Nonpharmacological Management of Apathy in Dementia: A Systematic Review

SPECIAL ARTICLE

Nonpharmacological Management ofApathy in Dementia: A Systematic Review

Henry Brodaty, M.B.B.S., M.D., D.Sc., F.R.A.C.P., F.R.A.N.Z.C.P.,Kim Burns, B.Psych. (Hons.)

Apathy is one of the most challenging and prevalent behavioral symptoms of de-mentia. It is associated with increased disability and caregiver frustration as wellas reduced quality of life, rehabilitation outcomes and survival after nursing homeadmission. A literature search to set criteria yielded 56 nonpharmacological inter-vention studies with outcomes relevant to apathy in dementia. Studies were ratedaccording to quality and categorized into 7 groups: exercise, music, multisensory, an-imals, special care programming, therapeutic activities and miscellaneous. Despite alack of methodological rigor, it is apparent that nonpharmacological interventionshave the potential to reduce apathy. This review indicates that therapeutic activities,particularly those provided individually, have the best available evidence for effec-tiveness in dementia. Recommendations are provided for quality research. (Am JGeriatr Psychiatry 2012; 20:549–564)

Key Words: Abulia, amotivation, apathy, nonpharmacological, passivity, psychosocial

A pathy represents a form of executive cognitivedysfunction,1 which overlaps with other psy-

chological and behavioral aspects such as mood, per-sonality, and cognitive functioning.2 Definitions tendto emphasize diminished reward and goal-directedbehaviors.3 Apathy can describe an internal state oflack of interest or a state of behavioral inaction.4 Theapathy spectrum includes reduced initiative, inter-est, motivation, spontaneity, affection, energy, enthu-siasm, emotion, and persistence as well as bluntedaffect.5,6 The nosology of apathy is blurred, and ithas received little attention in the scientific literaturein spite of its prevalence.7–9 Synonyms for apathy in-

Received June 25, 2010; revised January 31, 2011; accepted February 25, 2011. From the Academic Department for Old Age Psychiatry(ADfOAP), Prince of Wales Hospital (HB, KB); and Dementia Collaborative Research Centre, Faculty of Medicine, School of Psychiatry,University of New South Wales (HB), Randwick, New South Wales, Australia. Send correspondence and reprint requests to Professor HenryBrodaty, Dementia Collaborative Research Centre, AGSM, UNSW, Sydney, NSW 2052, Australia. e-mail: [email protected]. Supple-mental digital content is available for this article. Direct URL citations appear in the printed text and is provided in the HTML and PDFversions of this article on the journal’s Web site (www.AJGPonline.org).

C© 2012 American Association for Geriatric PsychiatryDOI: 10.1097/JGP.0b013e31822be242

clude passivity, abulia, and amotivation. Apathy canbe a symptom of many neuropsychiatric disordersor a syndrome per se.10,11 At a symptomatic level,Marin12 defines apathy as “loss of motivation due todisturbance of intellect, emotion or level of conscious-ness” and at syndromal level as primary motivationalloss or “loss of motivation not attributable to emo-tional distress, intellectual impairment or diminishedlevel of consciousness.” Individuals with apathy “doless, think less and feel less.”13 Stuss et al.14 proposesthree subtypes of apathy: emotional, cognitive, andbehavioral defined on the basis of the anatomical re-gions and psychological mechanisms involved.

Copyright © American Association for Geriatric Psychiatry. Unauthorized reproduction of thisarticle is prohibited.

Am J Geriatr Psychiatry 20:7, July 2012 549

Nonpharmacological Management of Apathy in Dementia

DIFFERENTIAL DIAGNOSIS

Diagnostic criteria for apathy were initially pro-posed by Marin.12,15 Lack of motivation is evidencedby diminished goal-directed behavior, goal-directedcognition, and emotion, relative to previous function-ing levels and not attributable to intellectual impair-ment, emotional distress, or diminished conscious-ness. Emotional distress is absent. These criteria havebeen adapted over time.16,17 Recent modificationspropose that diminished motivation must be presentmost of the time for at least 4 weeks and a minimumof one symptom should be evident from two of thebehavioral, cognitive, and emotional domains.18,19 Inaddition, symptoms should cause clinically signifi-cant functional impairment and not be attributableto physical disabilities, motor disabilities, or directphysiological effects of a substance.

Apathy is related to but distinct from depres-sion5,20–25 and dysphoria.1,26,27 Although there isan overlap in symptoms, individuals with apathypresent as compliant or passive, whereas those withdepression are deliberately avoidant.15 Further evi-dence of the distinction between apathy and depres-sion is the stronger association between degree ofapathy and degree of cognitive impairment, particu-larly in executive functioning, than in depression.3,28

Assessment of apathy in dementia is further com-plicated by the need to distinguish between dimin-ished behavior due to loss of motivation and lossof ability secondary to cognitive impairment.7,15 Theuse of antipsychotic, antidepressant, and neurolepticmedications, which can induce side effects such asfatigue, lethargy, listlessness, and reduced responseto stimuli, can initiate, maintain, or imitate apatheticbehaviors.29

FREQUENCY

Apathy has been associated with neurological, psy-chiatric, medical, drug-induced, and socioenviron-mental conditions.30 The frequency of apathy in neu-rological disorders ranges from 0% to 92%3 with thehighest prevalence reported in progressive supranu-clear palsy,31–34 frontotemporal dementia,35–38 andsevere Alzheimer disease (AD).39 The commonestcauses of clinically significant apathy are dementia

and schizophrenia.3 Our focus is on dementia, inwhich apathy is one of the most challenging, preva-lent, and persistent behavioral symptoms,1,25,27,40–54

particularly the subcortical dementias. In studies us-ing the Neuropsychiatric Inventory,55 a structuredcaregiver interview to assess the frequency and sever-ity of specific behaviors in dementia, apathy occurredin up to 70% of patients with AD.13,24,56–58

Apathy is a major clinical feature of demen-tia with subcortical and frontal pathology suchas dementia with Lewy bodies,59–61 Huntington’sdisease,33,62–66 Binswanger’s disease,67,68 and vascu-lar dementia.50,69 Apathy in AD has also been signifi-cantly related to older age and depression.25 Rates ofapathy in Parkinson’s disease range between 16.5%and 51%70–76 and following stroke between 22.5%and 27%.22,77–80 AD with a stroke prior to onset isalso associated with an increased risk of apathy.81 Ap-athy following a cerebrovascular event has been as-sociated with older age and right fronto-subcorticalpathway pathology.22 In mild cognitive impairment,apathy occurs in between 11.1%82 and 39.8%42,83,84 ofcases, which is intermediate between rates in elderlynormal controls and AD85,86 and predicts a higherrate of conversion to AD.82–84,87–89

Discrepancies in the frequency of estimates of apa-thy in neuropsychiatric conditions may be attributedto a lack of standardized diagnostic criteria58,90 andassessment methods.7,17,91 Furthermore, apathy maybe underreported because as a negative symptom, itis more difficult for family caregivers to identify andquantify in comparison to other behavioral symp-toms of dementia.1

Effects of Apathy

Apathy is associated with increased disability andfrustration as well as decreased quality of life in pa-tients and caregivers alike.92 Families not recogniz-ing an apathetic state may become increasingly re-sentful as they misperceive the patient as lazy.11,93–95

The potential for apathy to prevent patients seek-ing assistance, to be misdiagnosed with depressionor to become noncompliant with treatment furtherexacerbates the degree of dysfunction.93 Apathy issignificantly related to reduced independence in ac-tivities of daily living,28,96,97 survival duration afternursing home admission,98 and poor outcomes inrehabilitation.86,99


550 Am J Geriatr Psychiatry 20:7, July 2012

Brodaty and Burns

Patients with apathy may retain capacity but notself-initiative and hence may undertake activities ingroups that they are unable to do alone.77 Morbidityand mortality may also be indirectly related to ap-athy as residents in long-term care tend to be lessnoticed by care staff and receive fewer direct carehours.29,75 In addition, behavioral deficits influencestaff-resident interactions and quality of care100 aswell as staff distress, frustration, and job satisfaction.

In summary, apathy has significant consequencesand is common in neurological disorders, with thehighest prevalence occurring in people with de-mentia. While studies of its measurement, preva-lence, and etiology are increasing, management hasbeen largely neglected. Recognized guidelines for themanagement of apathy do not exist.101 Reports on theoutcomes of interventions are scattered among vari-ous diagnoses, and the evaluation of outcomes is dif-ficult and unwieldy. The focus of this review is anevaluation of the psychosocial interventions for ap-athy in dementia.

METHOD

A systematic search of MEDLINE (1950–2009),PsycINFO, EMBASE (1980–2009), Cochrane LibraryDatabase (2005–2009), Psycbite (2004–2009), andCINAHL was undertaken. The search terms apathy,abulia, amotivation, and passivity were combinedwith each of the following: nonpharmacological,psychological or psychosocial as well as demen-tia, AD, vascular dementia, multi-infarct dementia,frontotemporal dementia, Pick’s disease, subcorticaldementia, Lewy body dementia, or Binswanger’s dis-ease. This yielded a total of 156 potentially rele-vant papers, which were screened. Reference listsof relevant articles were hand searched and MeSHterms checked. Due to the limited number of stud-ies located, outcomes related to apathy in dementiawere also accepted. These include participation, in-terest, accepting invitations, curiosity, perseverance,engagement, self-initiative, motivation, interactionwith others, doing activities, pursuing involvement,and emotional responsiveness.

Articles were considered for inclusion if theywere available in English and full text. Studiesmet criteria if they included more than five partic-ipants with a diagnosis related to dementia and a

comparison group. All care settings were eligible.Where two or more articles based on similar stud-ies by the same authors were available, the betteror best study was selected for inclusion. This deci-sion was made according to the most recent, mostrelevant to apathy, and/or most complete study orthose with a greater number of participants. Arti-cles were excluded where studies comprised five orfewer participants;102–108 no comparison data wereprovided;93,109 another paper from the same researchgroup was included;96,110–115 participant group in-cluded other psychiatric disorders116 or individu-als without dementia;117 and/or outcomes relevantto apathy were not provided separately118–124 orquantitatively.119

To establish rater reliablility, two reviewers inde-pendently rated the methodological quality of 10studies according to criteria compiled by the au-thors and based on published guidelines.125–128 Thekappa measure of agreement indicated substantialagreement between the raters (0.76). Studies werejudged to be of good quality if they reached an ar-bitrary cut off score of 11/15, as outlined in ourcompanion paper.129 In addition, the National Healthand Medical Research Council (NHMRC) evidencehierarchy126,130,131 was used to determine levels of ev-idence for each intervention group. See companionpaper for a description.

RESULTS

Fifty-six studies met criteria for inclusion(see Tables, Supplemental Digital Content 1–7,http://links.lww.com/AJGP/A21, which outlineall studies meeting inclusion criteria). Studies weregrouped into broad categories with therapeuticactivities (see Table, Supplemental Digital Con-tent 6, http://links.lww.com/AJGP/A21, whichoutlines therapeutic activity interventions) incor-porating the greatest number followed by music(see Table, Supplemental Digital Content 2,http://links.lww.com/AJGP/A21, which outlinesmusic interventions). Research was primarily con-ducted in residential or hospital settings withnine studies incorporating community dwellers.Studies of purely community dwellers were rep-resented in the therapeutic activities132–135 andthe miscellaneous interventions136,137 groups only




(see Table, Supplemental Digital Content 7,http://links.lww.com/AJGP/A21, which outlinesmiscellaneous interventions), while the music138 andmultisensory139,140 groups (see Table, SupplementalDigital Content 3, http://links.lww.com/AJGP/A21,which outlines multisensory interventions) includedstudies which incorporated some community par-ticipants. Even then, many of the interventionsprovided to participants living in the communitywere delivered during attendance at day care orday hospital settings. Articles largely report researchwith positive or partially positive results with only10 studies reporting nonsignificant results. Durationof intervention ranged from single episode to 18months with five studies of 1 year or longer. Twenty-three studies report interventions lasting 4 weeks orless; four studies do not report the time frame.

The majority of studies (29/56) employed a within-subject design. While many studies included acomparison group or condition, when NHMRCguidelines for a randomized controlled trial (RCT)are applied only eight studies met criteria. A fur-ther 16 report randomization of participants yet themethod is not stated, unclear, or inadequate to con-ceal group allocation and are hence classified as pseu-dorandomized. Blinded ratings are reported in onlyeight studies while another seven indicate partialblinding. The majority of studies (47/56) indicatedthat participants were diagnosed using standardizedcriteria; however, in remaining studies, the diagnos-tic criteria were unclear, not stated, or inadequate.Sustainability of effects was typically not reported;seven studies included a follow-up period; and onlytwo of those reported follow-up data for 6 months orlonger. Statistical comparisons were frequently mul-tiple; however, only 12 studies adjusted for these.Sixteen studies included intention-to-treat analysesand six studies omitted statistical significance. Apa-thy was typically not a primary outcome of the in-cluded studies and specific apathy data were mostlyunavailable for treatment and/or control groups toenable effect sizes to be calculated. These limitationsinevitably affect the validity of reported outcomes.

Our quality ratings for accepted studies rangedfrom 2 to 13 out of a possible 15. Table 1 outlinesstudies that met criteria for an RCT or a quality rat-ing of 11 or higher. When studies were grouped byyear of publication or type of intervention, no pat-tern of increasing participant numbers or quality over

time emerged. The therapeutic activities category hadthe greatest number of higher quality studies (4 witha rating of 11 or better). This group includes an ar-ray of different intervention types as well as the morenovel approaches with greater emphasis on individ-ually tailored interventions. No other link was foundbetween intervention types and quality of studies orpositive outcomes.

Participant numbers were characteristically smallwith only 18 studies reporting 60 participants or moreat recruitment and only 16 providing evidence of suf-ficient power. When grouped by intervention type,therapeutic activities included the greatest number ofparticipants with a combined total of 712. Clearly, in-terventions for groups of participants yield highernumbers, yet the multisensory category reached anoverall total of 374 participants using interventionsfor individuals only. Twenty studies in all, primarilyfrom the multisensory and therapeutic interventiongroups, were administered to individuals; a furtherfive studies included interventions for both groupsand individuals while the majority reported group in-terventions. Of the studies delivered individually, 17were tailored for individual interests and/or skills, ofwhich 15 reported a positive or partially positive out-come. Eight of the nine nontailored, but individuallydelivered studies, reported a positive or partially pos-itive outcome.

Music therapies make up the largest homogenousgroup with 11 studies. Of these, only one met our cri-teria for quality research and none met criteria forRCTs although two studies included a control condi-tion. All trials were conducted in residential settings,and one study also incorporated day hospital atten-dees.

Table 2 summarizes the included studies,as rated according to NHMRC evidencehierarchy.126,130,131 Of the three exercise interventionstudies, two present nonsignificant outcomes, in-cluding one high-quality RCT at level II. All but oneof the 11 music studies show positive results; how-ever, no RCTs are included. Only two studies meetcriteria for level III-1 evidence, while the majority areranked at level III-3. Multisensory stimulation stud-ies include one RCT, with a nonsignificant outcome,ranked at level II. The remainder are ranked at levelIII-3 or lower although all have positive results. Allseven studies of animal interventions had positiveoutcomes, but none ranked above III-3 due to a



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=0.

014)

.

11

Law

ton

etal

.,19

98,U

nit

edSt

ates

155

Stim

ula

tio

n-

retr

eat

mo

del

of

care

(co

mb

ined

staf

ftr

ain

ing,

inte

rdis

ci-

plin

ary

care

pla

nn

ing,

acti

vity

pro

gram

min

g,an

dfa

mily

sup

po

rt)

vers

us

usu

alca

reo

ver

12m

on

ths

Clu

ster

edR

CT

.No

f/u

182

ITT

and

97IA

NH

resi

den

tsw

ith

mo

der

ate

tose

vere

dem

enti

ain

2SC

Us

(14

fem

ales

);in

terv

enti

on

gro

up

N=

88,

con

tro

lgro

up

N=

94

SCU

sra

nd

om

ized

usi

ng

aco

into

ss

No

Exte

rnal

beh

avio

rale

nga

gem

ent:

soci

alb

ehav

iors

,act

ivit

ies,

tim

eu

se,a

nd

gazi

ng

wit

hin

tere

stas

mea

sure

dw

ith

the

wit

hd

raw

alfa

cto

ro

fth

eM

OSE

S156

asw

ella

sa

beh

avio

rra

tin

gsc

ale

and

anac

tivi

typ

arti

cip

atio

nsc

ale

dev

elo

ped

by

the

auth

ors

.Ob

serv

atio

ns

wer

era

ted

usi

ng

the

Ob

serv

edEm

oti

on

Rat

ing

Scal

e157

(pre

vio

usl

ykn

ow

nas

the

Ph

ilad

elp

hia

Ger

iatr

icC

ente

rA

ffec

tR

atin

gSc

ale.

158)

Sign

ifica

nt

incr

ease

for

acti

vite

san

dti

me

use

inex

per

imen

tal

gro

up

(mu

ltiv

aria

teF

=2.

51,

df=

14,2

72,p

<0.

01)

bu

tn

ot

con

tro

lgro

up

.No

sign

ifica

nt

chan

ges

for

pas

sive

beh

avio

rso

rga

zin

gw

ith

inte

rest

;no

sign

ifica

nt

effe

ctfo

rgr

ou

p×

tim

ein

tera

ctio

no

nin

tere

st.

10

Th

erap

euti

cac

tivi

ties

Ch

apm

anet

al.,

2004

,Un

ited

Stat

es13

2

Co

gnit

ive-

com

mu

nic

atio

nst

imu

lati

on

pro

gram

wit

hh

om

eas

sign

men

tsp

lus

do

nep

ezil

vers

us

do

nep

ezil

on

lyo

ver

8w

eeks

RC

T.8

and

12m

on

ths

f/u

50IT

Tan

d41

IAco

mm

un

ity-

dw

ellin

go

lder

adu

lts

wit

hm

ildto

mo

der

ate

AD

(29

fem

ales

);in

terv

enti

on

gro

up

N=

26,

con

tro

lgro

up

N=

28

Ran

do

mas

sign

men

tge

ner

ated

usi

ng

SAS

stat

isti

cal

soft

war

e(S

AS

Inst

itu

te,C

ary,

NC

).

Ap

ath

yit

emra

ters

blin

ded

Ap

ath

ych

ange

sco

res

asm

easu

red

by

the

NP

I.55

Ap

ath

ych

ange

sco

res

for

the

cogn

itiv

e-co

mm

un

icat

ion

pro

gram

wit

hd

on

epez

ilap

pro

ach

edsi

gnifi

can

ce(M

=−1

.10,

p=

0.08

)su

gges

tin

gre

du

ced

apat

hy

ove

rti

me.

Low

erap

ath

ysc

ore

sm

ain

tain

edat

follo

w-u

p.

12

(Con

tin

ued

)



Brodaty and BurnsT

AB

LE1.

(Co

nti

nu

ed)

Stu

dy

Inte

rven

tio

ns

Stu

dy

Des

ign

Fo

llo

w-u

pN

um

ber

Met

ho

do

fR

and

om

izat

ion

Bli

nd

ing

of

Rat

ers

Ou

tco

mes

Rel

evan

tto

Ap

ath

ySi

gnifi

can

ceQ

ual

ity

Rat

ing

Git

linet

al.,

2008

,U

nit

edSt

ates

134

Tai

lore

dA

ctiv

ity

Pro

gram

,an

OT

inte

rven

tio

no

fac

tivi

ties

cust

om

ized

toca

pab

iliti

esd

uri

ng

6×

90m

inu

tes

ho

me

visi

tsan

d2

×15

min

ute

sp

ho

ne

con

tact

so

ver

4m

on

ths

vers

us

wai

t-lis

tco

ntr

ol/

del

ayed

inte

rven

tio

ngr

ou

p

Cro

sso

ver

RC

T.

No

f/u

60IT

Tan

d56

IAp

atie

nts

wit

hd

emen

tia

livin

gin

the

com

mu

nit

yan

dth

eir

care

give

rs(2

6fe

mal

es);

inte

rven

tio

ngr

ou

pN

=30

,co

ntr

olg

rou

pN

=30

Ran

do

miz

edu

sin

gra

nd

om

per

mu

ted

blo

cks.

Par

tici

pan

tsal

sose

rved

asth

eir

ow

nco

ntr

ols

Yes

Act

ivit

yen

gage

men

tm

easu

red

wit

ha

five

-item

,in

vest

igat

or-

dev

elo

ped

ind

exo

fca

regi

ver

rep

ort

.

Sign

ifica

nt

incr

ease

inac

tivi

tyen

gage

men

t(F

[1,1

08]=

5.1,

p=

0.03

,C

oh

en’s

d=

0.61

)an

dab

ility

toke

epb

usy

(F[1

,108

]=

6.2,

p=

0.02

Co

hen

’sd

=0.

71)

intr

eatm

ent

gro

up

bu

tn

ot

con

tro

lgro

up

12

Ko

lan

ow

ski,

2005

,U

nit

edSt

ates

159

Act

ivit

ies

mat

ched

tosk

illle

velo

nly

vers

us

acti

viti

esm

atch

edto

styl

eo

fin

tere

sto

nly

vers

us

acti

viti

esm

atch

edto

bo

thsk

illle

vela

nd

styl

eo

fin

tere

stim

ple

men

ted

for

up

to20

min

ute

sd

aily

ove

r12

con

secu

tive

day

s

Inte

rru

pte

dti

me

seri

esw

ith

ou

tp

aral

lelc

on

tro

lgr

ou

p.N

of/

u

33IT

Tan

d30

IAN

Hre

sid

ents

wit

hd

emen

tia

(23

fem

ales

)

Ord

ero

fco

nd

itio

nra

nd

om

ized

wit

hp

erm

ute

db

lock

edra

nd

om

izat

ion

sch

eme.

Par

tici

pan

tsse

rved

asth

eir

ow

nco

ntr

ols

Enga

gem

ent

rate

rsb

lind

ed

Pas

sivi

tyas

mea

sure

db

yth

e12

pas

sive

beh

avio

rit

ems

of

the

Pas

sivi

tyin

Dem

enti

aSc

ale16

0as

wel

las

enga

gem

ent

asm

easu

red

by

tim

eo

nta

skan

din

ten

sity

of

par

tici

pat

ion

.

Sign

ifica

nt

imp

rove

men

tin

pas

sivi

tyan

den

gage

men

t(p

≤0.

001)

wh

enac

tivi

ties

wer

em

atch

edto

styl

eo

fin

tere

sto

rm

atch

edto

bo

thsk

illle

vela

nd

styl

eo

fin

tere

st.

12

Po

litis

etal

.,20

04,

Un

ited

Stat

es16

1

Kit

-bas

edac

tivi

tyin

terv

enti

on

vers

us

on

eto

on

eti

me

and

atte

nti

on

inte

rven

tio

nfo

r30

min

ute

s,3

×p

erw

eek

ove

r4

wee

ks

RC

T.N

of/

u36

resi

den

tso

fa

spec

ialis

tlo

ng-

term

dem

enti

aca

refa

cilit

y(1

8fe

mal

es);

inte

rven

tio

ngr

ou

pN

=18

,co

ntr

olg

rou

pN

=18

Tab

leo

fra

nd

om

nu

mb

ers

inb

lock

so

f4

Rat

ers

mas

ked

totr

eatm

ent

assi

gnm

ent

Ap

ath

yd

om

ain

of

the

NP

I55an

dac

tivi

typ

arti

cip

atio

nas

mea

sure

db

yth

eC

RA

Ias

dev

elo

ped

by

Co

pp

erR

idge

Inst

itu

te.16

1

Sign

ifica

nt

wit

hin

gro

up

imp

rove

men

tso

nN

PI

apat

hy

inb

oth

kit-

bas

edin

terv

enti

on

gro

up

(z=

−1.

92,p

=0.

05)

and

on

eto

on

ein

terv

enti

on

gro

up

(z=

−2.

68,p

=0.

01).

No

sign

ifica

nt

dif

fere

nce

bet

wee

ngr

ou

ps

inac

tivi

typ

arti

cip

atio

no

nth

eC

RA

I

12

Mis

cella

neo

us

Cam

ber

get

al.,

1999

,U

nit

edSt

ates

162

Sim

Pre

s,i.e

.,p

erso

nal

ized

aud

iota

pes

wh

ich

aim

tore

plic

ate

the

pre

sen

ceo

fca

regi

ver

vers

us

pla

ceb

oau

dio

tap

eo

fem

oti

on

ally

neu

tral

new

spap

erar

ticl

esve

rsu

su

sual

care

for

17d

ays

ove

r4

wee

ksw

ith

a10

-day

was

ho

ut

per

iod

bet

wee

ntr

eatm

ents

Pse

ud

o-R

CT

.No

f/u

54re

sid

ents

wit

hd

emen

tia

fro

m9

NH

s(4

8fe

mal

es)

Inte

rven

tio

nap

plie

din

are

stri

ctiv

ely

ran

do

miz

edm

ann

erw

hen

staf

fch

ose

eith

erin

terv

enti

on

or

pla

ceb

ota

pe

tom

anag

ere

sid

ent

beh

avio

rs

NH

staf

fan

dtr

ain

edn

on

par

tici

-p

ant

ob

serv

ers

blin

ded

toau

dio

tap

eco

nte

nt

Wit

hd

raw

nb

ehav

ior

defi

ned

asla

cko

fin

tere

stin

peo

ple

,ac

tivi

ties

,or

thin

gsin

par

tici

pan

ts’e

nvi

ron

men

tco

mb

ined

wit

hsa

dm

oo

das

mea

sure

db

yth

ein

tere

stan

dp

leas

ure

item

so

fth

eO

bse

rved

Emo

tio

nR

atin

gSc

ale15

7

(pre

vio

usl

ykn

ow

nas

the

Ph

ilad

elp

hia

Ger

iatr

icC

ente

rA

ffec

tR

atin

gSc

ale15

8)

and

aw

ith

dra

wn

visu

alan

alo

gue

scal

ew

ith

anch

ors

of

“ap

ath

y”an

d“e

nga

gem

ent.

”

Staf

fo

bse

rvat

ion

logs

ind

icat

edth

atSi

mP

res

imp

rove

dw

ith

dra

wn

beh

avio

ro

nsi

gnifi

can

tly

mo

reo

ccas

ion

s(6

9%)

than

usu

alca

re(5

5%;

p<

0.00

)an

dp

lace

bo

(34%

;p<

0.00

);d

irec

to

bse

rvat

ion

ssh

ow

edn

osi

gnifi

can

td

iffe

ren

ces

bet

wee

nco

nd

itio

ns;

wee

kly

staf

fsu

rvey

sin

dic

ated

that

12

(Con

tin

ued

)




TA

BLE

1.

(Co

nti

nu

ed)

Stu

dy

Inte

rven

tio

ns

Stu

dy

Des

ign

Fo

llo

w-u

pN

um

ber

Met

ho

do

fR

and

om

-iz

atio

nB

lin

din

go

fR

ater

sO

utc

om

esR

elev

ant

toA

pat

hy

Sign

ifica

nce

Qu

alit

yR

atin

g

Dat

aco

llect

ion

met

ho

ds

incl

ud

ed

aily

staf

fo

bse

rvat

ion

logs

(to

tal

ob

serv

atio

ns=

1981

)d

irec

to

bse

rvat

ion

san

dw

eekl

yst

aff

beh

avio

ralr

atin

gsu

rvey

s

Sim

Pre

sin

crea

sed

leve

lof

inte

rest

sign

ifica

ntl

ym

ore

than

pla

ceb

o(p

=0.

01)

and

usu

alca

re(p

=0.

00)

Laie

tal

.,20

04,H

on

gK

on

g,C

hin

a163

Ind

ivid

ual

rem

inis

cen

cep

rogr

amw

eekl

yfo

r30

min

ute

so

ver

6w

eeks

vers

us

soci

alco

nta

ctco

mp

aris

on

pro

gram

vers

us

no

inte

rven

tio

n

RC

T.6

wee

kf/

u10

1IT

Tan

d86

IAN

Hre

sid

ents

wit

hd

emen

tia

(69

fem

ales

);in

terv

enti

on

gro

up

N=

36,c

on

tro

lgr

ou

pN

=30

,co

mp

aris

on

gro

up

N=

35

Fix

ed allo

cati

on

ran

do

miz

a-ti

on

164

Ass

esso

rsb

lind

edto

par

tici

-p

ant

assi

gn-

men

t

Enga

gem

ent,

e.g.

,in

tera

ctio

n,

self

-init

iate

dac

tivi

ties

,an

din

volv

emen

tas

mea

sure

dw

ith

the

Soci

alEn

gage

men

tSc

ale16

5,1

66

Sign

ifica

nt

dif

fere

nce

ove

rti

me

wit

hin

inte

rven

tio

ngr

ou

p(p

=0.

014)

bu

tn

ot

the

com

par

iso

no

rco

ntr

olg

rou

ps.

No

sign

ifica

nt

dif

fere

nce

bet

wee

nsu

bje

ctef

fect

so

rw

ith

insu

bje

ctef

fect

sfo

rin

tera

ctio

nb

etw

een

tim

ean

dgr

ou

po

rb

etw

een

tim

ean

dre

gula

rp

rogr

am

13

Sch

rijn

e-m

aeke

rset

al.,

2002

,N

eth

erla

nd

s167

Emo

tio

n-o

rien

ted

care

,168

bas

edo

nva

lidat

ion

,169

rem

inis

cen

ce,

and

sen

sory

stim

ula

tio

nap

pro

ach

esve

rsu

su

sual

care

ove

r12

mo

nth

s

Clu

ster

edp

seu

do

-RC

T.

No

f/u

151

resi

den

tsw

ith

cogn

itiv

eim

pai

rmen

tan

db

ehav

iora

lpro

ble

ms

atte

nd

ing

stru

ctu

red

day

-car

eu

nit

sin

16N

Hs

(136

fem

ales

);in

terv

enti

on

gro

up

N=

77,c

on

tro

lgr

ou

pN

=74

NH

sra

nd

om

-iz

ed.

Met

ho

dn

ot

stat

ed

No

Ap

ath

etic

and

no

nso

cial

beh

avio

rsu

bsc

ales

of

the

sho

rtve

rsio

no

fth

eG

IP15

3at

bas

elin

e,3

mo

nth

s,6

mo

nth

s,an

d12

mo

nth

s

No

sign

ifica

nt

dif

fere

nce

bet

wee

nin

terv

enti

on

and

con

tro

lgro

up

sfo

rap

ath

etic

or

no

nso

cial

beh

avio

rs.

11

Tad

aka

and

Kan

agaw

a,20

07,

Jap

an13

7

RT

du

rin

g60

–90

min

ute

sw

eekl

yse

ssio

ns

vers

us

rou

tin

ed

ayca

rese

rvic

eo

ver

8co

nse

cuti

vew

eeks

RC

T.6

mo

nth

f/u

60IT

Tan

d50

IAel

der

lyat

ten

dee

so

fco

mm

un

ity

day

care

wit

hd

emen

tia

(20

AD

,30

VaD

,42

fem

ales

);in

terv

enti

on

gro

up

N=

30,c

on

tro

lgr

ou

pN

=30

Co

mp

ute

r-ge

ner

ated

ran

do

miz

a-ti

on

wit

hin

sub

sets

of

dem

enti

aty

pe

No

Deg

ree

of

wit

hd

raw

alas

mea

sure

db

yth

ew

ith

dra

wal

sub

scal

eo

fth

eM

OSE

S156

Sign

ifica

nt

imp

rove

men

to

nw

ith

dra

wal

for

RT

inA

Dgr

ou

pim

med

iate

lyfo

llow

ing

inte

rven

tio

nb

ut

no

tat

follo

w-u

p(p

<0.

05);

sign

ifica

nt

imp

rove

men

tim

med

iate

lyfo

llow

ing

inte

rven

tio

nan

dat

follo

wu

po

nw

ith

dra

wal

for

RT

inV

aDgr

ou

p(p

<0.

01)

11

Not

es:N

H:n

ursi

ngho

me;

MSS

:mul

tise

nsor

yst

imul

atio

n;B

RS:

Beh

avio

ralR

atin

gSc

ale;

CR

AI:

Cop

per

Rid

geA

ctiv

itie

sIn

dex

;f/

u:fo

llow

up;G

IP:G

edra

gsob

serv

atie

scha

alvo

ord

eIn

tram

ural

ePs

ycho

geri

atri

e[D

utch

Beh

avio

rR

atin

gSc

ale

for

Psyc

hoge

riat

ric

Inpa

tien

ts];

IA:i

nan

alys

is;I

TT:

inte

ntio

nto

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Brodaty and Burns

TABLE 2. Summary of NHMRC Levels of Evidence for Included Studies

Positive Outcome Nonsignificant OutcomeNHMRC levels ofevidencea126 II III IV II III IV

Intervention groupExercise 0 1 0 1 1 0Music 0 8 1 0 0 1Multisensory stimulation 0 5 0 1 0Animals 0 4 3 0 0 0Special care

programming1 1 2 0 1 0

Therapeutic activities 1 12 0 2 0 0Miscellaneous 1 6 0 0 3 0

Notes: aNo level I systematic reviews included.

lack of controlled studies. Special care programmingincludes five studies of which one met criteria forlevel II, one met criteria for level III-2, and threeranked at III-3 or less. Four of the five studies havepositive results. Therapeutic activity studies ratebetter overall with three RCTs at level II and sevenstudies at III-1. All but two report positive outcomes.Miscellaneous interventions, including two RCTsranked at level II and five pseudorandomized con-trolled trials at level III-1, are a heterogenous groupmaking it difficult to draw conclusions.

DISCUSSION

Apathy while common in dementia58 is often ig-nored even though it contributes to lower quality oflife in people with dementia170,171 and causes signifi-cant distress to caregivers.101,150,172 Interventions arewarranted,1,100,173–176 but there is a paucity of soundresearch to guide clinicians and caregivers. Manynonpharmacological interventions are the subject ofa limited number of studies,177 and others such asremotivation therapy,178 structured daily routine, arttherapy, psychomotor therapy, humor therapy,179 andvalidation therapy169 are not represented here or havebeen excluded.

From the literature reviewed, the only interventionwith sufficient quality studies, here defined as 11 ormore on our research quality scale, was Therapeu-tic Activities. Some benefit for apathy in dementiais apparent, although this is a heterogeneous group,which includes stimulation, creative activities, cook-ing, Montessori methods, and behavioral elements,often individually tailored. Some positive results,

although even less impressive, were reported for mu-sic, exercise, multisensory stimulation, pet therapy,and special care units. However, the evidence for ef-ficacy of these interventions is far from convincing,as the standard of research was generally low, withonly 12 out of 57 studies reaching an arbitrary stan-dard of 11 out of 15 on a rating scale of quality. Fur-thermore, there is scant evidence of sustainability ofeffect once intervention ceases. Studies that reportedmaintenance of benefits in the community reflect con-tinued activities by family caregivers.

A lack of quality research is not necessarily in-dicative of a lack of efficacy.174 Studies may reportanecdotal, qualitative evidence, which can be difficultto capture quantitatively and high-quality researchparticularly in large numbers is labor-intensive andexpensive. Likewise, reliance on randomized studiesexcludes possibilities arising from the natural setting.While this creates potential threats to validity, suchsituations are impractical to randomize. Validityis a key criterion when assessing research quality,but applicability and clinical relevance are alsoimportant.180 Although significant differences maynot be demonstrated with a repeated-measures de-sign, this may nonetheless be an appropriate choicedue to the predicted trajectory of increasing apathywith dementia severity.39,181,182 Stabilization of par-ticipants’ apathy, in the face of disease progression,may indicate that the intervention is beneficial evenwithout evidence of improvement.

Quality research is necessary to determine conse-quences of providing or delaying pharmacologicalinterventions.183 Although general treatment prin-ciples for behavioral and psychological symptomsof dementia (BPSD) recommend commencing with




psychosocial interventions,184 initial treatment forBPSD is often pharmacological possibly becauseof the lack of evidence for nonpharmacologicalapproaches.183 As effect sizes were largely inaccessi-ble, comparison of nonpharmacological versus phar-macological interventions alone or in combinationwas not viable. Only one study in this review evalu-ated a psychosocial intervention in combination withdrug treatment.132 Scientific and financial invest-ment into the pharmacological treatment of cognitiveimpairment in dementia plainly outweighs invest-ment into management of behavioral symptoms,185

although neuropsychiatric features may be as signifi-cant as cognitive losses.186

LIMITATIONS

The potential confounds of studying apathy in de-mentia are numerous: a lack of standardized, assess-ment guidelines for diagnosing apathy; difficultiesin differentiating it from and overlap with depres-sion, fatigue syndromes, and parkinsonism;187–190 un-derreporting of apathy;72 and similar symptoms sec-ondary to medications such as psychotropics andbeta-blockers.29 Furthermore, severity of dementialikely influences the success of interventions trialed,yet many studies treated participants as a homoge-nous group. The degree to which findings can begeneralized across the stages of dementia is largelyunknown.191 While 12 studies specified a level of de-mentia, small participant numbers preclude separat-ing these according to disease severity.

The multiple components of psychosocial interven-tions often overlap making it difficult to determinewhich aspect is the active ingredient.184 Where stud-ies report similar interventions, differing care envi-ronments and procedures lead to difficulty in de-termining consistency of delivery. Likewise, manydisparate instruments and tools have been usedto collect behavioral data, with only some beingwell-validated. Consistency in gathering and report-ing outcomes would facilitate useful comparisonsbetween studies and aid in developing effectivemanagement strategies. Distal outcomes of apatheticbehaviors such as time to residential care placement,effects on caregivers, and complications of immobil-ity are also neglected.

Research is hampered by the difficulties of recruit-ing and retaining numbers to ensure sufficient power.Ethical issues also arise when recruiting and ob-taining consent from apathetic participants. Further-more, maintaining compliance with interventionsand study design in the “real world” often requiresmuch supervision, support, and encouragement onthe caregiver’s part. When individual improvementsare not evident, caregivers’ motivation and commit-ment may diminish. Both, family and paid caregiversare classically overloaded in their roles thereby in-creasing the risk of withdrawal from studies.

The impoverished physical and social environmentof institutional care can further inhibit motivation,as can sensory impairments.9 Within residential fa-cilities, avoiding contamination across groups posesan additional challenge. The mere presence of re-searchers or any intervention, beyond the daily rou-tine, can incite stimulation and interest among theresidents, their families, and staff, making it impossi-ble to provide true control conditions for comparison.Usual care or programming varies markedly betweenresearch contexts and hence differences between con-trol and intervention conditions are inconsistent. Fi-nally, funding is difficult to obtain for nonpharma-cological research. Limited synthesis of studies wasperformed, but meta-analysis was not possible due tovariations in the delivery of interventions, outcomemeasurement, and reporting as well as methodology.

FUTURE RESEARCH

Apathy is as a major source of caregiver distressand frustration for those living at home.192 As a neg-ative symptom, however, apathy tends to pose lessovert disruption and economic consequences in resi-dential care settings relative to the more agitated andaggressive BPSD.193,194 Improved quality of life andcare, through reduced apathy, is more difficult to rec-ognize and quantify. Targeting apathy may alert care-givers at home or in residential care settings to an ad-ditional problem that would not normally demandtheir attention. The secondary benefits of successfulinterventions may be better evident in social gains ormaintenance of functional abilities as well as staff re-tention, job satisfaction, and/or increased family in-put in residential care.



Brodaty and Burns

Research has proposed matching activities to indi-vidual interests and retained skills to engage personswith dementia and maintain involvement.195–197

A biopsychosocial approach to managing apathyrecognizes that there are multiple contributorsto apathetic behaviors. Acknowledging individ-uality, personal history, and previous interestsmay forecast individual strategies for engagingthose with apathetic behaviors101,178,198 as well asvariations in response.199 Person-centered care200

likewise seeks to view the person as a whole, in-corporating the individual’s personal and socialpsychology. While a “one size fits all” approachto managing apathy in dementia may be inappro-priate, individualized programs require additionalresources. The benefits to care providers and orga-nizations must ultimately outweigh implementationcosts.

The implications of this review are that non-pharmacological interventions have the potentialto reduce apathy in dementia. Apathy is complexand multifaceted and further rigorous research isneeded201–203 including the investigation of integra-tive approaches possibly in combination with phar-macological interventions.94 Future research shouldconsider confounds such as depression, medicationeffects, metabolic disorders, environmental differ-ences, and concurrent acute and/or chronic illnesses.Randomized, blinded, controlled studies with apathyas a primary outcome and longer-term follow-up us-ing validated, reliable outcome measures of apathywould advance the evaluation of nonpharmacolog-ical management. In the meantime, the use of ther-apeutic activities has the best available evidence foreffectiveness, particularly when these are providedindividually.

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Nonpharmacological Management of Apathy in Dementia: A Systematic Review