Clinical and neuroimaging prognostic markers in Alzheimer's Disease and Lewy Body Dementia: The role of muscle status and nutrition

Alzheimer's Disease and Lewy body dementia are the two most common neurodegenerative dementias. They have a progressive course with devastating consequences for the people living with these diseases and their families, but there are large individual variations. Finding early markers and markers of progression and prognosis could promote actions to improve the quality of life of the people affected with these diseases. Nutrition and muscle status are closely related and have systemic functions and interactions that affect the brain. This thesis describes the role of nutritional and muscle status biomarkers in the prognosis of people diagnosed with mild Alzheimer's disease, Lewy body dementia, and mild subjective cognitive decline. Methods For the aim of this thesis, I used data from 2 community-based prospective Norwegian multicenter cohort studies: DemVest (The Dementia Study of Western Norway) and DDI (Dementia Disease Initiation). In DemVest, patients with mild dementia, defined as a Mini-Mental Status Examination (MMSE) score; equal or higher to 20 or Clinical Dementia Rating (CDR) global score equal to 1, with different types of dementia, were included. The DDI study was designed to investigate early cognitive impairment and dementia markers. DDI participants included in this thesis were those classified as having Subjective cognitive decline (SCD) according to the SCD-I framework. Comprehensive clinical assessments, including measures of cognition, daily functioning and anthropometric measurement, blood samples, and brain MRI were performed in both studies. Brain morphology was studied using FreeSurfer segmentation and muscle morphology using slice O-Matic software. Results This thesis findings first indicate that nutritional status has an essential role in the 5-year prognosis of people living with dementia in the capacity to perform daily life activities and mortality. Second, the quality of the muscle, here the muscle of the tongue, and its amount of fat infiltration were associated with malnutrition onset in people with dementia. Finally, in patients with SCD, muscle function measured with the timed up and go test (TUG) was associated with cognitive decline. TUG, in addition, was associated with cortical thickness in areas related with cognitive and motor functioning. Conclusion Nutritional and muscular status predict prognosis in people with SCD and with dementia. These findings suggest that interventions focused on these areas may improve outcomes such as cognition, function, and survival in these groups

Influencia de hábitos saludables en la incidencia de fragilidad

La fragilidad es un estado clínico definido como un aumento en la vulnerabilidad de un individuo para desarrollar resultados adversos cuando se expone a eventos estresantes que conducen a una disminución funcional y una menor calidad de vida, así como a mayores tasas de mortalidad. Este estudio pretende identificar actividades que puedan prevenir el desarrollo de fragilidad en los adultos mayores. Métodos El Estudio Mexicano de Salud y Envejecimiento es una cohorte de adultos mexicanos de 50 años o más con cuatro oleadas (2001, 2003, 2012 y 2015). Para el propósito de esta tesis se usaron las olas de 2012 y 2015. Con el fin de evaluar la asociación de actividades de estilo de vida saludable con la fragilidad incidente. La fragilidad se estimó utilizando el índice de fragilidad. Se calculó como la relación entre los déficits reales y 39 potenciales que el participante podría haber presentado en la evaluación. Los sujetos clasificados como frágiles en 2012 fueron eliminados, teniendo una muestra final de 6.087. Se usaron modelos de regresión logística con variables de ajuste para evaluar las probabilidades de fragilidad incidente dado la realización o no de las actividades de estilo de vida saludable (ejercicio, vacunación, actividades de no fumadores y de detección). Resultados De la medición inicial, el 55.2% eran hombres y la edad promedio fue de 62.18 (± SD 8.48) años. La incidencia de fragilidad fue del 37.85%. De todas las actividades evaluadas, la actividad física fue la única que tuvo una asociación con disminución de la fragilidad incidente. Los adultos mayores que realizaban actividad física tenían una menor presencia de fragilidad (48.88% vs. 42.23%, p <0.0001); teniendo un odds-ratio de 0.79 (95% CI 0.71-0.88, p <0.0001) en el modelo de regresión logística ajustado. Conclusiones Los adultos mayores que refirieron que se ejercitaron durante el último año, tuvieron una menor incidencia de fragilidad, incluso cuando se ajustaron las variables de confusión.Frailty is a clinical state defined as an increase in an individual’s vulnerability to developing adverse health-related outcomes. We propose healthy behaviors should impact the incidence of frailty. Methods A total of 6,087 community-dwelling persons aged 50 years old or older who participated in the Mexican Health and Aging Study where followed over three years. We analyze the association between healthy behaviors (physical activity, vaccination, no history of smoking, and screening activities for early detection of cancer) and incidence of frailty. Frailty was defined using a 39-item frailty index. Multivariate logistic regression models were used to assess the odds of frailty occurring according to the four health-related behaviors mentioned above. Results At baseline, 55.2% of the subjects were male, the mean age was 62.2 (SD ± 8.5) years old, and the incidence of frailty was 37.8%. Older adults who reported being more physically active had a lower incidence of frailty (48.9% vs. 42.2%, p< 0.0001). Of the health behaviors included in the adjusted multivariate models, physical activity was the only one independently associated with lower risk of frailty (odds ratio: 0.79, 95% confidence interval 0.71-0.88, p< 0.001). Discussion and Implications Older adults who were more physically active had a lower 3-year incidence of frailty even after adjusting for confounding variables. Increasing physical activity could therefore represent a strategy for reducing the incidence of frailty and its consequences.Especialista en GeriatríaEspecializació

Association between physical activity and cognition in Mexican and Korean older adults

Introduction: As the world's population ages, the prevalence of cognitive impairment associated with age in- creases. This increase is particularly pronounced in Asia and South-America. The objective of this study was to investigate separately the longitudinal association of physical activity and cognitive function in; older adults in Mexico and South Korea. Materials and Methods: This is a secondary analysis of two surveys, The Mexican Health and aging Study (MHAS) (n = 5853) and Korean Longitudinal Study of aging (KLoSA) (n = 5188), designed to study the aging process of older adults living in Mexico and South Korea. Participants older than 50 years were selected from rural and urban areas achieving a representative sample. Physical activity was assessed using self-report. Cognition was assessed using Cross-Cultural Cognitive Examination (CCCE) and Minimental state examination (MMSE) in Mexico and South Korea respectively. Here we investigate the longitudinal association between physical activity and cognition during 3 years for MHAS and 4 years for KLoSA using multiple linear regression analyses. Results: The prevalence of physical activity was 40.68 % in MHAS and 35.57 % in KLoSA. In the adjusted longitudinal multivariate analysis, an independent association was found between physical activity and MMSE score OR 0.0866 (CI 0.0266-0.1467 p-value 0.0047) in the Korean older adults, while there was no significant association in MHAS. Conclusions: Physical activity could have a protective effect on the cognitive decline associated with aging in the Korean population.publishedVersio

Utility Continuous Stimulation of Pedunculopontine Nucleus fortreating Parkinson’s Disease

El núcleo pedunculopontino contiene gran cantidad de conexiones que modulan la actividad motora en los humanos; por este motivo, se ha planteado que su estimulación profunda tendría beneficios significativos en el tratamiento de la enfermedad de Parkinson. Con una carga orgánica y social significativa, la enfermedad de Parkinson reúne una serie designos y síntomas, principalmente motores, que afectan significativamente la calidad de vida de los pacientes que la padecen. Actualmente, se encuentran dentro de un área de investigación con gran potencial parad ar manejo a los síntomas de esta enfermedad, y se desconoce si su estimulación cerebral profunda podría orientar futuras intervenciones con resultados óptimos. Por esta razón, la revisión busca esclarecer la utilidad de este procedimiento; sin embargo, es bastante controvertido y su evidencia escasa, además de que es difícil centrarse únicamente en un núcleo para resolver los problemas relacionados con dicha enfermedad.1-5he pendunculopontine nucleus contains many connections responsibleof modulate motor activity. It has been suggested that deep stimulationwould have significant benefits in the treatment of Parkinson's disease,intervention that could improve the patient’s quality of life and generatea positive impact in public health due Parkinson's disease has importantorganic and social burden. There is a growing area of research in thisfield, however is still uncertain if deep brain stimulation could guidefuture interventions with optimal results. For this reason, we pretend toclarify the existing knowledge of this procedure, nevertheless, it is quitecontroversial, we consider that it is difficult to focusing on a uniquenucleus to solve the problems associated with this disease

Actions to be taken for improving functional prognosis in dementia

The growing incidence of dementia has led to an increased need for specialized care and higher health and social costs. Functional decline is the main cause of dementia complications. Per definition, dementia diagnosis and severity stratification require a certain degree of functional impairment [1]. Therefore, it is important to determine strategies to prevent functional deterioration in both, general population and especially people with dementia. The number of older adults with some degree of disability will triple by 2050 due to the increase in the aging population and the prevalence of age-related diseases that lead to functional impairment [2]. Therefore, functional impairment and disability in old people are increasingly becoming a major public health concern. Furthermore, functional impairment severely impairs quality of life and consumes a large proportion of the public health resources, creating an important burden for health care systems. It is well known that functional loss and disability in dementia are the main consequences of cognitive decline. Therefore, most of the efforts in dementia management have been directed to stop or reverse cognitive decline. However, functional loss and disability are also the consequence of other conditions that are common in old age and comorbid with dementia, such as frailty, sarcopenia, malnutrition, falls, pulmonary or cardiovascular diseases, polypharmacy, depression, and neuropsychiatric symptoms (NPS) [3].Q3Q2The growing incidence of dementia has led to an increased need for specialized care and higher health and social costs. Functional decline is the main cause of dementia complications. Per definition, dementia diagnosis and severity stratification require a certain degree of functional impairment [1]. Therefore, it is important to determine strategies to prevent functional deterioration in both, general population and especially people with dementia. The number of older adults with some degree of disability will triple by 2050 due to the increase in the aging population and the prevalence of age-related diseases that lead to functional impairment [2]. Therefore, functional impairment and disability in old people are increasingly becoming a major public health concern. Furthermore, functional impairment severely impairs quality of life and consumes a large proportion of the public health resources, creating an important burden for health care systems. It is well known that functional loss and disability in dementia are the main consequences of cognitive decline. Therefore, most of the efforts in dementia management have been directed to stop or reverse cognitive decline. However, functional loss and disability are also the consequence of other conditions that are common in old age and comorbid with dementia, such as frailty, sarcopenia, malnutrition, falls, pulmonary or cardiovascular diseases, polypharmacy, depression, and neuropsychiatric symptoms (NPS) [3].https://orcid.org/0000-0001-5680-7880https://scholar.google.com/citations?view_op=search_authors&mauthors=carlos+alberto+cano-gutierrez&hl=es&oi=aohttps://scienti.minciencias.gov.co/cvlac/visualizador/generarCurriculoCv.do?cod_rh=0000054895&lang=esRevista Nacional - Indexad

Polypharmacy is associated with functional decline in Alzheimer's disease and Lewy body dementia

Antecedentes: en la demencia, varios factores pueden influir en el deterioro funcional además de la cognición. En Este estudio, nuestro objetivo es estudiar la posible asociación del número de medicamentos prescritos con funcional trayectorias de declive durante un seguimiento de cinco años en personas diagnosticadas con enfermedad de Alzheimer leve (EA) o Demencia con cuerpos de Lewy (LBD). Métodos: Este es un análisis longitudinal de un estudio de cohorte noruego titulado "El estudio de la demencia de occidente Noruega". Se incluyeron 196 pacientes con diagnóstico reciente de EA (n = 111) y LBD (n = 85), seguidos anualmente durante 5 años. Realizamos modelos lineales de efectos mixtos para analizar la asociación del número de medicamentos con declive funcional medido por la Escala Rápida de Calificación de Discapacidad - 2. Resultados: La media de medicamentos prescritos al inicio del estudio fue 4,18∓2,60, para AD 3,92∓2,51 y LBD 4,52∓2,70. El número de medicamentos aumentó durante el seguimiento; en el quinto año, la media de EA fue de 7,28∓4,42 y para LBD 8.11∓5.16. El uso de más medicamentos se asoció con un deterioro funcional más rápido en la EA (Est. 0.04, SE0.01, valor p 0.003) y LBD (Est 0.08, SE 0.03, valor p 0.008) después de ajustar por edad, sexo, comorbilidad, síntomas neuropsiquiátricos y cognición. Para cada medicamento agregado durante el seguimiento, funcional las trayectorias empeoraron en un 1% para AD y 2% para LBD. El número de medicamentos no se asoció con factores cognitivos. disminución. Conclusión: Encontramos que un mayor número de medicamentos se relacionó con un deterioro funcional más rápido, tanto en la EA y LBD. La prescripción, especialmente en la demencia, debe evaluarse cuidadosamente, por lo que el pronóstico en la demencia podría posiblemente se mejore.Q1Q1Background: In dementia, a number of factors may influence functional decline in addition to cognition. In this study, we aim to study the potential association of the number of prescribed medications with functional decline trajectories over a five-year follow-up in people diagnosed with mild Alzheimer's disease (AD) or Lewy Body dementia(LBD). Methods: This is a longitudinal analysis of a Norwegian cohort study entitled “The Dementia Study of Western Norway”. We included 196 patients newly diagnosed with AD (n=111) and LBD (n=85), followed annually for 5 years. We conducted linear mixed-effects models to analyze the association of the number of medications with functional decline measured by the Rapid Disability Rating Scale – 2. Results: The mean prescribed medications at baseline was 4.18∓2.60, for AD 3.92∓2.51 and LBD 4.52∓2.70. The number of medications increased during the follow-up; at year five the mean for AD was 7.28∓4.42 and for LBD 8.11∓5.16. Using more medications was associated with faster functional decline in AD (Est 0.04,SE0.01, p-value 0.003) and LBD (Est 0.08, SE 0.03, p-value 0.008) after adjusting for age, sex, comorbidity, neuropsychiatric symptoms, and cognition. For each medication added during the follow-up, functional trajectories worsened by 1% for AD and 2% for LBD. The number of medications was not associated with cognitive decline. Conclusion: We found that higher number of medications was related to a faster functional decline, both in AD and LBD. Prescription especially in dementia should be carefully assessed, thus prognosis in dementia might possibly be improved.https://orcid.org/0000-0001-5832-0603https://scholar.google.com/citations?user=MrICwaMAAAAJ&hl=enhttps://scienti.minciencias.gov.co/cvlac/visualizador/generarCurriculoCv.do?cod_rh=0001429659&lang=esRevista Internacional - Indexad

Tongue muscle mass is associated with total grey matter and hippocampal volumes in Dementia with Lewy Bodies

Background Age-related neurodegeneration, sarcopenia, and ectopic fat accumulation are conditions with shared pathways that remain poorly understood. We have measured muscle volume and fat accumulation in masseter and tongue muscle, and aim to explore their association with the total grey matter volume using MRI in older adults recently diagnosed with Alzheimer's disease (AD) and Dementia with Lewy bodies (DLB). Methods In this cross-sectional study, people newly diagnosed with mild AD (n=33) and DLB (n=20) underwent structural head MRI. Muscle volume and intramuscular fat (iMAT) of the tongue and masseter were computed using Slice-O-Matic software for segmentation. Total grey volume and hippocampal volumetric segmentation were performed with the FreeSurfer image analysis suite version 6.0. Independent regression models were employed to analyse the associations. Results Tongue iMAT was higher and total grey volume lower in DLB compared to AD. In the DLB group, tongue muscle was positively associated with total grey matter volume Est 0.92 (SE 0.24 p-value 0.002), left- Est 0.01 (SE 0.0028 p-value 0,002), and right- Est 0.0088 (SE 0.0027 p-value: 0.005) hippocampal volume. There were no statistically significant results for AD. Conclusion Tongue muscle volume was positively associated with hippocampal and total grey volume in DLB. Longitudinal designs are required to explore the extent and significance of this association.acceptedVersio

Body mass index trajectories and associations with cognitive decline in people with Lewy body dementia and Alzheimer's disease

Background and Aims In older adults with dementia, low body mass index (BMI) is associated with higher mortality and other adverse health outcomes. BMI or nutritional status trajectories from diagnosis have not yet been well described in dementia, especially in people with Lewy body dementia (LBD); a group that has a poorer prognosis. With this study, we aimed to evaluate the BMI trajectory in people diagnosed with mild LBD and Alzheimer's disease (AD). Methods The Dementia Study of Western Norway is a cohort study with annual assessments. Five-year measurements of BMI from 196 patients (LBD = 85 and AD = 111) diagnosed with mild dementia were analyzed using adjusted linear mixed-effects models. Results There were no differences between LBD and AD in baseline BMI, age, or mini-mental status examination (MMSE). During the follow-up, we observed a significant decrease in BMI in the LBD group across the study period (estimation [Est.]: −0.63, SE: 0.14; p < 0.001). By contrast, there was no significant change in BMI trajectory associated with AD diagnosis (Est.: 0.05, SE: 0.15; p = 0.730). Further, the introduction of an interaction term between diagnosis and time in the study showed that this difference (BMI trajectories) was significant (Est.: −0.63, SE: 0.14; p < 0.001). In addition, there was a significant interaction between MMSE total score and the follow-up time; the lower the MMSE, the lower the BMI (Est.: 0.01, SE: 0.01; p = 0.044). Conclusion In LBD, BMI significantly decreased with disease progression. In addition, low cognitive performance was associated with a reduction in BMI. These results highlight the importance of BMI evaluation in people with dementia, particularly patients diagnosed with LBD, and suggest that patients with LBD could be targeted for dietary intervention to maintain body weight.publishedVersio

COPD In Costa Rican Elder Older Adults and Its Association with Sarcopenia

Background: Sarcopenia is associated with to multiples comorbidities, including moreover those with some degree of inflammation. Chronic inflammatory states generate hypercatabolism and replacement of lean muscle mass for adipose tissue, decreasing muscle strength, power and function leading to disability and dependence. Here we study COPD as an important chronic inflammatory disease Strong associations have been reported between COPD and sarcopenia. The aim of this study is to evaluate the associations of COPD and sarcopenia with clinical outcomes, pulmonary function and health status and mortality. Methods: Data was taken of the CRELES- retirement cohort survey, a longitudinal study taken place in Costa Rica with a representative sample of 2820 elder adults born before 1945. Starting in 2010 with a second wave starting in 2012. The variable ‘presence of sarcopenia in patients with COPD’ was used to identify associations with independent variables (sociodemographic factors, self-rated health, comorbidities, functional status, cognitive status, pulmonary function, hospitalizations and mortality). Results: From a total of 2,827 60-year or older adults, 9.83% (n=278) were categorized as sarcopenic. A total of 18.09% referred as having a lung disease, from which 24.82% had sarcopenia (p=0.002). When grouping with sarcopenia and lung disease status, 74.24% did not had any of the conditions, 15.56% had just lung disease without sarcopenia, 7.67% had only sarcopenia without having lung disease and 2.53% had both conditions. The only group that had a higher risk of mortality was that having both conditions, with a hazard ratio of 1.81 (95% CI 1.27–2.58, p=0.001), after adjusting for age and sex. Conclusions: Older adults with lung disease have a significant higher prevalence of sarcopenia and a higher risk of mortality, than either any of the conditions alone. Special care to older adults with lung disease is important in order to detect sarcopenia and emphasize on those interventions that could impact this condition along with the regular treatment of the lung disease. This in turn could ameliorate prognosis of older adults with both conditions.Completo150-150Background: Sarcopenia is associated with to multiples comorbidities, including moreover those with some degree of inflammation. Chronic inflammatory states generate hypercatabolism and replacement of lean muscle mass for adipose tissue, decreasing muscle strength, power and function leading to disability and dependence. Here we study COPD as an important chronic inflammatory disease Strong associations have been reported between COPD and sarcopenia. The aim of this study is to evaluate the associations of COPD and sarcopenia with clinical outcomes, pulmonary function and health status and mortality. Methods: Data was taken of the CRELES- retirement cohort survey, a longitudinal study taken place in Costa Rica with a representative sample of 2820 elder adults born before 1945. Starting in 2010 with a second wave starting in 2012. The variable ‘presence of sarcopenia in patients with COPD’ was used to identify associations with independent variables (sociodemographic factors, self-rated health, comorbidities, functional status, cognitive status, pulmonary function, hospitalizations and mortality). Results: From a total of 2,827 60-year or older adults, 9.83% (n=278) were categorized as sarcopenic. A total of 18.09% referred as having a lung disease, from which 24.82% had sarcopenia (p=0.002). When grouping with sarcopenia and lung disease status, 74.24% did not had any of the conditions, 15.56% had just lung disease without sarcopenia, 7.67% had only sarcopenia without having lung disease and 2.53% had both conditions. The only group that had a higher risk of mortality was that having both conditions, with a hazard ratio of 1.81 (95% CI 1.27–2.58, p=0.001), after adjusting for age and sex. Conclusions: Older adults with lung disease have a significant higher prevalence of sarcopenia and a higher risk of mortality, than either any of the conditions alone. Special care to older adults with lung disease is important in order to detect sarcopenia and emphasize on those interventions that could impact this condition along with the regular treatment of the lung disease. This in turn could ameliorate prognosis of older adults with both conditions

Asociación entre tamización de cáncer de próstata, vinculación al sistema de salud y factores asociados en adultos mayores: análisis secundario de la encuesta SABE Bogotá, Colombia

Introduction Prostate cancer is a high prevalence disease in our male population. Early diagnosis is important in order to improve its prognosis. The aim of this article is to describe the factors associated with prostate cancer screening of older adults in Bogotá, Colombia. Materials and methods The study used data from the Bogotá 2012 Health, WellBeing, and Ageing (Salud, Bienestar y Envejecimiento [SABE]) survey, which included 736 men aged 60 years or older. The dependent variable used was self-reported prostate screening in the last 2 years. An analysis was performed to determine the between this variable and socio-demographic variables and comorbidities using multivariate analysis. Results There was a prevalence of prostate cancer of 3.15%, with 57.8% of the population having had at least one prostate examination. Those affiliated to a health insurance scheme were more likely to be screened than the uninsured with an OR: 8.81, 95% CI: 2.92-26.63, P less than .001, as those affiliated to subsidized social security health scheme OR: 3.70, 95% CI: 1.20-11.41, P =.023, respectively). Conclusion There is inequity in the opportunity of screening for prostate cancer according to the type of health insurance scheme. Early detection strategies must be strengthened in order to include the entire population. Further studies are needed to provide more information on this issue. © 2018, Sociedad Colombiana de Urología. Publicado por Thieme Revinter Publicações Ltda., Rio de Janeiro, Brazil