The present study examined whether baseline physical performance and gray matter volume are related to falls during a 12-month follow-up period in community-dwelling older adults with MCI. Our results indicated that older adults with MCI exhibiting poor balance had a greater risk of falls during the 12-month follow-up period, while adjusting for age, sex, body mass index, and history of falling at baseline. In addition, baseline lower gray matter volume in the middle frontal gyrus and superior frontal gyrus was associated with the occurrence of subsequent falls. To our knowledge, this is the first study to examine the association between lower gray matter density and risk of falls in older adults with MCI.

Problems with gait and balance have been reported to have the strongest association with falling [2, 31]. Slower walking speed has been found to be an independent predictor of falling [32, 33]. Poor balance represented by increased postural sway and gait asymmetry has been reported to approximately triple the risk of falling [2]. A previous systematic review and meta-analysis provided a summary estimate for falls due to balance impairment at a relative risk of 1.42 [34]. Therefore, an assessment of balance and gait for older adults, particularly those without a history of falling, has been recommended [35]. Moreover, cognitive impairment has been associated with the risk of falls as well as deficits of physical function [2]. A recent systematic review and meta-analysis confirmed that cognitive deficits detected in clinical assessment are associated with an increased fall risk in community and institution-dwelling older adults [36]. A number of studies have examined the risk of falls in older adults with dementia [37]. However, little research has focused on individuals with MCI. MCI is increasingly recognized as a substantial clinical problem in older populations [38], so it is important to determine risk factors for falling among older individuals with MCI, and to develop effective fall-prevention strategies. A previous study showed that older women with MCI demonstrated a greater number of risk factors for falling compared with older women without MCI [14]. The results of the present study indicate that poor balance assessed by one-legged standing time predicts falls in people with MCI prospectively over 12 months. Although fallers exhibited slower walking speed compared with non-fallers, walking speed was not associated with the occurrence of subsequent falls after adjusting for age, sex, body mass index, and history of falling at baseline. There was no difference in the extension strength between fallers and non-fallers. The results of this study indicate that poor balance is the important factor related to an increased risk of falling among people with MCI. Muscle weakness and problems with mobility had been considered to be the important contributors to the risk of falling in older people [5], and there are presumably some relationships. In study cohorts including older people with MCI and similar lower muscle strength, like the present study, poor balance may have a greater impact on increased risk of falling than walking performance. Certainly, poor balance could be one of the predictors of walking decline among older people [39]. Balance ability may be an important dimension of physical functioning to predict the occurrence of subsequent falls among older people with MCI, as well as those with intact cognition. The present study has advantages including the examination of occurrence of subsequent falls during a 12-month follow-up period and neuroimaging assessments in older adults with MCI. However, our sample was not large, and selection bias may affect the results of the relationships between physical performance and occurrence of subsequent falls. Therefore, future studies with larger numbers of MCI subjects and a longitudinal design are needed to add evidence to the present results.

Unlike previous investigations, the current study included MRI scanning and a follow-up assessment of falls in community-dwelling older adults with MCI. The results provide the first evidence that lower gray matter volume in the middle and superior frontal gyrus is related to the occurrence of subsequent falls among older adults with MCI. Age-related changes in the brain may contribute to the subtle onset of motor disturbances in older people. Previous brain-imaging studies of older adults have reported that age-related changes in the brain, such as lower global brain volume, WMH, and microbleeds, are associated with clinical measures of poor balance and slow gait [40–43]. The association between MRI-detected lower brain volume and falls in older adults with MCI has not been examined longitudinally. In the present study, fallers exhibited decreased gray matter density compared with non-fallers in the bilateral middle frontal gyrus and superior frontal gyrus corresponding to premotor cortex and supplementary motor area. These particular regions are likely to play an important role in predicting fall-risk because the middle frontal gyrus is involved in controlling behavior with spatial and sensory guidance.

Growing evidence suggests that brain function is associated with physical function, as confirmed by neuroimaging techniques. Structural changes of the brain in older people are reported to be related to physical performance, such as gait dysfunction [44, 45], postural instability [24], and lack of cardiorespiratory fitness [46]. Activation in the frontal cortex, including the premotor cortex and the supplementary motor areas, have been reported to increase during human gait by studies using near-infrared spectroscopic imaging [47–50]. Previous studies have reported that lower brain volume in the prefrontal areas is associated with slower gait in high-functioning or cognitively normal older adults [23, 40, 51]. Other neuroimaging studies have indicated that gait requires complex visuo-sensorimotor coordination, and is associated with activation of the medial frontoparietal region, e.g. the primary sensory and motor areas, supplementary motor area, lateral premotor cortex, cingulate cortex, superior parietal lobule, precuneus, and the infratentorial region including the dorsal region [52–54]. The middle frontal gyrus is involved in motor output and the direct control of behavior, as well as planning, spatial guidance, and sensory guidance of movement [55]. Lower gray matter volume in the premotor cortex and supplementary motor area may be risk factors for falls in older adults. Falls often occur when older individuals attempt to avoid an obstacle in their path, requiring the control of behavior and the planning of movement under sensory guidance. The premotor cortex and supplementary motor area may play an important role in preventing falls when spatial and sensory guidance are required for movement.

Several limitations of the current study should be noted. First, fall experience during the 12-month follow-up period were confirmed with two face-to-face interviews at 6-months and 12-months after baseline, while previous studies have reported that monthly fall diaries and follow-up telephone calls provide more accurate measures of fall frequency [56, 57]. Second, participants who had at least one fall during the 12-month follow-up period were categorized as fallers in this study. A previous study reported that single fallers are more similar to nonfallers than to recurrent fallers on a range of medical, physical, and psychological risk factors [58]. Other studies defined fallers as people who had at least one injurious or two non-injurious falls [17, 59]. In addition, our MRI scans were performed using a 1.5-T system with relatively low resolution. We performed the VBM analysis to identify the locations of group differences in gray matter volume. Therefore, we consider that our results cannot provide evidence for whether the effects of physical performance are independent of the gray matter volume or whether the latter confounds the association between the former and the fall risk. Although it is unclear whether lower gray matter volume is related to poor balance in older adults with MCI, the current study revealed that poor balance and lower gray matter volume in the middle frontal gyrus and superior frontal gyrus were associated with falls. To clarify these points, we consider that future studies including larger numbers of subjects and countable data for structural changes in the brain (e.g., described volumes in cubic millimeters) are needed.