Introduction: Obesity and associated risk factors have been linked to cognitive decline before. Objectives: In the present study, we evaluated potential cumulative negative effects of overweight and obesity on cognitive performance in euthymic patients with bipolar disorder (BD) in a longitudinal design. Methods: Neurocognitive measures (California Verbal Learning Test, Trail Making Test [TMT] A/B, Digit-Symbol-Test, Digit-Span, d2 Test), anthropometrics (e.g., body mass index [BMI]), and clinical ratings (Hamilton Depression Scale, Young Mania Rating Scale) were collected over a 12-month observation period. Follow-up data of 38 patients with BD (mean age 40 years; 15 males, 23 females) were available. Results: High baseline BMI predicted a decrease in the patient’s performance in the Digit-Span backwards task measuring working memory performance. In contrast, cognitive performance was not predicted by increases in BMI at follow-up. Normal weight bipolar patients (n = 19) improved their performance on the TMT B, measuring cognitive flexibility and executive functioning, within 1 year, while overweight bipolar patients (n = 19) showed no change in this task. Conclusions: The results suggest that overweight can predict cognitive performance changes over 12 months.

1.
Beydoun
MA
,
Beydoun
HA
,
Wang
Y
.
Obesity and central obesity as risk factors for incident dementia and its subtypes: a systematic review and meta-analysis
.
Obes Rev
.
2008
May
;
9
(
3
):
204
18
.
[PubMed]
1467-7881
2.
Cheng
G
,
Huang
C
,
Deng
H
,
Wang
H
.
Diabetes as a risk factor for dementia and mild cognitive impairment: a meta-analysis of longitudinal studies
.
Intern Med J
.
2012
May
;
42
(
5
):
484
91
.
[PubMed]
1444-0903
3.
Pedditzi
E
,
Peters
R
,
Beckett
N
.
The risk of overweight/obesity in mid-life and late life for the development of dementia: a systematic review and meta-analysis of longitudinal studies
.
Age Ageing
.
2016
Jan
;
45
(
1
):
14
21
.
[PubMed]
0002-0729
4.
Veronese
N
,
Facchini
S
,
Stubbs
B
,
Luchini
C
,
Solmi
M
,
Manzato
E
, et al.
Weight loss is associated with improvements in cognitive function among overweight and obese people: A systematic review and meta-analysis
.
Neurosci Biobehav Rev
.
2017
Jan
;
72
:
87
94
.
[PubMed]
0149-7634
5.
van den Berg
E
,
Kloppenborg
RP
,
Kessels
RP
,
Kappelle
LJ
,
Biessels
GJ
.
Type 2 diabetes mellitus, hypertension, dyslipidemia and obesity: A systematic comparison of their impact on cognition
.
Biochim Biophys Acta
.
2009
May
;
1792
(
5
):
470
81
.
[PubMed]
0006-3002
6.
Martin
AA
,
Davidson
TL
.
Human cognitive function and the obesogenic environment
.
Physiol Behav
.
2014
Sep
;
136
:
185
93
.
[PubMed]
0031-9384
7.
Zhao
C
,
Noble
JM
,
Marder
K
,
Hartman
JS
,
Gu
Y
,
Scarmeas
N
.
Dietary Patterns, Physical Activity, Sleep, and Risk for Dementia and Cognitive Decline
.
Curr Nutr Rep
.
2018
Dec
;
7
(
4
):
335
45
.
[PubMed]
2161-3311
8.
Bennett
S
,
Grant
MM
,
Aldred
S
.
Oxidative stress in vascular dementia and Alzheimer’s disease: a common pathology
.
J Alzheimers Dis
.
2009
;
17
(
2
):
245
57
.
[PubMed]
1387-2877
9.
Biessels
GJ
,
Reagan
LP
.
Hippocampal insulin resistance and cognitive dysfunction
.
Nat Rev Neurosci
.
2015
Nov
;
16
(
11
):
660
71
.
[PubMed]
1471-003X
10.
Yaffe
K
,
Kanaya
A
,
Lindquist
K
,
Simonsick
EM
,
Harris
T
,
Shorr
RI
, et al.
The metabolic syndrome, inflammation, and risk of cognitive decline
.
JAMA
.
2004
Nov
;
292
(
18
):
2237
42
.
[PubMed]
0098-7484
11.
Lackner
N
,
Mangge
H
,
Reininghaus
EZ
,
McIntyre
RS
,
Bengesser
SA
,
Birner
A
, et al.
Body fat distribution and associations with metabolic and clinical characteristics in bipolar individuals
.
Eur Arch Psychiatry Clin Neurosci
.
2015
Jun
;
265
(
4
):
313
9
.
[PubMed]
0940-1334
12.
Vancampfort
D
,
Vansteelandt
K
,
Correll
CU
,
Mitchell
AJ
,
De Herdt
A
,
Sienaert
P
, et al.
Metabolic syndrome and metabolic abnormalities in bipolar disorder: a meta-analysis of prevalence rates and moderators
.
Am J Psychiatry
.
2013
Mar
;
170
(
3
):
265
74
.
[PubMed]
0002-953X
13.
Zhao
Z
,
Okusaga
OO
,
Quevedo
J
,
Soares
JC
,
Teixeira
AL
.
The potential association between obesity and bipolar disorder: A meta-analysis
.
J Affect Disord
.
2016
Sep
;
202
:
120
3
.
[PubMed]
0165-0327
14.
Calkin
C
,
van de Velde
C
,
Růzicková
M
,
Slaney
C
,
Garnham
J
,
Hajek
T
, et al.
Can body mass index help predict outcome in patients with bipolar disorder?
Bipolar Disord
.
2009
Sep
;
11
(
6
):
650
6
.
[PubMed]
1398-5647
15.
Fagiolini
A
,
Kupfer
DJ
,
Houck
PR
,
Novick
DM
,
Frank
E
.
Obesity as a correlate of outcome in patients with bipolar I disorder
.
Am J Psychiatry
.
2003
Jan
;
160
(
1
):
112
7
.
[PubMed]
0002-953X
16.
Harvey
PD
,
Strassnig
M
.
Predicting the severity of everyday functional disability in people with schizophrenia: cognitive deficits, functional capacity, symptoms, and health status
.
World Psychiatry
.
2012
Jun
;
11
(
2
):
73
9
.
[PubMed]
1723-8617
17.
Depp
CA
,
Strassnig
M
,
Mausbach
BT
,
Bowie
CR
,
Wolyniec
P
,
Thornquist
MH
, et al.
Association of obesity and treated hypertension and diabetes with cognitive ability in bipolar disorder and schizophrenia
.
Bipolar Disord
.
2014
Jun
;
16
(
4
):
422
31
.
[PubMed]
1398-5647
18.
Lackner
N
,
Bengesser
SA
,
Birner
A
,
Painold
A
,
Fellendorf
FT
,
Platzer
M
, et al.
Abdominal obesity is associated with impaired cognitive function in euthymic bipolar individuals
.
World J Biol Psychiatry
.
2016
Oct
;
17
(
7
):
535
46
.
[PubMed]
1814-1412
19.
Yim
CY
,
Soczynska
JK
,
Kennedy
SH
,
Woldeyohannes
HO
,
Brietzke
E
,
McIntyre
RS
.
The effect of overweight/obesity on cognitive function in euthymic individuals with bipolar disorder
.
Eur Psychiatry
.
2012
Apr
;
27
(
3
):
223
8
.
[PubMed]
0924-9338
20.
Depp
CA
,
Mausbach
BT
,
Harmell
AL
,
Savla
GN
,
Bowie
CR
,
Harvey
PD
, et al.
Meta-analysis of the association between cognitive abilities and everyday functioning in bipolar disorder
.
Bipolar Disord
.
2012
May
;
14
(
3
):
217
26
.
[PubMed]
1398-5647
21.
Arts
B
,
Jabben
N
,
Krabbendam
L
,
van Os
J
.
Meta-analyses of cognitive functioning in euthymic bipolar patients and their first-degree relatives
.
Psychol Med
.
2008
Jun
;
38
(
6
):
771
85
.
[PubMed]
0033-2917
22.
Bourne
C
,
Aydemir
Ö
,
Balanzá-Martínez
V
,
Bora
E
,
Brissos
S
,
Cavanagh
JT
, et al.
Neuropsychological testing of cognitive impairment in euthymic bipolar disorder: an individual patient data meta-analysis
.
Acta Psychiatr Scand
.
2013
Sep
;
128
(
3
):
149
62
.
[PubMed]
0001-690X
23.
Goldstein
BI
,
Kemp
DE
,
Soczynska
JK
,
McIntyre
RS
.
Inflammation and the phenomenology, pathophysiology, comorbidity, and treatment of bipolar disorder: a systematic review of the literature
.
J Clin Psychiatry
.
2009
Aug
;
70
(
8
):
1078
90
.
[PubMed]
0160-6689
24.
Bond
DJ
,
Torres
IJ
,
Lee
SS
,
Kozicky
JM
,
Silveira
LE
,
Dhanoa
T
, et al.
Lower cognitive functioning as a predictor of weight gain in bipolar disorder: a 12-month study
.
Acta Psychiatr Scand
.
2017
Mar
;
135
(
3
):
239
49
.
[PubMed]
0001-690X
25.
Strassnig
M
,
Kotov
R
,
Cornaccio
D
,
Fochtmann
L
,
Harvey
PD
,
Bromet
EJ
.
Twenty-year progression of body mass index in a county-wide cohort of people with schizophrenia and bipolar disorder identified at their first episode of psychosis
.
Bipolar Disord
.
2017
Aug
;
19
(
5
):
336
43
.
[PubMed]
1398-5647
26.
Mora
E
,
Portella
MJ
,
Martinez-Alonso
M
,
Teres
M
,
Forcada
I
,
Vieta
E
, et al.
The Impact of Obesity on Cognitive Functioning in Euthymic Bipolar Patients: A Cross-Sectional and Longitudinal Study
.
J Clin Psychiatry
.
2017
Sep/Oct
;
78
(
8
):
e924
32
.
[PubMed]
0160-6689
27.
Wittchen
HU
,
Zaudig
M
,
Fydrich
T
.
Structured Clinical Interview for DSM-IV Axis I and II—SCID
.
Göttingen
:
Hogrefe
;
1997
.
28.
Hamilton
M
.
Hamilton depression scale. ECDEU Assessment Manual For Psychopharmacology
. Revised Edition.
Rockville (MD)
:
National Institute of Mental Health
;
1976
. pp.
179
92
.
29.
Young
RC
,
Biggs
JT
,
Ziegler
VE
,
Meyer
DA
.
A rating scale for mania: reliability, validity and sensitivity
.
Br J Psychiatry
.
1978
Nov
;
133
(
5
):
429
35
.
[PubMed]
0007-1250
30.
Lehrl
S.
Manual zum MWT-B: Mehrfachwahl-Wortschatz-Intelligenztest. Balingen: Spitta-Verlag;
2005
.
31.
Niemann
H
,
Sturm
W
,
Thöner-Otto
A
,
Willmers
K
. CVLT: California verbal learning Test. Frankfurt: Pearson;
2008
. Helmstaedter C, Lendt M, Lux S. Verbaler Lern- und Merkfähigkeitstest (VLMT). Deutsche Version des Rey Auditory Verbal Learning Test AVLT. Göttingen: Hogrefe; 2001.
32.
Helmstaedter C, Lendt M, Lux S. Verbaler Lern- und Merkfähigkeitstest (VLMT). Deutsche Version des Rey Auditory Verbal Learning Test AVLT. Göttingen: Hogrefe; 2001.
33.
Reitan
RM
.
Trail Making Test: Manual for administration and scoring
.
Tucson
:
Reitan Neuropsychology Laboratory
;
1992
.
34.
Petermann
F
. WAIS-IV: Deutschsprachige Adaptation nach David Wechsler: Manual 1, Grundlagen, Testauswertung und Interpretation. 2nd ed. Frankfurt: Pearson;
2014
. Brickenkamp R, Schmidt-Atzert L, Liepmann D. Test d2 – Revision: Aufmerksamkeits- und Konzentrationstest. Göttingen: Hogrefe; 2010.
35.
Brickenkamp R, Schmidt-Atzert L, Liepmann D. Test d2 – Revision: Aufmerksamkeits- und Konzentrationstest. Göttingen: Hogrefe; 2010.
36.
Mur
M
,
Portella
MJ
,
Martínez-Arán
A
,
Pifarré
J
,
Vieta
E
.
Persistent neuropsychological deficit in euthymic bipolar patients: executive function as a core deficit
.
J Clin Psychiatry
.
2007
Jul
;
68
(
7
):
1078
86
.
[PubMed]
0160-6689
37.
Alvarez
JA
,
Emory
E
.
Executive function and the frontal lobes: a meta-analytic review
.
Neuropsychol Rev
.
2006
Mar
;
16
(
1
):
17
42
.
[PubMed]
1040-7308
38.
Fagundo
AB
,
de la Torre
R
,
Jiménez-Murcia
S
,
Agüera
Z
,
Granero
R
,
Tárrega
S
, et al.
Executive functions profile in extreme eating/weight conditions: from anorexia nervosa to obesity
.
PLoS One
.
2012
;
7
(
8
):
e43382
.
[PubMed]
1932-6203
39.
McCabe
DP
,
Roediger
HL
 3rd
,
McDaniel
MA
,
Balota
DA
,
Hambrick
DZ
.
The relationship between working memory capacity and executive functioning: evidence for a common executive attention construct
.
Neuropsychology
.
2010
Mar
;
24
(
2
):
222
43
.
[PubMed]
0894-4105
40.
Hofmann
W
,
Gschwendner
T
,
Friese
M
,
Wiers
RW
,
Schmitt
M
.
Working memory capacity and self-regulatory behavior: toward an individual differences perspective on behavior determination by automatic versus controlled processes
.
J Pers Soc Psychol
.
2008
Oct
;
95
(
4
):
962
77
.
[PubMed]
0022-3514
41.
Strassnig
M
,
Cornacchio
D
,
Harvey
PD
,
Kotov
R
,
Fochtmann
L
,
Bromet
EJ
.
Health status and mobility limitations are associated with residential and employment status in schizophrenia and bipolar disorder
.
J Psychiatr Res
.
2017
Nov
;
94
:
180
5
.
[PubMed]
0022-3956
42.
Tanji
J
,
Hoshi
E
.
Role of the lateral prefrontal cortex in executive behavioral control
.
Physiol Rev
.
2008
Jan
;
88
(
1
):
37
57
.
[PubMed]
0031-9333
43.
Gunstad
J
,
Lhotsky
A
,
Wendell
CR
,
Ferrucci
L
,
Zonderman
AB
.
Longitudinal examination of obesity and cognitive function: results from the Baltimore longitudinal study of aging
.
Neuroepidemiology
.
2010
;
34
(
4
):
222
9
.
[PubMed]
0251-5350
44.
Gunstad
J
,
Paul
RH
,
Cohen
RA
,
Tate
DF
,
Spitznagel
MB
,
Gordon
E
.
Elevated body mass index is associated with executive dysfunction in otherwise healthy adults
.
Compr Psychiatry
.
2007
Jan-Feb
;
48
(
1
):
57
61
.
[PubMed]
0010-440X
45.
Farr
OM
,
Tsoukas
MA
,
Mantzoros
CS
.
Leptin and the brain: influences on brain development, cognitive functioning and psychiatric disorders
.
Metabolism
.
2015
Jan
;
64
(
1
):
114
30
.
[PubMed]
0026-0495
46.
Gonzales
MM
,
Kaur
S
,
Eagan
DE
,
Goudarzi
K
,
Pasha
E
,
Doan
DC
, et al.
Central adiposity and the functional magnetic resonance imaging response to cognitive challenge
.
Int J Obes
.
2014
Sep
;
38
(
9
):
1193
9
.
[PubMed]
0307-0565
47.
Kesse-Guyot
E
,
Andreeva
VA
,
Touvier
M
,
Jeandel
C
,
Ferry
M
,
Hercberg
S
, et al.;
SU.VI.MAX 2 Research Group
.
Overall and abdominal adiposity in midlife and subsequent cognitive function
.
J Nutr Health Aging
.
2015
Feb
;
19
(
2
):
183
9
.
[PubMed]
1279-7707
48.
Bond
DJ
,
Andreazza
AC
,
Hughes
J
,
Dhanoa
T
,
Torres
IJ
,
Kozicky
JM
, et al.
Association of peripheral inflammation with body mass index and depressive relapse in bipolar disorder
.
Psychoneuroendocrinology
.
2016
Mar
;
65
:
76
83
.
[PubMed]
0306-4530
49.
Goldsmith
DR
,
Rapaport
MH
,
Miller
BJ
.
A meta-analysis of blood cytokine network alterations in psychiatric patients: comparisons between schizophrenia, bipolar disorder and depression
.
Mol Psychiatry
.
2016
Dec
;
21
(
12
):
1696
709
.
[PubMed]
1359-4184
50.
Modabbernia
A
,
Taslimi
S
,
Brietzke
E
,
Ashrafi
M
.
Cytokine alterations in bipolar disorder: a meta-analysis of 30 studies
.
Biol Psychiatry
.
2013
Jul
;
74
(
1
):
15
25
.
[PubMed]
0006-3223
51.
Misiak
B
,
Stańczykiewicz
B
,
Kotowicz
K
,
Rybakowski
JK
,
Samochowiec
J
,
Frydecka
D
.
Cytokines and C-reactive protein alterations with respect to cognitive impairment in schizophrenia and bipolar disorder: A systematic review
.
Schizophr Res
.
2018
Feb
;
192
:
16
29
.
[PubMed]
0920-9964
52.
Rosenblat
JD
,
Brietzke
E
,
Mansur
RB
,
Maruschak
NA
,
Lee
Y
,
McIntyre
RS
.
Inflammation as a neurobiological substrate of cognitive impairment in bipolar disorder: Evidence, pathophysiology and treatment implications
.
J Affect Disord
.
2015
Dec
;
188
:
149
59
.
[PubMed]
0165-0327
53.
Spyridaki
EC
,
Avgoustinaki
PD
,
Margioris
AN
.
Obesity, inflammation and cognition
.
Curr Opin Behav Sci
.
2016
;
9
:
169
75
. 2352-1546
54.
Gunathilake
R
,
Oldmeadow
C
,
McEvoy
M
,
Inder
KJ
,
Schofield
PW
,
Nair
BR
, et al.
The Association Between Obesity and Cognitive Function in Older Persons: How Much Is Mediated by Inflammation, Fasting Plasma Glucose, and Hypertriglyceridemia?
J Gerontol A Biol Sci Med Sci
.
2016
Dec
;
71
(
12
):
1603
8
.
[PubMed]
1079-5006
55.
Mansur
RB
,
Rizzo
LB
,
Santos
CM
,
Asevedo
E
,
Cunha
GR
,
Noto
MN
, et al.
Adipokines, metabolic dysfunction and illness course in bipolar disorder
.
J Psychiatr Res
.
2016
Mar
;
74
:
63
9
.
[PubMed]
0022-3956
56.
Platzer
M
,
Fellendorf
FT
,
Bengesser
SA
,
Birner
A
,
Dalkner
N
,
Hamm
C
, et al.
Adiponectin is decreased in bipolar depression
.
World J Biol Psychiatry
.
2018
Sep
;
•••
:
1
8
.
[PubMed]
1562-2975
57.
Mazza
E
,
Poletti
S
,
Bollettini
I
,
Locatelli
C
,
Falini
A
,
Colombo
C
, et al.
Body mass index associates with white matter microstructure in bipolar depression
.
Bipolar Disord
.
2017
Mar
;
19
(
2
):
116
27
.
[PubMed]
1398-5647
58.
Barber
R
,
Scheltens
P
,
Gholkar
A
,
Ballard
C
,
McKeith
I
,
Ince
P
, et al.
White matter lesions on magnetic resonance imaging in dementia with Lewy bodies, Alzheimer’s disease, vascular dementia, and normal aging
.
J Neurol Neurosurg Psychiatry
.
1999
Jul
;
67
(
1
):
66
72
.
[PubMed]
0022-3050
59.
Stanek
KM
,
Grieve
SM
,
Brickman
AM
,
Korgaonkar
MS
,
Paul
RH
,
Cohen
RA
, et al.
Obesity is associated with reduced white matter integrity in otherwise healthy adults
.
Obesity (Silver Spring)
.
2011
Mar
;
19
(
3
):
500
4
.
[PubMed]
1930-7381
60.
Diniz
BS
,
Teixeira
AL
,
Cao
F
,
Gildengers
A
,
Soares
JC
,
Butters
MA
, et al.
History of bipolar disorder and the risk of dementia: a systematic review and meta-analysis
.
Am J Geriatr Psychiatry
.
2017
Apr
;
25
(
4
):
357
62
.
[PubMed]
1064-7481
61.
Birner
A
,
Seiler
S
,
Lackner
N
,
Bengesser
SA
,
Queissner
R
,
Fellendorf
FT
, et al.
Cerebral white matter lesions and affective episodes correlate in male individuals with bipolar disorder
.
PLoS One
.
2015
Aug
;
10
(
8
):
e0135313
.
[PubMed]
1932-6203
62.
Xu
WL
,
Atti
AR
,
Gatz
M
,
Pedersen
NL
,
Johansson
B
,
Fratiglioni
L
.
Midlife overweight and obesity increase late-life dementia risk: a population-based twin study
.
Neurology
.
2011
May
;
76
(
18
):
1568
74
.
[PubMed]
0028-3878
63.
Himmerich
H
,
Minkwitz
J
,
Kirkby
K
.
Weight gain and metabolic changes during treatment with antipsychotics and antidepressants.
Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets-Immune, Endocrine & Metabolic Disorders).
2015
;15(4):252-260.
64.
McKnight
RF
,
Adida
M
,
Budge
K
,
Stockton
S
,
Goodwin
GM
,
Geddes
JR
.
Lithium toxicity profile: a systematic review and meta-analysis
.
Lancet
.
2012
Feb
;
379
(
9817
):
721
8
.
[PubMed]
0140-6736
65.
Forlenza
OV
,
De-Paula
VJ
,
Diniz
BS
.
Neuroprotective effects of lithium: implications for the treatment of Alzheimer’s disease and related neurodegenerative disorders
.
ACS Chem Neurosci
.
2014
Jun
;
5
(
6
):
443
50
.
[PubMed]
1948-7193
66.
Heishman
SJ
,
Kleykamp
BA
,
Singleton
EG
.
Meta-analysis of the acute effects of nicotine and smoking on human performance
.
Psychopharmacology (Berl)
.
2010
Jul
;
210
(
4
):
453
69
.
[PubMed]
0033-3158
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