Correlates of the conversion from mild cognitive impairment to dementia

RESUMO: Apesar do diagnóstico de Défice Cognitivo Ligeiro (DCL) corresponder a uma condição com grande probabilidade de progressão para demência, sobretudo para Doença de Alzheimer (DA), estudos longitudinais têm mostrado que alguns doentes podem não converter para demência e manter o diagnóstico de DCL mesmo após muitos anos. O objectivo do nosso primeiro estudo foi determinar se doentes que mantêm o diagnóstico de DCL a longo prazo (10 anos) estão realmente estáveis ou apenas em declínio lento, e identificar as características clínicas e neuropsicológicas que se associam à estabilidade a longo prazo. Procurámos na Cognitive Complaints Cohort (CCC) casos de MCI que mantiveram esse diagnóstico ao longo de pelo menos uma década. Para cada doente com DCL estável a longo prazo, 2 indivíduos com DCL que converteram para demência durante o seguimento, emparelhados para idade e escolaridade, foram seleccionados da mesma base de dados. As avaliações neuropsicológicas inicial e final foram comparadas entre os doentes com DCL estável a longo prazo e os DCL conversores. Os preditores neuropsicológicos da estabilidade a longo termo foram procurados na avaliação inicial. Indivíduos com DCL estável a longo prazo (n=22) e DCL conversor (n=44) não diferiram em termos de distribuição de género, escolaridade, idade à data da primeira avaliação e intervalo entre início dos sintomas e primeira avaliação. O tempo de seguimento foi em média de 11 anos para os DCL estáveis a longo prazo e 3 anos para os DCL conversores. Os testes neuropsicológicos iniciais e finais não foram significativamente diferentes nos indivíduos com DCL estável a longo prazo. Observou-se um declínio global nos doentes com DCL conversor. Resultados melhores num teste de memória, Evocação de Palavras após Interferência - Total, e num teste de abstracção não verbal, Matrizes Coloridas Progressivas de Raven, previram estabilidade clínica a longo termo (10 anos). Alguns doentes com DCL permanecem clínica e neuropsicologicamente estáveis ao longo de uma década. Melhores desempenhos na avaliação inicial em provas de memória e abstracção não verbal previram estabilidade a longo termo. Os doentes diagnosticados com Défice Cognitivo Ligeiro amnéstico (DCLa) têm risco aumentado de progressão para demência. Tornou-se possível, através do uso de biomarcadores, diagnosticar DA em doentes com DCLa. No entanto, presentemente, é impraticável submeter todos os doentes com DCLa a pesquisa de biomarcadores. Tendo em conta que a avaliação neuropsicológica é necessária para fazer um diagnóstico formal de DCLa, seria interessante que pudesse ser usada para predizer o estado amilóide dos doentes com DCLa. Participantes com DCLa, estado amilóide conhecido (Aβ+ or Aβ-) e avaliação neuropsicológica abrangente foram seleccionados da base de dados CCC para o segundo estudo. As provas neuropsicológicas iniciais dos doentes com DCLa Aβ+ e Aβ- foram comparadas. Uma análise de regressão logística binária foi conduzida para modelar a probabilidade de ser Aβ+. Dos 216 doentes com DCLa estudados, 117 eram Aβ+ e 99 eram Aβ-. Os doentes com DCLa Aβ+ tiveram piores desempenhos em vários testes de memória, nomeadamente Evocação de Palavras - Total, Memória Lógica - Evocação Imediata e após Interferência, e Aprendizagem de Pares Verbais Associados (Pares de Palavras), assim como no Teste Trail B, um teste de função executiva. Num modelo de regressão logística binário, apenas a Memória Lógica - Evocação após Interferência reteve significado estatístico. Por cada ponto adicional no resultado deste teste, a probabilidade de ser Aβ+ decresceu em 30.6%. O modelo resultante classificou correctamente 64.6% dos casos DCLa no que diz respeito ao seu estado amilóide. A avaliação neuropsicológica permanece um passo fundamental no diagnóstico e caracterização dos doentes com DCLa; no entanto, os testes neuropsicológicos têm um valor limitado na distinção entre indivíduos com DCLa com patologia amilóide daqueles com outras etiologias. O diagnóstico de DA confirmado por biomarcadores permite ao doente fazer decisões importantes acerca da sua vida. Contudo, permanecem dúvidas acerca da rapidez da progressão dos sintomas e do declínio cognitivo futuro. Medidas neuropsicológicas foram extensamente estudadas na previsão do tempo até conversão para demência em indivíduos com DCL na ausência de informação acerca de biomarcadores. Medidas neuropsicológicas semelhantes poderiam ser úteis na estimativa de tempo de progressão para demência em doentes com DCL devido a DA. O objectivo do nosso terceiro trabalho foi o de estudar a contribuição das medidas neuropsicológicas para estimar o tempo até conversão para demência em doentes com DCL devido a DA. Indivíduos com esta condição foram incluídos a partir da CCC e o efeito do desempenho neuropsicológico numa avaliação inicial no tempo até conversão para demência foi analisado. Na avaliação inicial, os conversores tiveram pontuações mais baixas do que os não conversores em medidas de iniciativa verbal, raciocínio não verbal e memória episódica. A prova de raciocínio não verbal (Matrizes Coloridas Progressivas de Raven) foi o único indicador com significado estatístico num modelo de regressão multivariado de Cox. O decréscimo de um desvio-padrão associou-se a 29.0% de aumento de risco de conversão para demência. Aproximadamente 50% dos doentes com mais de um desvio padrão abaixo da média no z score desta prova haviam convertido para demência aos 3 anos de seguimento. No DCL devido a DA, pior desempenho numa prova de raciocínio não verbal associou-se ao tempo até conversão para demência. Esta prova, que apresenta declínio ligeiro nas fases mais precoces da DA, parece transmitir informação importante no que diz respeito à conversão para demência.ABSTRACT: Although the diagnosis of Mild Cognitive Impairment (MCI) corresponds to a condition likely to progress to dementia, essentially Alzheimer’s disease (AD), longitudinal studies have shown that some patients may not convert to dementia and maintain the diagnosis of MCI even after many years. The objective of our first study was to determine whether patients that maintain the diagnosis of MCI in the long term (10 years) are really stable or just declining slowly, and to identify clinical and neuropsychological characteristics associated with long-term stability. The Cognitive Complaints Cohort (CCC) was searched for MCI cases who maintained that diagnosis for at least 10 years. For each long-term-stable MCI patient, two MCI patients that converted to dementia during follow-up, matched for age and education, were selected from the same database. The baseline and last neuropsychological evaluations for long-term-stable MCI and converter MCI were compared. Baseline neuropsychological predictors of long-term stability were searched for. Long-term-stable MCI (n=22) and converter MCI (n=44) patients did not differ in terms of gender distribution, education, age at first assessment and time between symptom onset and first evaluation. Time of follow-up was on average 11 years for long-term-stable MCI and 3 years for converter MCI. The baseline and follow-up neuropsychological tests were not significantly different in long-term-stable MCI patients, whereas a general decline was observed in converter MCI patients. Higher scores on one memory test, the Word Delayed Total Recall, and on the non-verbal abstraction test, Raven’s Coloured Progressive Matrices, at the baseline predicted long-term (10 years) clinical stability. Some patients with MCI remain clinically and neuropsychologically stable for a decade. Better performances at baseline in memory and non verbal abstraction tests predict long-term stability. Patients diagnosed with amnestic Mild Cognitive Impairment (aMCI) are at high risk of progressing to dementia. It became possible, through the use of biomarkers, to diagnose those patients with aMCI who have AD. However, it is presently unfeasible that all patients undergo biomarker testing. Since neuropsychological testing is required to make a formal diagnosis of aMCI, it would be interesting if it could be used to predict the amyloid status of patients with aMCI. Participants with aMCI, known amyloid status (Aβ+ or Aβ-) and a comprehensive neuropsychological evaluation were selected from the CCC database for this study. Neuropsychological tests were compared in Aβ+ and Aβ- aMCI patients. A binary logistic regression analysis was conducted to model the probability of being Aβ+. Of the 216 aMCI patients studied, 117 were Aβ+ and 99 were Aβ-. Aβ+ aMCI patients performed worse on several memory tests, namely Word Total Recall, Logical Memory Immediate and Delayed Free Recall, and Verbal Paired Associate Learning, as well as on Trail Making Test B, an executive function test. In a binary logistic regression model, only Logical Memory Delayed Free Recall retained significance, so that for each additional score point in this test, the probability of being amyloid positive decreased by 30.6%. The resulting model correctly classified 64.6% of the aMCI cases regarding their amyloid status. The neuropsychological assessment remains an essential step to diagnose and characterise patients with aMCI, however, neuropsychological tests have limited value to distinguish the aMCI patients who have amyloid pathology from those who might suffer from other clinical conditions. Diagnosis of AD confirmed by biomarkers allows the patient to make important life decisions. However, doubt about the fleetness of symptoms progression and future cognitive decline remains. Neuropsychological measures were extensively studied in prediction of time to conversion to dementia for MCI patients in the absence of biomarker information. Similar neuropsychological measures might also be useful to predict the progression to dementia in patients with MCI due to AD. The objective of our third work was to study the contribution of neuropsychological measures to predict time to conversion to dementia in patients with MCI due to AD. Patients with MCI due to AD were enrolled from the CCC and the effect of neuropsychological performance on time to conversion to dementia was analyzed. At baseline converters scored lower than non-converters at measures of verbal initiative, non-verbal reasoning and episodic memory. The test of non-verbal reasoning (Raven’s Coloured Progressive Matrices) was the only statistically significant predictor in a multivariate Cox regression model. A decrease of one standard deviation was associated with 29.0% of increase in the risk of conversion to dementia. Approximately 50% of patients with more than one standard deviation below the mean in the z score of that test had converted to dementia at 3 years of follow-up. In MCI due to AD, lower performance in a test of non-verbal reasoning was associated with time to conversion to dementia. This test, that reveals little decline in the earlier phases of AD, appears to convey important information concerning conversion to dementi

Macro-Level Cognitive and Linguistic Function in Early Stage Alzheimer’s Disease and Mild Cognitive Impairment

Alzheimer’s disease (AD) is a global health concern, particularly as there is currently no cure for the disease. Interventions to slow progression of disease, pharmacological or non-pharmacological, need to be targeted early on before any significant neurodegeneration has occurred, as these changes are irreversible, and lost cognitive function cannot be recovered. This makes it imperative to detect pathological cognitive decline as early as possible. Although biomarkers have received a lot of attention in this regard, they have several limitations, particularly outside of research settings, such as cost and availability. Cognitive markers, other than traditional neuropsychological test measures, on the other hand, have received comparatively less attention with regards to early detection; and, particularly cognitive markers that are rooted in real-world, everyday cognition, have been lacking. Due to the disease being incurable, interventions are aimed at maintaining independent living and good quality of life for as long as possible. This necessitates outcomes that can measure meaningful change in cognition and everyday functioning. The goal of the present dissertation was to identify gaps in the current literature on cognitive and linguistic assessments that are embedded in aspects of everyday cognition in AD, and work towards developing paradigms to address the gaps. Due to the emphasis on early detection, the work focused on patients in the very early stage of AD and on its preceding stage of Mild Cognitive Impairment (MCI). In light of evidence reporting the inability of AD patients to follow narratives, be it verbal or non-verbal, a systematic review of text comprehension studies was conducted to characterize and evaluate macro-level measures of discourse comprehension in their sensitivity to early stage AD, and their ability to distinguish pathological ageing due to AD or MCI from cognitive ageing. Results showed that, not only AD patients, but also MCI patients were significantly more impaired on macro-level measures of comprehension compared to cognitively healthy older adults. These findings were consistent across all eight studies included in the review, indicating a robust effect, though there were minor differences in the sensitivity of different measures. Next, moving towards non-verbal narratives, a novel picture-based paradigm assessing event cognition, with a focus on event integration and macro-event recognition, was introduced. This study aimed to examine the macro-level processing of events by using a format requiring integration of micro-events, depicted in pictures, into a larger macro-event. AD and MCI patients’ ability to connect the micro-events temporally and causally to identify the depicted macro-event was assessed. As hypothesized, the findings showed that patient groups had significant difficulties in determining temporal order of micro-events, even when provided with a verbal cue, as well as in conceptualizing the macro-event from the presented micro-events, when compared to healthy older adults. Finally, using traditional neuropsychological tests, the cognitive processes involved in performing the macro-event recognition task were determined by examining correlations. Primarily, semantic memory and executive functioning appear to play a role. However, the strength of correlations was fairly moderate, indicating added value of event recognition task in cognitive assessment. Taken together, these findings show the sensitivity of macro-level cognitive and linguistic markers based in everyday cognition in the early stages of AD, and highlight the positive role of such cognitive assessment methods in bringing together objective assessment methods and everyday cognition

Automatic speech analysis to early detect functional cognitive decline in elderly population

This study aimed at evaluating whether people with a normal cognitive function can be discriminated from subjects with a mild impairment of cognitive function based on a set of acoustic features derived from spontaneous speech. Voice recordings from 90 Italian subjects (age >65 years; group 1: 47 subjects with MMSE>26; group 2: 43 subjects with 20≤ MMSE ≤26) were collected. Voice samples were processed using a MATLAB-based custom software to derive a broad set of known acoustic features. Linear mixed model analyses were performed to select the features able to significantly distinguish between groups. The selected features (% of unvoiced segments, duration of unvoiced segments, % of voice breaks, speech rate, and duration of syllables), alone or in addition to age and years of education, were used to build a learning-based classifier. The leave-one-out cross validation was used for testing and the classifier accuracy was computed. When the voice features were used alone, an overall classification accuracy of 0.73 was achieved. When age and years of education were additionally used, the overall accuracy increased up to 0.80. These performances were lower than the accuracy of 0.86 found in a recent study. However, in that study the classification was based on several tasks, including more cognitive demanding tasks. Our results are encouraging because acoustic features, derived for the first time only from an ecologic continuous speech task, were able to discriminate people with a normal cognitive function from people with a mild cognitive decline. This study poses the basis for the development of a mobile application performing automatic voice analysis on-the-fly during phone calls, which might potentially support the detection of early signs of functional cognitive decline

Marqueurs discursifs de neurodégénérescence liée à la pathologie Alzheimer

La maladie d’Alzheimer (MA) et les aphasies progressives primaires (APP) s’accompagnent de perturbations du langage expressif parfois subtiles, mais précoces dans l’évolution de ces maladies neurodégénératives. Considérés dans une approche automatisée, ces changements pourraient constituer des marqueurs de dégénérescence identifiés de façon non invasive et peu onéreuse. À ce titre, ils font l’objet d’études visant à automatiser leur utilisation clinique. Cependant, l’intégration des marqueurs langagiers à une approche diagnostique centrée sur les biomarqueurs reste à faire. À cette fin, la présente thèse a deux objectifs. D’abord, recenser systématiquement les marqueurs du discours qui distinguent le mieux les personnes avec une MA de témoins en santé. Ensuite, appliquer une approche automatisée et à un large éventail de marqueurs de discours pour identifier, dans un groupe hétérogène de patients avec une APP, lesquels ont une pathologie Alzheimer sous-jacente. Afin de mettre en contexte ces deux objectifs, nous proposons une introduction générale comprenant les éléments suivants : la pathophysiologie de la MA et des APP, le rôle croissant des biomarqueurs dans la prise de décision clinique dans les maladies neurodégénératives, les études pionnières du discours en neurodégénérescence, ainsi que de récentes études computationnelles sur les marqueurs de discours dans la MA et les APP. Nos résultats font émerger un patron multidimensionnel (acoustique, lexical, syntaxique, sémantique et pragmatique) de changements langagiers qui distinguent les personnes avec une MA de témoins en santé, avec une prépondérance des marqueurs lexicosémantiques. Dans le groupe de patients avec une APP avec une imagerie amyloïde positive ou négative, nous mesurons ensuite le pouvoir de classification d’un court échantillon de discours et montrons qu’il peut être avantageusement comparé à d’autres biomarqueurs. Nous discutons du patron spécifique de marqueurs discriminants pour ce sous-groupe de patients, notamment l’importance des marqueurs psycholinguistiques pour prédire le résultat de l’imagerie amyloïde à partir du discours.Alzheimer’s disease (AD) and primary progressive aphasias (PPA) feature changes in expressive language that appear early in the course of the disease. Within an automated analysis framework, these language changes could offer a non-invasive and inexpensive alternative to the collection of biomarkers which are not readily available in most settings. Current research is thus focused on the automated analysis of language data for clinical use. The usefulness of connected speech (CS) markers has not yet been established in a diagnostic perspective focused on biomarkers. To this aim, the present thesis contains two phases. First, we systematically review the CS markers that best differentiate persons with AD from healthy controls. Second, we automatically extract a wide array of CS markers in a heterogenous group of PPA patients by combining expert knowledge and the latest natural language processing software. A machine-learning classification approach identifies PPA patients for the presence of underlying AD pathology. The most discriminant CS features are identified. To integrate the two phases of the thesis, we provide a general introduction with the following sections: the pathophysiology of AD and PPAs, the growing importance of biomarkers in clinical decision-making for neurodegenerative diseases, the seminal studies of CS in neurodegenerative diseases, and the latest computational studies of CS markers in AD and PPA. Our results bring forth a multidimensional pattern (acoustic, lexical, syntactic, semantic, pragmatic) of language changes that distinguish people with AD from healthy controls, with an emphasis on lexical-semantic features. In the group of PPA patients with either positive or negative amyloid imaging, we then describe the classificatory power of a short sample of CS and show that it compares favorably to other biomarkers. We discuss the specific pattern of discriminant markers for this subgroup of patients, in particular the role of psycholinguistics

The Linguistic and Cultural Aspects of Neuropsychological Assessment in People with Dementia

Objectives: Given the public health crisis that Alzheimer's disease (AD) has become (Naylor et al., 2012),neuropsychological assessment tools that provide timely and accurate identification of cognitive decline in older adults have gained increasing focus in the scientific literature. Accurate evaluation of cognitive function and early identification of cognitive changes are paramount to understanding the disease course of AD and improving effective treatments and patients' quality of life. To this end, language offers a cognitive neuropsychological approach to identifying cognitive decline in the early stages of AD. Moreover, it represents a multi-dimensional variable that may influence the neuropsychological test performance of older adults due to its potential contribution to cognitive reserve. Therefore, the present thesis aims at combining two aspects of language to explore its potential in the early detection of AD and its association with neuropsychological test performance in older adults and cross-cultural neuropsychology. Study 1 assessed the currently available studies to explore whether discourse processing, particularly macro-structural discourse comprehension, offers a novel approach to neuropsychological testing in distinguishing normal cognitive aging from AD pathology-related decline. Study 2 evaluated the results of the studies that examined the impact of bilingualism on neuropsychological test performance in monolingual and bilingual older adults to inform the neuropsychological evaluation of these groups in clinical practice. Study 3 investigated the influence of bilingualism and its associated factors, namely, cultural background and acculturation, on cognitive screening tests in three clinically diagnosed AD patient groups to identify a cross-culturally/linguistically appropriate measure of cognition. Method: Data of Study 1 and Study 2 were based on the original research studies published in English investigating discourse comprehension and bilingualism in healthy older adults, individuals with mild cognitive impairment (MCI), and AD. A literature search focusing on these topics with participant groups aged 60 years and over was conducted in PubMed, Web of Science, and PsycINFO databases. Study 1 included eight articles consisting of studies only with cross sectional designs. Study 2 was comprised of twenty-seven articles, of which sixteen articles had cross-sectional designs. On the other hand, Study 3 was original research based on a cross sectional design targeting culturally/linguistically diverse patients diagnosed with AD. Specifically, the study sample consisted of Turkish immigrant (n=21) and monolingual, non-immigrant German (n=20) and Turkish (n=24) patients with AD. All participants were administered the Mini-Mental State Examination (MMSE), Rowland Universal Dementia Assessment Scale (RUDAS), a dementia severity rating scale, and a self-report measure of depression. Additionally, self-report measures of bilingualism and acculturation were conducted with Turkish-immigrant participants with AD. Results: Study 1 revealed that people with AD and MCI have significant deficits in discourse comprehension, which are not observed in cognitively normal older adults of any age. On five of six discourse comprehension measures, groups with AD were significantly worse than healthy older adults, with one measure yielding mixed findings. Furthermore, compared to the cognitively healthy groups, individuals with MCI showed significant performance deficits in discourse comprehension measures similar to those with AD. Study 2 indicated better performance for bilingual older adults on executive function tests when compared to their monolingual counterparts. On the other hand, bilinguals were found to perform poorer than monolinguals on tests assessing the language domain. However, these findings did not remain robust when the impact of bilingualism on test performance was investigated longitudinally. Lastly, Study 3 provided further evidence on the linguistic and educational bias of the MMSE when employed in culturally and linguistically diverse individuals with AD. Bilingualism was linked to better performance on the MMSE in the Turkish immigrant group. German patients with AD obtained higher scores on this test than the other two groups. Furthermore, RUDAS was shown to be a better alternative for assessing global cognition in German and Turkish individuals with AD. Conclusion: The macro-structural discourse comprehension assessment paradigm has shown promising results in identifying the preclinical stages of AD. Further research on this paradigm may help develop a diagnostic tool with a clinical value that can be utilized for differential diagnosis, predicting conversion from MCI to dementia in research and clinical settings. On the other hand, another aspect of linguistic skills, namely, the evaluation of research on the link between bilingualism and neuropsychological test performance, did not provide definitive answers to the question of bilingual advantages and disadvantages addressed in the second study due to methodological challenges in the field. However, it identified a comprehensive and critical list of clinically and empirically relevant bilingualism-associated variables which may guide future research and neuropsychological practice. In light of the Study 2 findings, Study 3 filled an important gap in the literature by exploring cultural, demographic, and immigration related factors that may influence neuropsychological testing experiences in Germany. The study findings may help the field of cross-cultural neuropsychology serve culturally and linguistically diverse populations more efficiently. Overall, the present thesis contributed to the literature by highlighting the importance and potential of linguistic abilities in the clinical diagnosis and neuropsychological evaluation of individuals with dementia

AI and Non AI Assessments for Dementia

Current progress in the artificial intelligence domain has led to the development of various types of AI-powered dementia assessments, which can be employed to identify patients at the early stage of dementia. It can revolutionize the dementia care settings. It is essential that the medical community be aware of various AI assessments and choose them considering their degrees of validity, efficiency, practicality, reliability, and accuracy concerning the early identification of patients with dementia (PwD). On the other hand, AI developers should be informed about various non-AI assessments as well as recently developed AI assessments. Thus, this paper, which can be readable by both clinicians and AI engineers, fills the gap in the literature in explaining the existing solutions for the recognition of dementia to clinicians, as well as the techniques used and the most widespread dementia datasets to AI engineers. It follows a review of papers on AI and non-AI assessments for dementia to provide valuable information about various dementia assessments for both the AI and medical communities. The discussion and conclusion highlight the most prominent research directions and the maturity of existing solutions.Comment: 49 page

Computer-based characterization of language alterations throughout the Alzheimer's disease continuum

According to the American and Canadian Alzheimer’s Associations, research into methods for the early detection of Alzheimer’s disease is imperative. Many studies have emphasized the numerous advantages for patients, family members and governments of detecting the disease at the pre-clinical stage of its continuum. However, at this stage, changes are very subtle, making their detection a challenging task. Alterations in language functions have been found years before the dementia stage of the disease continuum. For this reason, many researchers have focused their efforts on investigating methods for identifying cues of the presence of the disease hidden in language. One type of cognitive test commonly used in this type of research consists of standardized picture description tasks. These tasks elicit the speech of patients through a visual stimulus, and are usually part of cognitive assessment batteries used in clinical practice. The tasks have the advantage of presenting patients with a single constrained thematic, which limits the vocabulary and facilitates comparisons across patients and languages. However, they also limit the variety of syntactic structures, hindering some linguistic analyses, and being a part of usual clinical examinations, may increase nervousness in some patients. The study of spontaneous conversations is an alternative to using picture description tasks for language analyses. Spontaneous conversations have the advantage of allowing the use of unconstrained idiosyncratic syntactic structures and vocabulary. They are also less stressful to patients and could be conducted with a nurse, a caregiver or a person familiar to the patient. Nevertheless, many factors, such as socio-demographic and cultural differences, may define the linguistic characteristics of individuals. Consequently, a characterization of the changes in language functions that occur during the continuum of the disease could be helpful in the monitoring of patient-specific changes. This doctoral thesis presents a computer-based methodology for evaluating patients’ performance during standardized picture description tasks, and for assessing language functions in the context of these tasks and in spontaneous conversations. We believe that both evaluations can complement each other and provide an inexpensive and noninvasive method for monitoring language functions. In practice, picture description tasks could be realized routinely at the doctor’s office, while spontaneous conversations could be held at more regular intervals and at more convenient locations for the patient. For our work, we compared the computed performance and language functions of patients during standardized picture description tasks against a population with similar socio-demographic characteristics. For this, our proposed method evaluated the informativeness and pertinence of the descriptions of patients, as well as their lexical richness. Using our metrics, we trained machine learning algorithms to estimate their adeptness at differentiating Alzheimer’s patients from healthy controls. We obtained an area under the curve of 0.83 in this task. We also achieved an area under the curve of 0.79 for classifying healthy controls and patients with mild cognitive impairment, which is often a pre-clinal precursor of Alzheimer’s disease. In addition, we proposed an automated method for evaluating lexical richness, vocabulary distribution, speech fluidity and the use of specific syntactic structures among older French speakers during spontaneous conversations. We characterized the changes that four speakers underwent as they transitioned from a healthy state to some form of cognitive disease, including Alzheimer’s disease. We observed marked differences in our proposed metrics between those individuals that would develop a cognitive disease and healthy matched controls, even when analyzing transcriptions of conversations from up to ten years before the time of diagnosis. As a concomitant contribution of this doctoral work, we designed the protocol and created the Spanish cohort of the Carolinas’ Conversations Collection. This cohort includes longitudinal video-recordings and transcriptions of spontaneous conversations of older Spanish speakers in Mexico and Ecuador. These recollections are the result of the combined efforts of six institutions from four different countries, and will be available for research purposes upon request. This undertaking is aimed at lessening the scarcity of data of this type, and at encouraging research on language and communication in the older population

Knowledge, attitudes, and stigma relating to rarer dementias among members of the general public in an international cohort

Part one presents a conceptual introduction reviewing the literature on dementia related knowledge, attitudes, and stigma among the general public, and discusses the implications for the less common forms of dementia. This thesis is a study within the studies of the Rare Dementia Support (RDS) Impact study: a 5-year programme of research exploring the impact of multicomponent support groups for those living with rare dementias. It is a collaboration between University College London (UCL), Bangor University and Nipissing University in Canada (http://www.raredementiasupport.org/research/) and is joint funded by the Economic & Social Research Council (ESRC) and National Institute for Health Research (NIHR) and ethical approval for the study was granted by UCL Ethics Committee (Reference: Project ID: 8545/004). The presented thesis is my own work, supervised by Dr. Joshua Scott Yes. I was involved in the design of the study, completed the data collection and analysis independently with exception for the following contributors: • Emilie Brotherhood involved in the ethical approval amendment and applications for this thesis. • Joanna Stroud (Head of Online Learning at UCL) who set the study’ surveys up on Future Learn the open education platform which houses The Many Faces of Dementia Massive Open Online Course. Joanna also linked the Surveys to Qualtrics

Do informal caregivers of people with dementia mirror the cognitive deficits of their demented patients?:A pilot study

Recent research suggests that informal caregivers of people with dementia (ICs) experience more cognitive deficits than noncaregivers. The reason for this is not yet clear. Objective: to test the hypothesis that ICs ‘mirror' the cognitive deficits of the demented people they care for. Participants and methods: 105 adult ICs were asked to complete three neuropsychological tests: letter fluency, category fluency, and the logical memory test from the WMS-III. The ICs were grouped according to the diagnosis of their demented patients. One-sample ttests were conducted to investigate if the standardized mean scores (t-scores) of the ICs were different from normative data. A Bonferroni correction was used to correct for multiple comparisons. Results: 82 ICs cared for people with Alzheimer's dementia and 23 ICs cared for people with vascular dementia. Mean letter fluency score of the ICs of people with Alzheimer's dementia was significantly lower than the normative mean letter fluency score, p = .002. The other tests yielded no significant results. Conclusion: our data shows that ICs of Alzheimer patients have cognitive deficits on the letter fluency test. This test primarily measures executive functioning and it has been found to be sensitive to mild cognitive impairment in recent research. Our data tentatively suggests that ICs who care for Alzheimer patients also show signs of cognitive impairment but that it is too early to tell if this is cause for concern or not