Introduction: Patients with chronic kidney disease (CKD) exhibit a higher probability of having cognitive impairment or dementia than those without CKD. The beneficial effects of physical exercise on cognitive function are known in the general older population, but more research is required in older adults with CKD. Methods: Eighty-one outpatients (aged ≥65 years) with CKD stage G3–G4 were assessed for eligibility. Among them, 60 were randomized (single-center, unblinded, and stratified) and 53 received the allocated intervention (exercise n = 27, control n = 26). Patients in the exercise group undertook group-exercise training at our facility once weekly and independent exercises at home twice weekly or more, for 24 weeks. Patients in the control group received general care. General and specific cognitive functions (memory, attention, executive, and verbal) were measured, and differences in their scores at baseline and at the 24-week follow-up visit were assessed between the 2 groups. Results: Forty-four patients completed the follow-up at 24 weeks (exercise n = 23, control n = 21). Patients in the exercise group showed significantly greater changes in Wechsler Memory Scale-Revised Logical Memory delayed recall (exercise effect: 2.82, 95% CI: 0.46–5.19, p = 0.03), and immediate and delayed recall (exercise effect: 5.97, 95% CI: 1.13–10.81, p = 0.02) scores than those in the control group. Conclusions: The 24-week exercise intervention significantly improved the memory function in older adults with pre-dialysis CKD. This randomized controlled trial suggests that physical exercise is a useful nonpharmacological strategy for preventing cognitive decline in these patients.

1.
Yaffe
K
,
Ackerson
L
,
Kurella Tamura
M
,
Le Blanc
P
,
Kusek
JW
,
Sehgal
AR
,
Chronic kidney disease and cognitive function in older adults: findings from the chronic renal insufficiency cohort cognitive study
.
J Am Geriatr Soc
.
2010 Feb
;
58
(
2
):
338
45
. .
2.
Kurella
TM
,
Wadley
V
,
Yaffe
K
,
McClure
LA
,
Howard
G
,
Go
R
,
Kidney function and cognitive impairment in US adults: the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study
.
Am J Kidney Dis
.
2008 Aug
;
52
(
2
):
227
34
.
3.
Murray
AM
,
Bell
EJ
,
Tupper
DE
,
Davey
CS
,
Pederson
SL
,
Amiot
EM
,
The Brain in Kidney Disease (BRINK) cohort study: design and baseline cognitive function
.
Am J Kidney Dis
.
2016 Apr
;
67
(
4
):
593
600
. .
4.
Yeh
YC
,
Huang
MF
,
Hwang
SJ
,
Tsai
JC
,
Liu
TL
,
Hsiao
SM
,
Association of homocysteine level and vascular burden and cognitive function in middle-aged and older adults with chronic kidney disease
.
Int J Geriatr Psychiatry
.
2016 Jul
;
31
(
7
):
723
30
. .
5.
Seliger
SL
,
Siscovick
DS
,
Stehman-Breen
CO
,
Gillen
DL
,
Fitzpatrick
A
,
Bleyer
A
,
Moderate renal impairment and risk of dementia among older adults: the Cardiovascular Health Cognition Study
.
J Am Soc Nephrol
.
2004 Jul
;
15
(
7
):
1904
11
. .
6.
Wang
F
,
Zhang
L
,
Liu
L
,
Wang
H
.
Level of kidney function correlates with cognitive decline
.
Am J Nephrol
.
2010
;
32
(
2
):
117
21
. .
7.
Helmer
C
,
Stengel
B
,
Metzger
M
,
Froissart
M
,
Massy
ZA
,
Tzourio
C
,
Chronic kidney disease, cognitive decline, and incident dementia: the 3C Study
.
Neurology
.
2011 Dec
;
77
(
23
):
2043
51
. .
8.
Darsie
B
,
Shlipak
MG
,
Sarnak
MJ
,
Katz
R
,
Fitzpatrick
AL
,
Odden
MC
.
Kidney function and cognitive health in older adults: the Cardiovascular Health Study
.
Am J Epidemiol
.
2014 July
;
180
(
1
):
68
75
. .
9.
Berger
I
,
Wu
S
,
Masson
P
,
Kelly
PJ
,
Duthie
FA
,
Whiteley
W
,
Cognition in chronic kidney disease: a systematic review and meta-analysis
.
BMC Med
.
2016 Dec
;
14
(
1
):
206
. .
10.
Raphael
KL
,
Wei
G
,
Greene
T
,
Baird
BC
,
Beddhu
S
.
Cognitive function and the risk of death in chronic kidney disease
.
Am J Nephrol
.
2012 Jan
;
35
(
1
):
49
57
. .
11.
Bai
K
,
Pan
Y
,
Lu
F
,
Zhao
Y
,
Wang
F
,
Zhang
L
.
Cognitive function and 3-year mortality in the very elderly Chinese population with chronic kidney disease
.
Clin Interv Aging
.
2018 Oct
;
13
:
2055
60
. .
12.
Harhay
MN
,
Xie
D
,
Zhang
X
,
Hsu
CY
,
Vittinghoff
E
,
Go
AS
,
Cognitive impairment in non–dialysis-dependent CKD and the transition to dialysis: findings from the Chronic Renal Insufficiency Cohort (CRIC) study
.
Am J Kidney Dis
.
2018 Oct
;
72
(
4
):
499
508
.
13.
Bull
FC
,
Al-Ansari
SS
,
Biddle
S
,
Borodulin
K
,
Buman
MP
,
Cardon
G
,
World Health Organization 2020 guidelines on physical activity and sedentary behaviour
.
Br J Sports Med
.
2020 Dec
;
54
(
24
):
1451
62
. .
14.
Norton
S
,
Matthews
FE
,
Barnes
DE
,
Yaffe
K
,
Brayne
C
.
Potential for primary prevention of Alzheimer’s disease: an analysis of population-based data
.
Lancet Neurol
.
2014 Aug
;
13
(
8
):
788
94
.
15.
Santos-Lozano
A
,
Pareja-Galeano
H
,
Sanchis-Gomar
F
,
Quindós-Rubial
M
,
Fiuza-Luces
C
,
Cristi-Montero
C
,
Physical activity and Alzheimer disease: a protective association
.
Mayo Clin Proc
.
2016 Aug
;
91
(
8
):
999
1020
. .
16.
Gow
AJ
,
Bastin
ME
,
Muñoz Maniega
S
,
Valdés Hernández
MC
,
Morris
Z
,
Murray
C
,
Neuroprotective lifestyles and the aging brain: activity, atrophy, and white matter integrity
.
Neurology
.
2012 Oct
;
79
(
17
):
1802
8
. .
17.
Kelly
ME
,
Loughrey
D
,
Lawlor
BA
,
Robertson
IH
,
Walsh
C
,
Brennan
S
.
The impact of exercise on the cognitive functioning of healthy older adults: a systematic review and meta-analysis
.
Ageing Res Rev
.
2014 Jul
;
16
:
12
31
. .
18.
Erickson
KI
,
Voss
MW
,
Prakash
RS
,
Basak
C
,
Szabo
A
,
Chaddock
L
,
Exercise training increases size of hippocampus and improves memory
.
Proc Natl Acad Sci U S A
.
2011 Feb
;
108
(
7
):
3017
22
. .
19.
Viggiano
D
,
Wagner
CA
,
Martino
G
,
Nedergaard
M
,
Zoccali
C
,
Unwin
R
,
Mechanisms of cognitive dysfunction in CKD
.
Nat Rev Nephrol
.
2020 Aug
;
16
(
8
):
452
69
. .
20.
Etgen
T
,
Bickel
H
,
Förstl
H
.
Metabolic and endocrine factors in mild cognitive impairment
.
Ageing Res Rev
.
2010 Jul
;
9
(
3
):
280
8
. .
21.
Etgen
T
.
Kidney disease as a determinant of cognitive decline and dementia
.
Alzheimers Res Ther
.
2015 Mar
;
7
(
1
):
29
. .
22.
Matsuo
S
,
Imai
E
,
Horio
M
,
Yasuda
Y
,
Tomita
K
,
Nitta
K
,
Revised equations for estimated GFR from serum creatinine in Japan
.
Am J Kidney Dis
.
2009 Jun
;
53
(
6
):
982
92
. .
23.
American College of Sports Medicine
.
ACSM’s guidelines for exercise testing and prescription
. 10th ed.
Philadelphia
:
Lippincott Williams & Wilkins
;
2017
.
24.
Japanese Society of Renal Rehabilitation
.
Guideline for renal rehabilitation 2018
.
Tokyo
:
Nankodo
;
2018
. [in Japanese].
25.
Borg
GA
.
Psychophysical bases of perceived exertion
.
Med Sci Sports Exerc
.
1982 Jun
;
14
(
5
):
377
81
. .
26.
Folstein
MF
,
Folstein
SE
,
McHugh
PR
.
“Mini-mental state.” A practical method for grading the cognitive state of patients for the clinician
.
J Psychiatr Res
.
1975 Nov
;
12
(
3
):
189
98
.
27.
Wechsler
D
.
WMS-R: Wechsler memory scale – revised
.
San Antonio
:
Psychological Corp
;
1987
.
28.
Koike
A
,
Sugishita
M
.
[The Japanese version of the Wechsler memory scale–revised]
.
Nihon Rinsho
.
2011 Oct
;
69 Suppl 8
:
408
12
. [in Japanese].
29.
Reitan
RM
,
Wolfson
D
.
The Halstead-Reitan neuropsychological test battery: theory and clinical interpretation
. 2nd ed.
Tucson
:
Neuropsychology Press
;
1993
.
30.
Crossley
M
,
D’Arcy
C
,
Rawson
NS
.
Letter and category fluency in community-dwelling Canadian seniors: a comparison of normal participants to those with dementia of the Alzheimer or vascular type
.
J Clin Exp Neuropsychol
.
1997 Feb
;
19
(
1
):
52
62
. .
31.
Yesavage
JA
,
Sheikh
JI
.
Geriatric Depression Scale (GDS). Recent evidence and development of a shorter version
.
Clin Geron
.
2008 Oct 25
;
5
:
165
73
.
32.
Bonetti
PO
,
Pumper
GM
,
Higano
ST
,
Holmes
DR
 Jr
,
Kuvin
JT
,
Lerman
A
.
Noninvasive identification of patients with early coronary atherosclerosis by assessment of digital reactive hyperemia
.
J Am Coll Cardiol
.
2004 Dec
;
44
(
11
):
2137
41
. .
33.
Matsuzawa
Y
,
Suleiman
M
,
Guddeti
RR
,
Kwon
TG
,
Monahan
KH
,
Lerman
LO
,
Age-dependent predictive value of endothelial dysfunction for arrhythmia recurrence following pulmonary vein isolation
.
J Am Heart Assoc
.
2016 Sep
;
5
(
9
):
e003183
. .
34.
Ohno
S
,
Kohjitani
A
,
Miyata
M
,
Tohya
A
,
Yamashita
K
,
Hashiguchi
T
,
Recovery of endothelial function after minor-to-moderate surgery is impaired by diabetes mellitus, obesity, hyperuricemia and sevoflurane-based anesthesia
.
Int Heart J
.
2018 May
;
59
(
3
):
559
65
. .
35.
Horio
M
,
Imai
E
,
Yasuda
Y
,
Watanabe
T
,
Matsuo
S
;
Collaborators Developing the Japanese Equation for Estimated GFR
.
GFR estimation using standardized serum cystatin C in Japan
.
Am J Kidney Dis
.
2013 Feb
;
61
(
2
):
197
203
. .
36.
Nouchi
R
,
Taki
Y
,
Takeuchi
H
,
Sekiguchi
A
,
Hashizume
H
,
Nozawa
T
,
Four weeks of combination exercise training improved executive functions, episodic memory, and processing speed in healthy elderly people: evidence from a randomised controlled trial
.
Age
.
2014 Apr
;
36
(
2
):
787
99
.
37.
Williams
P
,
Lord
SR
.
Effects of group exercise on cognitive functioning and mood in older women
.
Aust N Z J Public Health
.
1997 Feb
;
21
(
1
):
45
52
. .
38.
ten Brinke
LF
,
Bolandzadeh
N
,
Nagamatsu
LS
,
Hsu
CL
,
Davis
JC
,
Miran-Khan
K
,
Aerobic exercise increases hippocampal volume in older women with probable mild cognitive impairment: a 6-month randomised controlled trial
.
Br J Sports Med
.
2015 Feb
;
49
(
4
):
248
54
. .
39.
Maki
Y
,
Ura
C
,
Yamaguchi
T
,
Murai
T
,
Isahai
M
,
Kaiho
A
,
Effects of intervention using a community-based walking program for prevention of mental decline: a randomised controlled trial
.
J Am Geriatr Soc
.
2012 Mar
;
60
(
3
):
505
10
.
40.
Mortimer
JA
,
Ding
D
,
Borenstein
AR
,
DeCarli
C
,
Guo
Q
,
Wu
Y
,
Changes in brain volume and cognition in a randomized trial of exercise and social interaction in a community-based sample of non-demented Chinese elders
.
J Alzheimers Dis
.
2012
;
30
(
4
):
757
66
. .
41.
Berger
I
,
Wu
S
,
Masson
P
,
Kelly
PJ
,
Duthie
FA
,
Whiteley
W
,
Cognition in chronic kidney disease: a systematic review and meta-analysis
.
BMC Med
.
2016 Dec
;
14
(
1
):
206
. .
42.
Palmer
ND
,
Sink
KM
,
Smith
SC
,
Xu
J
,
Bowden
DW
,
Hugenschmidt
CE
,
Kidney disease and cognitive function: African American-Diabetes Heart Study MIND
.
Am J Nephrol
.
2014 Oct
;
40
(
3
):
200
7
. .
43.
McAdams-DeMarco
MA
,
Konel
J
,
Warsame
F
,
Ying
H
,
González Fernández
M
,
Carlson
MC
,
Intradialytic cognitive and exercise training may preserve cognitive function
.
Kidney Int Rep
.
2018 Jan
;
3
(
1
):
81
8
. .
44.
Rossi
PG
,
Carnavale
BF
,
Farche
ACS
,
Ansai
JH
,
de Andrade
LP
,
Takahashi
ACM
.
Effects of physical exercise on the cognition of older adults with frailty syndrome: a systematic review and meta-analysis of randomized trials
.
Arch Gerontol Geriatr
.
2021 Mar–Apr
;
93
:
104322
. .
45.
Yamada
M
,
Kimura
Y
,
Ishiyama
D
,
Otobe
Y
,
Suzuki
M
,
Koyama
S
,
Effect of the COVID-19 epidemic on physical activity in community-dwelling older adults in Japan: a cross-sectional online survey
.
J Nutr Health Aging
.
2020 Jun
;
24
(
9
):
948
50
. .
46.
Assmann
SF
,
Pocock
SJ
,
Enos
LE
,
Kasten
LE
.
Subgroup analysis and other (mis)uses of baseline data in clinical trials
.
Lancet
.
2000 Mar
;
355
(
9209
):
1064
9
. .
47.
Lautenschlager
NT
,
Cox
KL
,
Flicker
L
,
Foster
JK
,
van Bockxmeer
FM
,
Xiao
J
,
Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease: a randomized trial
.
JAMA
.
2008 Sep
;
300
(
9
):
1027
37
. .
48.
Baker
LD
,
Frank
LL
,
Foster-Schubert
K
,
Green
PS
,
Wilkinson
CW
,
McTiernan
A
,
Effects of aerobic exercise on mild cognitive impairment: a controlled trial
.
Arch Neurol
.
2010 Jan
;
67
(
1
):
71
9
. .
49.
Gomes
TS
,
Aoike
DT
,
Baria
F
,
Graciolli
FG
,
Moyses
RMA
,
Cuppari
L
.
Effect of aerobic exercise on markers of bone metabolism of overweight and obese patients with chronic kidney disease
.
J Ren Nutr
.
2017 Sep
;
27
(
5
):
364
71
. .
50.
Watson
EL
,
Greening
NJ
,
Viana
JL
,
Aulakh
J
,
Bodicoat
DH
,
Barratt
J
,
Progressive resistance exercise training in CKD: a feasibility study
.
Am J Kidney Dis
.
2015 Aug
;
66
(
2
):
249
57
. .
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