RESUMEN
The present demographic changes toward an aging society caused a rise in the number of senior citizens and the incidence and burden of age-related diseases (such as cardiovascular diseases [CVD], cancer, nonalcoholic fatty liver disease [NAFLD], diabetes mellitus, and dementia), of which nearly half is attributable to the population ≥60 years of age. Deficiencies in individual nutrients have been associated with increased risks for age-related diseases and high intakes and/or blood concentrations with risk reduction. Nutrition in general and the dietary intake of essential and nonessential biofactors is a major determinant of human health, the risk to develop age-related diseases, and ultimately of mortality in the older population. These biofactors can be a cost-effective strategy to prevent or, in some cases, even treat age-related diseases. Examples reviewed herein include omega-3 fatty acids and dietary fiber for the prevention of CVD, α-tocopherol (vitamin E) for the treatment of biopsy-proven nonalcoholic steatohepatitis, vitamin D for the prevention of neurodegenerative diseases, thiamine and α-lipoic acid for the treatment of diabetic neuropathy, and the role of folate in cancer epigenetics. This list of potentially helpful biofactors in the prevention and treatment of age-related diseases, however, is not exhaustive and many more examples exist. Furthermore, since there is currently no generally accepted definition of the term biofactors, we here propose a definition that, when adopted by scientists, will enable a harmonization and consistent use of the term in the scientific literature.
Asunto(s)
Enfermedades Cardiovasculares/prevención & control , Demencia/prevención & control , Diabetes Mellitus/prevención & control , Suplementos Dietéticos , Neoplasias/prevención & control , Enfermedad del Hígado Graso no Alcohólico/prevención & control , Anciano , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/patología , Demencia/genética , Demencia/metabolismo , Demencia/patología , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patología , Fibras de la Dieta/administración & dosificación , Epigénesis Genética , Ácidos Grasos Omega-3/administración & dosificación , Ácido Fólico/administración & dosificación , Humanos , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patología , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Tiamina/administración & dosificación , Ácido Tióctico/administración & dosificación , Vitamina D/administración & dosificación , Vitamina E/administración & dosificaciónRESUMEN
The older-adult population is constantly increasing, hence aging and mechanisms leading to aging are a topic raising increasing interest. Hypovitaminosis D is common amongst old patients and has been proposed as causative of several chronic diseases. Here we review the role of hypovitaminosis D and vitamin D supplementation in sarcopenia and dementia, from bench to bedside.
Asunto(s)
Envejecimiento , Demencia , Sarcopenia , Deficiencia de Vitamina D , Vitamina D/uso terapéutico , Adulto , Anciano , Envejecimiento/efectos de los fármacos , Envejecimiento/metabolismo , Envejecimiento/patología , Encéfalo/metabolismo , Encéfalo/patología , Encéfalo/fisiopatología , Enfermedad Crónica , Demencia/metabolismo , Demencia/patología , Demencia/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Músculo Esquelético/fisiopatología , Sarcopenia/dietoterapia , Sarcopenia/metabolismo , Sarcopenia/patología , Sarcopenia/fisiopatología , Deficiencia de Vitamina D/dietoterapia , Deficiencia de Vitamina D/metabolismo , Deficiencia de Vitamina D/patología , Deficiencia de Vitamina D/fisiopatologíaRESUMEN
AIM: Coronary artery disease (CAD) and cognitive impairment are common in the elderly, with evidence for shared risk factors and pathophysiological processes. The coronary artery calcium (CAC) score is a marker of subclinical CAD, which may allow early detection of individuals prone to cognitive decline. Prior studies on associations of CAC and clinical CAD with cognitive impairment had discrepant results. This systematic review aims to evaluate the association of (sub)clinical CAD with cognitive function, cognitive decline, and diagnosis of mild cognitive impairment (MCI) or dementia. METHODS: A systematic search was conducted in MEDLINE, Embase, and Web of Science until February 2019, supplemented with citations tracking. Two reviewers independently screened studies and extracted information including odds ratios (ORs) and hazard ratios (HRs). RESULTS: Forty-six studies, 10 on CAC and 36 on clinical CAD, comprising 1,248,908 participants were included in the systematic review. Studies about associations of (sub)clinical CAD with cognitive function and cognitive decline had heterogeneous methodology and inconsistent findings. Two population-based studies investigated the association between CAC and risk of dementia over 6-12.2 years using different CAC scoring methods. Both found a tendency toward higher risk of dementia as CAC severity increased. Meta-analysis in 15 studies (663,250 individuals) showed an association between CAD and MCI/dementia (pooled OR 1.32, 95%CI 1.17-1.48) with substantial heterogeneity (I2=87.0%, pï¼0.001). Pooled HR of CAD for incident MCI/dementia over 3.2-25.5 years in six longitudinal studies (70,060 individuals) was 1.51 (95%CI 1.24-1.85), with low heterogeneity (I2=14.1%, p=0.32). Sensitivity analysis did not detect any study that was of particular influence on the pooled OR or HR. CONCLUSIONS: Limited evidence suggests the CAC score is associated with risk of dementia. In clinical CAD, risk of MCI and dementia is increased by 50%, as supported by stronger evidence.
Asunto(s)
Calcio/metabolismo , Disfunción Cognitiva/etiología , Enfermedad de la Arteria Coronaria/complicaciones , Vasos Coronarios/metabolismo , Demencia/etiología , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/patología , Demencia/metabolismo , Demencia/patología , Humanos , PronósticoRESUMEN
Intact memory and problem solving are key to functional independence and quality of life in older age. Considering the unprecedented demographic shift toward a greater number of older adults than children in the United States in the next few decades, it is critically important for older adults to maintain work productivity and functional independence for as long as possible. Implementing early interventions focused on modifiable risk factors for cognitive decline at midlife is a strategy with the highest chance of success at present, bearing in mind the current lack of dementia cures. We present a selective, narrative review of evidence linking nutrition, body composition, vascular health, and brain function in midlife to highlight the phenotypic heterogeneity of obesity-related brain vulnerability and to endorse the development of individually tailored lifestyle modification plans for primary prevention of cognitive decline.
Asunto(s)
Encéfalo/fisiopatología , Demencia/etiología , Obesidad/psicología , Composición Corporal , Distribución de la Grasa Corporal , Capacidad Cardiovascular , Demencia/patología , Demencia/prevención & control , Demencia/psicología , Dieta/efectos adversos , Grasas de la Dieta , Susceptibilidad a Enfermedades , Ejercicio Físico , Ácidos Grasos Omega-3/fisiología , Ácidos Grasos Omega-3/uso terapéutico , Humanos , Estilo de Vida , Trastornos de la Memoria/etiología , Trastornos de la Memoria/patología , Trastornos de la Memoria/prevención & control , Trastornos de la Memoria/psicología , Persona de Mediana Edad , Neuroimagen , Estado Nutricional , Obesidad/complicaciones , Obesidad/epidemiología , Obesidad/fisiopatología , Fenotipo , Dinámica Poblacional , Solución de Problemas , Enfermedades Vasculares/complicaciones , Enfermedades Vasculares/fisiopatologíaRESUMEN
In this review, we consider how the onset and progression of dementia can disrupt one's sense of self, and propose that music is an ideal tool for alleviating this distressing symptom. Various aspects of the self can be impaired in people with dementia, depending on how the self is defined. There are anecdotal reports that music can 'bring people back to themselves' in the face of dementia, but there have been scarce empirical investigations of this topic. Motivated by a consideration of the existing literature, we outline a novel theoretical framework that accounts for the relationship between music and the self in people with dementia. We propose that music has a number of 'design features' that make it uniquely equipped to engage multiple aspects of the self. We suggest that each design feature interacts with different aspects of the self to varying degrees, promoting overall wellbeing. We discuss how existing research on music and dementia fits within this framework, and describe two case studies in which music was an ideal stimulus for reaffirming their sense of self. Our framework may be useful for the diagnosis and treatment of impairments of self in people with dementia, and highlights how music, given its ability to engage all aspects of the self simultaneously, can result in an overall enhanced sense of self.
Asunto(s)
Estado de Conciencia , Demencia/terapia , Musicoterapia , Música , Personalidad , Demencia/patología , Demencia/psicología , HumanosRESUMEN
Importance: The eye is a sensory organ that is easily accessible for imaging techniques, allowing the measurement of the retinal nerve fiber layer (RNFL) thickness. The eye is part of the central nervous system, and its neurons may be susceptible to degeneration; therefore, changes in the RNFL thickness may reflect microstructural and volume alterations in the brain. Objective: To explore the association between the peripapillary RNFL thickness and brain alterations in the visual and limbic networks in elderly people without dementia. Design, Setting, and Participants: Cross-sectional analysis of the Three-City/Antioxydants, Lipides Essentiels, Nutrition et Maladies Oculaires (Alienor) Study cohort (April 2009 to December 2010). The dates of analysis were July 2017 to August 2018. The setting was a population-based study in France. The brain volume analysis included 104 participants, and the diffusion tensor imaging analysis included 79 participants. Main Outcomes and Measures: Global RNFL was assessed by spectral-domain optical coherence tomography. Brain volumes were assessed via T1-weighted magnetic resonance imaging by measurement of the global white and gray matter fractions and the hippocampal fraction. Brain microstructural alterations were assessed with diffusion tensor imaging at the level of the posterior thalamic radiations, the limbic system tracts (the fornix and cingulum bundles), and the posterior limb of the internal capsule (control region). Linear regression models adjusted for several confounders were performed. Results: Among a total of 104 participants, the mean (SD) age was 80.8 (3.9) years, and the cohort was 56.7% women (n = 59). The mean (SD) global RNFL thickness was 89.3 (12.9) µm. A thicker RNFL was associated with a greater hippocampal fraction (quantity of increase ß = 0.013; 95% CI, 0.001-0.025 per 10-µm increase in the RNFL thickness) and better diffusion tensor imaging variables in the global cingulum (mean diffusivity ß = -0.007; 95% CI, -0.015 to -0.000) and the hippocampal part of the cingulum (mean diffusivity ß = -0.009; 95% CI, -0.016 to -0.002 and radial diffusivity ß = -0.010; 95% CI, -0.018 to -0.002) and the posterior thalamic radiations (fractional anisotropy ß = 0.008; 95% CI, 0.000-0.017). No significant associations were found with other magnetic resonance imaging volumes or with other diffusion tensor imaging variables. In particular, there was no significant association with the control region of interest. Conclusions and Relevance: Results of this study suggest that in elderly individuals without dementia, a thicker RNFL was associated with better magnetic resonance imaging variables both in a region that included the visual pathways and in regions particularly involved in the neurodegenerative processes of Alzheimer disease.
Asunto(s)
Encéfalo , Demencia , Fibras Nerviosas , Neuronas Retinianas , Vías Visuales , Anciano , Anciano de 80 o más Años , Envejecimiento , Anisotropía , Encéfalo/patología , Estudios de Cohortes , Estudios Transversales , Demencia/diagnóstico , Demencia/patología , Imagen de Difusión por Resonancia Magnética/métodos , Imagen de Difusión Tensora/métodos , Diagnóstico Precoz , Femenino , Humanos , Hipotálamo/patología , Sistema Límbico/patología , Masculino , Fibras Nerviosas/patología , Valores de Referencia , Retina , Neuronas Retinianas/patología , Tomografía de Coherencia Óptica/métodos , Vías Visuales/patologíaRESUMEN
OBJECTIVES: Elevated total plasma homocysteine is a risk factor for Alzheimer's disease (AD) and there is some evidence that omega-3 polyunsaturated fatty acids (n-3 PUFAs) can modulate the effects of homocysteine-lowering B vitamins on AD related pathologies. Hence we investigated the relationship between total plasma homocysteine and cortical ß-amyloid (Aß) in older adults at risk of dementia. The role of erythrocyte membrane n-3 PUFAs (omega 3 index) on this relationship was also explored. DESIGN: This is a cross-sectional study using data from the Multidomain Alzheimer Preventive Trial (MAPT); a randomised controlled trial. SETTING: French community dwellers aged 70 or over reporting subjective memory complaints, but free from a diagnosis of clinical dementia. PARTICIPANTS: Individuals were from the MAPT trial (n = 177) with data on total plasma homocysteine at baseline and cortical Aß load. MEASUREMENTS: Cortical-to-cerebellar standard uptake value ratios were assessed using [18F] florbetapir positron emission tomography (PET). Total baseline plasma homocysteine was measured using an enzymatic cycling assay. Baseline omega 3 index was measured using gas chromatography. Cross-sectional associations were explored using adjusted multiple linear regression models. RESULTS: We found that total baseline plasma homocysteine was not significantly associated with cortical Aß as demonstrated using multiple linear regression models adjusted for age, sex, education, cognitive status, time interval between baseline and PET-scan, omega-3 index, MAPT group allocation and Apolipoprotein E ε4 status (B-coefficient -0.001, 95 % CI: -0.008,0.006, p = 0.838). Exploratory analysis showed that homocysteine was however significantly associated with cortical Aß in subjects with low baseline omega-3 index (< 4.72 %) after adjustment for Apolipoprotein E ε4 status (B-coefficient 0.041, 95 % CI: 0.017,0.066, p = 0.005, n = 10), but not in subjects with a high baseline omega-3 index (B-coefficient -0.010, 95 % CI: -0.023,0.003, p = 0.132, n = 66). CONCLUSIONS: The role of n-3 PUFAs on the relationship between homocysteine and cerebral Aß warrants further investigation.
Asunto(s)
Enfermedad de Alzheimer/prevención & control , Péptidos beta-Amiloides/metabolismo , Demencia/diagnóstico , Ácidos Grasos Omega-3/metabolismo , Homocisteína/efectos adversos , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/patología , Estudios Transversales , Demencia/patología , Femenino , Homocisteína/metabolismo , Humanos , Masculino , Factores de RiesgoRESUMEN
Differential scanning calorimetry was applied to evaluate the efficacy of preventive treatments with biologically active compounds of plant origin against neurodegenerative disorder in mice. As we reported recently, large differences exist between the heat capacity profiles of water-soluble brain proteome fractions from healthy animals and from animals with scopolamine-induced dementia: the profiles for healthy animals displayed well expressed exothermic event peaking at 40-45°C, by few degrees above body temperature, but still preceding in temperature the proteome endothermic denaturational transitions; the low-temperature exotherm was completely abolished by the scopolamine treatment. Here we explored this signature difference in the heat capacity profiles to assess the efficacy of preventive treatments with protectant drugs anticipated to slow down or block progression of dementia (myrtenal, ellagic acid, lipoic acid and their combinations, including also ascorbic acid). We found that these neuroprotectants counteract the scopolamine effect and partially or completely preserve the 'healthy' thermogram, and specifically the low-temperature exotherm. These results well correlate with the changes in the cognitive functions of the animals assessed using the Step Through Test for learning and memory. The exothermic event is deemed to be associated with a reversible process of fibrillization and/or aggregation of specific water-soluble brain protein fractions preceding their denaturation. Most importantly, the results demonstrate that the effect of scopolamine and its prevention by protectant substances are clearly displayed in the heat capacity profiles of the brain proteome, thus identifying DSC as a powerful method in drug testing and discovery.
Asunto(s)
Cognición/efectos de los fármacos , Demencia/prevención & control , Fármacos Neuroprotectores/farmacología , Proteoma/metabolismo , Animales , Demencia/metabolismo , Demencia/patología , Evaluación Preclínica de Medicamentos , Masculino , Ratones , Ratones Endogámicos ICR , Fármacos Neuroprotectores/química , Escopolamina/efectos adversos , Escopolamina/farmacologíaRESUMEN
OBJECTIVES: Type 2 diabetes mellitus (T2DM) increases the risk of brain atrophy and dementia. We aimed to elucidate deep grey matter (GM) structural abnormalities and their relationships with T2DM cognitive deficits by combining region of interest (ROI)-based volumetry, voxel-based morphometry (VBM) and shape analysis. METHODS: We recruited 23 T2DM patients and 24 age-matched healthy controls to undergo T1-weighted structural MRI scanning. Images were analysed using the three aforementioned methods to obtain deep GM structural shapes and volumes. Biochemical and cognitive assessments were made and were correlated with the resulting metrics. RESULTS: Shape analysis revealed that T2DM is associated with focal atrophy in the bilateral caudate head and dorso-medial part of the thalamus. ROI-based volumetry only detected thalamic volume reduction in T2DM when compared to the controls. No significant between-group differences were found by VBM. Furthermore, a worse performance of cognitive processing speed correlated with more severe GM atrophy in the bilateral dorso-medial part of the thalamus. Also, the GM volume in the bilateral dorso-medial part of the thalamus changed negatively with HbA1c. CONCLUSIONS: Shape analysis is sensitive in identifying T2DM deep GM structural abnormalities and their relationships with cognitive impairments, which may greatly assist in clarifying the neural substrate of T2DM cognitive dysfunction. KEY POINTS: ⢠Type 2 diabetes mellitus is accompanied with brain atrophy and cognitive dysfunction ⢠Deep grey matter structures are essential for multiple cognitive processes ⢠Shape analysis revealed local atrophy in the dorso-medial thalamus and caudatum in patients ⢠Dorso-medial thalamic atrophy correlated to cognitive processing speed slowing and high HbA1c. ⢠Shape analysis has advantages in unraveling neural substrates of diabetic cognitive deficits.
Asunto(s)
Encefalopatías/patología , Trastornos del Conocimiento/patología , Diabetes Mellitus Tipo 2/patología , Sustancia Gris/patología , Adulto , Anciano , Atrofia/patología , Estudios de Casos y Controles , Demencia/patología , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Tálamo/patologíaRESUMEN
A potent antioxidant, selenium might modulate dementia-induced progression of brain and blood oxidative and apoptotic injuries. The present study explores whether selenium protects against experimental dementia (scopolamine, SCOP)-induced brain, and blood oxidative stress, apoptosis levels, and cytokine production in rats. Thirty-two rats were equally divided into four groups. The first group was used as an untreated control. The second group was treated with SCOP to induce dementia. The third and fourth groups received 1.5 mg/kg selenium (sodium selenite) and SCOP + selenium, respectively. Dementia was induced in the second and forth groups by intraperitoneal SCOP (1 mg/kg) administration. Brain, plasma, and erythrocyte lipid peroxidation levels as well as plasma TNF-α, interleukin (IL)-1ß, and IL-4 levels were high in the SCOP group though they were low in selenium treatments. Selenium and selenium + SCOP treatments increased the lowered glutathione peroxidase activity, reduced glutathione, vitamins A and E concentrations in the brain, erythrocytes and plasma of the SCOP group. Apoptotic value expressions as active caspase-3, procaspase-9, and PARP were also increased by SCOP, while they were decreased by selenium and selenium + SCOP treatments. In conclusion, selenium induced protective effects against experimental dementia-induced brain, and blood oxidative injuries and apoptosis through regulation of cytokine production, vitamin E, glutathione concentrations, and glutathione peroxidase activity.
Asunto(s)
Antioxidantes/uso terapéutico , Apoptosis/efectos de los fármacos , Demencia/tratamiento farmacológico , Encefalitis/tratamiento farmacológico , Antagonistas Muscarínicos , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Escopolamina , Selenio/farmacología , Selenio/uso terapéutico , Envejecimiento/patología , Animales , Citocinas/metabolismo , Demencia/inducido químicamente , Demencia/patología , Encefalitis/patología , Femenino , Aprendizaje por Laberinto/efectos de los fármacos , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/tratamiento farmacológico , Trastornos de la Memoria/parasitología , Ratas , Ratas Wistar , Vitaminas/metabolismoRESUMEN
Previous reports have demonstrated that the combination of Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) botanical extracts, which are the components of an already approved cannabis-based medicine, reduce the Alzheimer-like phenotype of AßPP/PS1 transgenic mice when chronically administered during the early symptomatic stage. Here, we provide evidence that such natural cannabinoids are still effective in reducing memory impairment in AßPP/PS1 mice at advanced stages of the disease but are not effective in modifying the Aß processing or in reducing the glial reactivity associated with aberrant Aß deposition as occurs when administered at early stages of the disease. The present study also demonstrates that natural cannabinoids do not affect cognitive impairment associated with healthy aging in wild-type mice. The positive effects induced by Δ9-THC and CBD in aged AßPP/PS1 mice are associated with reduced GluR2/3 and increased levels of GABA-A Rα1 in cannabinoid-treated animals when compared with animals treated with vehicle alone.
Asunto(s)
Demencia/tratamiento farmacológico , Demencia/metabolismo , Modelos Animales de Enfermedad , Marihuana Medicinal/uso terapéutico , Animales , Demencia/patología , Humanos , Masculino , Trastornos de la Memoria/tratamiento farmacológico , Trastornos de la Memoria/metabolismo , Trastornos de la Memoria/patología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Receptores AMPA/antagonistas & inhibidores , Receptores AMPA/metabolismo , Receptores de GABA-A/metabolismo , Resultado del TratamientoRESUMEN
Nonhemorrhagic neurological deficits are underrecognized symptoms of intracranial dural arteriovenous fistulas (dAVFs) having cortical venous drainage. These symptoms are the consequence of cortical venous hypertension and portend a clinical course with increased risk of neurological morbidity and mortality. One rarely documented and easily misinterpreted type of nonhemorrhagic neurological deficit is progressive dementia, which can result from venous hypertension in the cortex or in bilateral thalami. The latter, which is due to dAVF drainage into the deep venous system, is the less common of these 2 dementia syndromes. Herein, the authors report 4 cases of dAVF with venous drainage into the vein of Galen causing bithalamic edema and rapidly progressive dementia. Two patients were treated successfully with endovascular embolization, and the other 2 patients were treated successfully with endovascular embolization followed by surgery. The radiographic abnormalities and presenting symptoms rapidly resolved after dAVF obliteration in all 4 cases. Detailed descriptions of these 4 cases are presented along with a critical review of 15 previously reported cases. In our analysis of these 19 published cases, the following were emphasized: 1) the clinical and radiographic differences between dAVF-induced thalamic versus cortical dementia syndromes; 2) the differential diagnosis and necessary radiographic workup for patients presenting with a rapidly progressive thalamic dementia syndrome; 3) the frequency at which delays in diagnosis occurred and potentially dangerous and avoidable diagnostic procedures were used; and 4) the rapidity and completeness of symptom resolution following dAVF treatment.
Asunto(s)
Malformaciones Vasculares del Sistema Nervioso Central/complicaciones , Malformaciones Vasculares del Sistema Nervioso Central/diagnóstico por imagen , Demencia/diagnóstico por imagen , Demencia/etiología , Tálamo/diagnóstico por imagen , Anciano , Malformaciones Vasculares del Sistema Nervioso Central/patología , Malformaciones Vasculares del Sistema Nervioso Central/terapia , Angiografía Cerebral , Diagnóstico Tardío , Demencia/patología , Demencia/terapia , Diagnóstico Diferencial , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Tálamo/patología , Tálamo/cirugía , Tomografía Computarizada por Rayos XRESUMEN
Previous epidemiologic studies suggest that antihypertensive drugs may be protective against cognitive decline. To determine if subjects enrolled in the University of Kentucky longitudinal aging study who used antihypertensive drugs showed diminished progression to dementia, we used a 3-parameter logistic regression model to compare the rate of progression to dementia for subjects who used any of the five common categories of antihypertensive drugs to those with similar demographic characteristics but who did not use antihypertensives. Regression modeling showed that subjects who used calcium channel blockers (CCBs) but not the other classes of antihypertensives showed a significant decrease in the rate of progression to dementia. Significantly, use of CCBs ameliorated the negative effects of the presence of APOE-4 alleles on cognitive decline. To determine if CCBs could minimize amyloid beta peptide (Aß(1-42)) production, H4 neuroglioma cultures transfected to overexpress APP were treated with various CCBs and Aß(1-42) levels and levels of proteins involved in Aß production were quantified. Results show that treatment with nifedipine led to a significant decrease in levels of Aß(1-42), with no significant decrease in cell viability. Collectively, these data suggest that use of CCBs significantly diminishes the rate of progression to dementia and may minimize formation of Aß(1-42).
Asunto(s)
Bloqueadores de los Canales de Calcio/uso terapéutico , Demencia/tratamiento farmacológico , Anciano , Péptidos beta-Amiloides/análisis , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Antihipertensivos/uso terapéutico , Apolipoproteína E4/genética , Bloqueadores de los Canales de Calcio/farmacología , Estudios de Casos y Controles , Línea Celular , Supervivencia Celular/efectos de los fármacos , Trastornos del Conocimiento/tratamiento farmacológico , Demencia/metabolismo , Demencia/patología , Progresión de la Enfermedad , Ensayo de Inmunoadsorción Enzimática , Humanos , Modelos Logísticos , Estudios Longitudinales , Persona de Mediana Edad , Nifedipino/farmacología , Nifedipino/uso terapéutico , Fragmentos de Péptidos/análisis , TransfecciónRESUMEN
The curry spice curcumin plays a protective role in mouse models of neurodegenerative diseases, and can also directly modulate aggregation of α-synuclein protein in vitro, yet no studies have described the interaction of curcumin and α-synuclein in genetic synucleinopathy mouse models. Here we examined the effect of chronic and acute curcumin treatment in the Syn-GFP mouse line, which overexpresses wild-type human α-synuclein protein. We discovered that curcumin diet intervention significantly improved gait impairments and resulted in an increase in phosphorylated forms of α-synuclein at cortical presynaptic terminals. Acute curcumin treatment also caused an increase in phosphorylated α-synuclein in terminals, but had no direct effect on α-synuclein aggregation, as measured by in vivo multiphoton imaging and Proteinase-K digestion. Using LC-MS/MS, we detected ~5 ng/mL and ~12 ng/mL free curcumin in the plasma of chronic or acutely treated mice, with a glucuronidation rate of 94% and 97%, respectively. Despite the low plasma levels and extensive metabolism of curcumin, these results show that dietary curcumin intervention correlates with significant behavioral and molecular changes in a genetic synucleinopathy mouse model that mimics human disease.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Conducta Animal/efectos de los fármacos , Curcumina/farmacología , Demencia/tratamiento farmacológico , Cuerpos de Lewy/efectos de los fármacos , Actividad Motora/efectos de los fármacos , alfa-Sinucleína/fisiología , Animales , Western Blotting , Cromatografía Liquida , Demencia/patología , Femenino , Humanos , Técnicas para Inmunoenzimas , Cuerpos de Lewy/patología , Masculino , Ratones , Ratones Transgénicos , Fosforilación/efectos de los fármacos , Espectrometría de Masas en TándemRESUMEN
Los síntomas psicológicos y conductuales de la demencia (SPCD) generan un sufrimiento sobreañadido en el anciano y en el cuidador, agravan el deterioro cognitivo y funcional y precipitan la institucionalización del anciano (1,2). En los últimos años se ha investigado acerca de La Terapia Asistida con Animales de Compañía (TAAC) como terapia no farmacológica para el control dichos síntomas, demostrando ser una buena alternativa coste- efectiva para el tratamiento. El presente estudio valora la efectividad de la terapia para el control de síntomas conductuales en pacientes con Demencia institucionalizados. Se realizó un estudio prospectivo, multicéntrico, de manera simultánea en 2 residencias de la Provincia de Toledo, con un total de 36 pacientes, 24 con deterioro cognitivo moderado-severo y SPCD, y 12 pacientes sin demencia con trastornos afectivos. De forma aleatorizada se distribuyeron los pacientes con demencia en un grupo de intervención con TAAC (12) y un grupo control sin TAAC (12), además del grupo de sanos (12). La intervención consistía en 16 sesiones, 2 sesiones cada semana de 35 minutos de duración. La medición se realizó con las escalas de MMSE, Barthel Modificado, Cornell, Quality Scale, NPI y MOPI, antes de iniciar las terapias y al finalizar las sesiones. La terapia asistida con animales resultó eficaz tras reducir agitación y agresividad según la puntuación de NPI (P0.004) y mejoró la calidad de vida según la escala Quality of Life (P 0,004), de los pacientes con TAAC
The psychological and behavioral symptoms of dementia (SPCD) generate additional suffering in the elderly and caregiver, exacerbate cognitive and functional impairment and precipitate the institutionalization of the elderly (1,2). In recent years, research has been conducted in Animal-Assisted Therapy (AAT) as a non-drug therapy to control the symptoms, proving to be a good cost-effective alternative for treatment. Our study aims to assess the effectiveness of therapy to control behavioral symptoms [RR1] in institutionalized patients with dementia. A prospective multicenter study is performed simultaneously at two residences in the province of Toledo, with a total of 36 patients, 24 with moderate-severe cognitive impairment and SPCD, and 12 patients without dementia and affective disorders. Dementia patients were randomly divided into an intervention group with TAAC (12) and a control group without AAT (12), besides the healthy group (12). The intervention consisted of 16 sessions, 2 sessions per week for 35 minutes in duration. The measurement was performed with MMSE scales, Modified Barthel, Cornell, Quality Scale, NPI and MOPI before starting the therapies and at the end of the sessions. The animal-assisted therapy was effective after reducing agitation and aggressiveness according to an NPI score (P0.004) and improved quality of life according to the Quality of Life Scale (P 0.004), for the patients with AAT
Asunto(s)
Femenino , Humanos , Masculino , Terapia Asistida por Animales/clasificación , Terapia Asistida por Animales/métodos , Perros/psicología , Demencia/patología , Demencia/psicología , Cuidadores/psicología , Terapia Asistida por Animales/normas , Terapia Asistida por Animales/tendencias , Perros/clasificación , Demencia/complicaciones , Demencia/metabolismo , España/etnología , Cuidadores/educación , Estudios ProspectivosRESUMEN
OBJECTIVE: We undertook a non-targeted lipidomics analysis of post-mortem cerebrospinal fluid (CSF), frontal cortex grey matter, and subjacent white matter to define potential biomarkers that distinguish cognitively intact subjects from those with incipient or established dementia. Our objective was to increase our understanding of the role of brain lipids in pathophysiology of aging and age-related cognitive impairment. METHODS: Levels of 650 individual lipids, across 26 lipid subclasses, were measured utilising a high-resolution mass spectrometric analysis platform. RESULTS: Monoacylglycerols (MAG), diacylglycerols (DAG), and the very-long-chain fatty acid 26:0 were elevated in the grey matter of the mild cognitive impairment (MCI) and old dementia (OD) cohorts. Ethanolamine plasmalogens (PlsEtn) were decreased in the grey matter of the young dementia (YD) and OD cohorts while and phosphatidylethanolamines (PtdEth) were lower in the MCI, YD and OD cohorts. In the white matter, decrements in sulphatide levels were detected in the YD group, DAG levels were elevated in the MCI group, and MAG levels were increased in the YD and OD groups. CONCLUSION: The parallel changes in grey matter MAGs and DAGs in the MCI and OD groups suggest that these two cohorts may have a similar underlying pathophysiology; consistent with this, MCI subjects were more similar in age to OD than to YD subjects. While PlsEtn and phosphatidylethanolamine were decreased in the YD and OD groups they were unaltered in the MCI group indicating that alterations in plasmalogen synthesis are unlikely to represent an initiating event in the transition from MCI to dementia.
Asunto(s)
Enfermedad de Alzheimer/metabolismo , Encéfalo/metabolismo , Disfunción Cognitiva/metabolismo , Demencia/metabolismo , Diglicéridos/metabolismo , Monoglicéridos/metabolismo , Plasmalógenos/metabolismo , Factores de Edad , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/líquido cefalorraquídeo , Enfermedad de Alzheimer/patología , Biomarcadores/líquido cefalorraquídeo , Biomarcadores/metabolismo , Disfunción Cognitiva/líquido cefalorraquídeo , Disfunción Cognitiva/patología , Demencia/patología , Diagnóstico , Diglicéridos/líquido cefalorraquídeo , Ácidos Docosahexaenoicos/líquido cefalorraquídeo , Ácidos Docosahexaenoicos/metabolismo , Femenino , Lóbulo Frontal/metabolismo , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Monoglicéridos/líquido cefalorraquídeo , Pruebas Neuropsicológicas , Plasmalógenos/líquido cefalorraquídeo , Sustancia Blanca/metabolismoRESUMEN
We previously reported that Alzheimer-related pathology in cerebral cortex of APP/PS1 and K3 tau transgenic mouse strains is mitigated by near infrared light (NIr). Here, we extend these observations to the cerebellum. One month of NIr treatment mitigated the deposition of ß-amyloid in cerebellar cortex of APP/PS1 mice, and the formation of neurofibrillary tangles, the hyperphosphorylation of tau, the damage caused by oxidative stress and the downregulation of cytochrome oxidase expression by Purkinje cells in the cerebellar cortex of K3 mice. These findings show the ability of NIr to mitigate degeneration in many - probably all - regions of the mouse brain.
Asunto(s)
Cerebelo/efectos de la radiación , Demencia/prevención & control , Rayos Infrarrojos , Precursor de Proteína beta-Amiloide/genética , Animales , Cerebelo/metabolismo , Cerebelo/patología , Demencia/metabolismo , Demencia/patología , Modelos Animales de Enfermedad , Terapia por Luz de Baja Intensidad , Ratones Transgénicos , Mitocondrias/metabolismo , Estrés Oxidativo , Placa Amiloide/patología , Presenilina-1/genética , Proteínas tau/genéticaRESUMEN
The association between hearing impairment, the diagnosis of dementia, and the role of sensory therapy has been proposed for some time, but further research is needed. Current understanding of this association requires the commitment of those experts who can integrate experience and research from several fields to be able to understand the link from hearing to dementia. A workshop whose panelists included experts from many areas, ranging from ear, nose and throat (ENT) to dementia's specialists, was promoted and organized by the Giovanni Lorenzini Medical Science Foundation (Milan, Italy; Houston, TX, USA) to increase the awareness of the relationship between hearing loss and dementia, and included questions and comments following a presentation from the clinical researcher, Frank Lin, who has been evaluating the relationship between hearing loss and cognitive decline since 2009.
Asunto(s)
Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/patología , Pérdida Auditiva/diagnóstico , Pérdida Auditiva/psicología , Animales , Cognición/fisiología , Demencia/diagnóstico , Demencia/patología , Demencia/psicología , Pérdida Auditiva/patología , HumanosRESUMEN
This is a qualitative review of the evidence linking dietary fat composition to the risk of developing dementia. The review considers laboratory and animal studies that identify underlying mechanisms as well as prospective epidemiologic studies linking biochemical or dietary fatty acids to cognitive decline or incident dementia. Several lines of evidence provide support for the hypothesis that high saturated or trans fatty acids increase the risk of dementia and high polyunsaturated or monounsaturated fatty acids decrease risk. Dietary fat composition is an important factor in blood-brain barrier function and the blood cholesterol profile. Cholesterol and blood-brain barrier function are involved in the neuropathology of Alzheimer's disease, and the primary genetic risk factor for Alzheimer's disease, apolipoprotein E-ε4, is involved in cholesterol transport. The epidemiologic literature is seemingly inconsistent on this topic, but many studies are difficult to interpret because of analytical techniques that ignored negative confounding by other fatty acids, which likely resulted in null findings. The studies that appropriately adjust for confounding by other fats support the dietary fat composition hypothesis.
Asunto(s)
Enfermedad de Alzheimer/etiología , Demencia/etiología , Grasas de la Dieta/efectos adversos , Ácidos Grasos/efectos adversos , Ácidos Grasos trans/efectos adversos , Enfermedad de Alzheimer/patología , Animales , Apolipoproteína E4/fisiología , Barrera Hematoencefálica/fisiología , Encéfalo/patología , Colesterol/sangre , Colesterol/metabolismo , Demencia/patología , Grasas Insaturadas en la Dieta , Humanos , RiesgoRESUMEN
Dentre as diferentes e recentes formas de intervenções não-farmacológicas para pacientes com demência realizadas no Brasil, não foram encontrados estudos que investigaram o efeito de um protocolo de caratê em pacientes com este quadro clínico, mais especificamente em idosos com diagnóstico de demência mista, doença de Alzheimer associada com demência vascular. Objetivo: O presente estudo teve como objetivo analisar os efeitos de um treinamento de caratê nas funções cognitivas e funcionais de um idoso com demência mista. Método: O participante, clinicamente diagnosticado com demência mista, passou por uma anamnese, seguida de avaliação cognitiva e funcional, antes e depois de um treinamento de quatro meses. O treinamento de caratê foi adaptado e sistematizado, visando fortalecimento muscular, flexibilidade, técnicas de posturas, ataque (socos e chutes), bloqueios (defesas) e katas (luta imaginária com váriosoponentes), três vezes por semana, com duração de uma hora sessão em dias não consecutivos. Resultados: Os resultados encontrados foram manutenção das funções cognitivas e melhora no equilíbrio estático e dinâmico. Conclusão: Conclui-se que o treinamento adaptado e sistematizado do caratê contribui para melhora de equilíbrio estático e dinâmico e manutenção do status cognitivo. Podendo contribuir assim para uma nova alternativa de intervenção não-farmacológica em idosos com demência mista.
Among the different forms and recent non-pharmacological interventions for dementia patients already performed in Brazil, there are no studies that have investigated the effect of a protocol of karate in patients with this clinical conditions, more specifically in the elderly with a diagnosisof mixed dementia, Alzheimer?s disease associated with vascular dementia. Objective: Thus, the present study aimed to analyze the effects of a karate training in cognitive and functional with an elderly mixed dementia. Method: The participant, clinically diagnosed with mixed dementia, underwent a anamnesis, followed by cognitive and functional assessment, pre and post training four months. The karate training was adapted and systematized, in order to muscle strengthening, flexibility, posture techniques, attack (punches and kicks), blocks (defenses) and kata (imaginary fightwith multiple opponents), three times per week, lasting an hour session on nonconsecutive days. Results: The findings were maintaining cognitive function and improvement in static and dynamic balance. Conclusion: It was concluded that training adapted and systematized karate contributes toimproved static and dynamic balance and maintenance of cognitive status. May, thus contribute to a new alternative non-pharmacological intervention in elderly patients with mixed dementia.