Does physical exercise improve perceptual skills and visuospatial attention in older adults? A review

The purpose of the present review is to summarize previous and current findings related to changes in visuospatial attention as a function of age and physical exercise and sports activities (especially martial arts). First, we present a brief overview of the adaptation mechanisms used by older adults’ brains, which involve functional and structural changes, to adjust to new demands. Second, we review the role of sport and physical exercise in the maintenance of visuospatial abilities that play an important role in well-being and healthy aging. Research with older adults, compared to younger people, could pose a number of challenges. It can be difficult to find older participants engaged in physical activity (PA), especially on a regular basis. Moreover, studies investigating visuospatial aspects such as peripheral vision or dynamic visual acuity in seniors are very scarce. In addition to cognitive and perceptual decline, older adults may suffer from ocular disease, refractive and oculo-motor decline or loss of visual skills. All these factors might contribute to the lack of research investigating PA and visuospatial attention in older adults. One of the main questions in the field of aging and PA concerns the type of exercise that might help to delay age-related cognitive and perceptual decline. This review examines and discusses the effects of aging on visuospatial attention and perceptual skills, and provides an overview of the potential beneficial effects of several types of physical exercise on brain and cognition. Finally, we look in particular at the effects of martial arts training (e.g., karate, judo, tai-chi) on aging and cognition. These topics are rarely dealt with in the area of PA and cognition in old age.

Some cognitive processes, such as verbal abilities and implicit memory, do not decline with age [1‐7]. In fact, some factors, such as wisdom and procedural knowledge about how to act in certain situations, even improve with age [8]. Despite these positive results, aging is usually associated with the slowing down of processing speed [9, 10], a significant decline in working memory [7] and long-term memory [11], and difficulty inhibiting irrelevant stimuli [12]. Young and older adults show different brain activity when performing verbal working memory [13] and verbal long-term memory tasks [14, 15], possibly reflecting compensation maneuvers by seniors to obtain similar results as before. Older adults often have a tendency to engage both the left and right hemispheres [13], or even different areas than those used by young adults when performing the same task [7]. To account for these differences in cerebral functioning, Park and Reuter-Lorenz proposed the scaffolding theory [7, 16]. According to this theory, increased activation, especially in frontal areas, serves as a compensatory mechanism used by older adults to respond to the demands of certain cognitive tasks. However, it has been suggested [17] that such age-related neural dedifferentiation could contribute to rather than compensate for cognitive age-related declines, as the involvement of additional brain regions of older adults might in part be due to the decrease in neuronal selectivity, which would be a consequence of rather than compensation for cognitive decline.

Neuroplasticity may also be considered as a compensatory mechanism. The brain is an adaptable organ, subject to a continuous learning process [18]. Neuroplasticity might modify the brain, both structurally and functionally, to respond to certain needs and demands [18, 19], reducing age-related slowing-down, and even delaying the onset of neurodegenerative diseases [20‐22]. It is a learning phenomenon that occurs throughout the life cycle and that persists despite cognitive slowing, varying in its actions between individuals. In fact, large differences may be found as a function of life-style, with some older adults showing severe cognitive losses while others perform similarly to young adults [23, 24]. Cognitive aging, then, may not fully conform to the typically established linear model (from growth to cognitive decline, fluid versus crystallized intelligence, or hardware versus software); on the contrary, seniors may optimize their resources through adaptation and compensation.

A large body of research has found that the preservation of perceptual and cognitive processes can depend on whether the older adults are physically active and whether they have a social lifestyle [1, 25‐28]. Not only does PA keep the body in better condition and help reduce the risk of certain diseases, but it also has considerable benefits for the cognitive and perceptual abilities of both young [29, 30] and older adults [1, 28, 31‐36]. Some studies [37] suggest that training can improve the processes associated with fluid intelligence in older people. However, in spite of the ability of the brain to adapt to new demands (neuroplasticity), of older people’s advantage in crystallized intelligence, and of their compensatory and optimization strategies, they generally perform at lower levels than young adults. Engaging in physical exercise or PA is one of the pillars of successful aging. Physical activity is an umbrella term that includes a large number of activities related to purposeful body movements [38].

In the following section, we review the role of different types of physical activity in maintaining perceptual and cognitive skills in older adults.

Given the rise of life expectancy, and hence the increased number of older adults, especially in developed societies, the number of people with age-related neurodegenerative diseases is expected to increase dramatically in the coming decades. This makes it urgent to identify ways to improve the quality of life of older adults, their families and carers, by promoting healthy aging. A large number of studies have focused on the importance of regular PA, not only as a way of improving physical health, reducing the risk of cardiovascular and neurodegenerative diseases, and delaying mortality [39], but also of delaying age-related cognitive decline and the onset of neurodegenerative diseases [19, 40]. See Tables 1 and 2.

Physical exercise in older adults might act as a “neuroprotector” [20‐22], preserving several cognitive functions in the older mind and brain. Specifically, some brain structures involved in the cognitive improvement that occurs with physical exercise (i.e. the hippocampus) are often related to Alzheimer’s disease [41]. The hippocampus usually loses weight with age, producing episodic memory declines and increasing the risk of dementia [42‐44]. For example, Erickson and colleagues found that the anterior hippocampus of older adults who did aerobic exercises for a year increased by 2% [43], while the anterior hippocampus of the older group who did stretching exercises during the same period increased by around 1.4%. The same study also yielded different results for these two types of physical exercise for the Brain-Derived Neurotrophic Factor (BDNF), which was higher for the group who did aerobic exercises. Other studies [45] also reported higher BDNF levels for the physically active group as well as an increase in local gray matter in prefrontal areas. BDNF seems to be related to dendritic expansion [46] and to long-term memory [47, 48]. It seems that a single bout of physical exercise has a significantly larger impact on BDNF serum levels than either mindfulness practice or cognitive training [49]. Physical activity produces selective changes that are not uniform across the brain, as improvements are only found in the anterior hippocampus [43]. A recent study [50] also found similar results; that is, that aerobic exercise is associated with increased hippocampus volume and better cognitive functioning. These results suggest that the anterior hippocampus increases more with aerobic exercise than with stretching or toning activities.

PA might affect brain structures other than the hippocampus. There have been fewer studies on the effect of sports on the volume of the basal ganglia, but it seems that motor fitness and coordination training is related to the volume of basal ganglia nuclei and with executive function tasks [51].

Colcombe and colleagues [33] found that PA affected brain flexibility and adaptability, possibly by improving vascular capacity and synaptic connections. The results revealed that athletes had higher attentional skills than sedentary participants. In particular, athletes showed better functioning of the prefrontal and parietal cortices and the anterior cingulate cortex, areas involved in attentional processing. Aerobic physical activity also tended to reduce both gray and white matter loss in older adults [52]. It seems then that cardiorespiratory fitness improves the structural integrity of the anterior cingulate [53].

Behavioral studies have also reported positive relationships between aging and physical exercise. For example, aerobic and balance training predicted enhanced processing speed, inhibition and working memory [54]. Older adults with an active life-style performed better on working memory, spatial memory, inhibition capacity, and the ability to switch between tasks [35]. Other findings are in the same line, showing better results for physically active older adults compared to sedentary elders of the same age. In particular, participants exhibited better verbal learning and memory, and better selective attention after 1 year of cardiovascular fitness intervention. Importantly, to maintain these abilities, it is necessary to continue physical activity [31]. A recent study [55] found that both young and older adults performed better in a fine motor task after performing a cardiovascular physical activity.

Thus, most research supports the view that physical activity helps to preserve both physical and cognitive abilities in old age (see Table 2). However, many older adults avoid sports activities, in part due to their insecurity or fear of injury or falls [56]. Some studies argue that aerobic and resistance training slows down age-related declines to a greater extent than other types of exercise [33, 52, 35, 43, 45, 57, 58]. For example, older participants who did resistance activity training performed better on a Stroop task than those doing balance and toning exercises [57]. Moreover, aerobic and resistance activity improves spatial memory, in both animals and humans [58]. Some reviews have also examined the effects of aerobic fitness on cognitive function [59]. Other types of exercise also seem to play an important role in preserving certain perceptual and cognitive skills; in particular, it has been suggested that coordination exercises improve the detection of stimuli in visual search tasks [60]. In a further functional magnetic resonance imaging (fMRI) study [61], it was found that seniors who carried out walking and coordination tasks showed less brain activation in the right dorsolateral prefrontal cortex when performing motor control tasks than those who did stretching exercises. It seems thus that aerobic and coordination exercises might help attenuate age-related cognitive decline. Crucially, the PA should be carried out on a regular basis, since perceptual and cognitive improvements are often reversed shortly after the end of the exercise. Improvements are usually larger when the exercise is performed regularly than when it is carried out in isolation [62]. Surprisingly, some studies reported greater cognitive effectiveness with just one training session [63] and even after 10 minutes of physical exercise [64]. The authors attributed improvements to the connection between the cerebellum, mainly specialized in motor tasks, and the frontal cortex. It seems that when there is greater task complexity, as in coordination exercises, more activity of the prefrontal cortex is required. Physical exercise would thus activate the frontal lobes, responsible for a large number of cognitive tasks. In addition to the studies that examined the individual effects of aerobic, coordination, stretching, balance, or physical exercises, some studies have investigated the combination of physical and cognitive training with video games. Exergame training could be a perfect activity for homebound older adults with lower education levels or who are reluctant to leave the house to participate in outdoor activities. The study of Eggenberger et al. [65] compared balance and stretching training with cognitive-motor video game dancing and showed that the video game dance group showed a greater reduction in left prefrontal cortex activity and also improved executive functions. Schättin et al. [66] found greater prefrontal theta activity and improved cognitive functioning in the exergame group than in the group participating in a classic balance activity. A recent training study with multiple neuroimaging measures [25] conducted with adults over 60 years of age showed that memory and executive functions improved after a six-week multi-domain exercise program that included aerobic, balance, weight lifting, and yoga carried out with a video game (Wii-fitness). Their magnetic resonance imaging (MRI) data revealed different levels of striatum volume loss, which was higher for controls than for the exercise group. The study [25] also found other brain differences between the exercise and control groups in the cingulate, temporal, parietal, and occipital regions.

Dance might also be a form of PA that combines exercise with cognitive factors and thus have stronger and longer-lasting effects on the brain and on executive functioning than conventional and repetitive physical exercises. For example, Müller et al. [67] investigated the effects on neuroplasticity of dance compared to conventional and repetitive fitness exercises (strength-endurance and flexibility training) in healthy older adults. After a training period, the dance group showed increased gray matter volume in the left precentral gyrus and enhanced performance in the attention and memory tests compared to the fitness group. In another study comparing conventional exercises (endurance, strength and flexibility) with dancing, results showed that although left hippocampal volume increased in both groups, only dancers showed increases in the left dentate gyrus and the right subiculum and improved performance in the balance tests [68]. In a recent study [69], however, no differences in brain volume or cognitive functioning were observed between two groups of physically active older adults; one group included adults engaged in various moderate sports activities, and the other were members of a dancing class. The lack of difference might be due to the low or moderate training of the dance group (once or twice a week).

To sum up, neuroimaging and behavioral studies have shown the different effects produced in cognition and brain functions as a result of the type of PA (see Tables 1 and 2). It seems that aerobic and cardiovascular fitness, compared to other types of exercise (nonaerobic), are associated with larger hippocampal volume that translates into improved memory [35, 43, 50]. Aerobic and cardiovascular exercises in older adults also seem to increase both brain volume in gray matter regions [45, 52], BDNF levels [43, 45] and neural connectivity that might be associated to better cognitive performance in executive functioning and spatial memory tasks [35, 43]. In general, this might result in better attention and inhibition of distracting information, making the older brain more flexible and efficient [31, 33, 60, 70, 71]. Most research has focused in aerobic/cardiorespiratory activity although motor fitness plays also an important role. Coordination training also improves cognitive functioning in older adults [28, 51, 60]. This type of exercise seems to be also involved in perceptual speed and in the visual–spatial network [28, 60, 72, 73]. This is not surprising given that coordination activity is based on: balance, eye-hand and/or leg-arm coordination and spatial orientation skills, and it also may require interacting with persons and other objects in the environment. Motor coordination may be also involved in cognitive processes like attention so as to coordinate or to prepare anticipatory movements. Visual-spatial areas might be working to train all these abilities. The effect of a combined training program including aerobic, coordination and cognitive demands is one of the best ways to improve cognition from a comprehensive point of view; this might be the case of dancing. In general, dancing seems to produce similar benefits to aerobic activities to improve cognition; this is shown by some studies, which found no differences (for example, in gray matter volume [69]) between dancers and practitioners in other aerobic exercises. Other studies have reported increased gray matter volume as well as improved attention and memory functions [67] in dancers compared to other nonaerobic PA. Increases in volume in some areas of the hippocampus as well as improvements in balance tasks (68) have also been reported in dancers compared to the practice of other types of exercises such as strength-endurance and flexibility. These increases lead to a larger reduction in the left prefrontal cortex activity thus improving executive functions in dancers compared to balance and stretching exercise practitioners.

The relations between aging, physical exercise and cognition have been widely investigated. However, there has been little research of the relationship between physical exercise, aging and perception, notably with regard to visuospatial skills. Visual abilities are closely linked to cognition and they are needed to understand and interpret the visual scene. In fact, some studies suggest that large proportions of the age-related variance in cognitive variables might be due to sensory (e.g., visual) rather than cognitive decline [74].

In the next section, we review the role of visuospatial attention in daily living and include studies that have shown the benefits to older adults of regular PA of different types, especially martial arts.

Visuospatial attention plays a central role in the performance of a variety of activities that are critical for an active and independent life. It is important for processing visual information and perceiving moving stimuli that appear in different areas of the visual field. Aging is associated with a decline in visual tracking abilities, lower accuracy in pursuing targets [75], a decline in saccade direction accuracy [76], difficulty perceiving moving stimuli [77], and poor performance in visual search tasks [78]. Furthermore, spatial location of stimuli in the visual field [79] and peripheral vision decline with age, especially at high eccentricities [26, 27, 80‐83] (from 5° of visual angle from fixation). Control of all these factors, amongst others, may be critical when attributing results to differences in cognitive processing, since some studies [84] found that after controlling for visual acuity, the age-related decline in P3b amplitude (an event-related potential –ERP- component related to decision-making/updating) in response to visual targets disappeared, suggesting that in some cases results might be due to sensory and not to cognitive processing. However, another ERP study [85] found that the prolongation of motor responses, rather than sensory factors, could account for the age-related differences. Specifically, the study found lower activation patterns over the contralateral motor cortex, responsible for generating motor responses.

Visuospatial attention improves with PA (see Table 2). A series of studies support the idea that physical activity make older adults more efficient than sedentary individuals in reaction time tasks, detecting stimuli located at the periphery of the visual field [86], and they are faster at identifying small details of moving stimuli [72]. At the same time, they show greater flexibility in attention-orientation tasks [70, 87]. However, any such visual advantages are not usually attributed to the existence of a superior visual system but the visual system might be more efficient in certain contexts [72]. Differences in the visual perception of athletes could therefore be related to the visual strategy used [visual network], possibly derived from a long and effortful learning process.

Although it is not known whether the abilities of athletes are innate or acquired after years of practice, the latter is generally considered more likely [72], as athletes acquire different skills depending on the type of sport involved. The type of motor learning that occurs in each case seems to be the basis of the visual skills shown by the athletes. An important question is whether the automation process involved in each case leads to the transfer of these skills to other basic tasks (not related to their sport), for example, in the rapid detection of items that appear in different parts of the visual field, including peripheral areas.

Peripheral vision (PV) is a crucial visuospatial skill that refers to the perception of stimuli that are outside the central part of the visual field. The more eccentric or distant from fixation the visual stimulus is, the more difficult it is to detect and the longer the reaction time required.

Peripheral vision is crucial for the analysis of the environment and plays an important role in our daily life. The fast detection of a stimulus that appears in the peripheral visual field is critical, especially for older individuals, who may often suffer falls that can be due to poor detection of obstacles located in their peripheral visual field. Regular PA decreases overall reaction time, favors the rapid perception of stimuli, and improves visual attention in older adults [70, 72, 86, 87].

Martial arts, as a fast moving sport, depending on movements tends to pay attention to what happens laterally, might be a perfect candidate to study PV. A study with young and older participants [26] investigated whether judo and karate athletes exhibit better peripheral vision skills than non-athletes of the same age, and whether there were differences depending on the type of sport. The study included younger and older judo and karate athletes and sedentary participants of the same age. Results showed that young karate athletes performed faster than both young judo athletes and non-athletes when stimuli appeared at the periphery of the visual field suggesting that this type of sport in the young group was important. It seems that karate, develops a set of skills that improve peripheral vision to a greater extent than judo. Importantly, for the older groups, both judo and karate athletes showed better peripheral skills than sedentary participants of the same age. However, there were no differences between judo and karate practitioners. A study with Tai-Chi practitioners aged 65 years and over revealed that they were more accurate and showed faster reaction times in a peripheral vision task than sedentary adults of the same age [73]. The results of that study also showed that Tai-Chi practitioners scored better on the rest of the subtests, which included visual search and cognitive tasks related to executive control.

A recent study conducted with older adults [88] also found an association between PA and the visual function. Specifically, more vigorous PA led to better performance on the Useful Field of View test (widely used to assess peripheral vision). Other studies conducted with older participants [86, 71, 89] also reported an association between PA and better scores on the Useful Field of View test. The two latter studies [71, 89] did not evaluate the PA itself, but used questionnaires to collect information about the participants’ PA. Unfortunately, these questionnaires did not assess accurately the type, intensity, or duration of the exercise. Another study [90], however, did not find any relationship between PA (also reported by participants with a questionnaire) and performance on the Useful Field of View test.

In sum, PV is a crucial ability for daily life that seems to improve with PA in both young and older adults. However, the exact mechanisms whereby exercise might act on the improvement and/or maintenance of PV abilities and the type of exercise still remain unclear. More studies are needed to clarify this question, especially in relation to older observers.

Gaze behavior is also a visuospatial factor that has important implications in our daily life as “where” and “when” we are looking is crucial. Although the analysis of gaze behavior and PA (for example, fixation frequency and duration, or reaction time to detect stimuli as a function of the location in the visual field) has attracted the attention of researchers, this area has been poorly investigated in older adults. In general, the way of perceiving usually converts the visual scene into an ellipse, with better detection of stimuli on the horizontal than on the vertical plane [91]. Moreover, it seems that gaze behavior changes with age, since some studies have found a relationship between aging, a decrease in stimuli detection in the lower areas of the visual field, and accidents and falls [92]. An important question is whether this perceptual pattern changes as a function of age and physical activity. A study with young and older karate and judo athletes and non-athletes [26] reported a horizontal–vertical anisotropy and a vertical meridian asymmetry. All groups detected stimuli presented on the horizontal meridian faster than those on the vertical meridian. They also detected stimuli in the lower visual areas faster than those in the upper areas. Here, age and sport did not modify the way of perceiving a visual scene. These results suggest that visual asymmetries occur at all ages and are basically unrelated to PA, but more research is needed to clarify this finding, as, to our knowledge, this is the only study focusing on aging, PA and perceptual asymmetries. Given the importance of this visuospatial skill, especially in the elderly to prevent falls and other types of accidents, more research is needed to investigate whether exercise might modify gaze behavior.

Another visuospatial ability needed to interact with the environment is dynamic visual acuity (DVA), which refers to the ability to resolve fine spatial details of an object when there is relative motion between the observer and the object [93]. DVA skills are necessary because the world around us is full of moving stimuli that we must be able to detect. These stimuli may appear following multiple trajectories, at different contrasts and at different speeds. DVA is a visuomotor skill that can also play an important role in the lives of elders given the large number of stimuli in motion that exist in our daily life. This type of visual ability, however, is one of the first to decline with age [94], along with the ability to track stimuli [75] and to perform saccadic movements in the right direction [76]. All these visual skills may be related to processing speed.

As with peripheral vision, using basic stimuli not related to the participants’ sport, several studies have reported differences between older athletes and non-athletes in the rapid detection of moving stimuli [27]. When playing sports, stimuli usually move, and athletes might develop a series of skills to enable better and faster detection of stimuli moving in several trajectories. Muiños and Ballesteros presented moving stimuli to both young and older groups of athletes and non-athletes and found that young and older athletes obtained higher DVA scores than non-athletes of the same age [27]. The results suggest that martial arts activity tends to preserve general DVA skills. Moreover, all the older participants showed similar and greater oblique effects. These results indicate that playing a sport does not preserve the ability to detect stimuli that move obliquely. Importantly, the differences between the older groups were greater and mainly concentrated in the high velocity condition.

Surprisingly, there is a lack of research investigating DVA with older athletes or older adults who play a sport on a regular basis. The studies that demonstrate a correlation between improved DVA and certain sports have been conducted with young participants. However, only a few studies have investigated the ability of physically active older adults to track moving stimuli. Accuracy while tracking moving stimuli is a basic ability assessed by dynamic visual acuity (DVA) tests. Bakken et al. [95] showed that after 8 weeks of aerobic exercise, older adults tracked moving stimuli better than at pretest (before training) and than the control group. A further study [96] also assessed eye-tracking ability to a moving stimulus. The participants were five age groups of skilled handball athletes. The oldest group included athletes aged between 43 and 51 years, and could be considered a young-old group. The results showed age-related declines in motor performance but not in perceptual performance, as seniors showed similar fixations (e.g., number, duration) as skilled younger athletes. Lobjois et al. [97] also reported better performance of physically active older adults when tracking a moving stimulus at different speeds. With increasing speed, the performance of all age groups decreased, as it becomes increasingly difficult to track and to detect the features of an object as speed increases. However, when the speed of the moving object increased, older tennis players performed better than older sedentary participants. A further study [98] with tennis players yielded similar results, showing that non-players of all ages (from 20 to 80) showed more errors responding to a stimulus with apparent movement. It is important to note that the differences between players and non-players were greater in the oldest group (70–80 years of age). Another study [99] used a moving dot on the screen to monitor saccades and eye movements, showing that the physically active older participants were more accurate and also showed superior posture control than non-active individuals.

To sum up, physically active individuals, especially those who engage in ball sports or fast-moving sports, such as tennis or martial arts, usually show better DVA or tracking abilities to a moving stimulus than sedentary individuals. When people age, sport helps to preserve their dynamic visual skills. However, given that tracking visual stimuli in general (including DVA) is one of the first abilities to decline with age, it may not be preserved by sports activity, especially for the oldest groups (e.g. 70–80 years old) and with objects on oblique trajectories. Taking part in a sport or being physically active might help generate a more appropriate motor response to a moving stimulus.

Older adults are particularly prone to falls or accidents that could largely be due to declines in many perceptual and cognitive abilities (e.g., poor reaction time and processing speed, loss in peripheral vision, attention decline). According to the reviewed literature, PA might partially attenuate such age-related perceptual and cognitive declines, and even delay the onset of neurodegenerative diseases such as Alzheimer’s, in various ways, including delaying brain volume loss in certain areas such as the hippocampus, acting on both gray and white matter, and enhancing brain connectivity. These changes in some brain areas and in functional connectivity may be reflected at a behavioral level, with improvements in many cognitive functions such as memory, processing and perceptual speed, attention, etc. One of the major questions in research is which type of PA leads to greater improvement. On this point, the literature contains different results as a function of the type of exercise. In general, aerobic exercise seems to be the most effective for improving cognitive areas, but researchers have also reported cognitive improvements with activities that require limb coordination. Aerobic and coordination exercises seem to be more beneficial to cognitive processes than other exercises such as stretching or balancing. However, studies generally report greater cognitive improvements with multi-domain training, involving both physical and cognitive exercises [38]. This could be the case of exergames, dancing and, perhaps to a lesser extent, some complex sports like martial arts. Exergames use video games to provide physical exercise. They comprise different types of exercise, including aerobic, coordination, balance, and cognition, which could produce different physical and cognitive changes. One of the main advantages of using this method, especially for older adults, is that the exercises can be done indoors, increasing the probability of doing them. Moreover, video games can be more enjoyable than classic keep-fit classes, as well as more comfortable and relaxing. Dancing shares many of these advantages, as it usually involves aerobic, coordination, balance and cognitive work (e.g., learning a dance routine). Another common feature is that they are both enjoyable and can be carried out as a leisure activity. Dancing also involves social contact, and it is well known that an active social life is one of the main factors of healthy aging.

A great deal of research on aging and PA has focused on cognitive changes, but little is known about visuospatial attention. It is widely accepted that peripheral vision deteriorates with age, but PA can improve it in both young and older individuals. The same is true for tracking abilities. Both skills are needed to interpret visual scenes and are important in everyday life. There are some types of sport that are more likely to improve PV, notably some martial arts, especially those that require paying attention to what is happening laterally. Some sports can improve DVA or tracking abilities more than others, particularly ball sports and martial arts. Eye function plays an important role for elders, as the way we see the world, where we look and when, can have critical implications. Further studies are needed to clarify all these issues.