1.1

Introduction

Older adults with both cognitive and physical impairments are at elevated risk for falls, disability, and institutionalization . Mild cognitive impairment (MCI) is a transitional state less severe than dementia but beyond that of typical age-related cognitive changes . There are two major sub-classifications of MCI, amnestic MCI (aMCI) and non-amnestic MCI (naMCI) . aMCI involves impairment of cognitive dimensions specific to memory and attention, while naMCI is characterized by reduced function in cognitive domains other than memory . Older adults with aMCI are at highest risk for developing Alzheimer’s disease (AD) . A temporal relationship exists between declining cognitive function and declining physical function in older adults with AD . Reduced physical function is evident prior to the onset of dementia , contributing to accelerated global decline and disability.

Older adults with MCI (amnestic and non-amnestic) demonstrate declining physical function including slower walking, reduced balance reactions and elevated risk for falling . Physical frailty, a convergence of cumulative stress from multiple physiological systems, is also associated with increased incident falls, activities of daily living (ADL) dependence, hospitalization and disability . Identification of physical frailty associated with severity of cognitive impairment is needed to develop early intervention and rehabilitation strategies aimed at assisting older adults in maintaining their health and independence.

A frailty index derived from the Cardiovascular Health Study includes the clinical presentation of three of five criteria: slow gait, low grip strength, low physical activity (PA), low energy, and unintentional weight loss . More broadly defined, slowness, low PA, low strength, exhaustion, and body composition represent dimensions of physical frailty . Of these dimensions slow gait speed, low PA and low grip strength have been reported to be predictive of cognitive impairment and incident disability in community-dwelling older adults . Concurrent presentation of slow gait speed and cognitive impairment has been reported to be more strongly associated with the onset of dementia than either slow gait speed alone or cognitive impairment alone .

Although a relationship between physical frailty and cognitive function have been reported, severity of cognitive impairment has not been studied in relation to key aspects of physical frailty. The Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) is associated with the rate of disease progression in older adults with mild to moderate AD , and has been shown to discriminate between very mild to mild dementia in addition to more advanced stages of AD , therefore, it may also be sensitive to reduced global cognitive function in individuals with aMCI.

In persons with aMCI, pathological mechanisms involved in AD may manifest as physical decline prior to the onset of dementia through alterations in memory, attention and executive function networks . Alternatively, age and age-related conditions may contribute to concurrent decline of physiological systems via underlying mechanisms such as inflammation and energetic pathways . Early identification of relationships between physical frailty and severity of cognitive impairment are important for timely interventions aimed at slowing or reversing functional decline and disability in persons with aMCI.

The purpose of this study was two-fold, first, to describe the prevalence of three dimensions of physical frailty in older adults with aMCI, and, second, to examine whether aspects of physical frailty are associated with severity of cognitive impairment. We hypothesized that dimensions of physical frailty would be associated with severity of cognitive impairment and dimensions of cognitive function after adjusting for sex, age, and age-related conditions.

1.2

Method

This study involved analysis of baseline data from the Resources and Activities for Life-Long Independence (RALLI) study, a randomized controlled trial of psychosocial and exercise interventions for sedentary older adults with aMCI, who were enrolled between July 2007 and October 2009. Participants were volunteers living in independent retirement residences who reported mild memory problems. Participants enrolled in the study were age 70 and older, sedentary, and classified as having aMCI based on screening interviews and a consensus meeting of an expert panel. Study recruitment and screening consisted of:

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  a phone screening;

  
  
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  an in-home screening with a semi-structured interview and neuropsychological tests;

  
  
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  an expert consensus panel of clinical psychologists.

Petersen criteria , using a combination of cognitive test scores, screening interview data, and consensus case review, were applied to identify persons with memory problems consistent with a clinical subtype of aMCI (single or multiple domain). Petersen criteria included:

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  memory complaint;

  
  
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  impaired memory for age and education;

  
  
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  preserved general cognitive function;

  
  
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  essentially preserved ADLs;

  
  
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  no diagnosis of dementia.

Neuropsychological screening included:

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  the Mini-Mental State Exam (MMSE) for global cognition ;

  
  
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  the Wechsler Memory Scale-Revised (WMS-R) Logical Memory I & II for immediate and delayed recall ;

  
  
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  the Clinical Dementia Rating (CDR) scale for severity rating of cognitive impairment .

Objective memory impairment was determined by: a score on the WMS-R Logical Memory tests that was 1 standard deviation below age- and education-adjusted norms , problems on memory recall items of the MMSE, and/or observed difficulty with everyday recall during the interview. Sedentary lifestyle was defined as less than 150 minutes of moderate-intensity exercise per week (over the past month) .

Potential participants were excluded if they:

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  were unable to walk independently with an assistive device;

  
  
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  were expecting to move away from the area;

  
  
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  had a known terminal illness;

  
  
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  were actively suicidal, hallucinating, or delusional;

  
  
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  had been hospitalized within 12 months;

  
  
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  had an uncontrolled chronic medical condition;

  
  
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  were blind or deaf;

  
  
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  or had a known central nervous system condition associated with dementia.

The local institutional review board approved all study procedures.

1.3

Results

Demographic, covariate, cognitive function, and physical frailty variables are summarized in Table 1 . The initial sample was composed of 201 participants; however, due to episodic missing data between 173 and 201 cases were included in the multiple linear regression analyses. For example, some participants did not complete the Trail Making Tests due to vision problems. The mean MMSE was 26.3 (SD = 3.2) and all participants had a 0.5 CDR, consistent with classifications for aMCI . The percent of participants that met criteria for the three dimensions of frailty were as follows: frail gait speed 57.3%, frail PA 58.2%, and frail grip strength 64.2% ( Table 2 ).

1.4

Discussion

In this study of sedentary older adults with aMCI, greater than 50% of participants were frail on dimensions of slow gait speed, low PA and low grip strength. Lower performance on dimensions of physical frailty was associated with worse performance on the ADAS-Cog, a measure of severity of cognitive impairment. In particular, slower usual gait speed was associated with elevated severity of cognitive impairment and worse performance within all dimension of memory, attention, and executive function, after adjusting for age, sex, and age-related covariates. Taken together, the results of this study provide support for a relationship between dimensions of physical frailty and severity of cognitive impairment in sedentary older adults with aMCI. Given that concurrent impairments in physical and cognitive domains accelerates functional decline and subsequent disability in older adults , these findings are clinically relevant for rehabilitation professionals when working with older adults with cognitive impairment.

In our study population, there was a high prevalence of slow gait speed, low PA and low grip strength. After adjusting for age and age-related covariates, associations between gait speed and severity of cognitive impairment remained. This was also true when examining dimensions of physical frailty in relation to individual cognitive dimensions. These findings suggest that factors other than age, sex and age-related factors account for associations between dimensions of physical frailty (slow gait and low PA) and lower cognitive function in older adults with aMCI.

Consistent with previous studies, our findings demonstrate associations between lower PA and lower executive function. In a cross-sectional study of healthy men and women, higher long-term PA levels were associated with higher executive function, but not with non-executive functions . Physical dysfunction and executive dysfunction have also been implicated in elevated risk for dementia in community-dwelling older adults, including persons with aMCI . Taken together, these results indicate that further research is warranted on PA as a preventive and rehabilitation strategy in persons with aMCI.

Our study showed that grip strength was associated with only attention (TMT-A), but found no relationship between grip strength and severity of cognitive impairment or other dimensions of cognitive function. In contrast, previous studies have reported a relationship between reduced grip strength and subsequent cognitive impairment , all-cause mortality , and greater AD pathology on autopsy . It is plausible that grip strength is less sensitive for detecting general muscle strength deficits in early stages of cognitive decline, but becomes a more sensitive measure in individuals with a diagnosis of AD, especially with disease progression. A study by Boyle et al. (2009) tested muscle strength in nine muscle groups of older adults and reported a reduced risk for MCI and AD associated with better muscle strength . Warranting further study on the presence and direction of this relationship, global cognitive decline preceded performance decline on grip strength and chair stands in older women in the Women’s Health Initiative Study .

Although the mechanisms underlying the relationship between physical frailty and cognitive function in older adults with aMCI remain unclear, several potential mechanisms related to AD pathology have been suggested. First, the slowing of gait prior to the onset of dementia may occur in conjunction with declining cognitive abilities, such as attention and perceptual speed for the planning and monitoring of physical performance . Second, gray matter structural atrophy in the prefrontal cortex and hippocampal regions in association with slower walking speed has been reported . Third, pathology not typically associated with AD, but instead associated with other dementia syndromes (e.g., Parkinson’s disease, vascular disease) may interfere with frontal-subcortial circuits . For example, white matter hyperintensities (WMH) in the brain, attributed to vascular and cardiovascular disease, are associated with greater severity of cognitive impairment as well as physical frailty. Older adults with MCI and mild AD showed greater WMH in association with higher (worse) scores on the ADAS-Cog in cross-sectional and longitudinal studies . Greater WMH burden has also been associated with worse performance in executive function, physical performance and falls in community-dwelling older adults . Finally, pathological mechanisms associated with physical frailty, such as age and age-related conditions may contribute to concurrent decline of physiological systems via underlying mechanisms such as inflammation and energetic pathways .

There are limitations to this study. The cross-sectional nature of this study does not allow for inference of causation; however, the results provide a basis for future research to examine mechanisms and causative relationships. There may be ceiling effects on measures of cognitive function in older adults with aMCI. Our participants were sedentary older adults with aMCI at baseline of a randomized clinical trial and our results are therefore generalizable only to older adults similar to our study population. Thus, more active, less cognitively impaired older adults may yield different associations between dimensions of physical frailty and cognitive function.

1.5

Conclusions

In this study of sedentary older adults with aMCI, dimensions of physical frailty were associated with severity of cognitive impairment and dimensions of cognitive function, after adjusting for age, sex, and age-related covariates. In particular, our study demonstrated that slower usual gait speed was associated with severity of cognitive impairment as measured with the ADAS-Cog. Further investigation is needed to address biological mechanisms and early intervention strategies that assist older adults with aMCI to maintain function and independence. Future research exploring the mechanisms that underlie associations between physical function and severity of cognitive impairment in older adults with aMCI may elucidate potential avenues for prevention and rehabilitation strategies.

Disclosure of interest

The authors declare that they have no conflicts of interest concerning this article.

Acknowledgements

This work was supported by the National Institutes on Aging at the National Institute of Health (grant number 2RO1 AG14777-06A2 ); the National Institutes of Health (grant number 2T32-HD-00742416A1 ); the National Institute of Nursing Research at the National Institutes of Health (grant number T32 NR007106 ); and the de Tornyay Healthy Aging Doctoral Scholarship (University of Washington, School of Nursing).

2.1

Introduction

Une personne âgée avec troubles cognitifs associés à une fragilité physique présente des risques élevés de chute, de situation de handicap et de recours à l’institutionnalisation . Le déficit cognitif léger ou Mild Cognitive Impairment (MCI) est un état transitionnel moins sévère que la démence mais plus marqué que les troubles cognitifs physiologiques liés à l’âge . Il existe deux sous-catégories de MCI, le MCI amnésique (aMCI) et le MCI non amnésique (naMCI) . Le aMCI se définit comme un déficit des domaines cognitives spécifiques à la mémoire et à l’attention, alors que le naMCI se caractérise par un déficit des autres domaines cognitifs excluant la mémoire . Les personnes âgées avec un aMCI sont plus à risque de développer la maladie d’Alzheimer (MA) . Il existe une relation temporelle entre le déclin des fonctions cognitives et le déclin des fonctions physiques chez la personne âgée atteinte de MA . La diminution des fonctions physiques précède l’apparition de la démence contribuant à l’accélération du déclin global et de la situation de handicap.

Chez les personnes âgées MCI (amnésique et non amnésique) les fonctions physiques sont diminuées, avec une marche ralentie, une instabilité et un déséquilibre entraînant un risque élevé de chutes . La fragilité physique, convergence de facteurs issus des différents systèmes physiologiques, est également associée à un risque élevé de chutes, de dépendance dans les activités de la vie quotidienne, d’hospitalisation et de handicap . Il est essentiel de dépister cette fragilité physique associée à un trouble cognitif sévère afin de mettre en place des interventions précoces et une stratégie adaptée de rééducation pour permettre à la personne âgée de garder son indépendance et un état de santé satisfaisant. Un indice de fragilité, dérivé de l’Étude sur la Santé Cardiovasculaire, souligne la présentation clinique de trois des cinq critères : vitesse de marche réduite, faible force de préhension, faible niveau d’activité physique (AP), baisse d’énergie et perte de poids involontaire . Plus largement, la lenteur, le faible niveau d’AP, le manque de force, la fatigue et l’indice de masse corporelle constituent les dimensions de la fragilité physique . Au sein de ces dimensions, la lenteur de marche, le faible niveau d’activité et le manque de force de préhension sont reconnues comme facteurs prédictifs de troubles cognitifs et d’accidents chez la personne âgée . La concomitance de la lenteur de marche et d’un trouble cognitif est fortement corrélée à un début de démence par rapport à la marche lente seule ou le trouble cognitif seul .

Bien qu’un lien entre fragilité physique et fonctions cognitives ait été démontré, la sévérité du trouble cognitif en relation avec les aspects clés de la fragilité physique n’a jamais été étudiée.

L’échelle Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) est liée à la progression de la maladie chez la personne âgée souffrant d’un Alzheimer léger à modéré permettant ainsi de faire la différence entre le stade très léger ( very mild MCI) et léger ( mild MCI) ainsi que les stades plus avancés de la MA , c’est pourquoi cet outil pourrait se révéler sensible à une baisse globale des fonctions cognitives chez les individus aMCI.

Chez la personne aMCI, les mécanismes pathologiques de la MA peuvent se manifester à travers un déclin physique précédent la démence avec une altération des fonctions exécutives, de la mémoire et de l’attention . De plus, l’âge et les pathologies liées à l’âge peuvent contribuer à un déclin concomitant des systèmes physiologiques à travers les mécanismes sous-jacents comme les processus inflammatoires et énergétiques . Une identification précoce des relations entre la fragilité physique et la sévérité du trouble cognitif est essentielle pour mettre en place rapidement des solutions pour ralentir ou inverser le déclin cognitif et le handicap chez la personne aMCI. L’objectif de cette étude est double, premièrement décrire la prévalence de trois dimensions de la fragilité physique chez la personne âgée aMCI et deuxièmement de déterminer si les aspects de la fragilité physique sont associés à la sévérité du trouble cognitif. Nous proposons l’hypothèse que les dimensions de la fragilité physique sont corrélées à la sévérité du trouble cognitif et aux dimensions des fonctions cognitives après correction en fonction de l’âge, du sexe et des complications liées à l’âge.

2.2

Méthode

Cette étude se basait sur l’analyse des données colligées lors de l’inclusion dans l’étude Resources and Activities for Life-Long Independence (RALLI), une étude randomisée et contrôlée sur les interventions psychosociales et l’exercice physique chez des patients âgés sédentaires aMCI recrutés de juillet 2007 à octobre 2009. Les participants étaient des volontaires, non dépendants, en maisons de retraite avec une plainte mnésique. Les participants inclus dans l’étude âgés de 70 ans et plus, étaient sédentaires et diagnostiqués aMCI sur la base d’une visite d’inclusion et d’un consensus multidisciplinaire d’experts. Le recrutement et la sélection consistaient en :

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  une présélection par téléphone ;

  
  
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  une sélection à domicile avec interrogatoire semi-structuré et tests neuropsychologiques ;

  
  
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  consensus multidisciplinaire lors d’une réunion d’experts en psychologie clinique.

Les critères de Petersen , associant les scores de tests cognitifs, les données de l’interrogatoire de la visite de sélection et l’avis consensuel au cas par cas, étaient appliqués afin d’identifier les personnes ayant des troubles de la mémoire en accord avec un sous-type clinique aMCI (domaine unique ou multiple). Les critères de Petersen étaient :

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  plainte mnésique ;

  
  
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  trouble cognitif par rapport à l’âge et le niveau d’éducation ;

  
  
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  fonction cognitive générale préservée ;

  
  
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  activités de la vie quotidienne essentiellement maintenues ;

  
  
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  aucun diagnostic de démence.

Les tests neuropsychologiques utilisés lors de la sélection étaient :

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  le Mini-Mental State Exam (MMSE) pour évaluer la fonction cognitive globale ;

  
  
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  l’échelle de la mémoire de Wechsler révisée (WMS-R) mémoire logique I et II pour le rappel immédiat et différé ;

  
  
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  l’échelle Clinical Dementia Rating (CDR) pour évaluer la sévérité du trouble cognitif .

Le trouble cognitif objectif était déterminé par un score aux tests de mémoire logique de l’échelle WMS-R correspondant à une déviation standard au-dessous des normes corrigées en fonction de l’âge et du niveau d’éducation , des problèmes sur les items de rappel du MMSE, et/ou difficultés observées à se rappeler les évènements quotidiens durant l’interrogatoire. La sédentarité était définie comme moins de 150 minutes d’exercice modérée par semaine (au cours du dernier mois) . Les participants potentiels étaient exclus s’ils :

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  ne pouvaient pas se déplacer seuls ou avec une aide technique ;

  
  
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  devaient quitter la région ;

  
  
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  étaient reconnus comme atteints d’une maladie terminale ;

  
  
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  étaient suicidaires ou souffraient d’hallucinations ou de troubles psychiatriques ;

  
  
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  avaient été hospitalisés au cours des 12 derniers mois ;

  
  
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  souffraient d’une maladie chronique non contrôlée ;

  
  
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  étaient sourds ou aveugles ;

  
  
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  ou avaient une pathologie du système nerveux central associée à la démence.

Le comité d’éthique local a approuvé tous les paramètres de l’étude.

2.3

Résultats

Les caractéristiques démographiques, les covariances des fonctions cognitives et de la fragilité physique sont résumées dans le Tableau 1 . L’échantillon initial comportait 201 participants, cependant à cause d’une absence ponctuelle de données entre 173 et 201 cas furent inclus dans les analyses de régression linéaire multiple. Par exemple, certains participants ne pouvaient compléter les Trails Making Tests à cause de problèmes de vue. Le score MMSE moyen était de 26,3 (écart-type = 3,2) et tous les participants avait un CDR de 0,5, ce qui est cohérent avec les classifications du aMCI . Les pourcentages de participants remplissant les critères d’inclusion pour les trois dimensions de la fragilité étaient : 57,3 % pour la vitesse de marche, 58,2 % pour l’AP et 64,2 % pour la force de préhension ( Tableau 2 ).

Tableau 1

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