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1.
Alzheimers Dement ; 20(5): 3687-3695, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38574400

RESUMEN

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.


Asunto(s)
Enfermedad de Alzheimer , Péptidos beta-Amiloides , Enfermedades de los Pequeños Vasos Cerebrales , Hipocampo , Tomografía de Emisión de Positrones , Humanos , Hipocampo/patología , Hipocampo/diagnóstico por imagen , Enfermedades de los Pequeños Vasos Cerebrales/patología , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Masculino , Anciano , Femenino , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/diagnóstico por imagen , Péptidos beta-Amiloides/metabolismo , Sustancia Blanca/patología , Sustancia Blanca/diagnóstico por imagen , Atrofia/patología , Imagen por Resonancia Magnética , Anciano de 80 o más Años , Neuroimagen , Estudios de Cohortes
2.
Can J Aging ; : 1-12, 2023 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-37694538

RESUMEN

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.

3.
Alzheimers Dement ; 19(10): 4542-4548, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-36919891

RESUMEN

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.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Enfermedad de Alzheimer/diagnóstico , Atrofia , Disfunción Cognitiva/diagnóstico , Progresión de la Enfermedad , Fluorodesoxiglucosa F18
4.
J Clin Epidemiol ; 158: 111-118, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36931477

RESUMEN

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.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Anciano , Humanos , Enfermedad de Alzheimer/diagnóstico , Teorema de Bayes , Disfunción Cognitiva/diagnóstico , Progresión de la Enfermedad
5.
Can Geriatr J ; 24(3): 200-208, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34484503

RESUMEN

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.

6.
J Alzheimers Dis ; 73(4): 1385-1405, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31958093

RESUMEN

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.


Asunto(s)
Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/metabolismo , Ácido Aspártico/análogos & derivados , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/metabolismo , Ácido Glutámico/metabolismo , Giro del Cíngulo/diagnóstico por imagen , Hipocampo/metabolismo , Memoria Episódica , Sustancia Blanca/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Ácido Aspártico/metabolismo , Imagen de Difusión Tensora , Femenino , Giro del Cíngulo/metabolismo , Humanos , Sistema Límbico/diagnóstico por imagen , Sistema Límbico/metabolismo , Espectroscopía de Resonancia Magnética , Masculino , Pruebas de Estado Mental y Demencia , Persona de Mediana Edad , Pruebas Neuropsicológicas , Proyectos Piloto , Sustancia Blanca/metabolismo
7.
Alzheimers Dement (N Y) ; 5: 501-507, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31650006

RESUMEN

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.

8.
PLoS One ; 12(6): e0178529, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28582450

RESUMEN

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.


Asunto(s)
Enfermedad de Alzheimer/líquido cefalorraquídeo , Amígdala del Cerebelo/metabolismo , Cerebelo/metabolismo , Hipocampo/metabolismo , Imagen por Resonancia Magnética/métodos , Núcleo Accumbens/metabolismo , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/fisiopatología , Amígdala del Cerebelo/fisiopatología , Péptidos beta-Amiloides/líquido cefalorraquídeo , Estudios de Casos y Controles , Cerebelo/fisiopatología , Bases de Datos Factuales , Femenino , Fluorodesoxiglucosa F18/administración & dosificación , Hipocampo/fisiopatología , Humanos , Masculino , Núcleo Accumbens/fisiopatología , Fragmentos de Péptidos/líquido cefalorraquídeo , Tomografía de Emisión de Positrones , Radiofármacos/administración & dosificación
9.
JAMA Neurol ; 74(7): 857-865, 2017 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-28505243

RESUMEN

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.


Asunto(s)
Disfunción Cognitiva/fisiopatología , Demencia/fisiopatología , Progresión de la Enfermedad , Marcha/fisiología , Desempeño Psicomotor/fisiología , Anciano , Anciano de 80 o más Años , Biomarcadores , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Pruebas Neuropsicológicas , Riesgo
10.
Healthc Q ; 19(4): 55-62, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28130953

RESUMEN

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.


Asunto(s)
Creación de Capacidad/métodos , Demencia/terapia , Atención Primaria de Salud/organización & administración , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Memoria , Persona de Mediana Edad , Ontario , Encuestas y Cuestionarios
11.
J Gerontol A Biol Sci Med Sci ; 71(11): 1476-1482, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-26984391

RESUMEN

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.


Asunto(s)
Disfunción Cognitiva/epidemiología , Demencia/epidemiología , Anciano Frágil , Evaluación Geriátrica , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Indicadores de Salud , Humanos , Incidencia , Masculino , Pruebas Neuropsicológicas , Fenotipo , Prevalencia , Factores de Riesgo , Velocidad al Caminar
12.
Dement Geriatr Cogn Disord ; 39(1-2): 68-80, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25358336

RESUMEN

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.


Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Ácido Aspártico/análogos & derivados , Inhibidores de la Colinesterasa/uso terapéutico , Trastornos del Conocimiento/tratamiento farmacológico , Creatina/metabolismo , Giro del Cíngulo/metabolismo , Fenilcarbamatos/uso terapéutico , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/metabolismo , Ácido Aspártico/metabolismo , Trastornos del Conocimiento/metabolismo , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Pruebas Neuropsicológicas , Rivastigmina
13.
Can J Aging ; 33(3): 307-19, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25111053

RESUMEN

The implementation in Ontario of 15 primary-care-based interprofessional memory clinics represented a unique model of team-based case management aimed at increasing capacity for dementia care at the primary-care level. Each clinic tracked referrals; in a subset of clinics, charts were audited by geriatricians, clinic members were interviewed, and patients, caregivers, and referring physicians completed satisfaction surveys. Across all clinics, 582 patients were assessed, and 8.9 per cent were referred to a specialist. Patients and caregivers were very satisfied with the care received, as were referring family physicians, who reported increased capacity to manage dementia. Geriatricians' chart audits revealed a high level of agreement with diagnosis and management. This study demonstrated acceptability, feasibility, and preliminary effectiveness of the primary-care memory clinic model. Led by specially trained family physicians, it provided timely access to high-quality collaborative dementia care, impacting health service utilization by more-efficient use of scarce geriatric specialist resources.


Asunto(s)
Demencia/terapia , Adulto , Anciano , Anciano de 80 o más Años , Instituciones de Atención Ambulatoria , Cuidadores , Femenino , Humanos , Masculino , Memoria , Persona de Mediana Edad , Grupo de Atención al Paciente , Satisfacción del Paciente , Atención Primaria de Salud
14.
J Neurosci Methods ; 227: 35-46, 2014 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-24518149

RESUMEN

BACKGROUND: The change in volume of anatomic structures is as a sensitive indicator of Alzheimer disease (AD) progression. Although several methods are available to measure brain volumes, improvements in speed and automation are required. Our objective was to develop a fully automated, fast, and reliable approach to measure change in medial temporal lobe (MTL) volume, including primarily hippocampus. METHODS: The MTL volume defined in an atlas image was propagated onto each baseline image and a level set algorithm was applied to refine the shape and smooth the boundary. The MTL of the baseline image was then mapped onto the corresponding follow-up image to measure volume change (ΔMTL). Baseline and 24 months 3D T1-weighted images from the Alzheimer Disease Neuroimaging Initiative (ADNI) were randomly selected for 50 normal elderly controls (NECs), 50 subjects with mild cognitive impairment (MCI) and 50 subjects with AD to test the algorithm. The method was compared to the FreeSurfer segmentation tools. RESULTS: The average ΔMTL (mean±SEM) was 68±35mm(3) in NEC, 187±38mm(3) in MCI and 300±34mm(3) in the AD group and was significantly different (p<0.0001) between all three groups. The ΔMTL was correlated with cognitive decline. COMPARISON WITH EXISTING METHOD(S): Results for the FreeSurfer software were similar but did not detect significant differences between the MCI and AD groups. CONCLUSION: This novel segmentation approach is fully automated and provides a robust marker of brain atrophy that shows different rates of atrophy over 2 years between NEC, MCI, and AD groups.


Asunto(s)
Algoritmos , Enfermedad de Alzheimer/patología , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Lóbulo Temporal/patología , Anciano , Anciano de 80 o más Años , Disfunción Cognitiva/patología , Femenino , Hipocampo/patología , Humanos , Masculino , Persona de Mediana Edad , Estadística como Asunto
15.
Alzheimers Dement ; 9(5 Suppl): S63-71, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23643459

RESUMEN

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.


Asunto(s)
Trastornos del Conocimiento/etiología , Demencia , Actividades Cotidianas , Factores de Edad , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/psicología , Estudios de Cohortes , Demencia/clasificación , Demencia/complicaciones , Demencia/psicología , Demencia Vascular/complicaciones , Demencia Vascular/psicología , Progresión de la Enfermedad , Humanos , Enfermedad por Cuerpos de Lewy/complicaciones , Enfermedad por Cuerpos de Lewy/psicología , Persona de Mediana Edad , Pruebas Neuropsicológicas , Factores Sexuales , Encuestas y Cuestionarios , Estados Unidos
16.
Brain ; 136(Pt 3): 859-71, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23436505

RESUMEN

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.


Asunto(s)
Disfunción Cognitiva/metabolismo , Trastornos Neurológicos de la Marcha/metabolismo , Marcha/fisiología , Corteza Motora/metabolismo , Anciano , Disfunción Cognitiva/complicaciones , Disfunción Cognitiva/fisiopatología , Femenino , Trastornos Neurológicos de la Marcha/etiología , Trastornos Neurológicos de la Marcha/fisiopatología , Humanos , Espectroscopía de Resonancia Magnética , Masculino , Corteza Motora/patología , Corteza Motora/fisiopatología
17.
J Magn Reson Imaging ; 36(2): 476-82, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22396226

RESUMEN

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.


Asunto(s)
Ventrículos Cerebrales/anatomía & histología , Imagenología Tridimensional/instrumentación , Imagen por Resonancia Magnética/métodos , Fantasmas de Imagen , Diseño de Equipo , Análisis de Falla de Equipo , Humanos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
18.
Neurocase ; 16(5): 408-17, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20401803

RESUMEN

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.


Asunto(s)
Amnesia , Atención/fisiología , Trastornos del Conocimiento , Discriminación en Psicología/fisiología , Tiempo de Reacción , Percepción Visual/fisiología , Anciano , Anciano de 80 o más Años , Amnesia/complicaciones , Amnesia/fisiopatología , Amnesia/psicología , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/fisiopatología , Trastornos del Conocimiento/psicología , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas
19.
Prog Neuropsychopharmacol Biol Psychiatry ; 34(1): 104-10, 2010 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-19833161

RESUMEN

Galantamine is a cholinesterase inhibitor and allosteric potentiating ligand modulating presynaptic nicotinic acetylcholine receptors that is used in the treatment of Alzheimer disease (AD). The purpose of this study was to determine if galantamine treatment would result in detectable hippocampal metabolite changes that correlated with changes in cognition, as measured by the Mini-Mental State Examination (MMSE) and the Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog). Short echo-time proton magnetic resonance (MR) spectra were acquired from within the right hippocampus of ten patients using a 4 Tesla magnetic resonance imaging (MRI) scanner. Spectra were used to quantify absolute metabolite levels for N-acetylaspartate (NAA), glutamate (Glu), choline (Cho), creatine (Cr), and myo-inositol (mI). Patient scans and cognitive tests were performed before and 4 months after beginning galantamine treatment, which consisted of an 8 mg daily dose for the first month and a 16 mg daily dose for the remaining three months. The levels of Glu, Glu/Cr, and Glu/NAA increased after four months of treatment, while there were no changes in MMSE or ADAS-cog scores. Additionally, changes (Delta) in Glu over the four months (DeltaGlu) correlated with DeltaNAA, and Delta(Glu/Cr) correlated with DeltaMMSE scores. Increased Glu and the ratio of Glu to Cr measured by MR spectroscopy after galantamine treatment were associated with increased cognitive performance. The increase in Glu may be related to the action of galantamine as an allosteric potentiating ligand for presynaptic nicotinic acetylcholine receptors, which increases glutamatergic neurotransmission.


Asunto(s)
Enfermedad de Alzheimer/patología , Inhibidores de la Colinesterasa/farmacología , Galantamina/farmacología , Ácido Glutámico/metabolismo , Hipocampo/efectos de los fármacos , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/tratamiento farmacológico , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Mapeo Encefálico , Colina/metabolismo , Inhibidores de la Colinesterasa/uso terapéutico , Creatina/metabolismo , Femenino , Galantamina/uso terapéutico , Humanos , Inositol/metabolismo , Espectroscopía de Resonancia Magnética/métodos , Masculino , Escala del Estado Mental , Pruebas Neuropsicológicas , Análisis de Regresión
20.
J Neuroeng Rehabil ; 6: 35, 2009 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-19772593

RESUMEN

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.


Asunto(s)
Cognición/fisiología , Disfunción Cognitiva/fisiopatología , Evaluación de la Discapacidad , Prueba de Esfuerzo/normas , Marcha/fisiología , Anciano , Anciano de 80 o más Años , Atención/fisiología , Prueba de Esfuerzo/instrumentación , Prueba de Esfuerzo/métodos , Femenino , Humanos , Masculino , Reproducibilidad de los Resultados
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