Clinical implications of cerebral age-related white matter cerebral changes

Tese de doutoramento, Medicina (Neurologia), Universidade de Lisboa, Faculdade de Medicina, 2013Cerebral age-related white matter changes (WMC) designate the changes of the radiological appearance of cerebral white matter, detected either in CT scan or in MRI, of probable vascular aetiology, that are frequently described in elderly people (1,2,3). The clinical significance of those changes has gained attention in the last three decades and remains a controversial issue. Some demographic and vascular risk factors are associated with higher risk of developing more severe WMC, and among these, mainly aging, hypertension and stroke (2, 3, 4). WMC are more frequent in demented patients (5). White matter changes have been implicated in cognitive decline, gait disturbances, urinary dysfunction, personality changes and depression (6), however contradictory results inhibit the consensus in this topic (7). Several questions remained unanswered when we started our study, namely concerning long term cognitive implications of WMC in subjects living in full autonomy. Furthermore, no convincing data was available regarding information on the risk of evolution for any type of dementia taking into account the global spectrum of risk factors. The objectives of this thesis were 1. to study the influence of WMC and vascular risk factors on the neuropsychological performance and on the progression for dementia of non-disabled independent elderly people with WMC; 2. to study the implications of self-perceived memory complaints; 3. to study the meaning of late onset depressive symptoms; and, 4. to clarify if regular physical activity reduces the risk of dementia in elderly subjects with WMC. Our study was conducted within a large European multicentre collaboration (the LADIS study: 11 European centres: Amsterdam, Copenhagen, Florence – coordinator centre-, Graz, Göteborg, Lisbon, Helsinki, Huddinge, Mannheim, Newcastle-upon-Tyne and Paris), that was designed to assess the role of WMC as an independent predictor of the transition from an autonomous functional status to disability in elderly subjects and the role of WMC progression in this transition (8). The Lisbon center took responsibility of all cognitive evaluation and definition of criteria and monitorization of cognitive diagnosis. Inclusion criteria for the study were: (i) 65–84 years of age; (ii) changes in WMC on MRI of any degree, according to the scale of Fazekas (9); and (iii) no disability, as determined by the Instrumental Activities of Daily Living scale (IADL) (10). Patients were referred for the study with minor complaints, incidental findings on cranial imaging caused by non-specific events without impact on daily living activities or were otherwise volunteers (8). Subjects were evaluated at baseline and yearly during 3 years with a comprehensive protocol including registry of demographic and vascular risk factors, co-morbidities, evaluation of depression, quality of life and a neuropsychological battery. Clinical evaluation included the classification of cognitive impairment according to usual clinical criteria (11). MRI was performed at baseline and at 3-year follow-up. The inclusion of subjects started in July 2001, 639 patients were enrolled (mean age 74.1 years-old, SD 5.0, 55% women, 9.6 years of educational level, SD 3.8). From the initial sample, 89% (568), 78.4% (501), and 75% (480) of the patients were followed up in a clinical visit at months 12, 24 and 36. After a median follow-up period of 2.9 years, information on the transition from full autonomy into disability was available for 633 (99%) patients. Forty-three subjects died (6.7% of study sample) until the third year of follow-up. Fifty-one patients missed the complete cognitive evaluation in any of the follow-up clinical visits. For those 51 patients no cognitive diagnosis was attributed, although vital status and IADL were known in those patients. Considering the cognitive diagnosis performed in the last clinical visit, dementia was diagnosed in 90 patients (Vascular dementia, 54; Alzheimer disease, 22; Alzheimer disease with vascular component, 12; Frontotemporal dementia, 2), and 147 patients had cognitive impairment not dementia (Vascular cognitive impairment non dementia - CIND, 86; mild cognitive impairment - MCI, 61). Our study showed that: 1. The severity of WMC is related with worse performance on global measures of cognition, executive functions, speed/motor control, and tests of attention, naming and visuoconstructional praxis in elderly subjects living independently. The impact of WMC on neuropsychological performance was present even when controlling for demographic variables (age and education), vascular risk factors and temporal lobe atrophy. 2. WMC severity is a predictor of cognitive impairment (dementia and not dementia) in elderly subjects with WMC, overtime. WMC and stroke predicted vascular dementia but not Alzheimer’s dementia, while medial temporal atrophy predicted both Alzheimer’s dementia and vascular dementia. Vascular risk factors (diabetes, hypertension and previous stroke) emerged as relevant factors with influence on neuropsychological tests in older people living with full autonomy, independently of WMC severity. After 3 years, diabetes at baseline was the only vascular risk factor that predicted cognitive impairment of any type (dementia and not dementia). 3. Memory complaints are a strong predictor of Alzheimer’s disease and Alzheimer’s disease with vascular component during the follow-up, independently of depressive symptoms and global cognition status at baseline in older subjects with WMC. To the best of our knowledge this is the first study that approaches implications of memory complaints in independent elderlies with white matter changes. Prediction Our study has some limitations, mainly related with a sample selection that was not drawn from the community. Participants were selected in outpatient clinics due to the presence of white matter changes. Patients could have minor complaints or could otherwise be volunteers. So we must be cautious in the generalization of our results. The other main limitation is associated with technological evolution, as the study was designed 10 years ago. However, this study was conducted in the a large heterogeneous population, rigorously assessed with a systematic and comprehensive evaluation, and this sample probably represents the first moment when non-disabled elderly subjects with cerebral white matter changes seek medical attention, and this fact is meaningful for clinical practice. Moreover, despite some missing information in the cognitive evaluation overtime, 99% of the initial sample had information on follow-up data, and follow-up was long enough to have conversion for cognitive impairment and dementia. Moreover, a substantial part of the initial sample was able to repeat MRI.After our work, we think that there is sufficient evidence to sustain that WMC are not an innocuous finding associated with ageing. In clinical practice, we deal frequently with elderly subjects that require an appointment due to the detection of cerebral white matter changes. Our data support the fact that WMC are implicated in the evolution for disability and for cognitive impairment. Furthermore, we identified several risk factors that are implicated in the progression for cognitive impairment, such as diabetes and stroke that appear as potential factors for intervention when preventing dementia. Our results emphasize the key role of both vascular risk factor control and physical activity in reducing the risk of cognitive impairment with ageing. Unfortunately, insufficient information exists concerning the recommendations for the control of the risk factors identified in the elderly in order to prevent dementia. Similarly, there is no recommendation regarding type and intensity of physical activity, influence of other leisure activities and type of intervention in subjects with depressive symptoms in order to be effective when preventing cognitive impairment in subjects with WMC. On the other hand there are still no known drugs specifically designed (or being currently in development) for the prevention of cognitive impairment in small vessel disease, other than those that aim to treat vascular risk factors. One of the clear areas of increasing interest is the impact of diet, risk factors control and physical and leisure activities on cognitive functioning in subjects with white matter changes. These relationships have to be determined by means of interventional studies that should be controlled by imagiological vascular biomarkers. These biomarkers must include sensitive tools for the measure of cerebral WMC as a hallmark of small vessel disease, including novel MRI sequences (diffusion, perfusion and spectroscopy) that allow the visualization of tissue changes in areas of white matter that appear normal using conventional MRI. Additionally, other biomarkers must be taken into account, namely other manifestations of small vessel disease (such as mibrobleeds and lacunes) and atrophy (either regional, including medial temporal lobe atrophy, or global) as potential confounders. Numbers of included subjects must be large enough to allow the control of multiple concomitant factors that can confound the interpretation of results and interfere with the statistical power. Clearly such a study can only be possible in a multicentric setting. Although designing a clinical trial is always limited to the knowledge available at a given time, we are convinced that: 1. any project aiming to study factors that influence cognitive changes in elderly should be controlled for white matter changes; 2. most available sensitive methods for detecting WMC should be used; 3. WMC severity is a potential end-point in cognitive trials.As alterações da substância branca cerebral associadas à idade (ASBC) designam as alterações radiológicas da substância branca cerebral detectadas quer por tomografia axial computadorizada como por ressonância magnética, de etiologia vascular provável, que são frequentemente descritos nas pessoas idosas (1,2,3). O significado clínico destas alterações tem sido objecto de investigação nas últimas três décadas e continua um assunto controverso. Alguns factores demográficos e factores de risco vascular associam-se a maior risco de ASBC mais severas, e entre aqueles, sobretudo a idade, a hipertensão e o acidente vascular cerebral (2, 3, 4). As ASBC são mais frequentes em doentes com demência (5). As ASBC têm sido implicadas no declínio cognitivo, em alterações da marcha, na disfunção urinária e em alterações da personalidade e depressão (6), no entanto, os resultados contraditórios dos diversos estudos têm impedido um consenso neste campo (7). Várias questões permaneciam em aberto quando iniciámos o estudo, especialmente a questão de saber se as ASBC poderiam implicar deterioração cognitiva a longo termo, em indivíduos completamente independentes com algum grau de ASBC. Adicionalmente, não existia nenhum dado que evidenciasse algum risco de evolução para algum sub-tipo de demência, tendo em consideração o espectro global dos factores de risco concomitantes. Os objectivos deste trabalho foram 1) investigar a influência das ASBC e dos factores de risco vasculares no desempenho neuropsicológico e na progressão para demência em indivíduos idosos com alterações das ASBC, independentes nas actividades de vida diária; 2) investigar as implicações das queixas de memória nos mesmo indivíduos; 3) investigar o significado dos sintomas depressivos de início tardio; e, 4) esclarecer se a actividade física regular reduz o risco de demência em indivíduos idosos com ASBC. Este trabalho foi levado a cabo integrado num estudo cooperativo multicêntrico Europeu (o estudo LADIS: 11 centros europeus: Amsterdão, Copenhaga, Florença –centro coordenador-, Graz, Gotemburgo, Lisboa, Helsínquia, Huddinge, Mannheim, Newcastle-upon-Tyne e Paris), que foi desenhado para avaliar o papel das ASBC como factor preditor independente da transição de um estado de completa autonomia funcional para incapacidade no idoso, e ainda o papel da progressão das ASBC nesta transição (8). O centro de Lisboa teve a responsabilidade de definir a avaliação cognitiva, os critérios cognitivos e ainda a monitorização dos diagnósticos cognitivos ao longo do estudo. Os critérios de inclusão do estudo foram: (i) 65–84 anos; (ii) ASCB de qualquer gravidade (de acordo com a escala de Fazekas) detectadas na ressonância magnética (RMN) crânio-encefálica (CE) (9); e (iii) sem alteração da autonomia, determinada pela Escala de Actividades Instrumentais de Vida Diária (IADL) (10). Os doentes foram referenciados para o estudo por terem ASBC em tomografia axial computadorizada (TAC) ou RMN CE (8). Os participantes foram avaliados na inclusão e depois anualmente durante 3 anos, com um protocolo extenso que incluiu o registo das variáveis demográficas, dos factores de risco vasculares, da patologia concomitante, avaliação da depressão, da qualidade de vida, avaliação neurológica e médica e avaliação neuropsicológica. A avaliação clínica incluiu a classificação de defeito cognitivo de acordo com os critérios clínicos usuais (11). A RMN foi efectuada na inclusão e repetida após os 3 anos de seguimento. A inclusão dos participantes iniciou-se em Julho 2001, tendo sido incluídos 639 indivíduos (idade média 74.1 anos, SD 5.0, 55% género feminino, 9.6 anos de nível de escolaridade, SD 3.8). Da amostra inicial, 89% (568), 78.4% (501), e 75% (480) dos participantes foram seguidos nas visitas clínicas de mês 12, 24 e 36, respectivamente. Após um período de seguimento médio de 2.9 anos, obteve-se informação da transição de completa autonomia para incapacidade em 633 (99%) participantes. Quarenta e três participantes morreram (6.7% da amostra inicial) até ao 3º de seguimento. Cinquenta e um participantes faltaram a todas as visitas clínicas de seguimento. Para estes cinquenta e um participantes não foi possível atribuir um diagnóstico de estado cognitivo no seguimento, apesar de ser conhecido o estado vital e funcional. Considerando os diagnóstico cognitivos efectuados na última visita clínica, foi feito diagnóstico de demência em 90 participantes (Demência vascular, 54; doença de Alzheimer, 22; doença de Alzheimer com componente vascular, 12; Demência fronto-temporal, 2), e foi efectuado diagnóstico de defeito cognitivo não demência em 147 participantes (Defeito cognitivo vascular sem critérios de demência - CIND, 86; Defeito cognitivo ligeiro - MCI, 61). O nosso estudo mostrou que: 1. A gravidade das ASBC se relaciona com pior desempenho nas medidas globais de cognição, nas funções executivas, na velocidade e controlo motor e em testes de atenção, nomeação, e capacidades visuo-construtivas em indivíduos idosos que vivem de forma independente. O impacto das ASBC no desempenho neuropsicológico manteve-se mesmo quando se controlou a análise para variáveis demográficas (idade e educação), factores de risco vascular e atrofia do lobo temporal. 2. A gravidade das ASBC é preditora de defeito cognitivo (demência e não demência) em indivíduos idosos com ASBC, ao longo do tempo. As ASBC e ter tido acidente vascular cerebral são preditores de demência vascular mas não de doença de Alzheimer, enquanto que a atrofia do lobo temporal é preditor de doença de Alzheimer e de demência vascular. Os factores de risco vascular (diabetes, hipertensão e acidente vascular cerebral prévio) surgiram como factores relevantes com influência no desempenho neuropsicológico em indivíduos idosos que vivem autonomamente, independentemente da gravidade das ASBC. Após 3 anos, a diabetes na inclusão foi o único factor que foi preditor de defeito cognitivo de qualquer tipo (demência e não demência).3. As queixas de memória de indivíduos idosos com ASBC são preditoras de doença de Alzheimer com e sem componente vascular ao longo do tempo, independentemente da presença de sintomas depressivos e do estado global cognitivo na inclusão. A elevada frequência de participantes com queixas de memória que desenvolveram doença de Alzheimer ao longo do seguimento reforçou a importância das queixas de memória nos idosos, mesmo que tenham evidência de doença de pequenos vasos cerebral. 4. Os sintomas depressivos estão associados a pior desempenho cognitivo (em medidas de avaliação cognitivas globais, funções executivas e velocidade) na inclusão e são preditores de posterior declínio cognitivo ao longo do seguimento. Estes resultados estão de acordo com a hipótese da “depressão vascular” para os sintomas depressivos de início tardio. Os sintomas depressivos poderiam ser a expressão de lesão vascular e não o resultado de uma patologia do humor. É ainda possível que os sintomas depressivos e as ASBC tenham um efeito aditivo ou sinergístico para o desenvolvimento de demência ao longo do tempo. 5. A actividade física reduz o risco de progressão para defeito cognitivo, especialmente demência vascular, mas não para doença de Alzheimer, em indivíduos idosos com ASBC. Uma das explicações possíveis para esta redução de risco pode ser o controlo dos factores de risco vascular, uma vez que a actividade física se associa a um estilo de vida mais saudável. Os nossos resultados apoiam a perspectiva de que os sujeitos idosos com factores de risco vascular e evidência de ASBC beneficiam de actividade física regular. O estudo tem algumas limitações, nomeadamente relacionadas com a selecção da amostra, que não foi retirada da comunidade. Os participantes foram seleccionados de consultas externas por terem ASBC de qualquer gravidade. A outra limitação prende-se com a evolução tecnológica, pois o estudo foi desenhado há 10 anos. No entanto, este estudo foi realizado numa amostra heterogénea de dimensão considerável, com uma abordagem rigorosa, sistemática e muito completa. Acresce ainda que apesar de alguma perda de informação na avaliação cognitiva ao longo do tempo, 99% da amostra inicial teve informação quanto ao estado vital e funcional no fim dos três anos de seguimento. Adicionalmente o seguimento foi suficiente para permitir conversão para defeito cognitivo incluindo demência, e um número considerável de participantes fez RMN de seguimento. Após este trabalho pensamos existir evidência suficiente para afirmar que as ASBC não são um achado inócuo associado à idade. Os nossos resultados indicam que as ASBC severas estão implicadas na transição para defeito cognitivo. Identificámos ainda vários factores de risco implicados na progressão para defeito cognitivo, como a diabetes e o AVC, que surgem como factores de potencial intervenção para prevenir demência. Os nossos resultados salientam ainda o papel do controlo de factores de risco vasculares como da actividade física na redução do risco cognitivo associado à idade. Infelizmente ainda não há dados que sustentem recomendações específicas quanto ao tipo de controlo dos factores de risco vascular e tipo de actividade física como preventiva do desenvolvimento de demência. Esta é uma área de claro interesse da investigação futura. Tais recomendações têm que partir de estudos intervencionais que controlem os marcadores imagiológicos vasculares. Estes devem incluir técnicas que permitam não só avaliar áreas de ASBC nas sequências convencionais como sequências que permitam maior sensibilidade de detecção de ASBC, quando os exames convencionais são aparentemente normais. Devem ainda incluir técnicas destinadas a avaliar outras alterações de pequenos vasos cerebrais, como micro-hemorragias e ser controlados para os potenciais factores confundentes (como a atrofia cerebral). Para este objectivo os estudos têm que ter dimensão suficiente, o que só nos parece possível numa base multicêntrica. Por último, as ASBC surgem como um potencial objectivo primário para estudos de intervenção na área dos ensaios cognitivos.The LADIS Study was partially supported by the European Union within the Vth European Framework Program ‘Quality of life and management of living resources’, between 1998 and 2002, contract No. QLRT-2000-0044

Lifestyle and Genetic Contributions to Cognitive Decline and Hippocampal Structure and Function in Healthy Aging

Background: Engagement in cognitively stimulating activities (CA) and leisure time physical activity (PA) have been associated with maintaining cognitive performance and reducing the likelihood of cognitive decline in older adults. However, neural mechanisms underlying protective effects of these lifestyle behaviors are largely unknown. In the current study, we investigated the effect of self-reported PA and CA on hippocampal volume and semantic processing activation during a fame discrimination task, as measured by functional magnetic resonance imaging (fMRI). We also examined whether possession of the apolipoprotein E (APOE) ?4 allele could moderate the effect of PA or CA on hippocampal structure or function. Methods: Seventy-eight healthy, cognitively intact older adults underwent baseline neuropsychological assessment, hippocampal volume measurement via manually-traced structural MRI, and task-activated fMRI. Results: After 18 months, 27 participants declined by one standard deviation or more on follow-up neuropsychological testing. Logistic regression analyses revealed that CA alone or in combination with baseline hippocampal structure or functional activity did not predict the probability of cognitive decline. In contrast, PA interacted with APOE 4 status such that engagement in PA reduced the risk of cognitive decline in APOE 4 carriers only. Furthermore, the benefits of PA appeared to diminish with reduced functional activity or volume in the hippocampus. Conclusions: Our findings suggest that increased leisure time PA is associated with reduced probability of cognitive decline in persons who are at high risk for AD. The beneficial effects of PA in this group may be related to enhancement of the functional and structural integrity of the hippocampus

TOWARDS EVIDENCE-BASED AND DATA-DRIVEN RECOMMENDATIONS PROMOTING INDEPENDENCE IN LATER LIFE: GAIT SPEED, FALLS, AND ACTIVITIES OF DAILY LIVING IN OLDER ADULTS

Background: Falls in older adults are a significant public health challenge. Fall prevention as well as intervention after a fall both are critical to reduce the negative consequences and improve quality of life in older age. Purpose: 1) Quantify the association between gait speed and fall risk in a cross-sectional analysis for older adults with and without cognitive impairment. 2) Determine if there is an association between change in gait speed and fall risk in a longitudinal analysis including older adults with and without cognitive impairment. 3) Quantify the association between falls and difficulty with activities of daily living (ADLs) and instrumental activities of daily living (IADLs) and determine the trajectory of difficulty with ADLs/IADLs pre- and post-fall for older. Methods: The study population for this research was the Ginkgo Evaluation of Memory Study, a randomized controlled trial, conducted from 2000-2008, including 3069 older adults from four locations in the United States. The longitudinal study design, number of measures, and rigorous ascertainment of MCI and dementia provided an excellent data set for this research, which included a cross-sectional analysis of gait speed and falls, a longitudinal analysis of change in gait speed and falls, and falls and difficulty with ADLs/IADLs using Cox proportional hazards models, and latent class trajectory modeling to determine trajectories of difficulty with ADLs/IADLs pre- and post- fall. Results: 1) The results of this study provide evidence of a significant association between faster gait speed and lower fall risk for older adults. 2) A decrease in gait speed of more than 0.15 m/s (mean speed 0.93 m/s) over 12 months is associated with increased risk of falls for older. 3) Falls are associated with an increased risk of difficulty with ADLs/IADLs, which persists and worsens over time for some older adults. Conclusion: Gait speed and change in gait speed could be used as screening tools for fall risk in older adults with and without mild cognitive impairment. Understanding the characteristics of older adults more likely to have difficulty with ADLs and IADLs post-fall can be utilized to target interventions to decrease fall-related negative outcomes

Sowing in the autumn season : exploring benefits of green care farms for dementia patients

In the Netherlands an increasing number of farms combine agricultural production with care services for people with care needs. It is generally believed that these green care farms (GCFs) have beneficial effects on the health status of a diversity of target groups. At present, empirical studies testing this hypothesis are scarce. The main objective of the studies described in this thesis was to gain insight into the potential benefits of day care at GCFs for community‐dwelling older dementia patients. Day care at GCFs was therefore compared with day care at regular day care facilities (RDCFs). In view of the differences between both day care types regarding the day care setting and day care program it was hypothesized that they would differ in their effects on the health status of dementia patients. In two cross‐sectional studies it was tested to what extent the day program of dementia patients at GCFs differed from those at RDCFs. It appeared that at GCFs, dementia patients were (physically) more active, participated in more diverse activities, were more outdoors, and had more opportunities to perform activities in smaller groups than those at RDCFs. It was tested whether these differences resulted into different effects for five domains of health: dietary intake, cognition, emotional well‐being, behaviour, and functional performance. In a comparative cross‐sectional study dietary intake of dementia patients attending day care at GCFs or RDCFs was recorded both at home and during their time at the day care facility. The study showed that dementia patients attending day care at GCFs had significantly higher intakes of energy, carbohydrate, and fluid than their counterparts attending day care at RDCFs. In a cohort study, rates of change during 1 year in cognitive functioning, emotional well‐being, behavioural symptoms, and functional performance were compared between dementia patients attending day care at GCFs and RDCFs. Functioning in these domains remained rather stable and no differences were observed between subjects from GCFs and RDCFs. In the cohort study, also caregiver burden of family caregivers of these dementia patients was assessed. Caregivers’ quality of life, emotional distress, and feelings of competence remained rather stable in family caregivers of dementia patients from both day care settings. In conclusion, the present work has shown that GCFs exceeded RDCFs in offering older dementia patients a diverse day program and in stimulating their dietary intake. The latter may result into a better preserved nutritional status in dementia patients attending day care at GCFs than in those attending day care at RDCFs. GCFs and RDCFs were equally effective in preventing significant decrease of cognitive functioning, emotional well‐being, and functional performance and in preventing significant increase of the number of behavioural symptoms. Both day care types further prevented significant increase of caregiver burden. Day care at GCFs is a new and valuable addition to the present care modalities for community‐dwelling older dementia patients and their caregiver

Unexplained falls are frequent in patients with fall-related injury admitted to Orthopaedic wards: the UFO Study (Unexplained Falls in Older patients)

To evaluate the incidence of unexplained falls in elderly patients affected by fall-related fractures admitted to orthopaedic wards, we recruited 246 consecutive patients older than 65 (mean age 82 \ub1 7 years, range 65-101). Falls were defined "accidental" (fall explained by a definite accidental cause), "medical" (fall caused directly by a specific medical disease), "dementia-related" (fall in patients affected by moderate-severe dementia), and "unexplained" (nonaccidental falls, not related to a clear medical or drug-induced cause or with no apparent cause). According to the anamnestic features of the event, older patients had a lower tendency to remember the fall. Patients with accidental fall remember more often the event. Unexplained falls were frequent in both groups of age. Accidental falls were more frequent in younger patients, while dementia-related falls were more common in the older ones. Patients with unexplained falls showed a higher number of depressive symptoms. In a multivariate analysis a higher GDS and syncopal spells were independent predictors of unexplained falls. In conclusion, more than one third of all falls in patients hospitalized in orthopaedic wards were unexplained, particularly in patients with depressive symptoms and syncopal spells. The identification of fall causes must be evaluated in older patients with a fall-related injury

Mild cognitive impairment and dementia in a heterogeneous elderly population: prevalence and risk profile

OBJECTIVE: To describe the demographic, clinical and risk profile of Mild Cognitive Impairment and dementia in a sample of elderly South Africans within a residential setting. METHOD: One hundred and forty participants residing in a group of residential homes for the elderly were assessed by psychiatrists and assigned diagnoses of dementia or Mild Cognitive Impairment (MCI). Participants diagnosed with dementia were also offered haematological investigations and a CT scan of the brain. RESULTS: The sample consisted of 140 participants comprising 46.4% White, 29.3% Coloured, 20% Asian and 4.3% Black participants. There were 97 (69.3%) females and 106 (75.7%) participants had less than 12 years of education. Eleven (7.9%) dementia and 38 (27.1%) MCI cases were diagnosed. Increasing age was associated with cognitive impairment (MCI and dementia) (p=.020) but there was no association between gender and cognitive impairment (p=.165). MCI was significantly associated with a lower education level (p=.036) and no association was found between depression (current-p=.646; past-p=.719) and dementia or MCI. The presence of vascular risk factors (n=140) ranged from 66.4% (hypertension) to 14.3% (stroke). Subjective memory complaints were significantly associated with cognitive impairment (p=.001). Except for the use of the telephone (p=.225) and the television (p=.08), impairment in all domains of instrumental activities of daily living that were assessed were significantly associated with a dementia diagnosis. CONCLUSION: The study showed that cognitive impairment was associated with increasing age and low education levels. The presence of vascular risk factors places this population at risk for future cognitive decline.Web of Scienc

Application of Advanced Statistical Methods in an Aging Dataset

The focus of this thesis was to explore the application of advanced statistical methods in the Ginkgo Evaluation of Memory (GEM) Study. GEMS enrolled 3,069 participants age 75 or older with normal cognition or mild cognitive impairment. Those with dementia were excluded from participation. After extensive medical and neuropsychological screening, participants were randomly assigned to receive twice-daily doses of either 120 milligrams of ginkgo extract or an identical-appearing placebo. The 240 milligrams daily dose of ginkgo was selected based on current dosage recommendations and prior clinical studies indicating possible effectiveness at this dosage. The products used in the study were supplied by Schwabe Pharmaceuticals, a German company. We focused on two methods, a flexible Cox model (Gray’s model) and a trajectory procedure based on a mixture model that is implemented in the SAS procedure PROC TRAJ. The spline-based extension of the Cox model was applied to biomarker data; specifically: Cystatin-C, Beta Amyloid 40, Beta Amyloid 42, and a ratio of Beta Amyloid 42 over Beta Amyloid 40. We wanted to determine if the estimate of the log-hazard ratio changed over time for each of the biological measures. The trajectory analysis was used to determine if a patient’s illness trajectory continued on the same path towards demented or non-demented before experiencing a pneumonia event. The trajectory analysis was applied to the longitudinal trajectories of activities of daily living (ADL), independent activities of daily living (IADL) and modified mini-mental status exam (3MSE). The Cox Spline analysis resulted in no statistically significant information added to the models using the spline analysis. Trajectory analysis concluded that patients on a downward trajectory at baseline only escalated before the pneumonia event. As the average life expectancy continues in increase in humans, it is important to evaluate statistical methods in the elderly population to identify subpopulations that need more medical attention than the population at large. Thus, the public health significance of this thesis is that by identifying these subgroups that are distinctly different from the overall population, we can provide preventative care where needed more efficiently

Assessments for Mild Cognitive Impairment (MCI) and Functional Cognition: An Evidence-Based Practice Project

This Evidence-Based Practice (EBP) project addressed the following question: What occupational therapy and interdisciplinary assessments are currently used and have the best psychometric characteristics and are most effective for screening or evaluating functional cognition of individuals with mild cognitive impairment and measuring the outcomes of intervention programs for mild cognitive impairment

Risk of death or hospital admission among community-dwelling older adults living with dementia in Australia

Background: Older people living with dementia prefer to stay at home to receive support. But they are at high risk of death and/or hospital admissions. This study primarily aimed to determine risk factors for time to death or hospital admission (combined) in a sample of community-dwelling older people living with dementia in Australia. As a secondary study purpose, risk factors for time to death were also examined. Methods. This study used the data of a previous project which had been implemented during September 2007 and February 2009. The original project had recruited 354 eligible clients (aged 70 and over, and living with dementia) for Extended Aged Care At home Dementia program services during September 2007 and 2008. Client information and carer stress had been collected from their case managers through a baseline survey and three-monthly follow-up surveys (up to four in total). The principal data collection tools included Global Deterioration Scale, Modified Barthel Index, Instrumental-Dependency OARS, Adapted Cohen-Mansfield Agitation Inventory, as well as measures of clients' socio-demographic characteristics, service use and diseases diagnoses. The sample of our study included 284 clients with at least one follow-up survey. The outcome variable was death or hospital admission, and death during six, nine and 16-month study periods. Stepwise backwards multivariate Cox proportional hazards analysis was employed, and Kaplan-Meier survival analysis using censored data was displayed. Results: Having previous hospital admissions was a consistent risk factor for time to death or hospital admission (six-month: HR = 3.12; nine-month: HR = 2.80; 16-month: HR = 2.93) and for time to death (six-month: HR = 2.27; 16-month: HR = 2.12) over time. Previously worse cognitive status was a consistent risk factor over time (six- and nine-month: HR = 0.58; 16-month: HR = 0.65), but no previous use of community care was only a short-term risk factor (six-month: HR = 0.42) for time to death or hospital admission. Conclusions: Previous hospital admissions and previously worse cognitive status are target intervention areas for reducing dementia clients' risk of time to death or hospital admission, and/or death. Having previous use of community care as a short-term protective factor for dementia clients' time to death or hospital admission is noteworthy