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1.
J Virol ; : e0007224, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38814066

RESUMEN

Escape from cytotoxic T lymphocyte (CTL) responses toward HIV-1 Gag and Nef has been associated with reduced control of HIV-1 replication in adults. However, less is known about CTL-driven immune selection in infants as longitudinal studies of infants are limited. Here, 1,210 gag and 1,264 nef sequences longitudinally collected within 15 months after birth from 14 HIV-1 perinatally infected infants and their mothers were analyzed. The number of transmitted founder (T/F) viruses and associations between virus evolution, selection, CTL escape, and disease progression were determined. The analyses indicated that a paraphyletic-monophyletic relationship between the mother-infant sequences was common (80%), and that the HIV-1 infection was established by a single T/F virus in 10 of the 12 analyzed infants (83%). Furthermore, most HIV-1 CTL escape mutations among infants were transmitted from the mothers and did not revert during the first year of infection. Still, immune-driven selection was observed at approximately 3 months after HIV-1 infection in infants. Moreover, virus populations with CTL escape mutations in gag evolved faster than those without, independently of disease progression rate. These findings expand the current knowledge of HIV-1 transmission, evolution, and CTL escape in infant HIV-1 infection and are relevant for the development of immune-directed interventions in infants.IMPORTANCEDespite increased coverage in antiretroviral therapy for the prevention of perinatal transmission, paediatric HIV-1 infection remains a significant public health concern, especially in areas of high HIV-1 prevalence. Understanding HIV-1 transmission and the subsequent virus adaptation from the mother to the infant's host environment, as well as the viral factors that affect disease outcome, is important for the development of early immune-directed interventions for infants. This study advances our understanding of vertical HIV-1 transmission, and how infant immune selection pressure is shaping the intra-host evolutionary dynamics of HIV-1.

2.
Brain ; 147(7): 2449-2458, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38266149

RESUMEN

Apathy is one of the most common neuropsychiatric features of Huntington's disease. A hallmark of apathy is diminished goal-directed behaviour, which is characterized by a lower motivation to engage in cognitively or physically effortful actions. However, it remains unclear whether this reduction in goal-directed behaviour is driven primarily by a motivational deficit and/or is secondary to the progressive cognitive and physical deficits that accompany more advanced disease. We addressed this question by testing 17 individuals with manifest Huntington's disease and 22 age-matched controls on an effort-based decision-making paradigm. Participants were first trained on separate cognitively and physically effortful tasks and provided explicit feedback about their performance. Next, they chose on separate trials how much effort they were willing to exert in each domain in return for varying reward. At the conclusion of the experiment, participants were asked to rate their subjective perception of task load. In the cognitive task, the Huntington's disease group were more averse to cognitive effort than controls. Although the Huntington's disease group were more impaired than controls on the task itself, their greater aversion to cognitive effort persisted even after controlling for task performance. This suggests that the lower levels of cognitive motivation in the Huntington's disease group relative to controls was most likely driven by a primary motivational deficit. In contrast, both groups expressed a similar preference for physical effort. Importantly, the similar levels of physical motivation across both groups occurred even though participants with Huntington's disease performed objectively worse than controls on the physical effort task, and were aware of their performance through explicit feedback on each trial. This indicates that the seemingly preserved level of physical motivation in Huntington's disease was driven by a willingness to engage in physically effortful actions despite a reduced capacity to do so. Finally, the Huntington's disease group provided higher ratings of subjective task demand than controls for the cognitive (but not physical) effort task and when assessing the mental (but not the physical) load of each task. Together, these results revealed a dissociation in cognitive and physical motivation deficits between Huntington's disease and controls, which were accompanied by differences in how effort was subjectively perceived by the two groups. This highlights that motivation is the final manifestation of a complex set of mechanisms involved in effort processing, which are separable across different domains of behaviour. These findings have important clinical implications for the day-to-day management of apathy in Huntington's disease.


Asunto(s)
Cognición , Enfermedad de Huntington , Motivación , Humanos , Enfermedad de Huntington/psicología , Masculino , Femenino , Persona de Mediana Edad , Adulto , Cognición/fisiología , Toma de Decisiones/fisiología , Apatía/fisiología , Pruebas Neuropsicológicas , Anciano , Recompensa
3.
J Physiol ; 601(24): 5733-5750, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37917116

RESUMEN

Cardiorespiratory exercise is known to modulate motor cortical plasticity in young adults, but the influence of ageing on this relationship is unknown. Here, we compared the effects of a single session of cardiorespiratory exercise on motor cortical plasticity in young and older adults. We acquired measures of cortical excitatory and inhibitory activity of the primary motor cortex using transcranial magnetic stimulation (TMS) from 20 young (mean ± SD = 25.30 ± 4.00 years, 14 females) and 20 older (mean ± SD = 64.10 ± 6.50 years, 11 females) healthy adults. Single- and paired-pulse TMS measurements were collected before and after a 20 min bout of high-intensity interval cycling exercise or an equivalent period of rest, and again after intermittent theta burst stimulation (iTBS). In both young (P = 0.027, Cohen's d = 0.87) and older adults (P = 0.006, Cohen's d = 0.85), there was an increase in glutamatergic excitation and a reduction in GABAergic inhibition from pre- to postexercise. However, in contrast to younger adults, older adults showed an attenuated plasticity response to iTBS following exercise (P = 0.011, Cohen's d = 0.85). These results demonstrate an age-dependent decline in cortical plasticity and indicate that a preceding bout of high-intensity interval exercise might be less effective for enhancing primary motor cortex plasticity in older adults. Our findings align with the hypothesis that the capacity for cortical plasticity is altered in older age. KEY POINTS: Exercise enhances motor cortical plasticity in young adults, but how ageing influences this effect is unknown. Here, we compared primary motor cortical plasticity responses in young and older adults before and after a bout of high-intensity interval exercise and again after a plasticity-inducing protocol, intermittent theta burst stimulation. In both young and older adults, exercise led to an increase in glutamatergic excitation and a reduction in GABAergic inhibition. Our key result was that older adults showed an attenuated plasticity response to theta burst stimulation following exercise, relative to younger adults. Our findings demonstrate an age-dependent decline in exercise-enhanced cortical plasticity and indicate that a preceding bout of high-intensity interval exercise might be less effective for enhancing primary motor cortex plasticity in older adults.


Asunto(s)
Corteza Motora , Plasticidad Neuronal , Femenino , Adulto Joven , Humanos , Anciano , Plasticidad Neuronal/fisiología , Corteza Motora/fisiología , Potenciales Evocados Motores/fisiología , Estimulación Magnética Transcraneal/métodos , Envejecimiento
4.
Int J Equity Health ; 21(Suppl 3): 167, 2022 11 23.
Artículo en Inglés | MEDLINE | ID: mdl-36419127

RESUMEN

In January 2020, SARS-CoV-2 virus was identified as a cause of an outbreak in China. The disease quickly spread worldwide, and the World Health Organization (WHO) declared the pandemic in March 2020.From the first notifications of spread of the disease, the WHO's Emergency Programme implemented a global COVID-19 surveillance system in coordination with all WHO regional offices. The system aimed to monitor the spread of the epidemic over countries and across population groups, severity of the disease and risk factors, and the impact of control measures. COVID-19 surveillance data reported to WHO is a combination of case-based data and weekly aggregated data, focusing on a minimum global dataset for cases and deaths including disaggregation by age, sex, occupation as a Health Care Worker, as well as number of cases tested, and number of cases newly admitted for hospitalization. These disaggregations aim to monitor inequities in COVID-19 distribution and risk factors among population groups.SARS-CoV-2 epidemic waves continue to sweep the world; as of March 2022, over 445 million cases and 6 million deaths have been reported worldwide. Of these, over 327 million cases (74%) have been reported in the WHO surveillance database, of which 255 million cases (57%) are disaggregated by age and sex. A public dashboard has been made available to visualize trends, age distributions, sex ratios, along with testing and hospitalization rates. It includes a feature to download the underlying dataset.This paper will describe the data flows, database, and frontend public dashboard, as well as the challenges experienced in data acquisition, curation and compilation and the lessons learnt in overcoming these. Two years after the pandemic was declared, COVID-19 continues to spread and is still considered a Public Health Emergency of International Concern (PHEIC). While WHO regional and country offices have demonstrated tremendous adaptability and commitment to process COVID-19 surveillance data, lessons learnt from this major event will serve to enhance capacity and preparedness at every level, as well as institutional empowerment that may lead to greater sharing of public health evidence during a PHEIC, with a focus on equity.


Asunto(s)
COVID-19 , Humanos , COVID-19/epidemiología , SARS-CoV-2 , Organización Mundial de la Salud , Bases de Datos Factuales , Pandemias
5.
J Aging Phys Act ; 30(5): 813-823, 2022 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-34929661

RESUMEN

Habits play an important role in physical activity (PA) engagement; however, these associations in older people are not well understood. The present study aimed to investigate the relationship between engagement in types of PA and their automaticity in older people, using an observational, cross-sectional design. Current hours engaged in planned exercise (excluding walking), planned walking, and incidental activities and the automaticity of those PA behaviors were measured in 127 community-dwelling Australians aged 65 years and older via an online questionnaire. After controlling for demographic and health factors (age, gender, education level, body mass index, history of falls, and anxiety and depression symptoms), higher automaticity scores were associated with more hours undertaking planned walking and incidental activity but not planned exercise. Although preliminary, these findings indicate that the role of habit in maintaining PA in older people may, therefore, differ depending on the type of activity.


Asunto(s)
Ejercicio Físico , Caminata , Anciano , Australia , Estudios Transversales , Hábitos , Humanos
6.
Cereb Cortex ; 30(1): 101-112, 2020 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-31041988

RESUMEN

A single bout of cardiovascular exercise can enhance plasticity in human cortex; however, the intensity required for optimal enhancement is debated. We investigated the effect of exercise intensity on motor cortex synaptic plasticity, using transcranial magnetic stimulation. Twenty healthy adults (Mage = 35.10 ± 13.25 years) completed three sessions. Measures of cortico-motor excitability (CME) and inhibition were obtained before and after a 20-min bout of either high-intensity interval exercise, moderate-intensity continuous exercise, or rest, and again after intermittent theta burst stimulation (iTBS). Results showed that high-intensity interval exercise enhanced iTBS plasticity more than rest, evidenced by increased CME and intracortical facilitation, and reduced intracortical inhibition. In comparison, the effect of moderate-intensity exercise was intermediate between high-intensity exercise and rest. Importantly, analysis of each participant's plasticity response profile indicated that high-intensity exercise increased the likelihood of a facilitatory response to iTBS. We also established that the brain-derived neurotrophic factor Val66Met polymorphism attenuated plasticity responses following high-intensity exercise. These findings suggest that high-intensity interval exercise should be considered not only when planning exercise interventions designed to enhance neuroplasticity, but also to maximize the therapeutic potential of non-invasive brain stimulation. Additionally, genetic profiling may enhance efficacy of exercise interventions for brain health.


Asunto(s)
Excitabilidad Cortical , Entrenamiento de Intervalos de Alta Intensidad , Corteza Motora/fisiología , Plasticidad Neuronal , Adulto , Factor Neurotrófico Derivado del Encéfalo/genética , Femenino , Genotipo , Humanos , Masculino , Polimorfismo de Nucleótido Simple , Estimulación Magnética Transcraneal
7.
J Int Neuropsychol Soc ; 25(5): 453-461, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30767839

RESUMEN

OBJECTIVES: Previous research has demonstrated an association between emotion recognition and apathy in several neurological conditions involving fronto-striatal pathology, including Parkinson's disease and brain injury. In line with these findings, we aimed to determine whether apathetic participants with early Huntington's disease (HD) were more impaired on an emotion recognition task compared to non-apathetic participants and healthy controls. METHODS: We included 43 participants from the TRACK-HD study who reported apathy on the Problem Behaviours Assessment - short version (PBA-S), 67 participants who reported no apathy, and 107 controls matched for age, sex, and level of education. During their baseline TRACK-HD visit, participants completed a battery of cognitive and psychological tests including an emotion recognition task, the Hospital Depression and Anxiety Scale (HADS) and were assessed on the PBA-S. RESULTS: Compared to the non-apathetic group and the control group, the apathetic group were impaired on the recognition of happy facial expressions, after controlling for depression symptomology on the HADS and general disease progression (Unified Huntington's Disease Rating Scale total motor score). This was despite no difference between the apathetic and non-apathetic group on overall cognitive functioning assessed by a cognitive composite score. CONCLUSIONS: Impairment of the recognition of happy expressions may be part of the clinical picture of apathy in HD. While shared reliance on frontostriatal pathways may broadly explain associations between emotion recognition and apathy found across several patient groups, further work is needed to determine what relationships exist between recognition of specific emotions, distinct subtypes of apathy and underlying neuropathology. (JINS, 2019, 25, 453-461).


Asunto(s)
Apatía/fisiología , Emociones/fisiología , Expresión Facial , Reconocimiento Facial/fisiología , Enfermedad de Huntington/fisiopatología , Percepción Social , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad
8.
Br J Nutr ; 122(11): 1271-1278, 2019 12 14.
Artículo en Inglés | MEDLINE | ID: mdl-31782379

RESUMEN

Anecdotal evidence suggests the use of bolus tube feeding is increasing in the long-term home enteral tube feed (HETF) patients. A cross-sectional survey to assess the prevalence of bolus tube feeding and to characterise these patients was undertaken. Dietitians from ten centres across the UK collected data on all adult HETF patients on the dietetic caseload receiving bolus tube feeding (n 604, 60 % male, age 58 years). Demographic data, reasons for tube and bolus feeding, tube and equipment types, feeding method and patients' complete tube feeding regimens were recorded. Over a third of patients receiving HETF used bolus feeding (37 %). Patients were long-term tube fed (4·1 years tube feeding, 3·5 years bolus tube feeding), living at home (71 %) and sedentary (70 %). The majority were head and neck cancer patients (22 %) who were significantly more active (79 %) and lived at home (97 %), while those with cerebral palsy (12 %) were typically younger (age 31 years) but sedentary (94 %). Most patients used bolus feeding as their sole feeding method (46 %), because it was quick and easy to use, as a top-up to oral diet or to mimic mealtimes. Importantly, oral nutritional supplements (ONS) were used for bolus feeding in 85 % of patients, with 51 % of these being compact-style ONS (2·4 kcal (10·0 kJ)/ml, 125 ml). This survey shows that bolus tube feeding is common among UK HETF patients, is used by a wide variety of patient groups and can be adapted to meet the needs of a variety of patients, clinical conditions, nutritional requirements and lifestyles.


Asunto(s)
Nutrición Enteral/métodos , Nutrición Enteral/estadística & datos numéricos , Servicios de Atención de Salud a Domicilio/estadística & datos numéricos , Encuestas y Cuestionarios , Adulto , Anciano , Anciano de 80 o más Años , Parálisis Cerebral/terapia , Estudios Transversales , Femenino , Neoplasias de Cabeza y Cuello/terapia , Humanos , Masculino , Persona de Mediana Edad , Reino Unido
9.
J Int Neuropsychol Soc ; 24(5): 417-423, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29282160

RESUMEN

OBJECTIVES: People with Huntington's disease (HD) experience poor social quality of life, relationship breakdown, and social withdrawal, which are mediated to some extent by socially debilitating neuropsychiatric symptoms, such as apathy and disinhibition. Social cognitive symptoms, such as impaired emotion recognition, also occur in HD, however, the extent of their association with these socially debilitating neuropsychiatric symptoms is unknown. Our study examined the relationship between emotion recognition and symptom ratings of apathy and disinhibition in HD. METHODS: Thirty-two people with premanifest or symptomatic-HD completed Part 1 of The Awareness of Social Inference Test (TASIT), which is a facial emotion recognition task. In addition, we obtained severity ratings for apathy and disinhibition on the Frontal Systems Behavior Scale (FrSBe) from a close family member. Our analyses used motor symptom severity as a proxy for disease progression. RESULTS: Emotion recognition performance was significantly associated with family-ratings of apathy, above and beyond their shared association with disease severity. We found a similar pattern for disinhibition ratings, which fell short of statistical significance. As expected, worse emotion recognition performance was correlated with higher severity in FrSBe symptom ratings. CONCLUSIONS: Our findings suggest that emotion recognition abilities relate to key socially debilitating neuropsychiatric symptoms in HD. Our results help to understand the functional significance of emotion recognition impairments in HD, and may have implications for the development of remediation programs aimed at improving patients' social quality of life. (JINS, 2018, 24, 417-423).


Asunto(s)
Inteligencia Emocional , Enfermedad de Huntington/psicología , Percepción Social , Adulto , Anciano , Expresión Facial , Femenino , Humanos , Enfermedad de Huntington/complicaciones , Masculino , Persona de Mediana Edad , Pruebas Psicológicas , Adulto Joven
11.
Int J Lang Commun Disord ; 52(2): 137-142, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-27363686

RESUMEN

BACKGROUND: Speech and language impairments are well-established in individuals with amyotrophic lateral sclerosis (ALS). However, knowledge about particular aspects of social communication and everyday conversational abilities is limited. AIMS: To investigate self- and informant-report ratings of social communicative abilities in ALS participants and matched healthy controls. METHODS & PROCEDURES: Thirty-two participants with ALS and 24 controls completed the La Trobe Communication Questionnaire (LCQ). Participants nominated a close other to provide an informant report on the LCQ. Demographic and clinical information was also collected. OUTCOMES & RESULTS: Informant ratings indicated greater difficulties in conversational initiation, effectiveness and partner sensitivity for ALS participants compared with controls. ALS participants did not rate their social communicative abilities as poorer than controls and self-reports only differed from informant ratings in the control group. LCQ scores were not significantly correlated with clinical/functional variables. CONCLUSIONS & IMPLICATIONS: Social communication can be reduced in ALS and individuals may lack insight into these difficulties. In order to understand and provide targeted interventions for such difficulties, clinical speech and language assessment should incorporate social communication assessment, including both a self- and informant-report format.


Asunto(s)
Esclerosis Amiotrófica Lateral/diagnóstico , Trastorno de Comunicación Social/diagnóstico , Anciano , Esclerosis Amiotrófica Lateral/psicología , Esclerosis Amiotrófica Lateral/terapia , Concienciación , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/psicología , Trastornos del Conocimiento/terapia , Equipos de Comunicación para Personas con Discapacidad , Disartria/diagnóstico , Disartria/psicología , Disartria/terapia , Femenino , Humanos , Relaciones Interpersonales , Masculino , Persona de Mediana Edad , Trastornos del Humor/diagnóstico , Trastornos del Humor/psicología , Trastornos del Humor/terapia , Pruebas Neuropsicológicas , Valores de Referencia , Trastorno de Comunicación Social/psicología , Trastorno de Comunicación Social/terapia , Encuestas y Cuestionarios
12.
Psychol Health Med ; 22(4): 483-492, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-26998807

RESUMEN

Behaviour change is increasingly recognised as a common feature of amyotrophic lateral sclerosis (ALS), and may be similar to that seen in frontotemporal dementia (FTD). The behaviours most disturbed in ALS, and those that relate most significantly to caregiver burden, however, have not been well established. Forty ALS participants and their caregivers, and 27 age- and gender-matched healthy controls and their relatives, participated in this study. ALS participants were assessed on a disease rating scale, and caregivers and control informants completed the revised version of the Cambridge Behaviour Inventory and a measure of burden. ALS caregivers reported significantly more disturbance than healthy control informants on the functional domains of everyday skills, self-care, and sleep, and in the behavioural domains of mood and motivation. There were no differences between groups in frequency of memory and orientation difficulties, or behaviours characteristic of FTD, such as changes to eating habits or stereotypic and motor behaviour, indicating that the behavioural profile in ALS may differ from FTD. In the ALS group, the domains with the strongest relationship to caregiver burden were everyday skills, motivation and memory, likely because poor motivation, memory dysfunction and difficulties completing activities of daily living require more carer support via direct supervision, prompting or hands on care. Services to support ALS patients and caregivers need to provide targeted interventions for those functional and behavioural changes which are most burdensome in the disease.


Asunto(s)
Actividades Cotidianas , Esclerosis Amiotrófica Lateral/complicaciones , Esclerosis Amiotrófica Lateral/psicología , Síntomas Conductuales/psicología , Cuidadores/psicología , Costo de Enfermedad , Actividades Cotidianas/psicología , Adulto , Anciano , Síntomas Conductuales/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad
13.
J Alzheimers Dis Rep ; 8(1): 697-708, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38746626

RESUMEN

Background: Digital dementia risk reduction interventions are cost-effective and scalable. However, it is unknown how they are perceived by people already experiencing cognitive concerns or decline. Objective: To understand the current use, interest, and preferences for online learning courses and interest in learning about factors influencing brain health and dementia risk among adults ≥45. To explore potential differences between individuals experiencing cognitive concerns and those without. Methods: Adults aged 45 and older completed a survey on technology use and healthy ageing (n = 249, Mean age = 65.6, 76.3% female). The Memory Assessment Clinic-Questionnaire was used to assess subjective memory decline, and 153 participants met the study criteria for cognitive concerns (≥25). Results: Almost all participants (98.4%) reported using two or more digital devices, and 51.8% reported increasing device usage following COVID-19. Most (92.1%) were interested in learning about healthy living and memory within an online course, and over 80% indicated a high interest in learning about dementia risk factors. People with cognitive concerns were more likely to report using a 'routine or system' to aid memory than people without (82.4% versus 62.9%, p = 0.001). However, no significant difference was found in technology use, course preferences, or interest in learning about different risk factors. Conclusions: We conclude that adults 45 years and over are interested in online methods for learning about brain health and offer unique insights into adapting dementia prevention programs for cognitive concerns.

14.
J Appl Gerontol ; : 7334648241238315, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38475694

RESUMEN

For older people, physical inactivity increases fall risk as well as other preventable health conditions. Despite the well-documented benefits of physical activity, uptake and adherence continue to challenge efforts aimed at increasing physical activity and reducing falls. Nested within a randomized controlled trial, this study reports on the factors influencing the physical activity behavior of people, aged between 70 and 90 years, engaged in StandingTall, a home-based balance exercise program proven to reduce falls in the community. The perception of aging, physical activity in older age, and the delivery of exercise were identified as major themes, with the perception of aging an overarching theme influencing both preferences for physical activity in older age and exercise delivery. Findings demonstrate the importance of considering the role of aging, the influence aging has on physical activity and exercise behavior, and how aging influences the delivery and design of exercise programs including falls prevention activities for older people.

15.
Front Psychol ; 14: 1089333, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36968757

RESUMEN

Introduction: Cardiorespiratory exercise has emerged as a promising candidate to modify disease progression in Huntington's disease (HD). In animal models, exercise has been found to alter biomarkers of neuroplasticity and delay evidence of disease, and some interventions-including exercise-have shown benefits in human HD patients. In healthy human populations, increasing evidence suggests that even a single bout of exercise can improve motor learning. In this pilot study, we investigated the effect of a single bout of moderate intensity aerobic exercise on motor skill learning in presymptomatic and early manifest HD patients. Methods: Participants were allocated to either an exercise (n = 10) or control (n = 10) group. They performed either 20 min of moderate intensity cycling or rest before practicing a novel motor task, the sequential visual isometric pinch force task (SVIPT). After 1 week, the retention of the SVIPT was measured in both groups. Results: We found that the exercise group performed significantly better during initial task acquisition. There were no significant differences in offline memory consolidation between groups, but total skill gain across both acquisition and retention sessions was greater in the group who exercised. The better performance of the exercise group was driven by improvements in accuracy, rather than speed. Discussion: We have shown that a single bout of moderate intensity aerobic exercise can facilitate motor skill learning in people with HD gene-expansion. More research is needed to investigate the underlying neural mechanisms and to further explore the potential for neurocognitive and functional benefits of exercise for people with HD.

16.
J Alzheimers Dis ; 94(2): 841-856, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37334601

RESUMEN

Dementia is understood to arise from a mixed etiology, enveloping chronic inflammatory and vascular impacts on the brain, driven by a constellation of modifiable risk factors which are largely mediated by lifestyle-related behaviors. These risk factors manifest over a prolonged preclinical period and account for up to 40% of the population attributable risk for dementia, representing viable targets for early interventions aimed at abating disease onset and progression. Here we outline the protocol for a 12-week randomized control trial (RCT) of a multimodal Lifestyle Intervention Study for Dementia Risk Reduction (LEISURE), with longitudinal follow-up at 6-months and 24-months post-intervention. This trial integrates exercise, diet, sleep, and mindfulness to simultaneously target multiple different etiopathogenetic mechanisms and their interplay in a healthy older adult population (aged 50-85 years), and assesses dementia risk reduction as the primary endpoint. The LEISURE study is located in the Sunshine Coast region of Australia, which has one of the nation's highest proportions of adults aged over 50 years (36.4%), and corresponding dementia prevalence. This trial is novel in its inclusion of mindfulness and sleep as multidomain lifestyle targets, and in its comprehensive suite of secondary outcomes (based on psychological, physical health, sleep activity, and cognitive data) as well as exploratory neuroimaging (magnetic resonance imaging and electroencephalography) and molecular biology measures. These measures will provide greater insights into the brain-behavioral underpinnings of dementia prevention, as well as the predictors and impacts of the proposed lifestyle intervention. The LEISURE study was prospectively registered (ACTRN12620000054910) on 19 January 2020.


Asunto(s)
Disfunción Cognitiva , Demencia , Humanos , Persona de Mediana Edad , Anciano , Estilo de Vida , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Ejercicio Físico , Demencia/epidemiología , Demencia/prevención & control , Demencia/patología , Actividades Recreativas , Disfunción Cognitiva/patología , Ensayos Clínicos Controlados Aleatorios como Asunto
17.
Sci Rep ; 12(1): 1104, 2022 01 20.
Artículo en Inglés | MEDLINE | ID: mdl-35058470

RESUMEN

Huntington's disease (HD) mouse models suggest that cardiovascular exercise may enhance neuroplasticity and delay disease signs, however, the effects of exercise on neuroplasticity in people with HD are unknown. Using a repeated-measures experimental design, we compared the effects of a single bout of high-intensity exercise, moderate-intensity exercise, or rest, on motor cortex synaptic plasticity in 14 HD CAG-expanded participants (9 premanifest and 5 early manifest) and 20 CAG-healthy control participants, using transcranial magnetic stimulation. Measures of cortico-motor excitability, short-interval intracortical inhibition and intracortical facilitation were obtained before and after a 20-min bout of either high-intensity interval exercise, moderate-intensity continuous exercise, or rest, and again after intermittent theta burst stimulation (iTBS). HD participants showed less inhibition at baseline compared to controls. Whereas the control group showed increased excitability and facilitation following high-intensity exercise and iTBS, the HD group showed no differences in neuroplasticity responses following either exercise intensity or rest, with follow-up Bayesian analyses providing consistent evidence that these effects were absent in the HD group. These findings indicate that exercise-induced synaptic plasticity mechanisms in response to acute exercise may be attenuated in HD, and demonstrate the need for future research to further investigate exercise and plasticity mechanisms in people with HD.


Asunto(s)
Capacidad Cardiovascular/fisiología , Enfermedad de Huntington/fisiopatología , Corteza Motora/fisiología , Plasticidad Neuronal/fisiología , Adulto , Anciano , Animales , Electromiografía/métodos , Potenciales Evocados Motores/fisiología , Ejercicio Físico/fisiología , Terapia por Ejercicio/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ritmo Teta/fisiología , Estimulación Magnética Transcraneal/métodos
18.
Neurodegener Dis Manag ; 12(3): 129-139, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35412856

RESUMEN

Aim: In Huntington's disease (HD) and Parkinson's disease (PD), apathy is a frequently cited barrier to participation in physical activity. Current diagnostic criteria emphasize dissociable variants of apathy that differentially affect goal-directed behavior. How these dimensions present and affect physical activity in HD and PD is unknown. Methods: Using a qualitative approach, we examined the experience of apathy and its impact on physical activity in 20 people with early-manifest HD or idiopathic PD. Results: Two major themes emerged: the multidimensionality of apathy, including initiation or goal-identification difficulties, and the interplay of apathy and fatigue; and facilitators of physical activity, including routines, safe environments and education. Conclusion: Physical activity interventions tailored to apathy phenotypes may maximize participant engagement.


Asunto(s)
Apatía , Enfermedad de Huntington , Enfermedad de Parkinson , Ejercicio Físico , Humanos , Motivación
19.
Mov Disord Clin Pract ; 8(3): 361-370, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33816664

RESUMEN

BACKGROUND: Apathy is a disorder of motivation common to Huntington's disease (HD). Recent conceptual frameworks suggest that apathy is not unitary but consists of discrete subtypes ("dimensions"). Which of the proposed dimensions are preferentially affected in HD, and how these dimensions evolve with disease progression is unknown. OBJECTIVES: The Dimensional Apathy Scale (DAS) separates apathy into Executive, Initiation and Emotional subscales. Using the DAS, we aimed to: 1) Determine the apathy subtypes prevalent in HD; 2) Compare the DAS against a unitary measure of apathy (Apathy Evaluation Scale, AES); 3) Assess the reliability of self- and observer-ratings; and 4) Determine the relationship between the DAS, and disease burden, total functional capacity (TFC) and the AES. METHOD: Fifty pre-manifest, 51 manifest-HD, 87 controls, and 50 HD-observers completed the DAS, AES, and TFC. RESULTS: Manifest-HD participants had the highest levels of apathy across all dimensions (30.4% on Executive subscale, 34.8% on Initiation subscale, and 15.2% on Emotional subscale), relative to pre-manifest and control participants. Self- and observer-ratings on the DAS did not differ. Hierarchical regressions across the entire gene-expanded sample showed that scores on the Initiation subscale correlated with AES scores; higher Executive subscale scores were related to higher disease burden; and Emotional subscale scores with lower total functional capacity. CONCLUSIONS: In this first study of the DAS in HD, manifest-HD participants were more apathetic than pre-manifest and control participants across all apathy subtypes. The DAS may be a useful tool for measuring different aspects of apathy in people with HD.

20.
Front Hum Neurosci ; 15: 661079, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34220470

RESUMEN

High-intensity exercise has enhanced motor learning in healthy young adults. Anodal-transcranial direct current stimulation (a-tDCS) may optimize these effects. This study aimed to determine the effects of a short-term high-intensity interval exercise intervention either with or without a-tDCS on the learning and retention of a novel motor task in middle-aged adults. Forty-two healthy middle-aged adults (age = 44.6 ± 6.3, female = 76%) were randomized into three groups: exercise and active a-tDCS, exercise and sham a-tDCS, and a non-exercise and sham a-tDCS control. Participants completed a baseline testing session, followed by three intervention sessions 48-h apart. The exercise groups completed 20-min of high-intensity exercise followed by a novel sequential visual isometric pinch task (SVIPT) while receiving 20-min of 1.5 mA a-tDCS, or sham tDCS. The control group completed 20-min of reading before receiving sham a-tDCS during the SVIPT. Learning was assessed by skill change within and between intervention sessions. Participants returned 5-7 days after the final intervention session and performed the SVIPT task to assess retention. All three groups showed evidence of learning on the SVIPT task. Neither group displayed enhanced overall learning or retention when compared to the control group. High-intensity exercise with or without a-tDCS did not improve learning or retention of a novel motor task in middle-aged adults. The methodological framework provides direction for future research to investigate the potential of differing exercise intensity effects on learning and retention.

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