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INTRODUCTION: Cerebral small vessel disease (SVD) and amyloid beta (Aß) pathology frequently co-exist. The impact of concurrent pathology on the pattern of hippocampal atrophy, a key substrate of memory impacted early and extensively in dementia, remains poorly understood. METHODS: In a unique cohort of mixed Alzheimer's disease and moderate-severe SVD, we examined whether total and regional neuroimaging measures of SVD, white matter hyperintensities (WMH), and Aß, as assessed by 18F-AV45 positron emission tomography, exert additive or synergistic effects on hippocampal volume and shape. RESULTS: Frontal WMH, occipital WMH, and Aß were independently associated with smaller hippocampal volume. Frontal WMH had a spatially distinct impact on hippocampal shape relative to Aß. In contrast, hippocampal shape alterations associated with occipital WMH spatially overlapped with Aß-vulnerable subregions. DISCUSSION: Hippocampal degeneration is differentially sensitive to SVD and Aß pathology. The pattern of hippocampal atrophy could serve as a disease-specific biomarker, and thus guide clinical diagnosis and individualized treatment strategies for mixed dementia.
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Doença de Alzheimer , Peptídeos beta-Amiloides , Doenças de Pequenos Vasos Cerebrais , Hipocampo , Tomografia por Emissão de Pósitrons , Humanos , Hipocampo/patologia , Hipocampo/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/patologia , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Masculino , Idoso , Feminino , Doença de Alzheimer/patologia , Doença de Alzheimer/diagnóstico por imagem , Peptídeos beta-Amiloides/metabolismo , Substância Branca/patologia , Substância Branca/diagnóstico por imagem , Atrofia/patologia , Imageamento por Ressonância Magnética , Idoso de 80 Anos ou mais , Neuroimagem , Estudos de CoortesRESUMO
INTRODUCTION: This study assesses experts' beliefs about important predictors of developing dementia in persons with mild cognitive impairment (MCI). METHODS: Structured expert elicitation, a methodology to quantify expert knowledge, was used to elicit the most important risk factors for developing dementia. We recruited 11 experts (6 neurologists, 3 geriatricians, and 2 psychiatrists). Ten experts fully participated in introductory meetings, two rounds of surveys, and discussion meetings. The data from these ten experts were utilized for this study. RESULTS: The expert elicitation identified age, CSF analysis, fluorodeoxyglucose-positron emission tomography (FDG-PET) findings, hippocampal atrophy, MoCA (or MMSE) score, parkinsonism, apathy, psychosis, informant report of cognitive symptoms, and global atrophy as the ten most important predictors of progressing to dementia in persons with MCI. DISCUSSION: Several dementia predictors are not routinely collected in existing registries, observational studies, or usual care. This might partially explain the low uptake of existing published dementia risk scores in clinical practice.
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Doença de Alzheimer , Disfunção Cognitiva , Humanos , Doença de Alzheimer/diagnóstico , Atrofia , Disfunção Cognitiva/diagnóstico , Progressão da Doença , Fluordesoxiglucose F18RESUMO
Increasingly, primary care collaborative memory clinics (PCCMCs) are being established to build capacity for person-centred dementia care. This paper reflects on the significance of PCCMCs within the system of care for older adults, supported with data from ongoing evaluation studies. Results highlight timelier access to assessment with a high proportion of patients being managed in primary care within a person-centred approach to care. Enhancing primary care capacity for dementia care with interprofessional and collaborative care will strengthen the system's ability to respond to increasing demands for service and mitigate the growth of wait times to access geriatric specialist assessment.
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Fortalecimento Institucional/métodos , Demência/terapia , Atenção Primária à Saúde/organização & administração , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Memória , Pessoa de Meia-Idade , Ontário , Inquéritos e QuestionáriosRESUMO
AIM: To determine whether 4 months of rivastigmine treatment would result in metabolic changes and whether metabolic changes correlate with changes in cognition in people with Alzheimer's disease (AD). METHODS: Magnetic resonance spectra were acquired from the posterior cingulate cortex of subjects with AD at 3 T. Magnetic resonance imaging scans and cognitive tests were performed before and 4 months after the beginning of the treatment. Metabolite concentrations were quantified and used to calculate the metabolite ratios. RESULTS: On average, the N-acetylaspartate/creatine (NAA/Cr) ratio decreased by 12.7% following 4 months of rivastigmine treatment, but changes in the NAA/Cr ratio correlated positively with changes in Mini-Mental State Examination scores. CONCLUSION: This positive correlation between changes in NAA/Cr and changes in cognitive performance suggests that the NAA/Cr ratio could be an objective indicator of a response to rivastigmine treatment.
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Doença de Alzheimer/tratamento farmacológico , Ácido Aspártico/análogos & derivados , Inibidores da Colinesterase/uso terapêutico , Transtornos Cognitivos/tratamento farmacológico , Creatina/metabolismo , Giro do Cíngulo/metabolismo , Fenilcarbamatos/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/metabolismo , Ácido Aspártico/metabolismo , Transtornos Cognitivos/metabolismo , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , RivastigminaRESUMO
Gait disorders are common in the course of dementia, even at the stage of mild cognitive impairment, owing to probable changes in higher levels of motor control. Since motor control message is ultimately supported in the brain by the primary motor cortex and since cortical lesions are frequent in the dementia process, we hypothesized that impairments of the primary motor cortex may explain the early gait disorders observed in mild cognitive impairment. Our purpose was to determine whether the neurochemistry of the primary motor cortex measured with proton magnetic resonance spectroscopy, and its volume, were associated with gait performance while single and dual-tasking in mild cognitive impairment. Twenty community dwellers with mild cognitive impairment, aged 76 years (11) [median (interquartile range)] (30% female) from the 'Gait and Brain Study' were included in this analysis. Gait velocity and stride time variability were measured while single (i.e. walking alone) and dual tasking (i.e. walking while counting backwards by seven) using an electronic walkway (GAITRite System). Ratios of N-acetyl aspartate to creatine and choline to creatine and cortical volume were calculated in the primary motor cortex. Participants were categorized according to median N-acetyl aspartate to creatine and choline to creatine ratios. Age, gender, body mass index, cognition, education level and subcortical vascular burden were used as potential confounders. Participants with low N-acetyl aspartate to creatine (n = 10) had higher (worse) stride time variability while dual tasking than those with high N-acetyl aspartate to creatine (P = 0.007). Those with high choline to creatine had slower (worse) gait velocity while single (P = 0.015) and dual tasking (P = 0.002). Low N-acetyl aspartate to creatine was associated with increased stride time variability while dual tasking (adjusted ß = 5.51, P = 0.031). High choline to creatine was associated with slower gait velocity while single (adjusted ß = -26.56, P = 0.009) and dual tasking (adjusted ß = -41.92, P = 0.022). Cortical volume correlated with faster gait velocity while single (P = 0.029) and dual tasking (P = 0.037), and with decreased stride time variability while single tasking (P = 0.034). Finally, the probability of exhibiting abnormal metabolite ratios in the primary motor cortex was 63% higher among participants with major gait disturbances in dual task. Those with compromised gait velocity in dual task had a 2.05-fold greater risk of having a smaller cortical volume. In conclusion, the neurochemistry and volume of the primary motor cortex were associated with gait performance while single and dual tasking. Stride time variability was mainly sensitive to neuronal function (N-acetyl aspartate to creatine), whereas gait velocity was more affected by inflammatory damage (choline to creatine) and volumetric changes. These findings may contribute to a better understanding of the higher risks of mobility decline and falls in subjects with mild cognitive impairment.
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Disfunção Cognitiva/metabolismo , Transtornos Neurológicos da Marcha/metabolismo , Marcha/fisiologia , Córtex Motor/metabolismo , Idoso , Disfunção Cognitiva/complicações , Disfunção Cognitiva/fisiopatologia , Feminino , Transtornos Neurológicos da Marcha/etiologia , Transtornos Neurológicos da Marcha/fisiopatologia , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Córtex Motor/patologia , Córtex Motor/fisiopatologiaRESUMO
BACKGROUND: The purpose of this study was to estimate differences in rates of functional decline in Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and vascular dementia (VaD) and whether differences vary by age or sex. METHODS: Data came from 32 U.S. Alzheimer's Disease Centers. The cohort of participants (n = 5848) were ≥60 years of age and had clinical dementia with a primary etiologic diagnosis of probable AD, DLB, or probable VaD; a Clinical Dementia Rating-Sum of Boxes score <16; and a duration of symptoms ≤10 years. Dementia diagnoses were assigned using standard criteria. Annual mean rate of change of the Functional Activities Questionnaire (FAQ) score was modeled using multiple linear regression with generalized estimating equations adjusted for demographics, comorbidities, years since onset, and cognitive status (mean follow-up = 2.0 years). RESULTS: FAQ declined more slowly over time in those with VaD compared with AD (difference in mean annual rate of change: -0.91; 95% confidence interval [CI]: -1.68, -0.14). VaD participants also declined at a slower rate than DLB participants, but this difference was not statistically significant (-0.61; 95% CI: -1.45, 0.24). There was no significant difference between DLB and AD. Within each group, rate of decline was more rapid for the youngest participants. CONCLUSIONS: In this sample, findings suggested that VaD patients declined in their functional abilities at a slower rate compared with AD patients and that there were no significant differences in rate of functional decline between patients with DLB compared with those with either AD or VaD. These results may provide guidance to clinicians about average expected rates of functional decline in three common dementia types.
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Transtornos Cognitivos/etiologia , Demência , Atividades Cotidianas , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/complicações , Doença de Alzheimer/psicologia , Estudos de Coortes , Demência/classificação , Demência/complicações , Demência/psicologia , Demência Vascular/complicações , Demência Vascular/psicologia , Progressão da Doença , Humanos , Doença por Corpos de Lewy/complicações , Doença por Corpos de Lewy/psicologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Fatores Sexuais , Inquéritos e Questionários , Estados UnidosRESUMO
Recruiting persons with dementia for clinical trials can be challenging. Building on a guide initially developed to assist primary-care-based memory clinics in their efforts to support research, a key stakeholder working group meeting was held to develop a standardized research recruitment process, with input from patients, care partners, researchers, and clinicians. Discussions in this half-day facilitated meeting focused on the wishes and needs of patients and care partners, policy and procedures for researchers, information provided to patients, and considerations for memory clinics. Patients and care partners valued the opportunity to contribute to science and provided important insights on how to best facilitate recruitment. Discussions regarding proposed processes and procedures for research recruitment highlighted the need for a new, patient-driven approach. Accordingly, a key stakeholder co-designed "Memory Clinic Research Match" program was developed that has the potential to overcome existing barriers and to increase recruitment for dementia-related research.
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OBJECTIVES: This study aims to develop and validate a Bayesian risk prediction model that combines research cohort data with elicited expert knowledge to predict dementia progression in people with mild cognitive impairment (MCI). STUDY DESIGN AND SETTING: This is a prognostic risk prediction modeling study based on cohort data (Alzheimer's disease neuroimaging initiative [ADNI]; n = 365) of research participants with MCI and elicited expert data. Bayesian Cox models were used to combine expert knowledge and ADNI data to predict dementia progression in people with MCI. Posterior distributions were obtained based on Gibbs sampler and the predictive performance was evaluated using ten-fold cross-validation via c-index, integrated calibration index (ICI), and integrated brier score (IBS). RESULTS: 365 people with MCI were included, mean age was 73 years (SD = 7.5), and 39% developed dementia within 3 years. When expert knowledge was incorporated, the c-index, ICI, and IBS values were 0.74 (95% CI 0.70-0.79), 0.06 (95% CI 0.05-0.08), and 0.17 (95% CI 0.14-0.19), respectively. These were similar to the model without expert knowledge data. CONCLUSION: The addition of expert knowledge did not improve model accuracy in this ADNI sample to predict dementia progression in individuals with MCI.
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Doença de Alzheimer , Disfunção Cognitiva , Idoso , Humanos , Doença de Alzheimer/diagnóstico , Teorema de Bayes , Disfunção Cognitiva/diagnóstico , Progressão da DoençaRESUMO
PURPOSE: To create a standardized, MRI-compatible, life-sized phantom of the brain ventricles to evaluate ventricle segmentation methods using T(1) -weighted MRI. An objective phantom is needed to test the many different segmentation programs currently used to measure ventricle volumes in patients with Alzheimer's disease. MATERIALS AND METHODS: A ventricle model was constructed from polycarbonate using a digital mesh of the ventricles created from the 3 Tesla (T) MRI of a subject with Alzheimer's disease. The ventricle was placed in a brain mold and surrounded with material composed of 2% agar in water, 0.01% NaCl and 0.0375 mM gadopentetate dimeglumine to match the signal intensity properties of brain tissue in 3T T(1) -weighted MRI. The 3T T(1) -weighted images of the phantom were acquired and ventricle segmentation software was used to measure ventricle volume. RESULTS: The images acquired of the phantom successfully replicated in vivo signal intensity differences between the ventricle and surrounding tissue in T(1) -weighted images and were robust to segmentation. The ventricle volume was quantified to 99% accuracy at 1-mm voxel size. CONCLUSION: The phantom represents a simple, realistic and objective method to test the accuracy of lateral ventricle segmentation methods and we project it can be extended to other anatomical structures.
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Ventrículos Cerebrais/anatomia & histologia , Imageamento Tridimensional/instrumentação , Imageamento por Ressonância Magnética/métodos , Imagens de Fantasmas , Desenho de Equipamento , Análise de Falha de Equipamento , Humanos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: The predicted growth of Canadians aged 65+ and the resultant rise in the demand for specialized geriatric services (SGS) requires physician resource planning. We updated the 2011 Canadian Geriatrics Society physician resource inventory and created projections for 2025 and 2030. METHODS: The number and full-time equivalents (FTEs) of geriatricians and Care of the Elderly (COE) physicians working in SGS were determined. FTE counts for 2025 and 2030 were estimated by accounting for retirements and trainees. A ratio of 1.25/10,000 population 65+ was used to predict physician resource requirements. RESULTS: Between 2011 and 2019 the number of geriatricians and COE physicians increased from 276 (235.8 FTEs) and 128 (89.9 FTEs), respectively, to 376 (319.6 FTEs) and 354 (115.5 FTEs). This increase did not keep pace with the 65+ population growth. The current gap between supply and need is expected to increase. DISCUSSION: The physician supply gap is projected to widen in 2025 and 2030. Increased recruitment and interdisciplinary team-based care, supported by enhanced funding models, and full integration of COE physicians in SGS could reduce this increasing gap. In contrast to pediatrician supply in Canada, the specialist physician resources available to the population 65+ reflect a disparity.
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A visual search task was used to investigate how visual attention and intraindividual variability changes with mild cognitive impairment (MCI). Specifically, we examined the contribution of shifting efficacy, distribution of attention, and controlled processing to declines in visual attention in two groups with MCI (single-domain amnestic and multi-domain amnestic), and measured changes in intraindividual variability. Our results demonstrate that visual search performance is attenuated in multi-domain amnestic MCI, but not single-domain amnestic MCI. In addition, we found that the multi-domain amnestic MCI group was more variable than the older controls and single-domain amnestic MCI participants. These between-group differences in search efficacy and intraindividual variability increased as a function of task complexity. We attribute these decrements in performance to changes in the control of attention and shifting efficacy, but not the distribution of attention.
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Amnésia , Atenção/fisiologia , Transtornos Cognitivos , Discriminação Psicológica/fisiologia , Tempo de Reação , Percepção Visual/fisiologia , Idoso , Idoso de 80 Anos ou mais , Amnésia/complicações , Amnésia/fisiopatologia , Amnésia/psicologia , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/fisiopatologia , Transtornos Cognitivos/psicologia , Feminino , Humanos , Masculino , Testes NeuropsicológicosRESUMO
Identification of biological changes underlying the early symptoms of Alzheimer's disease (AD) will help to identify and stage individuals prior to symptom onset. The limbic system, which supports episodic memory and is impaired early in AD, is a primary target. In this study, brain metabolism and microstructure evaluated by high field (7 Tesla) proton magnetic resonance spectroscopy (1H-MRS) and diffusion tensor imaging (DTI) were evaluated in the limbic system of eight individuals with mild cognitive impairment (MCI), nine with AD, and sixteen normal elderly controls (NEC). Left hippocampal glutamate and posterior cingulate N-acetyl aspartate concentrations were reduced in MCI and AD compared to NEC. Differences in DTI metrics indicated volume and white matter loss along the cingulum in AD compared to NEC. Metabolic and microstructural changes were associated with episodic memory performance assessed using Craft Story 21 Recall and Benson Complex Figure Copy. The current study suggests that metabolite concentrations measured using 1H-MRS may provide insight into the underlying metabolic and microstructural processes of episodic memory impairment.
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Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/metabolismo , Ácido Aspártico/análogos & derivados , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/metabolismo , Ácido Glutâmico/metabolismo , Giro do Cíngulo/diagnóstico por imagem , Hipocampo/metabolismo , Memória Episódica , Substância Branca/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Ácido Aspártico/metabolismo , Imagem de Tensor de Difusão , Feminino , Giro do Cíngulo/metabolismo , Humanos , Sistema Límbico/diagnóstico por imagem , Sistema Límbico/metabolismo , Espectroscopia de Ressonância Magnética , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Testes Neuropsicológicos , Projetos Piloto , Substância Branca/metabolismoRESUMO
BACKGROUND: Older adults with cognitive problems have a higher risk of falls, at least twice that of cognitively normal older adults. The consequences of falls in this population are very serious: fallers with cognitive problems suffer more injuries due to falls and are approximately five times more likely to be admitted to institutional care. Although the mechanisms of increased fall risk in cognitively impaired people are not completely understood, it is known that impaired cognitive abilities can reduce attentional resource allocation while walking. Since cognitive enhancers, such as cholinesterase inhibitors, improve attention and executive function, we hypothesise that cognitive enhancers may reduce fall risk in elderly people in the early stages of cognitive decline by improving their gait and balance performance due to an enhancement in attention and executive function. METHOD/DESIGN: Double blinded randomized controlled trial with 6 months follow-up in 140 older individuals with Mild Cognitive Impairment (MCI). Participants will be randomized to the intervention group, receiving donepezil, and to the control group, receiving placebo. A block randomization by four and stratification based on fall history will be performed. Primary outcomes are improvements in gait velocity and reduction in gait variability. Secondary outcomes are changes in the balance confidence, balance sway, attention, executive function, and number of falls. DISCUSSION: By characterizing and understanding the effects of cognitive enhancers on fall risk in older adults with cognitive impairments, we will be able to pave the way for a new approach to fall prevention in this population. This RCT study will provide, for the first time, information regarding the effect of a medication designed to augment cognitive functioning have on the risk of falls in older adults with Mild Cognitive Impairment. We expect a significant reduction in the risk of falls in this vulnerable population as a function of the reduced gait variability achieved by treatment with cognitive enhancers. This study may contribute to a new approach to prevent and treat fall risk in seniors in early stages of dementia. TRIAL REGISTRATION: The protocol for this study is registered with the Clinical Trials Registry, identifier number: NCT00934531 http://www.clinicaltrials.gov.
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Acidentes por Quedas/prevenção & controle , Transtornos Cognitivos/tratamento farmacológico , Indanos/uso terapêutico , Piperidinas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Inibidores da Colinesterase/uso terapêutico , Protocolos Clínicos , Transtornos Cognitivos/complicações , Pesquisa Participativa Baseada na Comunidade , Donepezila , Método Duplo-Cego , Feminino , Marcha , Humanos , Masculino , Seleção de Pacientes , Resultado do TratamentoRESUMO
BACKGROUND: Reliability of quantitative gait assessment while dual-tasking (walking while doing a secondary task such as talking) in people with cognitive impairment is unknown. Dual-tasking gait assessment is becoming highly important for mobility research with older adults since better reflects their performance in the basic activities of daily living. Our purpose was to establish the test-retest reliability of assessing quantitative gait variables using an electronic walkway in older adults with mild cognitive impairment (MCI) under single and dual-task conditions. METHODS: The gait performance of 11 elderly individuals with MCI was evaluated using an electronic walkway (GAITRite System) in two sessions, one week apart. Six gait parameters (gait velocity, step length, stride length, step time, stride time, and double support time) were assessed under two conditions: single-task (sG: usual walking) and dual-task (dG: counting backwards from 100 while walking). Test-retest reliability was determined using intra-class correlation coefficient (ICC). Gait variability was measured using coefficient of variation (CoV). RESULTS: Eleven participants (average age = 76.6 years, SD = 7.3) were assessed. They were high functioning (Clinical Dementia Rating Score = 0.5) with a mean Mini-Mental Status Exam (MMSE) score of 28 (SD = 1.56), and a mean Montreal Cognitive Assessment (MoCA) score of 22.8 (SD = 1.23). Under dual-task conditions, mean gait velocity (GV) decreased significantly (sGV = 119.11 +/- 20.20 cm/s; dGV = 110.88 +/- 19.76 cm/s; p = 0.005). Additionally, under dual-task conditions, higher gait variability was found on stride time, step time, and double support time. Test-retest reliability was high (ICC>0.85) for the six parameters evaluated under both conditions. CONCLUSION: In older people with MCI, variability of time-related gait parameters increased with dual-tasking suggesting cognitive control of gait performance. Assessment of quantitative gait variables using an electronic walkway is highly reliable under single and dual-task conditions. The presence of cognitive impairment did not preclude performance of dual-tasking in our sample supporting that this methodology can be reliably used in cognitive impaired older individuals.
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Cognição/fisiologia , Disfunção Cognitiva/fisiopatologia , Avaliação da Deficiência , Teste de Esforço/normas , Marcha/fisiologia , Idoso , Idoso de 80 Anos ou mais , Atenção/fisiologia , Teste de Esforço/instrumentação , Teste de Esforço/métodos , Feminino , Humanos , Masculino , Reprodutibilidade dos TestesRESUMO
INTRODUCTION: Innovative recruitment strategies are needed to better engage potential research participants at a preclinical stage of cognitive decline. METHODS: Local newspaper advertisements attracted community-dwelling people ≥55 years with memory concerns, who were interested in research, to self-refer for cognitive assessment and discuss cognitive research involvement. Respondents completed telephone screening and then attended an in-person cognitive screening assessment with a study partner. Case conferencing with a clinician researcher characterized a "clinical suspicion" of the participant's cognitive concern. RESULTS: Of 209 respondents who underwent in-person assessment, 203 participants were classified as having subjective cognitive decline (47%), mild cognitive impairment (44%), or dementia (9%). Thirty percent of participants were enrolled in observational studies or randomized controlled trials. DISCUSSION: Community-based engagement, cognitive screening, and case conferencing effectively combined to identify research participants at risk of cognitive decline and recruited participants into cognitive research studies. Those not recruited continued to be followed up longitudinally.
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The purpose of this study was to measure metabolite level changes in patients with newly diagnosed Alzheimer Disease (AD) following four months of donepezil treatment. A small number of cognitively normal elderly subjects were also scanned longitudinally (twice within one year) to assess the reproducibility. Short echo-time (1)H magnetic resonance spectra were acquired at 4.0 T in the right hippocampus. Subjects were scanned at the time of first diagnosis (prior to receiving donepezil) and then following four months of donepezil treatment (5 mg/day for the first month, 10 mg/day thereafter). Changes in absolute metabolite levels and metabolite ratios were quantified and compared. There was no change in measured cognitive function following four months of donepezil treatment in the AD patients. Decreased levels of N-acetylaspartate, choline, N-acetylaspartate/creatine, choline/creatine, and myo-inositol/creatine were observed in AD patients after four months of treatment. Cognitively normal elderly subjects showed an increase in myo-inositol/choline ratio following one year. The reduced levels of N-acetylaspartate in AD patients indicates continued decline in neuronal function and/or integrity. However decreased levels of choline and myo-inositol/creatine ratio may indicate a positive treatment effect.
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Doença de Alzheimer/metabolismo , Inibidores da Colinesterase/farmacologia , Hipocampo/efeitos dos fármacos , Indanos/farmacologia , Piperidinas/farmacologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Ácido Aspártico/metabolismo , Química Encefálica/efeitos dos fármacos , Colina/metabolismo , Inibidores da Colinesterase/uso terapêutico , Creatina/metabolismo , Donepezila , Feminino , Hipocampo/metabolismo , Humanos , Indanos/uso terapêutico , Inositol/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Masculino , Piperidinas/uso terapêutico , PrótonsRESUMO
Previous studies have demonstrated altered brain activity in Alzheimer's disease using task based functional MRI (fMRI), network based resting-state fMRI, and glucose metabolism from 18F fluorodeoxyglucose-PET (FDG-PET). Our goal was to define a novel indicator of neuronal activity based on a first-order textural feature of the resting state functional MRI (RS-fMRI) signal. Furthermore, we examined the association between this neuronal activity metric and glucose metabolism from 18F FDG-PET. We studied 15 normal elderly controls (NEC) and 15 probable Alzheimer disease (AD) subjects from the AD Neuroimaging Initiative. An independent component analysis was applied to the RS-fMRI, followed by template matching to identify neuronal components (NC). A regional brain activity measurement was constructed based on the variation of the RS-fMRI signal of these NC. The standardized glucose uptake values of several brain regions relative to the cerebellum (SUVR) were measured from partial volume corrected FDG-PET images. Comparing the AD and NEC groups, the mean brain activity metric was significantly lower in the accumbens, while the glucose SUVR was significantly lower in the amygdala and hippocampus. The RS-fMRI brain activity metric was positively correlated with cognitive measures and amyloid ß1-42 cerebral spinal fluid levels; however, these did not remain significant following Bonferroni correction. There was a significant linear correlation between the brain activity metric and the glucose SUVR measurements. This proof of concept study demonstrates that this novel and easy to implement RS-fMRI brain activity metric can differentiate a group of healthy elderly controls from a group of people with AD.
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Doença de Alzheimer/líquido cefalorraquidiano , Tonsila do Cerebelo/metabolismo , Cerebelo/metabolismo , Hipocampo/metabolismo , Imageamento por Ressonância Magnética/métodos , Núcleo Accumbens/metabolismo , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/fisiopatologia , Tonsila do Cerebelo/fisiopatologia , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Estudos de Casos e Controles , Cerebelo/fisiopatologia , Bases de Dados Factuais , Feminino , Fluordesoxiglucose F18/administração & dosagem , Hipocampo/fisiopatologia , Humanos , Masculino , Núcleo Accumbens/fisiopatologia , Fragmentos de Peptídeos/líquido cefalorraquidiano , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/administração & dosagemRESUMO
Importance: Gait performance is affected by neurodegeneration in aging and has the potential to be used as a clinical marker for progression from mild cognitive impairment (MCI) to dementia. A dual-task gait test evaluating the cognitive-motor interface may predict dementia progression in older adults with MCI. Objective: To determine whether a dual-task gait test is associated with incident dementia in MCI. Design, Setting, and Participants: The Gait and Brain Study is an ongoing prospective cohort study of community-dwelling older adults that enrolled 112 older adults with MCI. Participants were followed up for 6 years, with biannual visits including neurologic, cognitive, and gait assessments. Data were collected from July 2007 to March 2016. Main Outcomes and Measures: Incident all-cause dementia was the main outcome measure, and single- and dual-task gait velocity and dual-task gait costs were the independent variables. A neuropsychological test battery was used to assess cognition. Gait velocity was recorded under single-task and 3 separate dual-task conditions using an electronic walkway. Dual-task gait cost was defined as the percentage change between single- and dual-task gait velocities: ([single-task gait velocity - dual-task gait velocity]/ single-task gait velocity) × 100. Cox proportional hazard models were used to estimate the association between risk of progression to dementia and the independent variables, adjusted for age, sex, education, comorbidities, and cognition. Results: Among 112 study participants with MCI, mean (SD) age was 76.6 (6.9) years, 55 were women (49.1%), and 27 progressed to dementia (24.1%), with an incidence rate of 121 per 1000 person-years. Slow single-task gait velocity (<0.8 m/second) was not associated with progression to dementia (hazard ratio [HR], 3.41; 95% CI, 0.99-11.71; P = .05)while high dual-task gait cost while counting backward (HR, 3.79; 95% CI, 1.57-9.15; P = .003) and naming animals (HR, 2.41; 95% CI, 1.04-5.59; P = .04) were associated with dementia progression (incidence rate, 155 per 1000 person-years). The models remained robust after adjusting by baseline cognition except for dual-task gait cost when dichotomized. Conclusions and Relevance: Dual-task gait is associated with progression to dementia in patients with MCI. Dual-task gait testing is easy to administer and may be used by clinicians to decide further biomarker testing, preventive strategies, and follow-up planning in patients with MCI. Trial Registration: clinicaltrials.gov: NCT03020381.
Assuntos
Disfunção Cognitiva/fisiopatologia , Demência/fisiopatologia , Progressão da Doença , Marcha/fisiologia , Desempenho Psicomotor/fisiologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Feminino , Seguimentos , Humanos , Incidência , Masculino , Testes Neuropsicológicos , RiscoRESUMO
This study examined the nurse practitioner (NP) role in three long-term care facilities in Ontario, Canada, to identify factors that facilitate or impede the implementation of this role. Facility staff were surveyed about their perceptions of the NP role, and the NP assigned to the facilities was interviewed. Findings indicated the NP had a positive impact on practice activities and staff assessment skills. Ratings of effectiveness and satisfaction with the role were high, although they varied by facility and the frequency of staff interaction with the NP. This study indicated NPs can significantly impact the primary care of residents in long-term care facilities. The NP role can be facilitated by clear delineation of the scope of practice, optimal NP to resident ratios, and organizational support.
Assuntos
Assistência de Longa Duração/organização & administração , Profissionais de Enfermagem/organização & administração , Papel do Profissional de Enfermagem , Casas de Saúde/organização & administração , Atenção Primária à Saúde/organização & administração , Atitude do Pessoal de Saúde , Humanos , Relações Interprofissionais , Satisfação no Emprego , Profissionais de Enfermagem/psicologia , Pesquisa em Avaliação de Enfermagem , Pesquisa Metodológica em Enfermagem , Recursos Humanos de Enfermagem/psicologia , Ontário , Projetos Piloto , Autonomia Profissional , Apoio Social , Inquéritos e Questionários , Carga de TrabalhoRESUMO
BACKGROUND: Cognitive-frailty, defined as the presence of both frailty and cognitive impairment, is proposed as a distinctive entity that predicts dementia. However, it remains controversial whether frailty alone, cognitive-frailty, or the combination of cognitive impairment and slow gait pose different risks of incident dementia. METHODS: Two hundred and fifty-two older adults free of dementia at baseline (mean age 76.6±8.6 years) were followed up to 5 years with bi-annual visits including medical, cognitive, and gait assessments. Incident all-cause of dementia and cognitive decline were the main outcomes. Frailty was defined using validated phenotypic criteria. Cognition was assessed using the Montreal Cognitive Assessment while gait was assessed using an electronic walkway. Cox Proportional Hazards models were used to estimate the risk of cognitive decline and dementia for frailty, cognitive-frailty, and gait and cognition models. RESULTS: Fifty-three participants experienced cognitive decline and 27 progressed to dementia (incident rate: 73/1,000 person-years). Frailty participants had a higher prevalence of cognitive impairment compared with those without frailty (77% vs. 54%, p = .02) but not significant risk to incident dementia. Cognitive-frailty increased incident rate (80/1,000 person-years) but not risk for progression to dementia. The combination of slow gait and cognitive impairment posed the highest risk for progression to dementia (hazard ratio: 35.9, 95% confidence interval: 4.0-319.2; p = 0.001, incident rate: 130/1,000 person-years). None of the models explored significantly predicted cognitive decline. CONCLUSIONS: Combining a simple motor test, such as gait velocity, with a reliable cognitive test like the Montreal Cognitive Assessment is superior than the cognitive-frailty construct to detect individuals at risk for dementia. Cognitive-frailty may embody two different manifestations, slow gait and low cognition, of a common underlying mechanism.