This thesis presents research investigating objectively and subjectively examined cognitive impairment in Bipolar Disorder (BD) in comparison to disorders with similar cognitive symptomatologies. First, a systematic review and meta-analyses compared the cognitive performance between BD and Mild Cognitive Impairment (MCI) or dementia. Studies included in this review and meta-analyses assessed cognitive performances using multiple objective cognitive assessments. Results from these meta-analyses found greater impairment in BD relative to MCI on motor initiative abilities. Additionally, there were similarities in cognitive deficits on delayed memory recall and visuoconstructional abilities between BD and MCI. For the comparison between BD and dementia, we analyzed the findings of studies comparing BD across different mood states with different types of dementia, where BD in acute mood episode demonstrated greater deficits in attention, working memory, verbal memory, and executive function than behavioral variant frontotemporal dementia (bvFTD). In contrast, overall cognitive functioning and verbal fluency was more impaired in Alzheimer’s disease (AD) in comparison to BD during euthymia. Next, we shifted the focus on examining subjective cognitive complaints in BD relative to Major Depressive Disorder (MDD). Our study is unique from previous literature with the same aim considering that it only involved patients recently diagnosed with BD, and subjective complaints were assessed with the Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA), an instrument specific to cognitive complaints detected in BD. The findings demonstrate higher subjective cognitive complaints in euthymic BD in comparison to euthymic MDD, suggesting greater self-perceived difficulties in BD, even in the beginning of the illness. Taken together, findings from the studies presented in this thesis highlight the importance of early detection and intervention of cognitive impairments in BD, with the aim of enhancing cognitive abilities, and prevention of further cognitive degradation with the progression of the disorder / Thesis / Master of Science (MSc)

Yes / Early diagnosis of Alzheimer’s disease (AD) is essential if treatments are to be administered at an earlier point in time before neurons degenerate to a stage beyond repair. In order for early detection to occur tools used to detect the disorder must be sensitive to the earliest of cognitive impairments. Virtual reality (VR) technology offers opportunities to provide products which attempt to mimic daily life situations, as much as is possible, within the computational environment. This may be useful for the detection of cognitive difficulties. We develop a virtual simulation designed to assess visuospatial memory in order to investigate cognitive function in a group of healthy elderly participants and those with a mild cognitive impairment. Participants were required to guide themselves along a virtual path to reach a virtual destination which they were required to remember. The preliminary results indicate that this virtual simulation has the potential to be used for detection of early AD since significant correlations of scores on the virtual environment with existing neuropsychological tests were found. Furthermore, the test discriminated between healthy elderly participants and those with a mild cognitive impairment (MCI).

Alzheimer's disease~(AD) is the most frequent neurodegenerative dementia and a growing health problem. Early and accurate diagnosis and prediction of AD is crucial because treatment may be most efficacious if introduced as early as possible. Neuropsychological testing, which is clinically used, sometimes fails to recognize probable dementia, especially to recognize the disease at an early time point such as the mild cognitive impairment~(MCI), which is the prodromal stage of AD. Recently, there has been a realization that magnetic resonance imaging~(MRI) may help diagnoses of AD and MCI. In this dissertation, we introduce an MRI-analysis based algorithm to help diagnose the illness before irreversible neuronal loss has set in, and to help detect brain changes between MCI patients who may convert and may not convert to AD. Given a set of brain MR images, the algorithm first calculates the distance between each pair of images via a registration process. Then images are projected from a high dimensional Euclidean space to a low dimensional Euclidean subspace based on the calculated distances, with a dimension reduction method. Finally classical supervised classification approaches are employed to assign images to appropriate groups in the low dimensional space. The classification accuracy rates we obtained in our experiments are higher than, or at least comparable to, those reported in recently published papers. Moreover, this algorithm can be extended to explore the pathology distribution of AD. Exploring the distribution of AD pathology is of great importance to reveal AD related regional atrophy at specific stages of the disease and provide insight into longitudinal sequence of disease progression. Calculating distances between different brain structures produces different classification accuracy. Those structures yielding higher classification accuracy are considered as pathological regions. Our experimental results on pathology localization are also compared with the reproduced results using other existing popular algorithms; the observations are consistent. / Ph. D.

Yes / The health and well-being benefits of outdoor nature-based activity are increasingly recognised, but older people with cognitive impairment face significant barriers to access. The ENLIVEN project aims to promote access by gathering evidence and coproducing guidance for activity providers. As part of this project, we conducted a scoping review to characterise the types of outdoor nature-based activity for older people with dementia and other forms of cognitive impairment for which research evidence is available and the range of outcomes is examined. The protocol is available online. We systematically searched relevant databases from 1st January, 2009, to 20th October, 2022, and screened articles against the following criteria: participants were older people aged 65 and above with cognitive impairment arising from dementia or another health condition. The study described the formal provision of outdoor nature-based activity away from the person’s usual place of residence, and at least one outcome of participation in the activity was evaluated. Twenty-eight articles met inclusion criteria, all focused on people with dementia. In most cases, participants were attending day care or living in residential care, and sample sizes ranged from 4 to 136. Activities fell into three groups: green day care (fifteen articles), equine-assisted interventions (seven articles), and community nature-based activities (six articles). Outcome domains explored were connection with nature, activity engagement, impacts on clinical symptoms, functional ability, physical, psychological and social health,, and quality of life. Outdoor nature-based activity can be offered as an opportunity for meaningful occupation to enrich daily life, as a framework for day care provision, or as an intervention to address clinical needs. The evidence base for green day care is relatively established, but the potential for addressing specific clinical needs remains to be explored. The paucity of evidence regarding community provision, especially for those not attending formal care settings, suggests the need for effective knowledge exchange to stimulate initiatives in this area. / UK Research and Innovation (UKRI) Healthy Ageing Challenge and UKRI/Economic and Social Research Council (ESRC) through Grant ES/V016172/1.

The concept of resilience, which indicates people's capability of using resources in difficult circumstances in order to reduce or prevent negative effects and achieve positive outcomes, has given a new perspective to the scientific literature on the experience of late-life memory loss and the experience of caring for persons with memory loss. The current research was guided by incorporation of resilience into the stress process model for assessing personal and caregiver burden associated with mild and more severe memory loss. I conducted two studies to investigate the association of protective factors with the well-being of people with dementia or mild cognitive impairment and their caregivers. The first study focused on the well-being of older persons with dementia (PwDs). I employed data from a large national sample of older adults to examine how the perceived social cohesion of neighborhoods affects quality of life among people with and without cognitive impairment in conjunction with their engagement in valued leisure activities. Findings revealed that, regardless of cognitive health status, all participants who perceived high neighborhood social cohesion reported better quality of life along with more participation in valued activities. However, PwDs reported significantly lower perceived neighborhood social cohesion, less involvement in valued activities, and poorer quality of life than persons without cognitive impairment. The second study focused on the well-being of caregivers for older persons with mild cognitive impairment (PwMCIs). I used dyadic data from families dealing with mild cognitive impairment to examine how well-being of caregivers for PwMCIs differed according to whether PwMCI-caregiver dyads had similar or different perceptions of the PwMCIs' cognitive impairment severity. Caregivers reported lower caregiving burden when they and PwMCIs had a similar cognitive impairment representation, or when caregivers rated the PwMCIs’ cognitive functioning more positively than the PwMCIs rated themselves. Also, PwMCIs’ and caregivers' perceptions, and their concordance or discrepancy in those perceptions, varied across the multiple domains related to MCI symptoms. These findings demonstrate that care dyads' perception of MCI-related deficits is not a unitary construct, and that the context of PwMCIs’ and caregivers’ dyadic illness appraisals is significantly associated with the caregivers' well-being. Taken together, the results of these two studies illustrate the value of considering resilience processes in people with cognitive impairment and their caregivers. Examining dimensions of resilience, in association with assessment of the intersecting effects of personal, interpersonal, and environmental factors, provides additional information about the effects of cognitive impairment on older adults’ well-being and the effects of assisting someone with cognitive impairment on caregiver well-being. / Ph. D.

Although not all persons with mild cognitive impairment (MCI) go on to develop Alzheimer's disease (AD), MCI is recognized as an early stage of AD. The effects of AD are devastating to all concerned. Research has identified that recognition of AD in its earliest stages and institution of known treatment modalities can forestall the ultimate outcome. Identification of the first subtle signs of MCI can assist in the recognition of this prodromal phase, and allow for institution of therapy while still in the initial stages. Unfortunately, the development of MCI is insidious in nature, thus making it difficult to detect. The purpose of this study was to identify areas of functional decline that occur in MCI in an effort to improve its early identification. A mixed-methods design that combined qualitative and quantitative methods was used. Fifty-three participants with memory complaints were interviewed using a semi structured interview technique with open-ended questions, the Montreal Cognitive Assessment (MoCA), the Geriatric Depression Scale (GDS) and a list of eighty-five items previously identified as indicative of functional decline. Twenty-nine persons were divided into two groups: 1) those identified as probable MCI (consensus diagnosis) (n=15) and possible MCI (based on screening examination) (n=14) and 2) those identified as Normal (no cognitive impairment) (n=10), and their subjective functional deficits compared. The findings suggest that there were certain areas of functional decline more commonly experienced by persons in the MCI group than by unimpaired. These include difficulty recalling details of information and forgetting conversations. There were also other changes identified, such as adaptations on the part of persons with MCI (an increased dependence on memory aids, for example, lists and calendars) and a dec rease in social activities leading to an increase in social isolation. Additionally identified were functional activities that appear to remain intact in persons with early MCI. This study highlights the subtlety with which MCI assaults the functional abilities of individuals, thus making its early identification problematic. The results of this study will contribute by providing information that will help professionals who are assessing persons experiencing memory issues for the possible presence of MCI. Additionally, it is hoped that these findings will assist in the development of a measurement tool designed to assess for possible MCI. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2015. / FAU Electronic Theses and Dissertations Collection

Frontal lobe atrophy (FLA) is associated with late-life depression and cognitive impairment, although the pathogenesis of FLA in stroke is unclear. In an aim to ascertain whether FLA is affected by WMLs, we analyzed the MRIs of 471 Chinese ischemic stroke patients. Lobar atrophy was defined by a widely-used visual rating scale. WML severity was rated using the Fazekas scale. There was no correlation between PVH and DWMH and temporal and parietal atrophy. The results of this study suggest that FLA in ischemic stroke may be associated with SVD. / Poststroke depression (PSD) is the most common form of poststroke psychiatric morbidity. Small subcortical infarcts (SSIs) can result from small vessel disease (SVD) and large artery disease (LAD). No study has yet explored PSD in different etiological types of SSIs. To address this gap, 127 patients with SSIs resulting from LAD or SVD were examined. PSD was evaluated with the Geriatric Depression Scale (GDS) three months after stroke. The LAD group had a significantly higher frequency of PSD, and LAD was found to be a significant independent risk factor for PSD. This study suggests that cerebral blood perfusion may play an important role in PSD. / Post-stroke emotional lability (PSEL) is a distressing and embarrassing complaint among stroke survivors. Lesions located in various cortical and subcortical areas are thought to be involved in the pathophysiology of PSEL.The clinical significance of microbleeds (MBs) in the development of psychiatric conditions following stroke is unknown. We carried out a study to examine the association between PSEL and MBs in 519 Chinese patients with acute ischemic stroke admitted consecutively. PSEL was evaluated three months after the index stroke, and the number and location of MBs were evaluated with MRI. According to Kim's criteria, 74 (14.3%) of the patients had PSEL. Our results suggest that MBs in the thalamus may play a role in the development of PSEL. The importance of MBs in PSEL and other psychiatric conditions in stroke survivors warrants further investigation. / The first study reported in this thesis involved 328 Chinese ischemic stroke patients who were administered a series of neuropsychological tests covering seven domains three months after stroke. Two hundred and fifty-six of these patients were followed-up for one year. Volumetry of the infarcts, WMLs, and hippocampus atrophy on magnetic resonance imaging (MRI) was conducted. The prevalence of cognitive impairment was 54.9% at baseline and 52.4% at the one-year follow-up, although most of the patients (85.5%) remained cognitively stable. The evolution of cognitive impairment no dementia (CIND) at the one-year follow-up was bidirectional, with 11.2% progressing to dementia and 21.0% reverting to cognitive intact. WMLs volume rather than hippocampal volume was a significant predictor of cognitive impairment, cognitive decline, and delayed dementia. WMLs also had an independent effect on executive function, attention, visual memory, visuoconstruction, and visuomotor speed. / This thesis investigates the clinical and imaging characterization of cognitive impairment and psychiatric morbidity in Chinese stroke patients. The conclusions of the studies reported herein can be summarized as follows. (1) The prevalence of cognitive impairment is high among Chinese poststroke patients, but most remain cognitively stable at one year after stroke; WMLs rather than hippocampal atrophy predict cognitive impairment, longitudinal cognitive decline, and delayed dementia; (2) DLPFC atrophy is correlated with poor verbal fluency in elderly women with stroke, but not in their male counterparts; (3) LAD may be associated with PSD in patients with small subcortical infarcts; (4) MBs in the thalamus are associated with PSEL; (5) frontal lobe infarction and diabetes may be risk factors of insomnia symptoms in stroke patients; and (6) FLA in ischemic stroke may be associated with SVD. (Abstract shortened by UMI.) / Chen, Yangkun. / Adviser: Wai Kwong Tang. / Source: Dissertation Abstracts International, Volume: 72-04, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 217-238). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Ce travail de thèse s’articule autour de trois études complémentaires. La première aborde la validation française d’un test rapide d’évaluation des fonctions supérieures: le Barrow Neurological Institute Screen for higher cerebral functions (B.N.I.S). Cette étude a permis de rendre disponible en langue française un outil rapide qui évalue les fonctions cognitives classiques mais aussi les capacités émotionnelles et sociocognitives, fonctions généralement non intégrées dans ce type de test. La seconde étude, menée auprès de participants présentant un Mild Cognitive Impairment (M.C.I), a ensuite permis de mettre en évidence la nécessité de prendre en compte l’évaluation émotionnelle. Les participants M.C.I présentent un profil spécifique au B.N.I.S., notamment aux subtests d’affectivité, d’orientation, de mémoire et d’auto-évaluation de la performance mnésique. Enfin, la troisième étude analyse les performances de reconnaissance faciale des émotions et de raisonnement social au cours du vieillissement normal, le Mild Cognitive Impairment et la démence de type Alzheimer (DTA) au stade débutant. Nous observons un déclin des capacités de reconnaissance faciale des émotions et de raisonnement social au cours du vieillissement normal qui s’accentue significativement au cours de la DTA. Un profil spécifique est retrouvé pour le M.C.I avec un déclin en raisonnement social mais des capacités de reconnaissance faciale émotionnelle comparables aux sujets âgés du groupe contrôle. L’évaluation des capacités émotionnelles devrait être davantage intégrée aux bilans neuropsychologiques afin de mieux orienter les modalités de prise en charge de la population vieillissante. / This research presents three complementary studies: (1) the french validation of the Barrow Neurological Institute Screen for higher cerebral functions (B.N.I.S), developed by G. Prigatano in 1991. We have assessed 167 subjects from 15 to 84 years within a french population. The goal is :1) to promote a new short screening instrument dedicated to cognitive and emotional functions, usually emotional functions are not integrated in neuropsychological assessments ; (2) to apply the B.N.I.S to Mild Cognitive Impairment (M.C.I) subjects (N=39) in order to highlighted the importance of the emotional assessment in this type of population and found a specific profile at the substests named: affectivity, orientation, memory and self-assessment of the mnesic performance ; (3) to analyze, with more precision, the performance of emotional facial recognition and social reasoning during normal ageing (N=54), M.C.I (N=25) and Alzheimer disease (AD) at the early stage (N=17). A decline of sociocognitive capacities is observed during the ageing and seems to become more important during the course of M.C.I and the AD. A specific profile was found for each group. The assessment of emotional capacities seems relevant and should be more integrated into the neuropsychological assessments, in order to improve diagnosis and to propose the best modalities of care for the ageing population.

Mexican Americans face a significant health disparity related to the development of Mild Cognitive Impairment (MCI) when compared to other ethnic groups. Recent work has documented the utility of utilizing blood-based biomarkers in the detection of amnestic MCI among this population. Efforts to enhance the utility of biomarkers in detecting disease through the inclusion of select neuropsychological measures, an approach termed Molecular Neuropsychology, has shown promise. The present study sought to utilize the molecular neuropsychology approach and examine biobanked serum samples as well as neuropsychological assessments from the Health and Aging Brain among Latino Elders (HABLE) study. Random Forest analyses were conducted to determine the proteomic profile of MCI. Then separate linear regression analyses were conducted to determine the variance accounted for by the biomarkers within the select neuropsychological measures. Trail Making Test Part B was identified as having the least amount of variance and was combined with top five biomarkers within the MCI proteomic profile to create a biomarker-cognitive profile for detecting disease presence. This same method was applied to the amnestic and non-amnestic forms of MCI. The overall biomarker-cognitive profile was shown to be 90% accurate in the detection of MCI, with no significant increase when demographic variables were included into the model. Among amnestic MCI cases, the detection accuracy of the biomarker-cognitive profile was 92% and increased to 94% upon inclusion of demographic variables.

The absence of gold standard criteria for mild cognitive impairment (MCI) impedes the comparison of research findings and the development of primary and secondary prevention strategies addressing the possible conversion to dementia. The objective of Study 1 was to compare the predictive ability of different MCI models as markers for incipient dementia in a longitudinal population-based Canadian sample. The utility of well-documented MCI criteria using data from persons who underwent a clinical examination in the second wave of the Canadian Study of Health and Aging (CSHA) was examined. Demographic characteristics, average neuropsychological test performance, and prevalence and conversion rates were calculated for each classification. Receiver operating characteristic (ROC) analyses were employed to assess the predictive power of each cognitive classification. The highest prevalence and conversion rates were associated with case definitions of multiple-domain MCI. The only diagnostic criteria to significantly predict dementia five years later was the Cognitive Impairment, No Dementia (CIND) Type 2 case definition. It is estimated that more restrictive MCI case definitions fail to address the varying temporal increases in decline across different cognitive domains in the progression from normal cognitive functioning to dementia. Using data from the CSHA, the objective of Study 2 was to elucidate the clinical correlates that best differentiate between cognitive classifications. A machine learning algorithm was used to identify the symptoms that best discriminated between: 1) not cognitively impaired (NCI) and CIND; 2) CIND & demented; and 3) converting and non-converting CIND participants. Poor retrieval was consistently a significant predictor of greater cognitive impairment across all three questions. While interactions with other predictors were noted when differentiating CIND from NCI and demented from non-demented participants, retrieval was the sole predictor of conversion to dementia over five years. Importantly, the limited specificity and predictive values of the respective algorithms caution against their use as clinical markers of CIND, dementia, or conversion. Rather, it is recommended that the predictors serve as markers for ongoing monitoring and assessment. Overall, the results of both studies suggest that the architecture of pathological cognitive decline to dementia may not be captured by a single set of diagnostic criteria.