frailty and cognitive decline: how do they relate?

8/19/2019 Frailty and cognitive decline: how do they relate?

1/8Copyright © Lippincott Williams Wilkins. Unauthorized reproduction of this article is prohibited.

CURRENTOPINION Frailty and cognitive decline: how do they relate?

Marco Canevelli a,b

, Matteo Cesari b,c,d

, and Gabor Abellan van Kanb,c

Purpose of review

To provide a comprehensive review of the recent literature (published over the last 12 months) exploringthe relationship between frailty and cognition.

Recent findings

Fourteen studies were retained for the present review. No randomized controlled trial was found. Overall,the main findings of the selected studies appeared to be mainly confirmatory of the previous evidence. Inlongitudinal studies, physical frailty was found to predict the incidence of cognitive impairment anddementia. Cross-sectional studies showed that frail individuals have lower cognitive performance comparedwith nonfrail persons. Interestingly, few studies examined the association between frailty and specificcognitive functions and domains, reporting a significant impairment of attention and executive functionsFinally, we found several studies including cognitive measures in the operational definitions of frailty.

Summary

The present findings are suggestive of an almost complete lack of evidence on the addressed topic. Inparticular, randomized controlled trials are strongly needed in order to gain insights about the possibility of positively affecting the frailty syndrome by acting of cognition and improving cognitive impairment bytargeting the physical components of frailty. Moreover, these studies may produce the first evidences aboutthe novel concept of ‘cognitive frailty’ and its potential for reversibility.

Keywords

cognition, cognitive frailty, elderly, frailty, review

INTRODUCTION

Frailty is a multidimensional syndrome character-ized by increased vulnerability to stressors, as aresult of cumulative decline in different physiologi-cal systems occurring during the lifetime [1]. It isassociated with increased risk of adverse health-related outcomes in older persons including falls,disability, hospitalization, and mortality [2,3]. Thissyndrome is triggering considerable attention notonly in clinics and research, but also among publichealth authorities [4]. In fact, acting on frailty maypositively influence the aging process of the olderindividual, resulting in improved quality of life and

reduced costs of care [5].Several operational definitions have been devel-

oped in order to translate into practice the theor-etical concept of frailty. To date, most of theavailable definitions have privileged the physicaldimension of the frailty syndrome, mostly relyingon symptoms and signs like weight loss, muscleweakness, slow gait speed, and sedentary behavior[6]. Nevertheless, a growing body of evidence issuggesting that other factors (e.g., nutrition [7],mental health [8], and cognition [9

&

]) may influencethe frailty status of the older individual as well. In

particular, cognition is increasingly recognized

as a fundamental determinant of the individual’svulnerability and resiliency to stressors [10]. In fact,impaired cognitive functioning may affect the adop-tion of healthy lifestyle behaviors and the adherenceto preventive and therapeutic interventions. More-over, it is strongly related to socioeconomic disad-vantage with possible limitations in access tohealthcare services [10].

The relevant role that cognition may play inthe determination of the elder’s risk profile hasled some authors at proposing the addition of acognitive assessment within the operational defi-

nitions of frailty. Cognitive impairment has been

aDepartment of Neurology and Psychiatry, Memory Clinic, ‘Sapienza’

University, Rome, Italy, bGérontopôle, Centre Hospitalier Universitaire

de Toulouse, cInserm UMR1027 and dUniversité de Toulouse III Paul

Sabatier, Toulouse, France

Correspondence to Dr Marco Canevelli, Department of Neurology and

Psychiatry, Memory Clinic, ‘Sapienza’ University, Viale dell’Università 30,

00185 Rome, Italy. Tel: +39 6 49914604;fax: +39 6 49914604;e-mail:

[email protected]

Curr Opin Clin Nutr Metab Care 2015, 18:43–50

DOI:10.1097/MCO.0000000000000133

1363-1950 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins www.co-clinicalnutrition.com

REVIEW

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independently associated with several adverse out-comes (e.g., falls, hospitalization, and mortality),even when specific conditions (e.g., dementia andmild cognitive impairment [MCI]) were considered[11]. Cross-sectional studies have documented highrates of cognitive impairment in frail compared withrobust older persons, being observed in nearly 20%of frail individuals living in the community [12].Consistently, longitudinal studies have repeatedlyreported that physical frailty predicts the onset of future cognitive decline and incident dementia [9

&

].The reciprocal association (i.e., cognitive impair-ment predicts future frailty) has also been observed[13]. In addition to these epidemiological evidences,

various studies have suggested that several patho-physiological pathways (e.g., chronic inflam-mation, hormonal pathway, and vascular disease)and nutritional factors and deficiencies [14] (e.g.,vitamin D, Mediterranean diet and olive oil, vitaminB12 and folate, and aerobic exercise) may be poten-tially shared by frailty and cognitive impairment.Nevertheless, there is still a lack of experimentalevidence to support these observations [9

&

].As proof of the increased interest toward the

relationship between frailty and cognition, a novelconcept of ‘cognitive frailty’ has recently been pro-

posed by an international panel of experts [15&

]. Thenovel construct of ‘cognitive frailty’ was defined as aclinical condition characterized by the simul-taneous presence of both physical frailty and cog-nitive impairment, occurring in the absence of overtdementia diagnosis or underlying neurologicalconditions. In other words, cognitive frailty wasconceptualized as a non-neurodegenerative cogni-tive impairment sustained by (or associated with)physical frailty. The authors admitted that it maysimply indicate an early sign of future dementia (i.e.,anticipation of a still unknown diagnosis). At the

same time, older persons with cognitive impairmentunrelated to a neurodegenerative disease (butcaused by a physical condition) may benefit frominterventions against frailty and reduce their overallglobal risk profile (including possible ameliorationof the cognitive status). Such differentiationbetween the cognitive impairment due to neuro-

logical vs. physical causes may indeed help atimproving the design of personalized interventionsin the heterogeneous elderly population.

In view of the growing interest on this topic, theaim of the present study is to provide a comprehen-sive, updated review of the recent literature (pub-lished over the last 12 months) exploring therelationship between frailty and cognition.

LITERATURE SEARCH

We performed a Medline literature search of studiespublished over the last 12 months (from 1 June 2013to 31 May 2014) using the Medical Subject Heading(MeSH) terms ‘Human’ and ‘English’ combined withthe following terms: (‘frailty’ OR ‘frail’) AND (‘cog-nitive’ OR ‘cognition’ OR ‘dementia’ OR ‘Alzheimer’OR ‘memory’ OR ‘brain’). Overall, 102 articles wereretrieved. Based on titles and abstracts, a first set of articles (n¼65) was excluded because it was clearlyout of the specific aims of the present study. For theremaining studies, full articles were obtained andevaluated. Thus, 14 studies were finally selected[16–29].

RECENT EVIDENCE ON FRAILTY AND

COGNITION

In this section, the studies retained for the presentreview will be presented as grouped into threecategories: longitudinal studies, cross-sectionalstudies, and studies incorporating cognition in theoperational definition of frailty. No RCT was insteadfound.

Longitudinal studies

Over the last year, three studies have explored thelongitudinal relationship between frailty and cog-nitive functioning (Table 1). In a large study of 2619community-dwelling older adults, physical frailty(operationalized according to a modified versionof the frailty phenotype [6]) was associated with a2.57-fold increased risk of developing non-Alzheimer’s disease dementia (mean follow-up of 6.5 years) [18]. Conversely, frailty was not statisti-cally associated with incident Alzheimer’s disease.Interestingly, the association between frailty anddementia was found to vary according to the

KEY POINTS

The relationship between frailty and cognition is beingincreasingly investigated.

Available evidence from the observational studiesindicates that frail individuals have lower cognitiveperformance than nonfrail persons and increased risk

of cognitive decline.

Randomized controlled trials (RCTs) are needed inorder to gain insights about the interactions betweenfrailty and cognition.

The implementation of the novel concept of ‘cognitivefrailty’ may provide useful insights for better planningand designing preventive interventions and therapeuticactions against disability.

Ageing: biology and nutrition

44 www.co-clinicalnutrition.com Volume 18 Number 1 January 2015

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T a

b l e 1 .

S t u d i e s e x p l o r i n g t h e r e l a t i o n s h i p b e t w e e n f r a i l t y a n d c o g n i t i o n

p u b l i s h e d o v e r t h e l a s t 1 2 m o n t h s

R e

f e r e n c e

S t u

d y s

a m p

l e

S e

t t i n

g

D e

f i n

i t i o

n o

f f r

a i l t y

C o g n

i t i v

e a s s e s s m e n

t a

M a

i n r e s u

l t s

L o n g i t u d i n a l s t u d i e s

A l e n c a r e t a l . [ 1 6 ]

n ¼

2 0 7

o l d e r a d u l t s ( a g e d

6 5 y e a r s ) w i t h o r w i t h -

o u t c o

g n i t i v e i m p a i r m e n t

a t b a s e l i n e

C o m m u n i t y f o l l o w - u p :

1 2 m o n t h s

F r a i l t y p h e n o t y p e b

B C S B

C D R

M M S E

F r a i l t y a t b a s e l i n e w a s a s s o c i a t e d w i t h

c o g n i t i v e d e c l i n e a s m e a s u r e d b y

M M S E s c o r e

m o d i f i c a t i o n s a t t h e e n d

o f t h e f o l l o w - u p ( R R 4 . 6 ; 9 5 % C I

1 . 9 3 – 1 1 . 2 )

E s p i n o z a e t a l . [ 1 7 ]

n ¼

7 4 9


6 5 – 8

0 y e a r s )


8 . 2

2 . 9 y e a r s

F r a i l t y p h e n o t y p e

M M S E

F r a i l t y w a s a s s o c i a t e d w i t h i n c r e a s e d

r i s k o f m o r t a l i t y ( h a z a r d r a t i o 2 . 1 3 ;

9 5 % C I 1 . 4 5

– 3 . 1 4 )

W h e n a d j u s t i n g f o r c o g n i t i v e i m p a i r m e n t

a n d d e p r e s s i v e s y m p t o m s , t h i s a s s o c i -

a t i o n w a s n o

l o n g e r p r e s e n t ( h a z a r d

r a t i o 1 . 4 4 ; 9

5 % C I 0 . 9 1 – 2 . 2 8 )

G r a y e t a l . [ 1 8 ]

n ¼

2 6 1

9 n o n d e m e n t e d

o l d e r

a d u l t s ( a g e d

6 5 y e a r s )


6 . 5

3 . 9 y e a r s

M o d i f i e d f r a i l t y p h e n o t y p e

C A S I

C o m p r e h e n s i v e

n e u r o p s y c h o l o g i c a l

t e s t b a t t e r y

F r a i l t y w a s a s s o c i a t e d w i t h i n c r e a s e d r i s k

f o r n o n - A l z h e i m e r ’ s d i s e a s e d e m e n t i a

( h a z a r d r a t i o

2 . 5 7 ; 9 5 % C I

1 . 0 8 – 6 . 1 1 )

C r o s s - s e c t i o n a l s t u d i e s

A l e n c a r e t a l . [ 1 6 ]

n ¼

2 0 7


6 5 y e a r s ) w i t h o r w i t h -

o u t c o

g n i t i v e i m p a i r m e n t

a t b a s e l i n e

C o m m u n i t y


B C S B

C D R

M M S E

F r a i l i n d i v i d u a l s e x h i b i t e d a g r e a t e r f r e -

q u e n c y o f c o

g n i t i v e i m p a i r m e n t a n d

l o w e r M M S E

s c o r e s t h a n p r e f r a i l a n d

n o n f r a i l p a r t i c i p a n t s ( P <

0 . 0 0 1 )

A l e x a n d r e T d a e t a l . [ 1 9 ]

n ¼

1 4 1

3 o l d e r a d u l t s

( a g e d

6 0 y e a r s )

C o m m u n i t y


M M S E

C o g n i t i v e d e c l i n e ( i . e . , M M S E 1 8 ) w a s

a s s o c i a t e d w

i t h w e a k n e s s ( O R 4 . 2 0 ;

9 5 % C I 1 . 6 6

– 1 0 . 6 1 ) a n d s l o w n e s s

( O R 2 . 5 5 ; 9 5 % C I 1 . 0 1 – 6 . 4 4 ) i n

m a l e p a r t i c i p

a n t s

M c G o u g h e t a l . [ 2 0 ]

n ¼

2 0 1

s e d e n t a r y o l d e r

a d u l t s

( a g e d 7 0 y e a r s )

d i a g n

o s e d w i t h a M C I

R e s i d e n t i a l f a c i l i t i e s

P h y s i c a l s l o w n e s s ( g a i t s p e e d )

L o w p h y s i c a l a c t i v i t y ( s e l f - r e p o r t )

M u s c l e w e a k n e s s ( g r i p s t r e n g t h )

A D A S - C o g

C D R

M M S E

T M T - A / B

W M S - R L M I

S l o w e r g a i t s p e

e d w a s a s s o c i a t e d w i t h

g r e a t e r c o g n

i t i v e i m p a i r m e n t a s

m e a s u r e d b y

A D A S - C o g s c o r e

( ß ¼

- 0 . 1 9 ; P

¼

0 . 0 0 8 )

( C o n t i n u e d )

Frailty and cognition Canevelli et al.

1363-1950 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins www.co-clinicalnutrition.com 45

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T a

b l e 1 ( C o n t i n u e

d )

R e

f e r e n c e

S t u

d y s

a m p

l e

S e

t t i n

g

D e

f i n

i t i o

n o

f f r

a i l t y

C o g n

i t i v

e a s s e s s m e n

t a

M a

i n r e s u

l t s

M o r e i r a e t a l . [ 2 1 ]

n ¼

7 5 4

n o n d e m e n t e d

o l d e r


6 5 y e a r s )

C o m m u n i t y


M M S E

F r a i l w a s a s s o c

i a t e d w i t h l o w e r c o g n i t i v e

p e r f o r m a n c e

a s m e a s u r e d b y M M S E

s c o r e ( O R 0 .

7 9 ; 9 5 % C I , 0 . 7 6 – 0 . 8 3 )

O ’ H a l l o r a n e t a l . [ 2 2 ]

n ¼

4 3 1

7 i n d i v i d u a l s a g e d

5 0 y e a r s

C o m m u n i t y

M o d i f i e d f r a i l t y p h e n o t y p e

C R T C T T S A R T

P r e f r a i l t y a n d f r a i l t y w e r e a s s o c i a t e d

w i t h r e d u c e d

s u s t a i n e d a t t e n t i o n

p e r f o r m a n c e

a n d v a r i a b i l i t y

P o l i d o r o e t a l . [ 2 3 ]

n ¼

1 4 0

c o n s e c u t i v e i n d i -

v i d u a l s ( a g e d 5 6 – 9 6

y e a r s ) a d m i t t e d t o a n

I n t e r n a l M e d i c i n e w a r d

H o s p i t a l w a r d

F r a i l t y i n d e x ( 3 4 v a r i a b l e s i n c l u d e d )

M M S E

F r a i l p a t i e n t s h a d l o w e r M M S E s c o r e s

t h a n n o n f r a i l

i n d i v i d u a l s ( P <

0 . 0 1 )

A n e g a t i v e c o r r e l a t i o n b e t w e e n M M S E

s c o r e s a n d f r

a i l t y i n d e x ( r h o ¼

- 0 . 5 1 7 ,

P <

0 . 0 0 1 ) w

a s f o u n d

S h i m a d a e t a l . [ 2 4 ]

n ¼

5 1 0

4 o l d e r a d u l t s

( a g e d

6 5 y e a r s )

C o m m u n i t y


M M S E

N C G G - F A T

T h e c o m b i n e d p r e v a l e n c e o f f r a i l t y a n d

M C I w a s 2 . 7

%

A s i g n i f i c a n t a s s o c i a t i o n b e t w e e n f r a i l t y

a n d M C I w a s o b s e r v e d ( O R 2 . 0 ; 9 5 %

C I 1 . 5 – 2 . 5 )

A D A S - C o g , A l z h e i m e r ’ s D i s e a s e A s s e s s m e n t

S c a l e - C o g n i t i v e s u b s c a l e ; a M C I , a m n e s t i c m i l d c o g n i t i v e i m p a i r m e n t ; B C S B , B r i e f C o g n i t i v e S c r e e n i n g B a t t e r y ; C A S I , C o g n i t i v e A b i l i t i e s S c r e e n i n g I n s t r u m e n t ; C D R , C l i n i c a l

D e m e n t i a R a t i n g ; C I , c o n f i d e n c e i n t e r v a l ; C R

T , c h o i c e r e a c t i o n t i m e ; C T T , C o l o r T r a i l s T e s t ; M

M S E , M i n i M e n t a l S t a t e E x a m i n a t i o n ; N C G G - F

A T , N a t i o n a l C e n t e r f o r G e r i a t r i c s a n d G e r o n t o l o g y - F u n c t i o n a l A s s e s s m e n t

T o o l ; R R , r e l a t i v e r i s k ; S A R T , S u s t a i n e d A t t e n

t i o n t o R e s p o n s e T a s k ; T M T - A / B , T r a i l M a k i n g T e s t p a r t A a n d B ; W M S - R L M I , W e c h s l e r M e m o r y S c a l e - R e v i s e d L o g i c a l M e m o r y I .

a C o g n i t i v e f u n c t i o n s a n d d o m a i n s a s s e s s e d b y t h e a d o p t e d c o g n i t i v e t o o l s a n d m e a s u r e s : A D

A S - C o g : g l o b a l c o g n i t i v e p e r f o r m a n c e ; B C S B : g l o b a l c o g n i t i v e p e r f o r m a n c e ; C A S I : g l o b a l c o g n i t i v e p e r f o r m a n c e ; C D R :

d e m e n t i a s e v e r i t y ; C R T : c o n c e n t r a t i o n a n d c o g n i t i v e p r o c e s s i n g s p e e d ; C T T : e x e c u t i v e f u n c t i o n s ; M M S E : g l o b a l c o g n i t i v e p e r f o r m a n c e ; N C G

G - F A T : g l o b a l c o g n i t i v e p e r f o r m a n c e ; S A R T : s u s t a i n e d a t t e n t i o n ; T M T - A / B :

a t t e n t i o n a n d e x e c u t i v e f u n c t i o n s ; W M S - R L M

I : i m m e d i a t e a n d d e l a y e d r e c a l l .

b F r a i l t y p h e n o t y p e [ 6 ] : p r e s e n c e o f a t l e a s t t h r e e o f f i v e s i g n s / s y m p t o m s i n c l u d i n g p o o r m u s c

l e s t r e n g t h , s l o w g a i t s p e e d , u n i n t e n t i o n a l w e i g h t l o s s , e x h a u s t i o n , a n d s e d e n t a r y b e h a v i o r .



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baseline cognitive scores, being restricted only toparticipants with higher basal cognitive perform-ance (upper three quartiles of global cognitive func-tioning). Among the individual components of frailty, only slowness (as measured by reducedwalking speed) was significantly related to non-Alzheimer’s disease dementia (hazard ratio 2.13;

95% confidence interval 1.09–4.16). In anotherstudy [16], physical frailty (always defined accordingto the criteria proposed by Fried et al. [6]) was foundto predict subsequent cognitive decline (measuredusing the Mini Mental State Examination [MMSE])after 12 months of follow-up. On the contrary, noassociation was found between frailty and dementiaseverity as measured by the Clinical DementiaRating, and between frailty and incident cognitivedecline (defined as testing positive at the end of follow-up on both the MMSE and the Brief Cogni-tive Screening Battery). Finally, in the last study [17],the relationship between frailty and mortality wasinvestigated. In a sample of 749 older adults living inthe community, frailty was significantly associatedwith mortality over a mean follow-up of 8.2 years.Nevertheless, this association was no longer signifi-cant after adjustment for cognitive impairment(assessed by the MMSE) and depressive symptoms.Thus, the authors concluded that both cognitiveand mood factors may play a role in mediatingthe association between frailty and mortality.

Cross-sectional studies

Seven cross-sectional studies were identified(Table 1). Three studies described the associationbetween physical frailty and global cognitive per-formance assessed by the MMSE [16,21,23]. Overall,frail individuals were found to exhibit lower MMSEscores compared with nonfrail individuals. Physicalfrailty was also associated with a higher prevalenceof cognitive impairment (defined as a MMSE score18) [16]. Moreover, a negative correlation betweenthe MMSE score and frailty severity (measured by aFrailty Index) was observed [23]. Two out of thesethree studies enrolled community-dwelling older

adults. In the other one [23], individuals admittedto an internal medicine hospital ward were consecu-tively recruited. In another study conducted on 201sedentary elderly persons living in residential facili-ties, the association between individual frailty com-ponents and cognitive performance was specificallyexplored [20]. Slow gait speed was found to beassociated with the severity of cognitive impairment(measured by the Alzheimer’s Disease AssessmentScale-Cognitive subscale). Moreover, slow usual gaitspeed was associated with lower performance inthe cognitive dimensions of attention, executive

functions, and immediate recall. Higher levels of physical activity were associated with higher scoringon memory and executive functions tests, whereasgrip strength was only associated with attention.Accordingly, in a large study involving 4317 indi-viduals aged more than 50 years, both prefrailty andfrailty were shown to be strongly associated with

declining sustained attention [22]. Shimada et al.[24] estimated the prevalence of physical frailty andMCI in a sample of 5104 Japanese older adults livingin the community. The combined prevalence of frailty (defined according to the frailty phenotype)and MCI was 2.7%. A significant associationbetween frailty and MCI was observed. Finally, onlyone study explored the reciprocal associationbetween cognition and physical frailty [19]. Cogni-tive decline (defined as a MMSE score 18) wasfound to be associated with the individual frailtycomponents of weakness and slowness among maleparticipants, whereas no significant association wasfound in women.

Studies incorporating cognition in theoperational definition of frailty

In the last 12 months, five studies included cogni-tion in the operational definitions and screeningadopted for the identification of frail individuals(Table 2). In two studies [25,26], the cognitive assess-ment simply consisted of a single question referringto the presence of cognitive complaints or to aprevious dementia diagnosis. Patel et al. [27]

included impaired cognition in a Frailty Index com-posed of 19 clinical deficits. In another study, cog-nition was assessed by the use of a validatedscreening instrument evaluating global cognitivefunctioning (i.e., the Short Portable Mental StatusQuestionnaire) [28]. Finally, in the last study, amultistep cognitive assessment consisting of bothopen questions and structured cognitive testing wasincluded in the screening of frailty [29]. Notably, theability of 129 possible combinations of seven frailtymarkers (cognition, energy, mobility, mood, nutri-tion, physical activity, and strength) in predicting

disability among 6657 older adults followed up for6 years was also investigated [28]. The frailty‘model’ with the best predictive fit was found tobe composed of the five markers: cognition, mobi-lity, nutrition, physical activity, and strength.

DISCUSSION

The present review was aimed at retrieving anddiscussing the recent evidence concerning therelationship between frailty and cognition. Overall,relatively few studies addressed this topic over the



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T a

b l e 2 .

S t u d i e s i n c l u d i n g c o g n i t i o n i n t h e o p e r a t i o n a l d e f i n i t i o n a n d s c r e e n i n g o f f r a i l t y

R e

f e r e n c e

S t u

d y s a m p

l e

F r a

i l t y o p e r a

t i o n

a l i

z a

t i o n

/ s c r e e n

i n g

C o g n

i t i v

e a s s e s

s m e n

t

M a

i n r e s u

l t s

A a l d r i k s e t a l . [ 2 5 ]

n ¼

1 4 3 o l d e r a d u l t s ( a g e d

7 0 y e a r s ) w i t h c o l o r e c t a l

c a n c e r

G F I : f r a i l t y s c r e e n i n g t o o l c o m b i n i n g 1 5

p h y s i c a l , c o g n i t i v e , e m o t i o n a l , a n d

p s y c h o s o c i a l i t e

m s

S i n g l e q u e s t i o n :

‘ D o e s t h e p a t i e n t h a v e

a n y c o m p l a i n t s a b o u t h i s / h e r m e m o r y

o r i s t h e p a t i e n t k n o w n t o h a v e a

d e m e n t i a s y n d

r o m e ? ’

F r a i l t y w a s a s s o c i a t e d w i t h a n i n c r e a s e d

m o r t a l i t y r i s k

i n p a t i e n t s w h o u n d e r -

w e n t p a l l i a t i v e c h e m o t h e r a p y ( h a z a r d

r a t i o 2 . 7 2 ; 9

5 % C I : 1 . 5 8 – 4 . 6 9 )

N o o r s o m e t i m e s ¼

0 ; y e s ¼

1

A a l d r i k s e t a l . [ 2 6 ]

n ¼

5 5 o l d e r


7 0 y e a r s ) w i t h a d v a n c e d

b r e a s t c a n

c e r

G F I : f r a i l t y s c r e e n i n g t o o l c o m b i n i n g 1 5

p h y s i c a l , c o g n i t i v e , e m o t i o n a l , a n d

p s y c h o s o c i a l i t e

m s

S i n g l e q u e s t i o n :

‘ D o e s t h e p a t i e n t h a v e

a n y c o m p l a i n t s a b o u t h i s / h e r m e m o r y

o r i s t h e p a t i e n t k n o w n t o h a v e a

d e m e n t i a s y n d

r o m e ? ’

F r a i l t y w a s a s s o c i a t e d w i t h i n c r e a s e d


( h a z a r d r a t i o 3 . 4 0 ; 9 5 %

C I : 1 . 6 2 – 7 . 1 0 )

N o o r s o m e t i m e s ¼

0 ; y e s ¼

1

P a t e l e t a l . [ 2 7 ]

n ¼


6 0 – 1 0 5 y

e a r s ) w i t h

l o w - e n e r g y f e m o r a l

n e c k f r a c t u r e s

F r a i l t y I n d e x ( 1 9 c

l i n i c a l d e f i c i t s )

A b s e n c e / p r e s e n c e o f i m p a i r e d c o g n i t i o n

( a d j u d i c a t e d d

i a g n o s i s o f d e m e n t i a )

H i g h e r m o d i f i e d f r a i l t y i n d e x s c o r e s w e r e

a s s o c i a t e d w

i t h i n c r e a s e d 1 - y e a r ( O R

4 . 9 7 ; 9 5 % C

I 3 . 0 6 – 8 . 0 9 ) a n d 2 - y e a r

( O R 4 . 0 1 ; 9 5 % C I 2 . 6 1 – 6 . 1 6 )


S o u r i a l e t a l . [ 2 8 ]

n ¼

6 6 5 7 o l d e r a d u l t s ( a g e d

6 5 y e a r s ) f o l l o w e d u p

f o r 6 y e a r s

D i f f e r e n t c o m b i n a t i o n s o f s e v e n f r a i l t y

m a r k e r s ( c o g n i t i o n , e n e r g y , m o b i l i t y ,

m o o d , n u t r i t i o n , p h y s i c a l a c t i v i t y ,

s t r e n g t h )

M o d i f i e d S P M S Q

T h e b e s t f r a i l t y

m o d e l i n p r e d i c t i n g

d i s a b i l i t y i n c l u d e d c o g n i t i o n , m o b i l i t y ,

n u t r i t i o n , p h y

s i c a l a c t i v i t y a n d s t r e n g t h

V a n K e m p e n e t a l . [ 2 9 ] n ¼


7 6 . 8 4 . 8 y e a r s )

V a l i d a t i o n s t u d y

E A S Y - C a r e T O S : t w o - s t e p f r a i l t y s c r e e n -

i n g b a s e d o n t h

e i n d i v i d u a l f u n c t i o n i n g

i n d i f f e r e n t s o m a t i c , p s y c h o l o g i c a l ,

a n d s o c i a l d o m a i n s

F i r s t s t e p ( c o n d u c t e d b y g e n e r a l

p r a c t i t i o n e r s ) :

h i s t o r y o f c o g n i t i v e

d i s t u r b a n c e s

S e c o n d s t e p ( p e r f o r m e d b y a p r i m a r y

c a r e n u r s e ) :

T h e E A S Y - C a r e

T O S c o r r e l a t e d b e t t e r

w i t h t h e f r a i l t y i n d e x ( 0 . 6 3 ) t h a n w i t h

t h e f r a i l t y p h e n o t y p e ( 0 . 5 2 )

‘ D o y o u h a v e a n

y c o n c e r n s a b o u t

m e m o r y l o s s o

r f o r g e t f u l n e s s ? ’

‘ D o y o u h a v e p r o b l e m s w i t h b r a i n

f u n c t i o n s a s m e m o r y , a t t e n t i o n a n d

t h i n k i n g ? ’

M e m o r y t e s t ( 6 - C

I T )

6 - C I T , 6 - i t e m s C o g n i t i v e I m p a i r m e n t T e s t ; C I ,

c o n f i d e n c e i n t e r v a l ; G F I , G r o n i n g e n F r a i l t y I n d i c a t o r ; O R , o d d s r a t i o ; S P M S Q , S h o r t P o r t a b l e M

e n t a l S t a t u s Q u e s t i o n n a i r e ; T O S , T w o - s t e p O l d e

r p e r s o n s S c r e e n i n g .





last 12 months. The overwhelming majority of theselected studies assessed frailty using the criteriaproposed by Fried et al. [6]. This is not surprisingbecause these studies were primarily aimed atexploring the physical dimension of the frailty syn-drome. Most of the works adopted the measure of global cognitive functioning (in particular, the

MMSE) for assessing cognition, whereas only fewuse comprehensive neuropsychological test bat-teries. The sample populations mainly composedof community-dwelling older adults, whereas twostudies enrolled institutionalized [20] and hospital-ized [23] individuals.

It is noteworthy that no RCT was found, under-lining the scarcity of available evidence in the field.In fact, RCTs could provide useful information con-cerning the possibility of positively affecting thefrailty syndrome by acting of cognition and improv-ing cognitive impairment by targeting the physicalcomponents of frailty. Also, these studies may pro-duce the first evidences about the actual ‘existence’of the recently proposed concept of ‘cognitivefrailty’ and its potential for reversibility. As proof of the relevance of this topic (i.e., the possibility of simultaneously and reciprocally targeting thephysical and cognitive trajectories of older adults),several RCTs have been recently conducted to inves-tigate the efficacy of physical interventions inimproving cognitive functioning among healthyelderly individuals [30

&

,31]. These studies havemostly shown that physical exercise may result inenhanced cognitive performance. In parallel, some

RCTs are currently ongoing aiming at evaluating theeffectiveness of multidomain interventions (com-bining physical activity with nutritional advices,leisure activities, vascular care, and cognitive train-ing) in preventing cognitive decline among olderadults at risk of dementia [32]. Nevertheless, to date,no study has specifically targeted populations of frail elderly individuals.

Among the 14 retained studies, only five[16,18,20,22,24] were specifically focused on theinteractions between physical frailty and cognitivefunctioning. The remaining articles were primarily

centered on the identification and characterizationof the frailty syndrome among elderly individuals,and included measures of cognitive performanceonly as part of the comprehensive, multidimen-sional assessment of participants. The main findingsof the selected studies appeared to be mainly con-firmatory of the previous evidence [9

&

,11]. In longi-tudinal studies, physical frailty was found to predictthe incidence of cognitive impairment and demen-tia in older individuals. Cross-sectional studiesshowed that frail individuals have lower cognitiveperformance compared with nonfrail persons. The

relatively most novel evidence comes from the fewstudies examining the association between frailtyand specific cognitive functions and domains,showing a significant impairment of attentionand executive functions [20,22]. Previous studiesconducted on this topic had produced conflictingresults, showing that frailty (and its individual com-

ponents) was associated with the additional involve-ment of other cognitive functions such asprocessing speed, orientation, and verbal fluency[9

&

]. Finally, we found several studies includingmeasures of cognitive performance in the adoptedoperational definitions of frailty.

Interestingly, one study has indirectly increasedthe knowledge regarding the recently proposed con-struct of ‘cognitive frailty’ that has been conceptu-alized as the simultaneous occurrence of bothphysical frailty and cognitive impairment in theabsence of an overt dementia condition [15

&

]. Infact, though not directly mentioning this novelconcept, Shimada et al. [24] observed a combinedprevalence of frailty and MCI of 2.7% in a largesample population. To our knowledge, thisrepresents one of the first estimates of the preva-lence of cognitive frailty and should represent areference for future research on this topic.

CONCLUSION

During the last 12 months, a limited number of studies investigated the relationship between frailtyand cognition. The findings of these studies weremainly confirmatory of the previous evidence.

Moreover, no RCT was found, indicating an almostcomplete lack of evidence on this topic. These stud-ies are strongly advocated because they may provideimportant insights for better planning and design-ing preventive interventions and therapeuticactions against disability. Moreover, they couldconsent to explore the recently proposed conceptof ‘cognitive frailty’. In parallel, investigating theinteractions between the physical components of frailty and the specific cognitive functions anddomains may represent a useful approach to achievea better comprehension of the frailty syndrome.

Acknowledgements

None.

Financial support and sponsorship

None.

Conflicts of interest

Matteo Cesari has received a grant for a research project (unrelated to the present study) from Pfizer. He hasalso served as consultant for the preparation of educationmaterial for Novartis, France, and conducted oral





presentations at scientific meetings for Nestlé (all unre-lated to the present study). The other authors have noconflicts of interest to disclose.

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frailty and cognitive decline: how do they relate?

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