Background: Neuropsychiatric symptoms (NPS) in dementia have received much attention due to their high prevalence and their significant implications. NPS in mild cognitive impairment (MCI), a clinical concept proposed as an intermediate state between normal aging and dementia, is now gradually gaining in interest. We aimed to conduct a selective review to examine the prevalence rate of NPS in MCI and associations of NPS symptoms with disease progression. Summary: We searched the PubMed database for articles on NPS in MCI and included articles that fulfilled the inclusion criteria. NPS was present in 35–85% of MCI patients. The most common symptoms were depression, irritability, apathy, anxiety, agitation, and sleep problems. Although the associated risk for disease progression of some symptoms, such as apathy and anxiety, was more consistent across studies, evidence was conflicting for symptoms like depression and sleep problems. NPS tend to co-occur, and certain combinations of NPS had a mutual or cumulative effect on disease progression. Late-onset NPS, even in a mild form (mild behavioural impairment) were found to be associated with an increased risk of dementia, even in the absence of cognitive impairment. Key Messages: NPS are highly prevalent in MCI patients and associated with subsequent cognitive deterioration. Late-onset NPS should raise suspicions of neurodegeneration. Future studies with improvised methodology are required to understand the interrelations of NPS and the role they play in the prognosis for patients with MCI.

1.
Mallo
SC
,
Ismail
Z
,
Pereiro
AX
,
Facal
D
,
Lojo-Seoane
C
,
Campos-Magdaleno
M
, et al.
Assessing Mild Behavioral Impairment with the Mild Behavioral Impairment-Checklist in People with Mild Cognitive Impairment
.
J Alzheimers Dis
.
2018
;
66
(
1
):
83
95
.
[PubMed]
1387-2877
2.
Steinberg
M
,
Shao
H
,
Zandi
P
,
Lyketsos
CG
,
Welsh-Bohmer
KA
,
Norton
MC
, et al.;
Cache County Investigators
.
Point and 5-year period prevalence of neuropsychiatric symptoms in dementia: the Cache County Study
.
Int J Geriatr Psychiatry
.
2008
Feb
;
23
(
2
):
170
7
.
[PubMed]
0885-6230
3.
González-Salvador
T
,
Lyketsos
CG
,
Baker
A
,
Hovanec
L
,
Roques
C
,
Brandt
J
, et al.
Quality of life in dementia patients in long-term care
.
Int J Geriatr Psychiatry
.
2000
Feb
;
15
(
2
):
181
9
.
[PubMed]
0885-6230
4.
Lyketsos
CG
,
Steele
C
,
Baker
L
,
Galik
E
,
Kopunek
S
,
Steinberg
M
, et al.
Major and minor depression in Alzheimer’s disease: prevalence and impact
.
J Neuropsychiatry Clin Neurosci
.
1997
;
9
(
4
):
556
61
.
[PubMed]
0895-0172
5.
Steele
C
,
Rovner
B
,
Chase
GA
,
Folstein
M
.
Psychiatric symptoms and nursing home placement of patients with Alzheimer’s disease
.
Am J Psychiatry
.
1990
Aug
;
147
(
8
):
1049
51
.
[PubMed]
0002-953X
6.
Monastero
R
,
Mangialasche
F
,
Camarda
C
,
Ercolani
S
,
Camarda
R
.
A systematic review of neuropsychiatric symptoms in mild cognitive impairment
.
J Alzheimers Dis
.
2009
;
18
(
1
):
11
30
.
[PubMed]
1387-2877
7.
Petersen
RC
.
Mild cognitive impairment as a diagnostic entity
.
J Intern Med
.
2004
Sep
;
256
(
3
):
183
94
.
[PubMed]
0954-6820
8.
Cerejeira
J
,
Lagarto
L
,
Mukaetova-Ladinska
EB
.
Behavioral and psychological symptoms of dementia
.
Front Neurol
.
2012
May
;
3
:
73
.
[PubMed]
1664-2295
9.
Gallagher
D
,
Fischer
CE
,
Iaboni
A
.
Neuropsychiatric Symptoms in Mild Cognitive Impairment
.
Can J Psychiatry
.
2017
Mar
;
62
(
3
):
161
9
.
[PubMed]
0706-7437
10.
Rozzini
L
,
Vicini Chilovi
B
,
Conti
M
,
Delrio
I
,
Borroni
B
,
Trabucchi
M
, et al.
Neuropsychiatric symptoms in amnestic and nonamnestic mild cognitive impairment
.
Dement Geriatr Cogn Disord
.
2008
;
25
(
1
):
32
6
.
[PubMed]
1420-8008
11.
Lyketsos
CG
,
Lopez
O
,
Jones
B
,
Fitzpatrick
AL
,
Breitner
J
,
DeKosky
S
.
Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: results from the cardiovascular health study
.
JAMA
.
2002
Sep
;
288
(
12
):
1475
83
.
[PubMed]
0098-7484
12.
Modrego
PJ
,
Ferrández
J
.
Depression in patients with mild cognitive impairment increases the risk of developing dementia of Alzheimer type: a prospective cohort study
.
Arch Neurol
.
2004
Aug
;
61
(
8
):
1290
3
.
[PubMed]
0003-9942
13.
Palmer
K
,
Di Iulio
F
,
Varsi
AE
,
Gianni
W
,
Sancesario
G
,
Caltagirone
C
, et al.
Neuropsychiatric predictors of progression from amnestic-mild cognitive impairment to Alzheimer’s disease: the role of depression and apathy
.
J Alzheimers Dis
.
2010
;
20
(
1
):
175
83
.
[PubMed]
1387-2877
14.
Chan
WC
,
Lam
LC
,
Tam
CW
,
Lui
VW
,
Leung
GT
,
Lee
AT
, et al.
Neuropsychiatric symptoms are associated with increased risks of progression to dementia: a 2-year prospective study of 321 Chinese older persons with mild cognitive impairment
.
Age Ageing
.
2011
Jan
;
40
(
1
):
30
5
.
[PubMed]
0002-0729
15.
Ismail
Z
,
Agüera-Ortiz
L
,
Brodaty
H
,
Cieslak
A
,
Cummings
J
,
Fischer
CE
, et al.;
NPS Professional Interest Area of the International Society of to Advance Alzheimer’s Research and Treatment (NPS-PIA of ISTAART)
.
The Mild Behavioral Impairment Checklist (MBI-C): A Rating Scale for Neuropsychiatric Symptoms in Pre-Dementia Populations
.
J Alzheimers Dis
.
2017
;
56
(
3
):
929
38
.
[PubMed]
1387-2877
16.
Ismail
Z
,
Elbayoumi
H
,
Fischer
CE
,
Hogan
DB
,
Millikin
CP
,
Schweizer
T
, et al.
Prevalence of Depression in Patients With Mild Cognitive Impairment: A Systematic Review and Meta-analysis
.
JAMA Psychiatry
.
2017
Jan
;
74
(
1
):
58
67
.
[PubMed]
2168-622X
17.
Siafarikas
N
,
Selbaek
G
,
Fladby
T
,
Šaltytė Benth
J
,
Auning
E
,
Aarsland
D
.
Frequency and subgroups of neuropsychiatric symptoms in mild cognitive impairment and different stages of dementia in Alzheimer’s disease
.
Int Psychogeriatr
.
2018
Jan
;
30
(
1
):
103
13
.
[PubMed]
1041-6102
18.
Zhang
M
,
Wang
H
,
Li
T
,
Yu
X
.
Prevalence of Neuropsychiatric Symptoms across the Declining Memory Continuum: An Observational Study in a Memory Clinic Setting
.
Dement Geriatr Cogn Disord Extra
.
2012
Jan
;
2
(
1
):
200
8
.
[PubMed]
1664-5464
19.
Robert
PH
,
Berr
C
,
Volteau
M
,
Bertogliati-Fileau
C
,
Benoit
M
,
Guerin
O
, et al.;
PréAL Study Group
.
Importance of lack of interest in patients with mild cognitive impairment
.
Am J Geriatr Psychiatry
.
2008
Sep
;
16
(
9
):
770
6
.
[PubMed]
1064-7481
20.
Richard
E
,
Schmand
B
,
Eikelenboom
P
,
Yang
SC
,
Ligthart
SA
,
Moll van Charante
EP
, et al.;
Alzheimer’s Disease Neuroimaging Initiative
.
Symptoms of apathy are associated with progression from mild cognitive impairment to Alzheimer’s disease in non-depressed subjects
.
Dement Geriatr Cogn Disord
.
2012
;
33
(
2-3
):
204
9
.
[PubMed]
1420-8008
21.
Bayard
S
,
Jacus
JP
,
Raffard
S
,
Gely-Nargeot
MC
.
Apathy and emotion-based decision-making in amnesic mild cognitive impairment and Alzheimer’s disease
.
Behav Neurol
.
2014
;
2014
:
231469
.
[PubMed]
0953-4180
22.
Geda
YE
,
Smith
GE
,
Knopman
DS
,
Boeve
BF
,
Tangalos
EG
,
Ivnik
RJ
, et al.
De novo genesis of neuropsychiatric symptoms in mild cognitive impairment (MCI)
.
Int Psychogeriatr
.
2004
Mar
;
16
(
1
):
51
60
.
[PubMed]
1041-6102
23.
Forrester
SN
,
Gallo
JJ
,
Smith
GS
,
Leoutsakos
JM
.
Patterns of Neuropsychiatric Symptoms in Mild Cognitive Impairment and Risk of Dementia
.
Am J Geriatr Psychiatry
.
2016
Feb
;
24
(
2
):
117
25
.
[PubMed]
1064-7481
24.
Geda
YE
,
Roberts
RO
,
Mielke
MM
,
Knopman
DS
,
Christianson
TJ
,
Pankratz
VS
, et al.
Baseline neuropsychiatric symptoms and the risk of incident mild cognitive impairment: a population-based study
.
Am J Psychiatry
.
2014
May
;
171
(
5
):
572
81
.
[PubMed]
0002-953X
25.
Brodaty
H
,
Heffernan
M
,
Draper
B
,
Reppermund
S
,
Kochan
NA
,
Slavin
MJ
, et al.
Neuropsychiatric symptoms in older people with and without cognitive impairment
.
J Alzheimers Dis
.
2012
;
31
(
2
):
411
20
.
[PubMed]
1387-2877
26.
Leoutsakos
JM
,
Forrester
SN
,
Lyketsos
CG
,
Smith
GS
.
Latent Classes of Neuropsychiatric Symptoms in NACC Controls and Conversion to Mild Cognitive Impairment or Dementia
.
J Alzheimers Dis
.
2015
;
48
(
2
):
483
93
.
[PubMed]
1387-2877
27.
Mirza
SS
,
Ikram
MA
,
Bos
D
,
Mihaescu
R
,
Hofman
A
,
Tiemeier
H
.
Mild cognitive impairment and risk of depression and anxiety: A population-based study
.
Alzheimers Dement
.
2017
Feb
;
13
(
2
):
130
9
.
[PubMed]
1552-5260
28.
Somme
J
,
Fernández-Martínez
M
,
Molano
A
,
Zarranz
JJ
.
Neuropsychiatric symptoms in amnestic mild cognitive impairment: increased risk and faster progression to dementia
.
Curr Alzheimer Res
.
2013
Jan
;
10
(
1
):
86
94
.
[PubMed]
1875-5828
29.
Beaudreau
SA
,
O’Hara
R
.
Late-life anxiety and cognitive impairment: a review
.
Am J Geriatr Psychiatry
.
2008
Oct
;
16
(
10
):
790
803
.
[PubMed]
1064-7481
30.
Chen
C
,
Hu
Z
,
Jiang
Z
,
Zhou
F
.
Prevalence of anxiety in patients with mild cognitive impairment: A systematic review and meta-analysis
.
J Affect Disord
.
2018
Aug
;
236
:
211
21
.
[PubMed]
0165-0327
31.
Gallagher
D
,
Coen
R
,
Kilroy
D
,
Belinski
K
,
Bruce
I
,
Coakley
D
, et al.
Anxiety and behavioural disturbance as markers of prodromal Alzheimer’s disease in patients with mild cognitive impairment
.
Int J Geriatr Psychiatry
.
2011
Feb
;
26
(
2
):
166
72
.
[PubMed]
0885-6230
32.
Yates
JA
,
Clare
L
,
Woods
RT
;
Cognitive Function and Ageing Study: Wales
.
What is the Relationship between Health, Mood, and Mild Cognitive Impairment?
J Alzheimers Dis
.
2017
;
55
(
3
):
1183
93
.
[PubMed]
1387-2877
33.
Lopez
OL
,
Becker
JT
,
Sweet
RA
.
Non-cognitive symptoms in mild cognitive impairment subjects
.
Neurocase
.
2005
Feb
;
11
(
1
):
65
71
.
[PubMed]
1355-4794
34.
Beaulieu-Bonneau
S
,
Hudon
C
.
Sleep disturbances in older adults with mild cognitive impairment
.
Int Psychogeriatr
.
2009
Aug
;
21
(
4
):
654
66
.
[PubMed]
1041-6102
35.
Peters
ME
,
Rosenberg
PB
,
Steinberg
M
,
Norton
MC
,
Welsh-Bohmer
KA
,
Hayden
KM
, et al.;
Cache County Investigators
.
Neuropsychiatric symptoms as risk factors for progression from CIND to dementia: the Cache County Study
.
Am J Geriatr Psychiatry
.
2013
Nov
;
21
(
11
):
1116
24
.
[PubMed]
1064-7481
36.
Martin
JL
,
Ancoli-Israel
S
.
Sleep disturbances in long-term care
.
[vi.]
.
Clin Geriatr Med
.
2008
Feb
;
24
(
1
):
39
50
.
[PubMed]
0749-0690
37.
Lobo
A
,
López-Antón
R
,
de-la-Cámara
C
,
Quintanilla
MA
,
Campayo
A
,
Saz
P
;
ZARADEMP Workgroup
.
Non-cognitive psychopathological symptoms associated with incident mild cognitive impairment and dementia, Alzheimer’s type
.
Neurotox Res
.
2008
Oct
;
14
(
2-3
):
263
72
.
[PubMed]
1029-8428
38.
Teng
E
,
Lu
PH
,
Cummings
JL
.
Neuropsychiatric symptoms are associated with progression from mild cognitive impairment to Alzheimer’s disease
.
Dement Geriatr Cogn Disord
.
2007
;
24
(
4
):
253
9
.
[PubMed]
1420-8008
39.
Geda
YE
,
Roberts
RO
,
Knopman
DS
,
Petersen
RC
,
Christianson
TJ
,
Pankratz
VS
, et al.
Prevalence of neuropsychiatric symptoms in mild cognitive impairment and normal cognitive aging: population-based study
.
Arch Gen Psychiatry
.
2008
Oct
;
65
(
10
):
1193
8
.
[PubMed]
0003-990X
40.
Wise
EA
,
Rosenberg
PB
,
Lyketsos
CG
,
Leoutsakos
JM
.
Time course of neuropsychiatric symptoms and cognitive diagnosis in National Alzheimer’s Coordinating Centers volunteers
.
Alzheimers Dement (Amst)
.
2019
Apr
;
11
(
1
):
333
9
.
[PubMed]
2352-8729
41.
Dietlin
S
,
Soto
M
,
Kiyasova
V
,
Pueyo
M
,
de Mauleon
A
,
Delrieu
J
, et al.
Neuropsychiatric Symptoms and Risk of Progression to Alzheimer’s Disease Among Mild Cognitive Impairment Subjects
.
J Alzheimers Dis
.
2019
;
70
(
1
):
25
34
.
[PubMed]
1387-2877
42.
Steinberg
M
,
Corcoran
C
,
Tschanz
JT
,
Huber
C
,
Welsh-Bohmer
K
,
Norton
MC
, et al.
Risk factors for neuropsychiatric symptoms in dementia: the Cache County Study
.
Int J Geriatr Psychiatry
.
2006
Sep
;
21
(
9
):
824
30
.
[PubMed]
0885-6230
43.
Weamer
EA
,
DeMichele-Sweet
MA
,
Cloonan
YK
,
Lopez
OL
,
Sweet
RA
.
Incident Psychosis in Subjects With Mild Cognitive Impairment or Alzheimer’s Disease
.
J Clin Psychiatry
.
2016
Dec
;
77
(
12
):
e1564
9
.
[PubMed]
0160-6689
44.
Dillon
C
,
Serrano
CM
,
Castro
D
,
Leguizamón
PP
,
Heisecke
SL
,
Taragano
FE
.
Behavioral symptoms related to cognitive impairment
.
Neuropsychiatr Dis Treat
.
2013
;
9
:
1443
55
.
[PubMed]
1176-6328
45.
Taragano
FE
,
Allegri
RF
,
Krupitzki
H
,
Sarasola
DR
,
Serrano
CM
,
Loñ
L
, et al.
Mild behavioral impairment and risk of dementia: a prospective cohort study of 358 patients
.
J Clin Psychiatry
.
2009
Apr
;
70
(
4
):
584
92
.
[PubMed]
0160-6689
46.
van der Linde
R
,
Stephan
BC
,
Matthews
FE
,
Brayne
C
,
Savva
GM
;
Medical Research Council Cognitive Function and Ageing Study
.
Behavioural and psychological symptoms in the older population without dementia—relationship with socio-demographics, health and cognition
.
BMC Geriatr
.
2010
Nov
;
10
(
1
):
87
.
[PubMed]
1471-2318
47.
Rosenberg
PB
,
Mielke
MM
,
Appleby
BS
,
Oh
ES
,
Geda
YE
,
Lyketsos
CG
.
The association of neuropsychiatric symptoms in MCI with incident dementia and Alzheimer disease
.
Am J Geriatr Psychiatry
.
2013
Jul
;
21
(
7
):
685
95
.
[PubMed]
1064-7481
48.
Ruthirakuhan
M
,
Herrmann
N
,
Vieira
D
,
Gallagher
D
,
Lanctôt
KL
.
The Roles of Apathy and Depression in Predicting Alzheimer Disease: A Longitudinal Analysis in Older Adults With Mild Cognitive Impairment
.
Am J Geriatr Psychiatry
.
2019
Aug
;
27
(
8
):
873
82
.
[PubMed]
1064-7481
49.
Liew
TM
. Symptom Clusters of Neuropsychiatric Symptoms in Mild Cognitive Impairment and Their Comparative Risks of Dementia: A Cohort Study of 8530 Older Persons. J Am Med Dir Assoc.
2019
;20(8):1054.e1-.e9.
50.
Wadsworth
LP
,
Lorius
N
,
Donovan
NJ
,
Locascio
JJ
,
Rentz
DM
,
Johnson
KA
, et al.
Neuropsychiatric symptoms and global functional impairment along the Alzheimer’s continuum
.
Dement Geriatr Cogn Disord
.
2012
;
34
(
2
):
96
111
.
[PubMed]
1420-8008
51.
Ismail
Z
,
Smith
EE
,
Geda
Y
,
Sultzer
D
,
Brodaty
H
,
Smith
G
, et al.;
ISTAART Neuropsychiatric Symptoms Professional Interest Area
.
Neuropsychiatric symptoms as early manifestations of emergent dementia: provisional diagnostic criteria for mild behavioral impairment
.
Alzheimers Dement
.
2016
Feb
;
12
(
2
):
195
202
.
[PubMed]
1552-5260
52.
Cummings
JL
,
Mega
M
,
Gray
K
,
Rosenberg-Thompson
S
,
Carusi
DA
,
Gornbein
J
.
The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia
.
Neurology
.
1994
Dec
;
44
(
12
):
2308
14
.
[PubMed]
0028-3878
53.
Yokoi
Y
,
Takano
H
,
Sakata
M
,
Maruo
K
,
Nakagome
K
,
Matsuda
H
.
Discrete effect of each mild behavioural impairment category on dementia conversion or cognitive decline in patients with mild cognitive impairment
.
Psychogeriatrics
.
2019
Nov
;
19
(
6
):
591
600
.
[PubMed]
1346-3500
54.
Creese
B
,
Brooker
H
,
Ismail
Z
,
Wesnes
KA
,
Hampshire
A
,
Khan
Z
, et al.
Mild Behavioral Impairment as a Marker of Cognitive Decline in Cognitively Normal Older Adults
.
Am J Geriatr Psychiatry
.
2019
Aug
;
27
(
8
):
823
34
.
[PubMed]
1064-7481
55.
Petersen
RC
,
Smith
GE
,
Waring
SC
,
Ivnik
RJ
,
Tangalos
EG
,
Kokmen
E
.
Mild cognitive impairment: clinical characterization and outcome
.
Arch Neurol
.
1999
Mar
;
56
(
3
):
303
8
.
[PubMed]
0003-9942
56.
Apostolova
LG
,
Cummings
JL
.
Neuropsychiatric manifestations in mild cognitive impairment: a systematic review of the literature
.
Dement Geriatr Cogn Disord
.
2008
;
25
(
2
):
115
26
.
[PubMed]
1420-8008
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.