European Geriatric Medicine (2020) 11:83–93 https://doi.org/10.1007/s41999-020-00290-6 REVIEW The role of physical exercise and rehabilitation in delirium N. Gual1,2,3 · M. García‑Salmones1 · L. Brítez1 · N. Crespo1 · C. Udina1,2,3 · L. M. Pérez1,2 · M. Inzitari1,2,3 Received: 4 October 2019 / Accepted: 15 January 2020 / Published online: 17 February 2020 © European Geriatric Medicine Society 2020 Key summary points Aim Analyze the intersections between delirium, physical exercise and rehabilitation, to better understand their interrelation and to visualize future lines of research. Findings Delirium and physical function are closely related, since physical dysfunction is described as a risk factor and as a symptom of delirium, and there are also short- and long-term functional consequences related to delirium. Furthermore, physical therapy strategies included in multicomponent interventions to prevent delirium, have shown to be effective in managing delirium. Another important risk factor for delirium is frailty, that given its condition of being reversible basically through rehabilitation programs, begins to play an important role in the prevention and management of delirium, although more studies are needed. Message Although delirium is catalogued as a neurocognitive disorder, scientific evidence shows that it is also a motor dis- order. The motor component of delirium should be taken into account when designing interventions or strategies to address delirium. These interventions may have a special importance in frail older adults. Abstract Purpose This article aims to analyze the intersections between delirium, physical exercise and rehabilitation, to better understand their interrelation and to visualize future lines of research. Methods In this narrative review, after an overview of brain neurophysiology and function, as common substrates to under- stand the relationship between delirium and physical function, we explore the scientific evidence in: (1) physical dysfunction as a risk factor for delirium; (2) physical dysfunction as a symptom of delirium and (3) functional consequences related to delirium. Later, we analyze the physical therapy as one of the main strategies in multicomponent interventions to prevent delirium, by examining intervention studies including rehabilitation, which have shown to be effective in managing delirium. Finally, we analyze how frailty, delirium and physical exercise interact with each other. Results This review confirms the close relationship between delirium and physical dysfunction; therefore, it is not surprising that physical exercise is widely used in delirium preventive strategies. Although delirium is catalogued as a neurocognitive disorder, scientific evidence shows that it is also a motor disorder, which is to be expected, since a vast body of literature already supports an interaction between motor and cognitive function. Conclusion The motor component of delirium should be taken into account when designing interventions or strategies to address delirium. These interventions may have a special importance in frail older adults. Keywords Delirium · Motor dysfunction · Physical exercise · Rehabilitation · Delirium prevention strategies Introduction * N. Gual ngual@perevirgili.cat Delirium is one of the great geriatric syndromes and a 1 challenge for health professionals caring for older patients. Parc Sanitari Pere Virgili, Carrer d’Esteve Terradas 30, 08023 Barcelona, Spain It is a medical emergency characterized by a disturbance 2 in attention, awareness and cognitive function, developed REFiT Barcelona Research Group, Vall d’Hebrón Institute of Research (VHIR), Barcelona, Spain over a short period of time [1, 2]. Although delirium can 3 also develop in children and younger adults, its prevalence Universitat Autònoma de Barcelona, Barcelona, Spain 13 Vol.:(0123456789) 84 European Geriatric Medicine (2020) 11:83–93 is much higher in older people. Several studies have Methodology reported that up to one third of patients over 70 years of age admitted to any medical unit develop delirium [2], a For this narrative review, we have reviewed studies that percentage that increases up to 50% in surgical units and examine the relationship between delirium and physi- up to 85% in palliative care units [3]. The importance of cal function, physical exercise or rehabilitation. After an delirium is not only due to its high incidence, but also on overview of brain neurophysiology and function, as com- the serious consequences for those who suffer it. It has a mon substrates to understand this relationship, we have negative impact on quality of life, increasing morbidity, explored, the evidence in the available literature support- functional dependence [4, 5], the risk of institutionaliza- ing: (1) physical dysfunction as a risk factor for delirium; tion [6] and mortality [6–9]. Moreover, delirium has been (2) physical dysfunction as a symptom of delirium and associated with longer hospital stays [10] and higher eco- (3) functional consequences related to delirium. Then, nomic costs [11]. The association with all these negative we have reviewed intervention studies, centered on multi- results has been shown independent of possible confusing component interventions, including rehabilitation, which variables such as age, sex, comorbidities or severity of ill- have shown to be effective in managing delirium. For this nesses and dementia. purpose, we did a search in PubMed Database using a Among older people, it is well known that exercise and combination of terms representing delirium prevention, physical activity have an important role in maintaining multicomponent intervention, non-pharmacologic inter- independent living [12] functional capacity (maintaining vention, and Hospital Elder Life Program. Studies were muscle mass, strength and balance) [13, 14], prevention of included if they were randomized control trials and mean chronic diseases [15] and maintaining quality of life [16]. age of subject was ≥ 65 years. We excluded those articles Regarding the care of disabling acute or chronic condi- which intervention did not incorporate physical strategies. tions, physical therapy and rehabilitation are a pivotal part The initial search yielded 57 articles published between of the multidisciplinary and multifactorial approach. In January 1999 and June 2019. After exclusions, we only contrast, despite scientific evidence that supports it, the selected 10 original articles in the review. Finally, we have benefit of physical exercise on cognition is less known. examined how frailty, delirium and physical exercise inter- Available literature demonstrates not only that physical act with each other. activity is correlated to a better cognitive function and to a reduced risk of developing cognitive impairment [17, 18], but also that the performance of physical exercise or rehabilitation can improve cognitive function in older Effect of delirium and physical exercise population [19, 20], even in persons with preexisting on brain neurophysiology and function dementia [21]. Regarding delirium, the evidence shows positive influ- ences and benefits of physical exercise on this geriatric syn- (a) Delirium pathophysiology drome. In fact, delirium and physical function are closely related, since disability, immobility and functional decline The pathophysiology of delirium is complex and poorly are identified as risk factors of delirium [22, 23], and, on understood, with several hypothesis described in the litera- the other hand, all of them might be direct consequences ture: the neuronal aging, neuroinflammatory hypothesis, of delirium [4, 5]. So that, physical exercise is also part of oxidative stress theory, neuroendocrine dysregulation, many strategies which have been demonstrated as useful for circadian dysregulation, neurotransmitter hypothesis…. preventing delirium [24], as well as multicomponent inter- Given the development of different hypotheses, the large ventions [25]. number of precipitating and substrate factors, as well as The relationship between delirium and physical exercise the many phenotypic presentations and the interaction is highly complex and presents several specificities. Under- between different biological factors, it seems that a single standing this relationship may help developing health strat- hypothesis may not be sufficient to explain delirium and egies to improve the care of delirium patients, both in the that all these hypothesis may be complementary and not prevention and treatment of this syndrome. This article aims mutually exclusive [26]. In summary, there is a complex to track down and analyze the points, where delirium, physi- interaction between different systems, including immune, cal exercise, and rehabilitation intersect, to better understand hormonal and neuronal homeostasis in delirium. their interrelation and the gaps in knowledge, to visualize Based on published scientific evidence, various cere- future lines of research. bral structures are involved in delirium development [27], such as the brainstem, especially the ascending reticular 13 European Geriatric Medicine (2020) 11:83–93 85 activating system (ARAS), basal ganglia, thalamus and against cognitive decline and dementia [39]. Moreover, frontal, parietal and temporal cortices. For example, recent studies have also demonstrated that physical exercise strokes affecting specific structures can just cause delir- not only can prevent cognitive decline, it can also reverse ium [28]. Interestingly, these areas are also part of the the cognitive impairment associated to the hospitalization complex control of gait pathways, which includes brain- of older patients, improving specifically executive function stem, cerebellum, basal ganglia, thalamus, amygdala, hip- and verbal fluency [40]. pocampus and cortical regions such as the supplementary Since exercise can modify cardiovascular risk factors motor area, motor and premotor cortex, parietal and visual such as hypertension, dyslipidemia, diabetes mellitus and cortex [29]. Specifically, the prefrontal cortex is involved metabolic syndrome, it also improves cerebral vascular func- in the planning and control of movements [30], while is tion and reduces inflammation, acting as a protective agent also considered as a key region for attention [31], one of against cognitive deterioration. the main cognitive functions altered in delirium. Since Neurobiological studies have suggested that exercise can attention is one of the cognitive features necessary for a influence the brain at a supramolecular and molecular level safety walking, disturbances in this area can be directly [41]. In a supramolecular level, physical exercise stimulates correlated with motor function disorders and falls [32]. angiogenesis, neurogenesis, and synaptogenesis. Several It is important to note that for a safe and effective gait, in cerebral structural changes have been described, such as addition to good sensorimotor systems, a correct integra- decrease in white matter hyperintensities and increase in tion between executive, cognitive and affective dimensions different cerebral regions [42]. At a molecular level, exercise is essential [32]. produces changes in molecular growth factors such as brain- Furthermore, imbalances between acetylcholine and other derived neurotrophic factor (BDNF), which plays a crucial neurotransmitters such as serotonin, and dopamine play an role in neuroplasticity and neuroprotection, and increases the important role in delirium and are directly associated with production of insulin-like growth factor 1 (IGF-1), involved cognitive disturbances and motor disorders [33]. During in both neurogenesis and angiogenesis [43]. Animal and normal aging, concentrations of acetylcholine in the central human studies suggest that greater engagement in physical nervous system are decreased, leading to a vulnerable brain activity may preserve cortical gray matter structure and slow that can easily develop delirium with the use of anticholin- the accumulation of Aβ and tau burden [44]. ergic medication. Since reductions in acetylcholine concen- tration have been also associated to frontal and executive dysfunctions [34], it has been hypothesized that motor dis- Relationship between delirium and physical turbances as the manifestations of delirium may be caused function by the inability to plan and perform movements, due to this neurotransmitter dysregulation [35]. Physical function is central to maintain an independent life, its assessment is also key in the comprehensive geriatric (b) Physical exercise and cognitive function assessment and it is directly related to multiple health out- comes (post-surgical complications, functional dependence, The benefits of physical exercise, a subset of physical cognitive impairment, institutionalization and mortality activity that is planned, structured and repetitive [36], are among others) [45–47]. Therefore, it is not surprising that widely known in older adults. These include not only main- physical function is also strongly associated with delirium, taining physical function, preventing or delaying disability as can be seen throughout the process of an entire episode and a better control of chronic illnesses (i.e., cardiovascular of delirium: physical dysfunction as a risk factor before disease risk, bone health, respiratory function in chronic delirium, as a symptom during delirium and as negative pulmonary obstructive disease) [37, 38], but also protecting consequence after the delirium. Fig. 1  Relationship between physical activity and delirium Aer Before delirium Delirium delirium Predisposing Impaired physical funcon factors Motor Low physical acvity Funconal decline symptoms of Immobility delirium factors Precipitang Disability Physical restraints Falls 13 86 European Geriatric Medicine (2020) 11:83–93 In this section, we will analyze those three different managing agitation and preventing patients’ and staff injury moments in which physical dysfunction and delirium are during an episode of severe agitation [63], the recent avail- related (Fig. 1). able literature emphasizes the dangers associated to physical restraints, the importance of using restraints only as a last (a) Disorders in physical function as risk factors for delir- resource, and the promotion of restraint reduction initiatives ium [62]. Despite these recommendations, the prevalence of physical restraint can reach 53%, depending on the country, For delirium development, several factors are usually institution, patient’s characteristics and professional knowl- required, especially in older people. This widely accepted edge of alternatives [64, 65]. multifactorial delirium model includes a complex relation- ship between vulnerable people (with predisposing factors) (b) Motor dysfunction as symptom of delirium and their exposure to adverse events (precipitating factors) [48]. In both categories, predisposing and precipitating fac- Although the diagnosis of delirium pivots on cognitive tor, physical function plays a major role. disturbances such as attention and awareness disorders, There are two factors related to physical function that there is an objective pattern of fluctuating motor perfor- have been identified as predisposing factors for delirium. On mance that occurs in parallel to these cognitive disorders one hand, disability or prior functional impairment (under- [35]. Several studies point out that these motor disorders are stood as the inability to complete one or more activities of a clinical sign of delirium and not only a consequence, sug- daily life (ADLs)) is one of the main and persistent predis- gesting that delirium is not exclusively a cognitive disease, posing factors, conferring up to a fourfold increased risk but also a motor disorder [35, 66]. of delirium [2]. Moreover, as the disability increases, the In fact, when analyzing motor function, impairments of greater the risk of delirium, regardless of other factors [49]. worse motor function can be identified in patients with delir- On the other hand, a poor usual physical activity or patient’s ium in comparison with those without delirium, indepen- mobility before hospitalization has also been identified as dently of the presence of underlying dementia [67]. These an independent risk factor for developing postoperative features have been used to improve the diagnosis of delirium delirium [50]. superimposed on dementia (DSD), using only motor tools When analyzing the precipitating factors, immobility and like the Tinetti scale or the Hierarchical Assessment of Bal- specially the use of physical restraints are pointed as inde- ance and Mobility (HABAM) [35, 67]. pendent risk factors for delirium [2, 51]. Bedrest and low Another characteristic that supports the idea of delirium, levels of mobility, common in hospitalized older patients, are as also a motor disease is the classification of its subtypes. a well-documented problem associated with many adverse Although it can be divided according to its duration or inten- outcomes, including pressure ulcers, venous stasis and an sity of symptoms, it is usual to classify delirium according increased risk of hospital-associated pneumonia [52–54]. to the associated motor disorder: hyperactive or hypoac- Prolonged hospital immobility is also associated with sig- tive (identified by a marked increase or decrease in motor nificant reductions in muscle mass and strength, leading to activity), mixed (which combines moments of increase functional decline, longer hospital length of stay, institu- and decrease in motor activity throughout the day) and the tionalization, and death [54–56]. In addition to this strong non-motor delirium subtype (which has no motor activity impact on the health of hospitalized patients, immobility and disorders). Every motor subtype has his own associated its direct consequences (pressure ulcers, infectious compli- risk factors and consequences. The evidence suggests that cations and functional decline) have in turn been associated patients with more disability are at higher risk of an hypoac- to delirium development [57, 58]. tive delirium, which is independently associated with higher As we analyze in-hospital mobility of older patients, a mortality [68–70] and a higher global functional decline most of the time is spent lying in bed (83%), with only 3% compared to mixed and hyperactive delirium [70]. of the time standing or walking, despite an ability to walk Finally, the strong association between falls and delir- independently [55]. In a part of these patients, the mobility ium is another aspect supporting the idea of motor disorders is involuntary limited by bedrest orders from health profes- as symptoms of delirium. In a systematic review by Sillner sionals, although those orders are not always justified [56]. et al. [71], on one hand, delirium is a persistent risk factor Use of physical restraints, which includes belts, bedrails for falls with an relative risk that ranges from 1.4 to 12.6. or other devices limiting the person’s mobility, is not only On the other hand, delirium is also frequent (24–96%) in associated to delirium (increasing by 4.4 times the risk of patients that have fallen. Motor disturbances, in addition developing delirium) [2, 59], but also to many other com- to the impaired attention linked to delirium, are factors plications such as pressure ulcers, infections or urinary contributing to falls. Disturbances of attention (which is incontinence [60–62]. Although restraints can be helpful in the key in the control of gait and posture, especially under 13 European Geriatric Medicine (2020) 11:83–93 87 challenging circumstances [72]) contribute to reduce the physical function after 6–12 months to be comparable in ability to maintain gait with multiple environmental stimuli, patients who did and did not develop delirium [5, 76, 79], increasing automatically the risk of falling. Furthermore, while other studies point to a maintenance of the functional other delirium symptoms such as disorientation and altera- loss during more than 12 months after delirium [80]. Table 1 tion in perception, together with motor disturbances, create shows the short and long-term functional outcomes associ- an environment favorable to falls. In fact, there is evidence ated to delirium observed in different hospital settings. demonstrating that preventing delirium prevents falls [73]. (c) Functional impairment and disability as consequences Physical therapy, one of the main strategies of delirium in multicomponent interventions strategies to prevent delirium When delirium occurs, patients develop a sudden func- tional decline, which, although it can improve at the same Since delirium has a multifactorial etiology, a single com- time that delirium does, leads to poor functional and recov- ponent approach is not recommended. For this reason, inter- ery outcomes compared to those who did not develop ventions that have proven effective in preventing or treating delirium [4, 5]. In fact, the evidence shows that the longer delirium are multicomponent strategies that act on different the delirium lasts, the greater the functional loss [74, 75]. risk factors of delirium, such as cognitive impairment, sleep These results are consistent across different hospital set- deprivation, immobility, dehydration, and vision or hear- tings. Despite the evidence of worse functional recovery ing impairment [2, 57]. The Hospital Elder Life Program related to delirium is overwhelming at discharge and in the (HELP) [57], widely disseminated, is the first multicom- first months after delirium [76–78], the functional conse- ponent evidence-based intervention that showed efficacy in quences of delirium beyond 12 months are less known and preventing delirium in a cost-effective manner. The effec- even sometimes contradictory. Some publications consider tiveness of multicomponent nonpharmacological programs Table 1  Illustration of short and long-term functional results associated with delirium in different hospital settings Setting Function assessment Outcomes Non cardiac surgery BADLs and IADLs Delirium is associated with functional decline at 3 months [81] BADLs, IADLs and physical Delirium is associated to impaired functional recovery at 18 months [80] function questions Cardiac Surgery IADL Delirium is associated to functional decline at 1 month. There is a similar effect at 12 months although not significant [5] Short Form 36-Item questionnaire Delirium is associated with functional decline at 6 months [82] Orthopedic surgery ADLs, assessment of ambulation. Delirium is associated with functional decline and with a decline in ambulation at 1 month after hip fracture [77] BADLs Delirium is associated with functional decline at 6 month [83] BADLs and IADL Delirium is associated with functional decline at 24 months [84] Medical ward BADLs and IADL Delirium is not associated with functional decline at 6 months [79] BADLs Delirium is not associated with functional decline at 12 months [76] BADLs and IADL Delirium is associated with functional decline at 6 months [85] BADLs and IADL Delirium is associated with functional decline at 12 months in patients with and without dementia [86] Emergency department BADLs and IADL Delirium is associated with functional decline at 6 months [74] BADLs and IADL Delirium is not associated with functional decline at 18 months [87] BADLs and IADL Delirium in patients with a poor baseline function is associated with functional decline at 6 months [88] Intensive Care Unit BADLs Delirium is associated with functional decline at 6 months [89] BADLs and IADLs Delirium tends to associate functional decline at 12 months, although not statisti- cally significant [90] BADLs and IADLs Longer delirium duration is associated with disability in BADLs at 12 months, but not in IADLs [75] Modified Rankin Scale (mRS) Delirium is associated with functional decline at 1 month but not at 3 and 12 months [91] BADLs basic activities of daily life, IADL instrumental activities of daily life 13 88 European Geriatric Medicine (2020) 11:83–93 has been observed above all in the prevention and reduction to understand why from 2010 frailty has also been related to of delirium incidence, reaching a significant relative 40% delirium [109–111], and has been confirmed as a predispos- reduction [92], with also a reduction of falls and a tendency ing factor for delirium in a meta-analysis by Persico et al. to decrease length of stay and avoidance of institutionaliza- [112], although the paucity of studies. tion [51, 57]. Moreover, thanks to these programs we know Frailty, as well as delirium, is also a reversible condition that a significant amount of delirium cases is preventable, that can be prevented and treated. In the last years, many without entailing a high economic cost or high technologi- community interventions have tried to reverse frailty suc- cal complexity. cessfully [113–115]. Given the importance of physical function and mobility Given that frailty has a multifactorial cause, its approach in the development of delirium, almost all multicomponent cannot be exhaustively a physical intervention, and mul- interventions have included, among other aspects, functional ticomponent strategies are needed. However, programs strategies to reduce immobility and enhance physical exer- including physical exercise are essential in the prevention cise during hospitalization. The different functional strate- and treatment of frailty, according to the available scientific gies range from early mobilization, encourage walking (with evidence, and are likely to be effective if undertaken on a assistance, if necessary), increase mobilizations in bed, pro- regular basis over a prolonged period [116, 117]. mote autonomy in ADLs, perform physical exercises with After observing that physical exercise can reduce frailty, static bicycles, and in parallel suggest to avoid the use of clinicians have used this knowledge to include physical immobilizing equipment (e.g., bladder catheters, i.v. equip- exercise in prehabilitation programs for older frail adults ment or physical restraints), among others. Table 2 illustrates undergoing scheduled surgery, as a way to optimize their rehabilitation strategies carried out in multicomponent inter- physical condition and decrease possible negative outcomes ventions that have demonstrated efficacy in managing delir- linked to surgery and hospitalization. Usual prehabilitation ium. Apart from specific rehabilitation strategies or mobi- programs that include physical and nutritional interventions lization protocols, the studies highlight the importance of have demonstrated to reduce the incidence of post‐opera- encouraging or motivating patients to stay physically active, tive complications, shorten hospital stay and improve health‐ within its possibilities, as a way of empowering patients that related quality of life [118, 119], also in frail patients [120]. is also associated with better clinical outcomes [93]. Regarding delirium, we are beginning to observe positive effects of prehabilitation programs with a reduction in delir- ium incidence [121], although more studies are needed. Delirium prevention by targeting frailty with physical exercise Conclusions Frailty is a dysregulation of several physiological systems that generates a progressive decline in our homeostatic Delirium and physical function are closely related; therefore, capacity [103]. This condition implies, in the person suf- it is not surprising that physical exercise is widely used in fering from it, a state of increased vulnerability associated delirium preventive strategies. Although delirium is cata- with many negative health-related outcomes, including an logued as a neurocognitive disorder, we believe that scien- increase in morbidity, mortality and disability [104]. A clas- tific evidence shows that it is also a motor disorder, which sic definition of frailty is centered on a reduction of physical is to be expected, since a vast body of literature already performance (low gait speed, low strength, reduced physi- supports an interaction between motor and cognitive func- cal activity and exhaustion,) and malnutrition. To detect it, tion. This motor component of delirium should be take both specific frailty scales, such as the Clinical Frailty Scale into account when designing interventions or strategies to (CSF), specific Frailty Index or the Fried’s frailty phenotype, address delirium. Since motor function evolves, we have to can be used, as well as physical function test such as the be able to intervene in each of the critical moments, from Short-Physical Performance Battery (SPPB) or the Timed primary care, during hospital stay and after discharge. This Up and Go test (TUG) [105, 106]. Frailty represents a criti- interventions may have a special importance in frail older cal moment in older adults, leading to a progressive decrease adults. We cannot forget that delirium etiology is multifacto- in global capacity. In fact, to prevent disability during aging rial and that interventions to diminish their risk must also be is essential to recognize and manage frailty in the commu- multicomponent, including, of course, rehabilitation strate- nity [107, 108]. gies with the indispensable competence of a rehabilitation Since frailty is a factor that compromises the ability to team that will increase the probability of success. cope with internal and external stressful elements, it is easy 13 European Geriatric Medicine (2020) 11:83–93 89 Table 2  Different functional interventions carried out in multicomponent nonpharmacological programs that demonstrated evidence in manag- ing delirium Study Setting Results Functional intervention Chen 2011 [11] General surgery Reduction in delirium incidence (0% Early mobilization, including ambulation or active vs 16.7%) range-of-motion exercise 3 times daily Reduction in functional decline (− 11.8 points in BI vs − 27.9) Lundström 2007 [94] Reduction in delirium incidence (55% Mobilization within the first 24 postoperative vs 75%) hours Reduction in number of days with Training every day assisted by a PT, OT, and delirium (5 vs 10 days) caring staff Reduction in hospital LOS by 10 days Training based on functional retraining, with special focus on fall risk factors Encourage patients to do as much as they could by themselves before being helped Chen 2017 [95] Reduction in delirium incidence (6.6% Encouraging participants to ambulate as tolerated vs 15.1%) Physically assist patient to carry out activities 3 Reduction in hospital LOS by 2 days times a day: exercise in bed, riding a stationary bike by hand/foot, sitting out of bed, standing, ambulation Stenvall 2007 [96] Orthopedic surgery Reduction in delirium incidence and in Mobilization within the first 24 h after surgery delirium duration Basic ADL performance training, by caring staff. Reduction in number of falls (18 vs Encourage patients to do as much as they could 60 falls) by themselves before being helped Reduction in hospital LOS by 10 days Specific exercise and other rehabilitation proce- dures delivered by a PT and OT Rehabilitation based on functional retraining with special focus on fall risk factors Kratz 2008 [97] Medical and surgery ward 25% reduction in falls Early mobilization, including ambulating at least 25% reduction in the use of restraints 3 times a day > 50% reduction of medications that can cause delirium Inouye 2001 [98] Medical ward Reduction in delirium incidence (9.9% Early mobilization, including ambulation or active vs 15%) range-of-motion exercises three times daily Reduction in total number of days Minimizing use of immobilizing equipment with delirium (105 vs 161) Reduction in total number of delirium episodes (62 vs 90) Bo 2009 [99] Geriatric ward (or medi- Reduce in delirium incidence (6.6% Early mobilization and walking cal patients) vs 15.2%) Daily mobilized out of bed by nurses, apart from different patient-specific indications from medi- cal staff Individual active mobilization strongly encour- aged by clinical staff Assisted walking for frail patients routinely per- formed by PT Vidan 2009 [100] Reduction in delirium incidence Get patients out of bed every day during admis- (11.7% vs 18.5%) sion Reduction in functional decline Initiate mobilization in room and ward corridor. (45.5% vs 56.3%) Remind the patient to do so each day Change position in bed every 3 h if mobilization is not possible Avoid continuous fluid therapy, remove urinary catheter, avoid physical restraints Holt 2013 [101] Reduce in delirium incidence (4.6% Not specified vs 13.3%) Reduction in duration of delirium (mean) (0.06 vs 0.29 days) Reduction in severity of delirium (DRS-R-98 = 9.2% vs 16.9%) 13 90 European Geriatric Medicine (2020) 11:83–93 Table 2  (continued) Study Setting Results Functional intervention Schweickert 2009 [102] Intensive Care Unit Reduction in number of days with Early exercise and mobilization (physical and delirium (2 days vs 4 days) occupational therapy) during periods of daily Better functional outcomes (59% vs interruption of sedation 35% had an independent functional Progress through range-of-motion, sitting, stand- status at discharge) ing, walking, ADLs More ventilator-free days (23.5 vs 21.1 days) BI Barthel Index, PT physiotherapist, TO occupational therapist, ADL activities of daily life, LOS length of stay Authors’ contribution Concept: N.G., M.G., LM.P., M.I., Design: N.G., patients: recognition, risk factors, and psychomotor subtypes. 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