RESUMEN
Parkinson's disease (PD) is an incurable and progressive neurological disorder leading to deleterious motor and non-motor consequences. Presently, no pharmacological agents can prevent PD evolution or progression, while pharmacological symptomatic treatments have limited effects in certain domains and cause side effects. Identification of interventions that prevent, slow, halt or mitigate the disease is therefore pivotal. Exercise is safe and represents a cornerstone in PD rehabilitation, but exercise may have even more fundamental benefits that could change clinical practice. In PD, the existing knowledge base supports exercise as (1) a protective lifestyle factor preventing the disease (ie, primary prevention), (2) a potential disease-modifying therapy (ie, secondary prevention) and (3) an effective symptomatic treatment (ie, tertiary prevention). Based on current evidence, a paradigm shift is proposed, stating that exercise should be individually prescribed as medicine to persons with PD at an early disease stage, alongside conventional medical treatment.
RESUMEN
OBJECTIVE: To determine whether 24 weeks of high-intensity progressive aerobic exercise (PAE) affects brain MRI measures in people with multiple sclerosis (MS). METHODS: We conducted a randomized, controlled, phase 2 trial (with a crossover follow-up) including an exercise group (supervised PAE followed by self-guided physical activity) and a waitlist group (habitual lifestyle followed by supervised PAE). Mildly to severely impaired patients with MS aged 18-65 years were randomized (1:1). The primary outcome was percentage brain volume change (PBVC) after 24 weeks, analyzed using the intention-to-treat principle. RESULTS: Eighty-six participants were recruited. PBVC did not change over the intervention period (mean between-group change +0.12%, 95% confidence interval [CI] -0.27 to 0.51, p = 0.55). In contrast, cardiorespiratory fitness (+3.5 mL O2/min/kg, 2.0 to 5.1, p < 0.01) and annualized relapse rate (0.00, 0.00-0.07 vs +0.45, 0.28 to 0.61, p < 0.01) improved in the exercise group. CONCLUSION: These findings do not support a neuroprotective effect of PAE in terms of total brain atrophy in people with MS and it did not lead to a statistically significant difference in gray matter parenchymal fraction. PAE led to improvements in cardiorespiratory fitness and a lower relapse rate. While these exploratory findings cautiously support PAE as a potential adjunct disease-modifying treatment in MS, further investigations are warranted. CLINICALTRIALSGOV IDENTIFIER: NCT02661555. CLASSIFICATION OF EVIDENCE: This study provides Level I evidence that 24 weeks of high-intensity PAE did not elicit disease-modifying effects in PBVC in people with MS. Exploratory analyses showed that PAE may reduce relapse rate.
Asunto(s)
Encéfalo/diagnóstico por imagen , Entrenamiento de Intervalos de Alta Intensidad/métodos , Imagen por Resonancia Magnética/métodos , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/terapia , Adulto , Encéfalo/fisiología , Estudios Cruzados , Dinamarca/epidemiología , Ejercicio Físico/fisiología , Femenino , Estudios de Seguimiento , Entrenamiento de Intervalos de Alta Intensidad/tendencias , Humanos , Imagen por Resonancia Magnética/tendencias , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/fisiopatología , Resultado del TratamientoRESUMEN
(1) Background: Cognitive impairment is highly prevalent in multiple sclerosis (MS). Staying physically fit may be associated with preservation of cognitive performance in persons with MS (pwMS); (2) Objective: To investigate the association between aerobic capacity and the cognitive domains of information processing, learning and memory, and verbal fluency as well as single and composite z-scores of the Brief Repeatable Battery of Neuropsychological tests (BRBNT) in pwMS; (3) Methods: All subjects first performed the BRBNT and then a maximal oxygen consumption (VO2-max) test on a bicycle ergometer as a measure of aerobic capacity. Simple and multiple (adjusting for age, sex, and education level) regression analyses were performed to evaluate the relationship between aerobic capacity and cognitive performance in different domains. Published international norms were used to compute z-scores for each individual and composite BRBNT score. Furthermore, cognitive impairment was defined as one or more z-scores ≤-1.5 standard deviation (SD) of healthy controls; (4) Results: Eighty-four subjects were included (44.9 ± 9 years, 16.3 ± 2 education years, Expanded Disability Status Scale (EDSS): 2.6 ± 1.4, MS-type (relapsing-remitting, primary progressive, or secondary progressive): 73/6/5, disease duration: 9.9 ± 7 years, VO2-max: 28.4 ± 7.0 mL O2/min/kg). No significant associations between aerobic capacity and cognitive performance in the individual BRBNT tests were found, except that a weak relationship was found between aerobic capacity and the composite processing speed z-score (R² = 0.06, p = 0.02). The average global BRBNT z-score (-0.2 ± 0.66) was not associated with aerobic capacity. Comparison of the cognitively impaired group (34.5%) with the nonimpaired group (65.5%) showed lower aerobic capacity in the impaired group (25.9 ± 1 vs. 29.7 ± 1 mLO2/min/kg, p = 0.02); (5) Conclusions: Limited support was found for an association between performance in most cognitive domains and aerobic capacity in the present MS group with a third of patients showing signs of cognitive impairments.