- MCI
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mild cognitive impairment
- MTR
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motoric cognitive risk
The population of adults aged 60 years and older worldwide is projected to grow from 605 million in 2000 to 2 billion in 2050( 1 ). These findings have brought a sense of urgency to understanding ageing processes and the associated risk factors of many morbidities and mortality. Typically, the ‘normal ageing’ process entails a myriad of alterations in sensory, motor and cognitive functions that have been linked to nutritional deficiencies( Reference Inzitari, Doets and Bartali 2 ), poor quality of life( Reference Appollonio, Carabellese and Frattola 3 – Reference Yueh, Shapiro and MacLean 5 ), functional decline( Reference Kaye, Oken and Howieson 6 ), increased risks of falls( Reference Camicioli, Panzer and Kaye 7 – Reference Lord, Rogers and Howland 10 ) and impaired mobility( Reference Kaye, Oken and Howieson 6 ). Moreover, the causal role of nutritional deficiencies has been described for many of these premature cognitive and motoric decline( Reference Jensen and Friedmann 11 – Reference Vellas, Baumgartner and Wayne 15 ).
Disease-related motor impairments, including gait disorders and slowing of movements, are increasingly common with advancing age. A population-based study in the USA showed a 35% prevalence of clinically diagnosed gait disorders among community-dwelling persons over age 70( Reference Verghese, LeValley and Hall 16 ). The prevalence of cognitive impairments of varying severity also increases with age with one study reporting that 17% of adults aged 65 years and older in their population-based cohort had cognitive impairments without meeting criteria for dementia and 8% had dementia( Reference Graham, Rockwood and Beattie 17 ).
Increasingly, the simultaneous existence of both gait and cognitive impairments in ageing has been recognised. Camicioli et al.( Reference Camicioli, Wang and Powell 18 ) reported that gait impairments were seen in over 50% more of cognitively impaired participants compared with cognitively normal participants. While the co-occurrence of gait and cognitive impairments in older adults may reflect a simple co-existence of common age-related syndromes( Reference Camicioli, Wang and Powell 18 ), others have proposed that the co-occurrence of these two geriatric syndromes may be related to a common underlying pathology( Reference Holtzer, Verghese and Xue 19 , Reference Rosano, Brach and Longstreth 20 ). Moreover in many cases, poor diet and nutrition among elderly populations may accentuate these syndromes and in some cases may even be the underlying cause of pathologies. Nutritional deficiencies have been cited as risk factors for balance and mobility issues as well as falls in the elderly( Reference Vellas, Baumgartner and Wayne 15 , Reference Morley 21 ).
Intact gait control requires the efficient integration of many neural systems, including motor, sensory and cognitive processes, and cognitive subsystems such as memory, attention and executive function( Reference Holtzer, Verghese and Xue 19 , Reference Scherder, Eggermont and Swaab 22 ). Gait control is predominately mediated by frontal subcortical circuits. This circuitry is also known to facilitate memory, attention and executive functions( Reference Thompson 23 , Reference Alvarez and Emory 24 ). Therefore, as this circuitry is particularly susceptible to impairment as part of the normal ageing process, mechanisms such as poor diet and nutrition that are related to common pathologies such as vascular diseases and inflammation could trigger cognitive, motor or combined cognitive and motor impairments in older patients( Reference Pugh and Lipsitz 25 – Reference Domellof, Elgh and Forsgren 27 ).
In the following sections, we review several classifications of gait dysfunction, cognitive impairments and nutritional deficits, as well as some common mechanisms of pathological processes that have been linked to cognitive and motor dysfunctions. Furthermore, we will examine the clinical utility of diagnosing combined gait and cognitive impairments, and discuss emerging intervention strategies that build on the interplay of gait and cognitive functions.
Gait dysfunction, cognitive impairments and nutritional deficits
Gait dysfunction
Gait impairments can be classified into neurological or non-neurological subtypes following clinical examination of walking patterns. Neurological gait abnormalities result from focal or diffuse lesions affecting the neural pathways that link cortical motor centres to the peripheral neuromuscular systems( Reference Verghese, Lipton and Hall 28 ). Neurological gait abnormalities are further classified into: unsteady, ataxic, neuropathic, frontal, Parkinsonian, haemiparetic and spastic subtypes( Reference Verghese, Lipton and Hall 28 , Reference Sudarsky 29 ). Non-neurological gait abnormalities result from physical limitations to walking, such as arthritis or foot deformities. Combinations of neurological and non-neurological subtypes can also exist in older adults.
An alternate clinical gait classification divides abnormalities into low-, middle- and high-level disorders( Reference Nutt, Marsden and Thompson 30 , Reference Nutt 31 ). In low-level gait disorders, only one major afferent sensory system (visual, proprioceptive or vestibular) is affected. Middle-level disorders result from spasticity (due to myelopathy from cervical spondylosis and stroke), Parkinsonism or cerebellar ataxia. High-level gait disorders include cautious gait, frontal gait disorders and psychogenic gait disorders, and may result from disruptions in cortico-cortical and cortico-subcortical connections.
The reliability and validity of most gait classification systems have not been verified and many gait subtypes overlap. This may in part explain why there is a paucity of studies that have employed clinical gait subtypes, an essential part of the neurological evaluation, to predict geriatric outcomes.
Accurate identification of neurological gait subtypes enables anatomical localisation of lesions, guides investigations, and provides hints to the underlying pathology. Identifying gait subtypes is also helpful in risk prognostication for motor and cognitive outcomes in clinical practice. For instance, while neuropathic gaits that present with foot drops were reportedly associated with increased fall risk( Reference Verghese, Ambrose and Lipton 32 ), frontal gait disorders that present with short shuffling steps and difficulty lifting feet have been associated with increased risk of developing dementia, especially vascular dementia( Reference Verghese, Lipton and Hall 28 ).
Cognitive syndromes
Cognitive disorders, unlike gait disorders, are categorised on a spectrum of cognitive decline, beginning with cognitive normalcy, transitioning to intermediate states such as the mild cognitive impairment (MCI), and often reaching an endpoint of dementia. MCI is defined as an impairment in one or more domains of cognitive function, without interference in daily activities in non-demented individuals( Reference Petersen and Negash 33 ). It is sub-classified into three categories, amnestic MCI, which predominately involves memory impairments; non-amnestic MCI, which involves impairments in cognitive domains, such as executive function, language or visuo-spatial impairments, and lastly combined MCI, which involves multiple impairments across both memory and other cognitive domains( Reference Petersen 34 ). Patients who meet MCI criteria in clinical practice are at higher risk of transitioning to dementia( Reference Petersen 34 ).
Presence of neurological gait subtypes as well as quantitative gait impairments have been linked to MCI( Reference Verghese, Lipton and Hall 28 , Reference Verghese, Robbins and Holtzer 35 , Reference McGough, Kelly and Logsdon 36 ). Recent studies suggest that gait slowing may precede declines in cognitive tests in older adults( Reference Mielke, Roberts and Savica 37 , Reference Buracchio, Dodge and Howieson 38 ). Hence, gait may complement cognitive assessments in MCI. The role of gait assessment in predicting transitions to dementia in MCI patients requires further investigation.
Nutrition
A high prevalence of malnutrition and nutritional deficiencies has been reported among elderly populations( Reference Vellas, Baumgartner and Wayne 15 , Reference Morley 21 ). The elderly are particularly vulnerable for malnutrition due to many age-related pathological and physiological risk factors( Reference Inzitari, Doets and Bartali 2 ). Some common age-associated physiological risk factors among the elderly include a reduced sense of smell and taste, impaired absorption of certain micronutrients and minerals, such as vitamin D, and a reduced metabolic rate( Reference Inzitari, Doets and Bartali 2 ). Other risk factors include depression, isolation and use of medications, which may decrease appetites( Reference Inzitari, Doets and Bartali 2 ). Malnutrition and deficiencies are associated with negative physical and cognitive outcomes among the elderly( Reference Inzitari, Doets and Bartali 2 , Reference Vellas, Baumgartner and Wayne 15 , Reference Galland 39 , Reference Llewellyn, Lang and Langa 40 ). Specifically, vitamin deficiencies have been associated with poor physical function( Reference Inzitari, Doets and Bartali 2 , Reference Sohl, de Jongh and Heijboer 41 , Reference Wicherts, van Schoor and Boeke 42 ) as well as cognitive decline( Reference Llewellyn, Lang and Langa 40 ). Conversely, dietary patterns and adherence to specific diets have been shown to prevent risk factors, such as inflammation and vascular diseases that in turn are associated with both cognitive and mobility decline( Reference Solfrizzi, Panza and Frisardi 43 – Reference Ma, Hébert and Li 46 ). Thus, malnutrition and dietary deficiencies represent a modifiable link between mobility and cognitive decline with potential to slow or prevent the transition to disability and dementia.
Gait dysfunction and cognitive impairments
Mild cognitive impairment
MCI is diagnosed in individuals who have more cognitive deficiencies than expected for their age and education( Reference Petersen and Negash 33 ), and is considered to be a transitional stage between normal ageing and dementia. Deficits in fine and complex motor skills equilibrium, and limb coordination have been reported in older adults with MCI( Reference Kluger, Gianutsos and Golomb 47 , Reference Franssen, Souren and Torossian 48 ). In particular, results show participants with MCI to have reduced performance on assessments of balance, gait function and coordination when compared with normal controls( Reference Kluger, Gianutsos and Golomb 47 , Reference Franssen, Souren and Torossian 48 ). Moreover, early motor dysfunction, assessed by presence of gait slowing, co-exists with and may even precede the onset of cognitive decline in older adults( Reference Camicioli, Howieson and Oken 49 ). In addition to slow gait, poor performance on individual quantitative gait variables was reported to be more common in those with MCI when compared with individuals with no cognitive impairments( Reference Verghese, Robbins and Holtzer 35 ). These findings and others support( Reference Holtzer, Verghese and Xue 19 , Reference Rosano, Brach and Longstreth 20 , Reference Pugh and Lipsitz 25 , Reference Rosano, Aizenstein and Studenski 50 , Reference Holtzer, Friedman and Lipton 51 ) the notion that higher level cognitive processes such as executive attention and memory are associated with gait and indicate an important link between motoric and cognitive impairments in MCI. Therefore, quantitative gait assessments could provide early diagnostic clues of cognitive deficits in regions of the brain involved in gait very early on in its course.
Motoric cognitive risk syndrome
Despite growing evidence of the link between cognitive impairments and motor performance in ageing, there have been limited attempts to capitalise on these findings in dementia risk prognostications. The recently described motoric cognitive risk (MCR) syndrome offers preliminary support for a motor-based MCR syndrome that identifies older individuals at high risk for transitioning to dementia, especially vascular dementia( Reference Verghese, Wang and Lipton 52 ). MCR is diagnosed when a patient meets all four of the following criteria: (1) cognitive complaints; (2) slow gait (velocity one sd or more below age and sex appropriate mean values); (3) preserved activities of daily living; (4) absence of dementia. Thus, the MCR criteria are similar to those employed to define MCI, with the exception of the objective cognitive criteria in MCI being substituted by the slow gait requirement in MCR syndrome. MCR has strong predictive validity for dementia: older participants meeting criteria for MCR were over three times likely to develop dementia and more than twelve times likely to develop vascular dementia. Interestingly, MCR syndrome was a better predictor of dementia than cognitive complaints or slow gait alone. While there is overlap between MCR and MCI cases, MCR syndrome still predicted risk of dementia after accounting for MCI subtypes. Furthermore, this research provides a clinical approach to identify high-risk individuals and those who may benefit from preventive interventions.
Nutrition, gait and cognition
Nutritional deficiencies can simultaneously impact gait and cognition, and contribute to the growing prevalence of cognitive disorders and mobility disabilities worldwide. The negative effects of poor nutrition are potentially modifiable, suggesting that a better understanding of the impact of nutrition on gait decline and cognitive functions could be used as a springboard to develop new interventions to prevent or diminish gait and cognitive impairments in the elderly.
Nutritional deficiencies
Vitamin D deficiency is a prevalent condition among the elderly, affecting approximately 40–100% of those living in Western countries( Reference Llewellyn, Lang and Langa 40 , 53 ), and has been reported to negatively impact physical performance( Reference Sohl, de Jongh and Heijboer 41 , Reference Wicherts, van Schoor and Boeke 42 ). Vitamin D acts as a stimulant for calcium absorption; therefore, deficiencies resulting in reduced bone density and softening can make certain groups of people particularly vulnerable to fractures, osteoporosis and other consequences( 53 ). Studies have reported that vitamin D was positively associated with all three components of a physical performance test, including a walking test, chair rise and tandem stand( Reference Sohl, de Jongh and Heijboer 41 , Reference Wicherts, van Schoor and Boeke 42 ). Moreover, the authors reported the strongest predictor of physical decline was the walking test( Reference Sohl, de Jongh and Heijboer 41 ), indicating a potential role for vitamin D supplementation as a prevention strategy of future mobility disabilities in the elderly.
Low levels of vitamin D have also been associated with cognitive decline( Reference Llewellyn, Lang and Langa 40 ). A 6-year prospective study of the link between vitamin D deficiencies and cognitive decline indicated that those with severe deficiencies (serum 25-hydroxyvitamin D <25 nmol/l) had significant declines on tests of executive functions and general cognition over the study period( Reference Llewellyn, Lang and Langa 40 ). Thus, findings from this study present an early link between low levels of vitamin D, cognitive and motor decline in the early stages of neurodegenerative disease.
Inflammation and nutrition
While normal ageing is associated with a low-grade systemic inflammation, previous studies have linked higher levels of inflammatory markers to physical function and mobility impairments in older adults( Reference Maggio, Guralnik and Longo 26 , Reference Bruunsgaard, Pedersen and Pedersen 54 , Reference Starr, Evers and Saito 55 ). A recent review of the influence of nutrition on inflammation indicated that diets low in saturated fats including a high intake of fruit, vegetables and grains are associated with reduced inflammation( Reference Galland 39 ). Cross-sectional studies have demonstrated an association between high serum levels of IL-6 and TNF-α with worsening of functional and mobility status( Reference Penninx, Kritchevsky and Newman 56 – Reference Cesari, Penninx and Pahor 58 ). However, only elevated serum levels of IL-6 but not TNF-α were associated with increased rates of decline in gait speed when examined prospectively( Reference Verghese, Holtzer and Oh-Park 59 ); suggesting that not all inflammatory markers are involved in motoric decline.
In addition to mobility impairments, inflammation is also implicated in the cascade that leads to the development of amyloid neuritic plaques, one of the pathological hallmarks of Alzheimer's disease( Reference McGeer and McGeer 60 ). Studies have linked cognitive decline to deficiencies in micronutrients such as folates, B12 and vitamin C( Reference Inzitari, Doets and Bartali 2 , Reference Scarmeas, Stern and Tang 45 , Reference Solfrizzi, Panza and Capurso 61 ), which have been shown to lower levels of inflammation( Reference Chrysohoou, Panagiotakos and Pitsavos 62 ). Epidemiological studies have identified associations between specific inflammatory markers such as increased IL-6 levels with a decline in the ability to encode new information and recall learned information; aspects of cognition affected early in Alzheimer's disease( Reference Elderkin-Thompson, Irwin and Hellemann 63 ).
Vascular diseases, nutrition and cognition
The economic burden of CVD is well known with an estimated 17·3 million people dying annually due to a CVD and over 80% of those deaths being in middle or low-income countries( 64 ). The cause of this may primarily be due to the increased exposure to risk factors such as smoking and diets that are typically high in saturated fats and sodium( 64 ). These types of diets have been linked to vascular diseases such as atherosclerosis and hypertension( 65 ). Moreover, growing evidence suggests that vascular diseases such as hypertension, dyslipidemia, hyperinsulinemia, type 2 diabetes, obesity and subclinical atherosclerosis increase risk for cognitive decline and dementia( Reference Kalaria, Maestre and Arizaga 66 , Reference Breteler 67 ). This has spurred a growing interest in exploring the impact of whole types of foods (e.g., fruit and vegetables) and dietary patterns. The Mediterranean diet, which is high in consumption of fruit, vegetables and grains, and low in saturated fats, has been associated with a decreased risk for CVD, several forms of cancer, mortality and most recently to dementia( Reference Scarmeas, Stern and Tang 45 , Reference Scarmeas, Luchsinger and Schupf 68 – Reference Jacques and Tucker 70 ). Scarmeas et al. found that higher adherence to the Mediterranean diet was associated with lower risk of developing incident MCI and Alzheimer's disease( Reference Scarmeas, Stern and Mayeux 44 , Reference Scarmeas, Stern and Tang 45 ). Moreover, these investigators found that seniors who adhered to healthy diet and regular physical activity had a 12% risk reduction of Alzheimer's disease compared with those who did neither( Reference Scarmeas, Stern and Tang 45 ). Moreover, a recent review of diet and cognitive decline supported the protective role of the Mediterranean diet in preventing all vascular conditions linked to dementia( Reference Solfrizzi, Panza and Frisardi 43 ).
Vascular diseases, nutrition and gait
In elderly patients, vascular lesions are strongly associated with CVD such as hypertension, diabetes or hyperlipidemia( Reference Pantoni and Garcia 71 ), all of which are also associated with poor dietary habits( Reference Solfrizzi, Panza and Frisardi 43 ). The accumulation of vascular structural abnormalities can account for not only cognitive decline( Reference Garde, Mortensen and Krabbe 72 – Reference Leaper, Murray and Lemmon 74 ) but gait abnormalities as well( Reference Rosano, Brach and Longstreth 20 , Reference Rosano, Kuller and Chung 75 , Reference Rosano, Brach and Studenski 76 ). The severity of periventricular white matter lesions is associated with a decline in the speed of mental processing( Reference de Groot, de Leeuw and Oudkerk 73 ), as well as poorer performance in fluid intelligence measures( Reference Garde, Mortensen and Krabbe 72 , Reference Leaper, Murray and Lemmon 74 ). Subclinical white matter hyperintensities, brain infarcts and brain atrophy predicted a faster rate of decline in gait speed over time( Reference Rosano, Kuller and Chung 75 ). In addition to velocity, Rosano et al. demonstrated that a decline in stride length, and an increase in step length variability, was indicative of the presence of brain infarcts and white matter hyperintensities in an elderly population free from stroke, dementia or other neurological diseases( Reference Rosano, Brach and Longstreth 20 , Reference Rosano, Brach and Studenski 76 ). Vascular risk factors can lead to cerebral ischaemia secondary to impairment in arterial vasoreactivity, obstruction of small subcortical arterioles or hypoperfusion( Reference Pugh and Lipsitz 25 ). Vascular lesions can be either focal, resulting in lacunar infarctions, seen in the thalamus, basal ganglia, internal capsule or brainstem( Reference Fisher 77 ) or diffuse, affecting the periventricular white matter( Reference Cummings 78 ). The periventricular white matter consists of the ascending thalamocortical and descending corticospinal tracts, which subserve gait and balance functions( Reference Thompson 23 ). The frontal–subcortical connections, which control speed of cognitive processing and executive function, also travel within the periventricular white matter( Reference Alvarez and Emory 24 ). Owing to the close proximity of these two circuits, white matter lesions can simultaneously affect motor and cognitive functions, and may be caused by poor nutrition which result in pathologies that are potentially preventable through interventions to improve healthy lifestyle factors.
Interventions
Modifiable lifestyle variables such as diet, physical activity and cognitive interventions may prevent cognitive decline via effects on cardiovascular, stress, inflammation and other pathways. Defining the role of healthy lifestyle factors in dementia may translate into effective preventive interventions.
Physical activity and nutrition-based interventions
Physical activity and good nutrition contribute to healthy ageing and reduces morbidity and mortality( Reference Byberg, Melhus and Gedeborg 79 ). Physical activity has been shown to have protective effects against mortality in patients with chronic diseases such as CVD( Reference Kodama, Saito and Tanaka 80 ). Many studies have examined the effect of physical activity on cognitive performance in older individuals. For instance, Baker et al. demonstrated an improvement in executive function tests in individuals with normal cognition who underwent a 6-month aerobic exercise programme compared with healthy controls who participated in a stretching regimen( Reference Baker, Frank and Foster-Schubert 81 ). The researchers further demonstrated an improvement in executive function after a 6-month aerobic exercise programme in individuals with MCI( Reference Baker, Frank and Foster-Schubert 82 ). A French study enrolled patients with dementia from a nursing home, half of whom took part in three 60 min exercise sessions per week that strategically focused on improving walking, stamina and equilibrium( Reference Kemoun, Thibaud and Roumagne 83 ). The thirty-one individuals who underwent the physical intervention showed improvement in composite cognitive functions, while the sixteen participants in the usual care control group showed a decline in cognitive functions.
A recent review of the impact of nutrition interventions on health outcomes among community-dwelling older adults reported that interventions that involved active participation in personal nutrition plans were the most effective for positive outcomes for older adults( Reference Bandayrel and Wong 84 ). The findings from several studies revealed that nutritional intervention improved memory and decreased falls( Reference Bandayrel and Wong 84 ). Other studies have not supported the role of nutritional supplements in stroke prevention and treatment( Reference Saposnik 85 , Reference Hankey, Eikelboom and Baker 86 ). A meta-analysis of data of the influence of B-vitamins on stroke patients revealed that the effectiveness of B-complex vitamins as a stroke prevention strategy cannot be established( Reference Saposnik 85 ). One randomised control trial indicated that a daily supplement of folic acid and B-vitamins after a stroke was safe, but not effective in reducing the future incidence of stroke( Reference Hankey, Eikelboom and Baker 86 ). However, investigators on another clinical trial found a significant association between B-vitamins and folic acid supplements on depression reduction in stroke patients( Reference Almeida, Marsh and Alfonso 87 ). Although the effect of nutrition interventions on particular health outcomes has not been conclusive in each study, they have all provided evidence for potential benefits of nutrition awareness and improved dietary habits on overall health status( Reference Bandayrel and Wong 84 , Reference Saposnik 85 ). Moreover, collectively these studies support the link between gait and cognition by providing evidence that physical exercise and nutrition-based interventions may result in improvements in cognition and physical functioning.
Cognitive remediation and mobility
The reverse relationship between cognitive interventions and their effect on gait are being explored in recent studies. Cognitive remediation approaches using computerised programmes or cognitive training have demonstrated an improvement in attention and executive function as well as memory in cognitively normal older adults. Verghese et al.( Reference Verghese, Mahoney and Ambrose 88 ) conducted a pilot study in which twenty-four frail older adults were randomly assigned to either participate in a computerised cognitive remediation programme or were in a usual care group for a 12-week period. The cognitive remediation group showed an improvement in gait velocity during normal walking and during walking while talking conditions compared with their baseline performance. This small study suggests the possibility that cognitive remediation could be a new, non-pharmacological means of modifying gait performance, especially during dual-task conditions.
Participants who received training in dual-tasking have demonstrated improvements in walking abilities( Reference Schwenk, Zieschang and Oster 89 , Reference Mirelman, Maidan and Herman 90 ). Schwenk et al. evaluated the efficacy of a 12-week dual-task training programme in seniors with dementia. The participants were randomised to either a dual-task exercise session, involving walking while performing complex motor or cognitive activities, or a low-intensity exercise session( Reference Schwenk, Zieschang and Oster 89 ). After 12 weeks, the group that received dual-task training performed significantly better on gait in a complex dual-task condition compared with the control group. Mirelman et al. examined the efficacy of a treadmill training programme enhanced with virtual reality in patients with Parkinson's disease( Reference Mirelman, Maidan and Herman 90 ). After 6 weeks training, gait velocity, stride time and stride length significantly improved in normal and dual-tasking conditions, and gait variability decreased (improved) under the dual-task condition. These preliminary studies support the feasibility and validity of cognitive-based approaches to improve mobility.
Conclusions
Review of the literature suggests that the co-existence of gait and cognitive impairments in older adults are related to common underlying pathologies and are not an age-related phenomenon. Importantly, both mobility and cognitive dysfunctions have been linked to nutritional deficiencies which may have caused or prolonged deficits in both areas. Further studies need to address the common biological and brain substrates underlying cognitive-motor impairments and identify causal risk factors, such as nutritional deficits, to improve current risk assessment procedures and develop novel interventions to maintain functional independence in older individuals.
Acknowledgements
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Financial support
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Conflicts of interest
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Authorship
E.I.A. conducted literature searches and drafted the review. J.V. provided guidance, reviewed drafts and finalised the review article.
