke from the Helsinki University Hospital, Helsinki, Finland. The LADIS Study included a mixed sample of subjects (n=639) with age-related WMH, between 65 and 84 years old, gathered from 11 centres around Europe. Both studies included comprehensive clinical and neuropsychological assessments and detailed brain MRI. The relationships between the MRI findings and the neuropsychological test performance were analysed by controlling for relevant confounding factors such as age, education and other coexisting brain lesions. The results revealed that in elderly patients with ischaemic stroke, moderate to severe MTA was specifically related to impairment of memory and visuospatial functions, but mild MTA had no clinical relevance. Instead, WMH were primarily associated with executive deficits and mental slowing. These deficits mediated the relationship between WMH and other, secondary cognitive deficits. Cognitive decline was best predicted by the overall degree of WMH, whereas the independent contribution of regional WMH measures was low. Executive deficits were the most prominent cognitive characteristic in SIVD. Compared to other stroke patients, the patients with SIVD also presented more severe memory deficits, which were related to MTA. The cognitive decline in SIVD occurred independently of depressive symptoms and, relative to healthy control subjects, it was substantial in severity. In stroke patients, general cortical atrophy also turned out to be a strong predictor of cognitive decline in a wide range of cognitive domains. Moreover, in elderly subjects with WMH, overall CC atrophy was related to reduction in mental speed, while anterior CC atrophy was independently associated with frontal lobe-mediated executive functions and attention. The present study provides cross-sectional evidence for the involvement of WMH, MTA, general cortical atrophy and CC atrophy in VCI. The results suggest that there are multifaceted pathophysiological mechanisms behind VCI in the elderly, including both vascular ischaemic lesions and neurodegenerative changes. The different pathological changes are highly interrelated processes and together they may produce cumulative effects on cognitive decline.

Functional outcome and health-related quality of life after traumatic brain injury in the framework of the International Classification of Functioning, Disability and Health (ICF)

Traumatic brain injury (TBI) affects people of all ages and is a cause of long-term disability. In recent years, the epidemiological patterns of TBI have been changing. TBI is a heterogeneous disorder with different forms of presentation and highly individual outcome regarding functioning and health-related quality of life (HRQoL). The meaning of disability differs from person to person based on the individual s personality, value system, past experience, and the purpose he or she sees in life. Understanding of all these viewpoints is needed in comprehensive rehabilitation. This study examines the epidemiology of TBI in Finland as well as functioning and HRQoL after TBI, and compares the subjective and objective assessments of outcome. The frame of reference is the International Classification of Functioning, Disability and Health (ICF). The subjects of Study I represent the population of Finnish TBI patients who experienced their first TBI between 1991 and 2005. The 55 Finnish subjects of Studies II and IV participated in the first wave of the international Quality of life after brain injury (QOLIBRI) validation study. The 795 subjects from six language areas of Study III formed the second wave of the QOLIBRI validation study. The average annual incidence of Finnish hospitalised TBI patients during the years 1991-2005 was 101:100 000 in patients who had TBI as the primary diagnosis and did not have a previous TBI in their medical history. Males (59.2%) were at considerably higher risk of getting a TBI than females. The most common external cause of the injury was falls in all age groups. The number of TBI patients ≥ 70 years of age increased by 59.4% while the number of inhabitants older than 70 years increased by 30.3% in the population of Finland during the same time period. The functioning of a sample of 55 persons with TBI was assessed by extracting information from the patients medical documents using the ICF checklist. The most common problems were found in the ICF components of Body Functions (b) and Activities and Participation (d). HRQoL was assessed with the QOLIBRI which showed the highest level of satisfaction on the Emotions, Physical Problems and Daily Life and Autonomy scales. The highest scores were obtained by the youngest participants and participants living independently without the help of other people, and by people who were working. The relationship between the functional outcome and HRQoL was not straightforward. The procedure of linking the QOLIBRI and the GOSE to the ICF showed that these two outcome measures cover the relevant domains of TBI patients functioning. The QOLIBRI provides the patients subjective view, while the GOSE summarises the objective elements of functioning. Our study indicates that there are certain domains of functioning that are not traditionally sufficiently documented but are important for the HRQoL of persons with TBI. This was the finding especially in the domains of interpersonal relationships, social and leisure activities, self, and the environment. Rehabilitation aims to optimize functioning and to minimize the experience of disability among people with health conditions, and it needs to be based on a comprehensive understanding of human functioning. As an integrative model, the ICF may serve as a frame of reference in achieving such an understanding.

Disabled Revolutionary War Veterans and the Construction of Disability in the Early United States, c. 1776-1840

This thesis addresses the following broad research question: what did it mean to be a disabled Revolutionary War veteran in the early United States during the period from 1776 to roughly 1840? The study approaches the question from two angles: a state-centred one and an experiential one. In both cases, the theoretical framework employed comes from disability studies. Consequently, disability is regarded as a sociocultural phenomenon rather than a medical condition. The state-centred dimension of the study explores the meaning of disability and disabled veterans to the early American state through an examination of the major military pension laws of the period. An analysis of this legislation, particularly the invalid pension acts of 1793 and 1806, indicates that the early United States represents a key period in the development of the modern disability category. The experiential approach, in contrast, shifts the focus of attention away from the state towards the lived experiences of disabled veterans. It seeks to address the issue of whether or not the disabilities of disabled veterans had any significant material impact on their everyday lives. It does this through a comparison of the situation of 153 disabled veterans with that of an equivalent number of nondisabled veterans. The former group received invalid pensions while the latter did not. In comparing the material conditions of disabled and nondisabled veterans, a wide range of primary sources from military records to memoirs and letters are used. The most important sources in this regard are the pension application papers submitted by veterans in the early nineteenth century. These provide us with a unique insight into the everyday lives of veterans. Looking at the issue of experience through the window of the pension files reveals that there was not much difference in the broad contours of disabled and nondisabled veteran life. This finding has implications for the theorisation of disability that are highlighted and discussed in the thesis. The main themes covered in this study are: the wartime experiences of injured American soldiers, the military pension establishment of the early United States and the legal construction of disability, and the post-war working and family lives of disabled veterans. Keywords: disability, early America, veterans, military pensions, disabled people, Revolutionary War, United States, disability theory.

Honey flows through fertile valleys : The cognitive and evolutionary foundations of paradise representations

The aim of the study is to explain how paradise beliefs are born from the viewpoint of mental functions of the human mind. The focus is on the observation that paradise beliefs across the world are mutually more similar than dissimilar. By using recent theories and results from the cognitive and evolutionary study of religion as well as from studies of environmental preferences, I suggest that this is because pan-human unconscious motivations, the architecture of mind, and the way the human mind processes information constrain the possible repertoire of paradise beliefs. The study is divided into two parts, theoretical and empirical. The arguments in the theoretical part are tested with data in the empirical part with two data sets. The first data set was collected using an Internet survey. The second data set was derived from literary sources. The first data test the assumption that intuitive conceptions of an environment of dreams generally follow the outlines set by evolved environmental preferences, but that they can be tweaked by modifying the presence of desirable elements. The second data test the assumption that familiarity is a dominant factor determining the content of paradise beliefs. The results of the study show that in addition to the widely studied belief in supernatural agents, belief in supernatural environments wells from the natural functioning of the human mind attesting the view that religious thinking and ideas are natural for human species and are produced by the same mental mechanisms as other cultural information. The results also help us to understand that the mental structures behind the belief in the supernatural have a wider scope than has been previously acknowledged.

On the moderators of trait avoidance motivation in predicting cognitive biases and adjustment

The present research focused on motivational and personality traits measuring individual differences in the experience of negative affect, in reactivity to negative events, and in the tendency to avoid threats. In this thesis, such traits (i.e., neuroticism and dispositional avoidance motivation) are jointly referred to as trait avoidance motivation. The seven studies presented here examined the moderators of such traits in predicting risk judgments, negatively biased processing, and adjustment. Given that trait avoidance motivation encompasses reactivity to negative events and tendency to avoid threats, it can be considered surprising that this trait does not seem to be related to risk judgments and that it seems to be inconsistently related to negatively biased information processing. Previous work thus suggests that some variable(s) moderate these relations. Furthermore, recent research has suggested that despite the close connection between trait avoidance motivation and (mal)adjustment, measures of cognitive performance may moderate this connection. However, it is unclear whether this moderation is due to different response processes between individuals with different cognitive tendencies or abilities, or to the genuinely buffering effect of high cognitive ability against the negative consequences of high trait avoidance motivation. Studies 1-3 showed that there is a modest direct relation between trait avoidance motivation and risk judgments, but studies 2-3 demonstrated that state motivation moderates this relation. In particular, individuals in an avoidance state made high risk judgments regardless of their level of trait avoidance motivation. This result explained the disparity between the theoretical conceptualization of avoidance motivation and the results of previous studies suggesting that the relation between trait avoidance motivation and risk judgments is weak or nonexistent. Studies 5-6 examined threat identification tendency as a moderator for the relationship between trait avoidance motivation and negatively biased processing. However, no evidence for such moderation was found. Furthermore, in line with previous work, the results of studies 5-6 suggested that trait avoidance motivation is inconsistently related to negatively biased processing, implying that theories concerning traits and information processing may need refining. Study 7 examined cognitive ability as a moderator for the relation between trait avoidance motivation and adjustment, and demonstrated that cognitive ability moderates the relation between trait avoidance motivation and indicators of both self-reported and objectively measured adjustment. Thus, the results of Study 7 supported the buffer explanation for the moderating influence of cognitive performance. To summarize, the results showed that it is possible to find factors that consistently moderate the relations between traits and important outcomes (e.g. adjustment). Identifying such factors and studying their interplay with traits is one of the most important goals of current personality research. The present thesis contributed to this line of work in relation to trait avoidance motivation.

Cognitive Functioning in Young Adults with Depression, Anxiety Disorders, or Burnout Symptoms : Findings from a Population-based Sample

Background. Evidence of cognitive dysfunction in depressive and anxiety disorders is growing. However, the neuropsychological profile of young adults has received only little systematic investigation, although depressive and anxiety disorders are major public health problems for this age group. Available studies have typically failed to account for psychiatric comorbidity, and samples derived from population-based settings have also seldom been investigated. Burnout-related cognitive functioning has previously been investigated in only few studies, again all using clinical samples and wide age groups. Aims. Based on the information gained by conducting a comprehensive review, studies on cognitive impairment in depressive and anxiety disorders among young adults are rare. The present study examined cognitive functioning in young adults with a history of unipolar depressive or anxiety disorders in comparison to healthy peers, and associations of current burnout symptoms with cognitive functioning, in a population-based setting. The aim was also to determine whether cognitive deficits vary as a function of different disorder characteristics, such as severity, psychiatric comorbidity, age at onset, or the treatments received. Methods. Verbal and visual short-term memory, verbal long-term memory and learning, attention, psychomotor processing speed, verbal intelligence, and executive functioning were measured in a population-based sample of 21-35 year olds. Performance was compared firstly between participants with pure non-psychotic depression (n=68) and healthy peers (n=70), secondly between pure (n=69) and comorbid depression (n=57), and thirdly between participants with anxiety disorders (n=76) and healthy peers (n=71). The diagnostic procedure was based on the SCID interview. Fourthly, the associations of current burnout symptoms, measured with the Maslach Burnout Inventory General Survey, and neuropsychological test performance were investigated among working young adults (n=225). Results. Young adults with depressive or anxiety disorders, with or without psychiatric comorbidity, were not found to have major cognitive impairments when compared to healthy peers. Only mildly compromised verbal learning was found among depressed participants. Pure and comorbid depression groups did not differ in cognitive functioning, either. Among depressed participants, those who had received treatment showed more impaired verbal memory and executive functioning, and earlier onset corresponded with more impaired executive functioning. In anxiety disorders, psychotropic medication and low psychosocial functioning were associated with deficits in executive functioning, psychomotor processing speed, and visual short-term memory. Current burnout symptoms were associated with better performance in verbal working memory and verbal intelligence. However, lower examiner-rated social and occupational functioning was associated with problems in verbal attention, memory, and learning. Conclusions. Depression, anxiety disorders, or burnout symptoms may not be associated with major cognitive deficits among young adults derived from the general population. Even psychiatric comorbidity may not aggravate cognitive functioning in depressive or anxiety disorders among these young adults. However, treatment-seeking in depression was found to be associated with cognitive deficits, suggesting that these deficits relate to increased distress. Additionally, early-onset depression, found to be associated with executive dysfunction, may represent a more severe form of the disorder. In anxiety disorders, those with low symptom-related psychosocial functioning may have cognitive impairment. An association with self-reported burnout symptoms and cognitive deficits was not detected, but individuals with low social and occupational functioning may have impaired cognition.

The Freudian unconscious in the context of the cognitive orientation

For decades psychoanalysis was the discipline studying the unconscious, and other branches of study lacked competence to take a stand on the issues concerning the unconscious. From 1980s onwards intense study of the unconscious has been taken place in the scope of cognitive orientation. Thus, nowadays it is talked about both pyschoanalytic and cognitive unconscious. The aim of this thesis is to integrate psychoanalytic and cognitive views. When the "Freudian" conception of the unconscious is considered, there are four entangled issues: 1) what is the unconscious like, 2) how does the unconsciuos give rise to psychic disorders 3) why and how certain contents are missing from consciousness (repression of contents), 4) the emergence of those contents (becoming conscious of the repressed). The conventional psychoanalytic answer to the first question - and "the cornerstone of psychoanalysis" - is "the unconscious is mental". The issues 2)-4) depend radically on the answer given to the 1): "psychoanalytic" conceptualizations on them rest on the "cornerstone". That ground was challended in study I: it was argued that it has never been clear what does it mean that the unconscious is mental. Thus, it was stated that in the current state of art psychoanalysis should drop out the ephitet "mental" before the term unconscious. That claim creates a pressure to reappraise the convential "psychoanalytic" answers to the other questions, and that reappraisal was the aim of studies II and III. In study II the question 2) is approached in terms of implicit knowledge. Study III focuses on mechanisms, which determine which contents appear in the scope of consciousness, and also cause missing of contents from there (the questions 3) and 4)). In the core of study III there are distinctions concerning the processess occuring in the levels of the brain, consciousness, self-consciousness, and narrative self-consciousness. Studies I-III set "psychoanalytic" topics in the frames of cognitive view. The picture emerging from those studies is not especially useful for a clinican (psychotherapist). Studies IV and V focused that issue. Study IV is a rather serious critique toward neuropsychoanalysis. In it it was claimed that repressive functions of conscious states are in the core of clinical psychoanalysis, and functions in general cannot be reduced to neurophysiological terminology. Thus, the limits of neuropsychoanalysis are more strict than it has been realized: crucial clinical issues remain outside its scope. In study V it was focused on the confusing state of things that although unconscious fantasies do not exist, the idea on them has been an important conceptual tool for clinicans. When put in a larger context, the aim of study V is similar to that of study IV: to determine the relation between psychotherapists' and neuroscientists' terminologies. Studies III, IV and V apply the philosopher Daniel Dennett's model on different levels of explanation.

Cognitive deficits and the Paced Auditory Serial Addition Test performance among patients with multiple sclerosis

Multiple sclerosis (MS) is a chronic, inflammatory disease of the central nervous system, characterized especially by myelin and axon damage. Cognitive impairment in MS is common but difficult to detect without a neuropsychological examination. Valid and reliable methods are needed in clinical practice and research to detect deficits, follow their natural evolution, and verify treatment effects. The Paced Auditory Serial Addition Test (PASAT) is a measure of sustained and divided attention, working memory, and information processing speed, and it is widely used in MS patients neuropsychological evaluation. Additionally, the PASAT is the sole cognitive measure in an assessment tool primarly designed for MS clinical trials, the Multiple Sclerosis Functional Composite (MSFC). The aims of the present study were to determine a) the frequency, characteristics, and evolution of cognitive impairment among relapsing-remitting MS patients, and b) the validity and reliability of the PASAT in measuring cognitive performance in MS patients. The subjects were 45 relapsing-remitting MS patients from Seinäjoki Central Hospital, Department of Neurology and 48 healthy controls. Both groups underwent comprehensive neuropsychological assessments, including the PASAT, twice in a one-year follow-up, and additionally a sample of 10 patients and controls were evaluated with the PASAT in serial assessments five times in one month. The frequency of cognitive dysfunction among relapsing-remitting MS patients in the present study was 42%. Impairments were characterized especially by slowed information processing speed and memory deficits. During the one-year follow-up, the cognitive performance was relatively stable among MS patients on a group level. However, the practice effects in cognitive tests were less pronounced among MS patients than healthy controls. At an individual level the spectrum of MS patients cognitive deficits was wide in regards to their characteristics, severity, and evolution. The PASAT was moderately accurate in detecting MS-associated cognitive impairment, and 69% of patients were correctly classified as cognitively impaired or unimpaired when comprehensive neuropsychological assessment was used as a "gold standard". Self-reported nervousness and poor arithmetical skills seemed to explain misclassifications. MS-related fatigue was objectively demonstrated as fading performance towards the end of the test. Despite the observed practice effect, the reliability of the PASAT was excellent, and it was sensitive to the cognitive decline taking place during the follow-up in a subgroup of patients. The PASAT can be recommended for use in the neuropsychological assessment of MS patients. The test is fairly sensitive, but less specific; consequently, the reasons for low scores have to be carefully identified before interpreting them as clinically significant.

ADHD-aikuisten psykologinen kuntoutus : Neljän uuden lyhytintervention tutkimus

ADHD (attention deficit hyperactivity disorder) is developmental neurobiological disability. In adults, the prevalence of ADHD has been estimated to be about 4 %. In addition to the difficulties of attention, the problems in executive functioning are typical. The psychiatric comorbidities are common. The most extensively studied treatments are pharmacological. There is also evidence about the usefulness of the cognitive-behavioural therapy (CBT) in the treatment of adults with ADHD. There are some preliminary results about the effectiveness of cognitive training and hypnosis in children, but there is no scientific proof in adults. This dissertation is based on two intervention studies. In the first study, the usefulness of the new group CBT (n = 29) and the maintenance of the symptom reduction in the follow-up of six months were studied. In the second study, the usefulness of short hypnotherapy (n = 9), short individual CBT (n = 10) and computerized cognitive training (n = 9) were examined by comparing groups with each other and to the control group (n = 10). The participation in the group CBT and the participants' satisfaction were good. There were no changes in self-reports during waiting period of three months. After the rehabilitation, the symptoms decreased. Participants having symptom reduction during rehabilitation maintained their benefit through 6-month follow-up period. In a combined ADHD symptom score based on self-reports, seven participants in the hypnotherapy, six in the CBT, two in the cognitive training and two controls improved. Using independent evaluations, improvement was found in six of the hypnotherapy, seven of the CBT, two of the cognitive training and three of the control participants. There was no treatment-related improvement in cognitive performance. Thus, in the hypnotherapy and CBT groups, some encouraging improvement was seen. In the cognitive training group, there was improvement in the trained tasks but no generalization of the improvement. The results support the earlier results from the usefulness of CBT in the treatment of adults with ADHD. Also the hypnotherapy seems a useful rehabilitation. More research is needed to evaluate the usefulness of cognitive training. These promising results warrant further studies with more participants and with longer treatment duration. Also different measures of cognitive functioning and quality of life are needed. It is important in addition to the medication to arrange psychosocial interventions for the ADHD adults.

Predictors of disability retirement: From early intentions to retirement

The strong tendency of elderly employees to retire early and the simultaneous aging of the population have been major topics of policy and scientific debate. A key concern has been the financing of future pension schemes and possible labour shortage, especially in social and health services within the public sector. The aging of the population is inevitable, but efforts can be made to prevent or postpone early exit from the labour force, e.g., by identifying and intervening in the factors that contribute to the process of early retirement due to disability. The associations of intentions to retire early, poor mental health and different psychosocial factors with the process of disability retirement are still poorly understood. The purpose of this study was to investigate the associations of intentions to retire early, poor mental health, work and family related psychosocial factors and experiences of earlier life stages with the process of disability retirement. The data were derived from the Helsinki Health Study (HHS, N=8960) and the Health and Social Support Study (HeSSup, N=25 901). The Helsinki Health Study is an ongoing employee cohort study among middle-aged women and men. The Health and Social Support Study is an ongoing longitudinal study of a working-age sample representative of the Finnish population. The analyses were restricted to respondents 40 years of age or older. Age and gender adjusted prevalence and incidence rates were calculated. Associations were studied by using logistic, multinomial and Cox regression. Strong intentions to retire early were common among employees. Poor mental health, unfavourable working conditions and work-to-family conflicts were clearly associated with increased intentions to retire early. Strong intentions to retire early predicted disability retirement. Risk of disability retirement increased in a dose-response manner with increasing number of childhood adversities. Poor mental and somatic health, life dissatisfaction, heavy alcohol consumption, current smoking, obesity and low socioeconomic status were also predictors of disability retirement. The impact of poor mental health and adverse experiences from earlier life stages, work and family related psychosocial factors, e.g., work-family interface, the subjective experience of well-being and health related risk behaviours on the process of disability retirement should be recognised. Preventive measures against disability retirement should be launched before subjective experience of ill health, work disability and strong intentions to retire early emerge.