Randomized trial on the effects of a combined physical/cognitive training in aged MCI subjects: the Train the Brain study (original) (raw)

Train the Brain Consortium † Age-related cognitive impairment and dementia are an increasing societal burden. Epidemiological studies indicate that lifestyle factors, e.g. physical, cognitive and social activities, correlate with reduced dementia risk; moreover, positive effects on cognition of physical/cognitive training have been found in cognitively unimpaired elders. Less is known about effectiveness and action mechanisms of physical/cognitive training in elders already suffering from Mild Cognitive Impairment (MCI), a population at high risk for dementia. We assessed in 113 MCI subjects aged 65-89 years, the efficacy of combined physical-cognitive training on cognitive decline, Gray Matter (GM) volume loss and Cerebral Blood Flow (CBF) in hippocampus and parahippocampal areas, and on brain-blood-oxygenationlevel-dependent (BOLD) activity elicited by a cognitive task, measured by ADAS-Cog scale, Magnetic Resonance Imaging (MRI), Arterial Spin Labeling (ASL) and fMRI, respectively, before and after 7 months of training vs. usual life. Cognitive status significantly decreased in MCI-no training and significantly increased in MCI-training subjects; training increased parahippocampal CBF, but no effect on GM volume loss was evident; BOLD activity increase, indicative of neural efficiency decline, was found only in MCI-no training subjects. These results show that a non pharmacological, multicomponent intervention improves cognitive status and indicators of brain health in MCI subjects. The world is experiencing a substantial increase in the proportion of elderly adults in the population. With an aging society comes the increase in age related frailties, which may lead to cognitive impairments and to dementia, mostly in the form of Alzheimer's Disease (AD). Age is indeed the major risk factor for dementia: the age-specific incidence rates for AD demonstrate a doubling of incidence for about every six years of added life 1. The number of people with dementia worldwide was 35.6 million in 2010 and that is estimated to increase to 65.7 million by 2030 and 115.4 million by 2050 unless effective means of reducing the incidence of this disease are introduced 2. Several epidemiological studies have demonstrated that modifiable lifestyle factors, such as practicing physical exercise, being engaged in stimulating cognitive activities, maintaining an active social life into old age, and controlling nutrition, are correlated with maintaining good brain functioning, specifically in the elderly, and with reduced risk of developing dementia 3-8. Norton et al. 9 estimated that around one third of AD cases worldwide might be attributable to potentially modifiable risk factors which include several lifestyle habits. Interventions based on cognitive training 10 , diet 11 or physical activity 7,12,13 have indeed been found to produce positive effects on cognitive status in cognitively unimpaired adult or elderly subjects. Potential mechanisms underlying the effects of cognitive and physical activity on cognition, suggested also by studies in animal models, include increased hippocampal neurogenesis, increased Cerebral Blood Flow (CBF), and enhanced brain plasticity 14,15. An important point that has recently emerged both from the human and animal research, is that enhanced physical and cognitive activities seem to have additive effects on brain plasticity and age related cognitive decline 16. In this line, a very important study is the FINGER trial 17 , in which 1260 subjects, aged 60-77 years, with cognition in the mean level for age and elevated Dementia Risk Score, were randomized to a 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring, showing that cognitive performances improved more in the intervention than in the control group.