Introduction: Motoric cognitive risk (MCR) and amnestic mild cognitive impairment (aMCI) syndromes are each reliable predictors of incident Alzheimer’s disease (AD), but MCR may be a stronger predictor of vascular dementia than AD. This study contrasted cortical and hippocampal atrophy patterns in MCR and aMCI. Methods: Cross-sectional data from 733 older adults without dementia or disability (M age = 73.6; 45% women) in the multicountry MCR consortium were examined. MCR was defined as presence of slow gait and cognitive concerns. Amnestic MCI was defined as poor episodic memory performance and cognitive concerns. Cortical thickness and hippocampal volumes were quantified from structural MRIs. Multivariate and univariate general linear models were used to examine associations between cortical thickness and hippocampal volume in MCR and aMCI, adjusting for age, sex, education, total intracranial volume, white matter lesions, and study site. Results: The prevalence of MCR and aMCI was 7.64% and 12.96%, respectively. MCR was associated with widespread cortical atrophy, including prefrontal, insular, cingulate, motor, parietal, and temporal atrophy. aMCI was associated with hippocampal atrophy. Conclusion: Distinct patterns of atrophy were associated with MCR and aMCI. A distributed pattern of cortical atrophy – that is more consistent with VaD or mixed dementia– was observed in MCR. A more restricted pattern of atrophy – that is more consistent with AD – was observed in aMCI. The biological underpinnings of MCR and aMCI likely differ and may require tailored interventions.

1.
Alzheimer’s disease facts and figures
.
Alzheimers Dement
,
2021
;
17
(
3
):
327
406
.
2.
Chandler
MJ
,
Parks
AC
,
Marsiske
M
,
Rotblatt
LJ
,
Smith
GE
.
Everyday impact of cognitive interventions in mild cognitive impairment: a systematic review and meta-analysis
.
Neuropsychol Rev
.
2016
;
26
(
3
):
225
51
.
3.
Simon
SS
,
Yokomizo
JE
,
Bottino
CM
.
Cognitive intervention in amnestic Mild Cognitive Impairment: a systematic review
.
Neurosci Biobehav Rev
.
2012
;
36
(
4
):
1163
78
.
4.
Huang
X
,
Zhao
X
,
Cai
Y
,
Wan
Q
.
The cerebral changes induced by exercise interventions in people with mild cognitive impairment and Alzheimer's disease: a systematic review
.
Arch Gerontol Geriatr
.
2022
;
98
:
104547
.
5.
Petersen
RC
,
Roberts
RO
,
Knopman
DS
,
Boeve
BF
,
Geda
YE
,
Ivnik
RJ
, et al
.
Mild cognitive impairment: ten years later
.
Arch Neurol
.
2009
;
66
(
12
):
1447
55
.
6.
Petersen
RC
,
Smith
GE
,
Waring
SC
,
Ivnik
RJ
,
Tangalos
EG
,
Kokmen
E
.
Mild cognitive impairment: clinical characterization and outcome
.
Arch Neurol
.
1999
;
56
(
3
):
303
8
.
7.
Petersen
RC
.
Mild cognitive impairment as a diagnostic entity
.
J Intern Med
.
2004
;
256
(
3
):
183
94
.
8.
Petersen
RC
,
Doody
R
,
Kurz
A
,
Mohs
RC
,
Morris
JC
,
Rabins
PV
, et al
.
Current concepts in mild cognitive impairment
.
Arch Neurol
.
2001
;
58
(
12
):
1985
92
.
9.
Busse
A
,
Hensel
A
,
Gühne
U
,
Angermeyer
MC
,
Riedel-Heller
SG
.
Mild cognitive impairment: long-term course of four clinical subtypes
.
Neurology
.
2006
;
67
(
12
):
2176
85
.
10.
Jungwirth
S
,
Zehetmayer
S
,
Hinterberger
M
,
Tragl
KH
,
Fischer
P
.
The validity of amnestic MCI and non-amnestic MCI at age 75 in the prediction of Alzheimer’s dementia and vascular dementia
.
Int Psychogeriatr
.
2012
;
24
(
6
):
959
66
.
11.
Zhang
H
,
Sachdev
PS
,
Wen
W
,
Kochan
NA
,
Crawford
JD
,
Brodaty
H
, et al
.
Gray matter atrophy patterns of mild cognitive impairment subtypes
.
J Neurol Sci
.
2012
;
315
(
1–2
):
26
32
.
12.
Zhang
J
,
Liu
Y
,
Lan
K
,
Huang
X
,
He
Y
,
Yang
F
, et al
.
Gray matter atrophy in amnestic mild cognitive impairment: a voxel-based meta-analysis
.
Front Aging Neurosci
.
2021
;
13
:
627919
.
13.
Verghese
J
,
Annweiler
C
,
Ayers
E
,
Barzilai
N
,
Beauchet
O
,
Bennett
DA
, et al
.
Motoric cognitive risk syndrome: multicountry prevalence and dementia risk
.
Neurology
.
2014
;
83
(
8
):
718
26
.
14.
Verghese
J
,
Ayers
E
,
Barzilai
N
,
Bennett
DA
,
Buchman
AS
,
Holtzer
R
, et al
.
Motoric cognitive risk syndrome: multicenter incidence study
.
Neurology
.
2014
;
83
(
24
):
2278
84
.
15.
Verghese
J
,
Wang
C
,
Bennett
DA
,
Lipton
RB
,
Katz
MJ
,
Ayers
E
.
Motoric cognitive risk syndrome and predictors of transition to dementia: a multicenter study
.
Alzheimers Dement
.
2019
;
15
(
7
):
870
7
.
16.
Verghese
J
,
Wang
C
,
Lipton
RB
,
Holtzer
R
.
Motoric cognitive risk syndrome and the risk of dementia
.
J Gerontol A Biol Sci Med Sci
.
2013
;
68
(
4
):
412
8
.
17.
Gomez
GT
,
Gottesman
RF
,
Gabriel
KP
,
Palta
P
,
Gross
AL
,
Soldan
A
, et al
.
The association of motoric cognitive risk with incident dementia and neuroimaging characteristics: the Atherosclerosis Risk in Communities Study
.
Alzheimers Dement
.
2022
;
18
(
3
):
434
44
.
18.
Verghese
J
,
Wang
C
,
Lipton
RB
,
Holtzer
R
.
Motoric cognitive risk syndrome and the risk of dementia
.
J Gerontol A Biol Sci Med Sci
.
2013
;
68
(
4
):
412
8
.
19.
Blumen
HM
,
Allali
G
,
Beauchet
O
,
Lipton
RB
,
Verghese
J
.
A gray matter volume covariance network associated with the motoric cognitive risk syndrome: a multicohort MRI study
.
J Gerontol A Biol Sci Med Sci
.
2019
;
74
(
6
):
884
9
.
20.
Blumen
HM
,
Schwartz
E
,
Allali
G
,
Beauchet
O
,
Callisaya
M
,
Doi
T
, et al
.
Cortical thickness, volume, and surface area in the motoric cognitive risk syndrome
.
J Alzheimers Dis
.
2021
;
81
(
2
):
651
65
.
21.
Gubbi
S
,
Schwartz
E
,
Crandall
J
,
Verghese
J
,
Holtzer
R
,
Atzmon
G
, et al
.
Effect of exceptional parental longevity and lifestyle factors on prevalence of cardiovascular disease in offspring
.
Am J Cardiol
.
2017
;
120
(
12
):
2170
5
.
22.
Zhang
WB
,
Aleksic
S
,
Gao
T
,
Weiss
EF
,
Demetriou
E
,
Verghese
J
, et al
.
Insulin-like growth factor-1 and IGF binding proteins predict all-cause mortality and morbidity in older adults
.
Cells
.
2020
;
9
(
6
):
1368
.
23.
Beauchet
O
,
Allali
G
,
Annweiler
C
,
Verghese
J
.
Association of motoric cognitive risk syndrome with brain volumes: results from the GAIT study
.
J Gerontol A Biol Sci Med Sci
.
2016
;
71
(
8
):
1081
8
.
24.
Beauchet
O
,
Allali
G
,
Launay
C
,
Herrmann
FR
,
Annweiler
C
.
Gait variability at fast-pace walking speed: a biomarker of mild cognitive impairment
.
J Nutr Health Aging
.
2013
;
17
(
3
):
235
9
.
25.
Holtzer
R
,
Mahoney
J
,
Verghese
J
.
Intraindividual variability in executive functions but not speed of processing or conflict resolution predicts performance differences in gait speed in older adults
.
J Gerontol A Biol Sci Med Sci
.
2014
;
69
(
8
):
980
6
.
26.
Blumen
HM
,
Holtzer
R
,
Brown
LL
,
Gazes
Y
,
Verghese
J
.
Behavioral and neural correlates of imagined walking and walking-while-talking in the elderly
.
Hum Brain Mapp
.
2014
;
35
(
8
):
4090
104
.
27.
Callisaya
ML
,
Beare
R
,
Phan
TG
,
Chen
J
,
Srikanth
VK
.
Global and regional associations of smaller cerebral gray and white matter volumes with gait in older people
.
PLoS One
.
2014
;
9
(
1
):
e84909
.
28.
Srikanth
V
,
Phan
TG
,
Chen
J
,
Beare
R
,
Stapleton
JM
,
Reutens
DC
.
The location of white matter lesions and gait--a voxel-based study
.
Ann Neurol
.
2010
;
67
(
2
):
265
9
.
29.
Yesavage
JA
,
Brink
TL
,
Rose
TL
,
Lum
O
,
Huang
V
,
Adey
M
, et al
.
Development and validation of a geriatric depression screening scale: a preliminary report
.
J Psychiatr Res
.
1982
;
17
(
1
):
37
49
.
30.
Rabin
LA
,
Wang
C
,
Katz
MJ
,
Derby
CA
,
Buschke
H
,
Lipton
RB
.
Predicting Alzheimer's disease: neuropsychological tests, self-reports, and informant reports of cognitive difficulties
.
J Am Geriatr Soc
.
2012
;
60
(
6
):
1128
34
.
31.
Morris
JC
,
Edland
S
,
Clark
C
,
Galasko
D
,
Koss
E
,
Mohs
R
, et al
.
The consortium to establish a registry for Alzheimer’s disease (CERAD). Part IV. Rates of cognitive change in the longitudinal assessment of probable Alzheimer's disease
.
Neurology
.
1993
;
43
(
12
):
2457
65
.
32.
Galvin
JE
,
Roe
CM
,
Powlishta
KK
,
Coats
MA
,
Muich
SJ
,
Grant
E
, et al
.
The AD8: a brief informant interview to detect dementia
.
Neurology
.
2005
;
65
(
4
):
559
64
.
33.
Association
,
AP
,
Diagnostic and statistical manual of mental Disorders
.
1994
.
4
.
34.
Lipton
RB
,
Katz
MJ
,
Kuslansky
G
,
Sliwinski
MJ
,
Stewart
WF
,
Verghese
J
, et al
.
Screening for dementia by telephone using the memory impairment screen
.
J Am Geriatr Soc
.
2003
;
51
(
10
):
1382
90
.
35.
Duff
K
,
Beglinger
LJ
,
Schoenberg
MR
,
Patton
DE
,
Mold
J
,
Scott
JG
, et al
.
Test-retest stability and practice effects of the RBANS in a community dwelling elderly sample
.
J Clin Exp Neuropsychol
.
2005
;
27
(
5
):
565
75
.
36.
Grober
E
,
Merling
A
,
Heimlich
T
,
Lipton
RB
.
Free and cued selective reminding and selective reminding in the elderly
.
J Clin Exp Neuropsychol
.
1997
;
19
(
5
):
643
54
.
37.
Zimmerman
ME
,
Katz
MJ
,
Wang
C
,
Burns
LC
,
Berman
RM
,
Derby
CA
, et al
.
Comparison of “word” vs. “picture” version of the free and cued selective reminding test (FCSRT) in older adults
.
Alzheimers Dement
.
2015
;
1
(
1
):
94
100
.
38.
Elwood
RW
.
The Wechsler Memory Scale-Revised: psychometric characteristics and clinical application
.
Neuropsychol Rev
.
1991
;
2
(
2
):
179
201
.
39.
Rey
A
. Archives de psychologie; 1941.L’examen psychologique dans les cas d'encéphalopathie traumatique.(Les problems.).
40.
Osterrieth
P
.
Le test de copie d’une figure complexe; contribution a l'etude de la perception et de la memoire
.
Archives de psychologie
;
1944
.
41.
Brandt
J
.
The Hopkins Verbal Learning Test: development of a new memory test with six equivalent forms
.
Clin Neuropsychol
.
1991
;
5
(
2
):
125
42
.
42.
Brandt
J
,
Benedict
RH
.
Hopkins verbal learning test--revised: professional manual
.
Psychological Assessment Resources
;
2001
.
43.
Benedict
R
,
Schretlen
D
,
Groninger
L
,
Brandt
J
.
Hopkins verbal learning test–revised: normative data and analysis of inter-form and test-retest reliability
.
Clin Neuropsychologist
.
1998
;
12
(
1
):
43
55
.
44.
Desikan
RS
,
Ségonne
F
,
Fischl
B
,
Quinn
BT
,
Dickerson
BC
,
Blacker
D
, et al
.
An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest
.
Neuroimage
.
2006
;
31
(
3
):
968
80
.
45.
Fischl
B
,
van der Kouwe
A
,
Destrieux
C
,
Halgren
E
,
Ségonne
F
,
Salat
DH
, et al
.
Automatically parcellating the human cerebral cortex
.
Cereb Cortex
.
2004
;
14
(
1
):
11
22
.
46.
Iglesias
JE
,
Augustinack
JC
,
Nguyen
K
,
Player
CM
,
Player
A
,
Wright
M
, et al
.
A computational atlas of the hippocampal formation using ex vivo, ultra-high resolution MRI: application to adaptive segmentation of in vivo MRI
.
Neuroimage
.
2015
;
115
:
117
37
.
47.
Jovicich
J
,
Czanner
S
,
Han
X
,
Salat
D
,
van der Kouwe
A
,
Quinn
B
, et al
.
MRI-derived measurements of human subcortical, ventricular and intracranial brain volumes: reliability effects of scan sessions, acquisition sequences, data analyses, scanner upgrade, scanner vendors and field strengths
.
Neuroimage
.
2009
;
46
(
1
):
177
92
.
48.
Jovicich
J
,
Czanner
S
,
Greve
D
,
Haley
E
,
van der Kouwe
A
,
Gollub
R
, et al
.
Reliability in multi-site structural MRI studies: effects of gradient non-linearity correction on phantom and human data
.
Neuroimage
.
2006
;
30
(
2
):
436
43
.
49.
Jovicich
J
,
Marizzoni
M
,
Sala-Llonch
R
,
Bosch
B
,
Bartrés-Faz
D
,
Arnold
J
, et al
.
Brain morphometry reproducibility in multi-center 3T MRI studies: a comparison of cross-sectional and longitudinal segmentations
.
Neuroimage
.
2013
;
83
:
472
84
.
50.
Storsve
AB
,
Fjell
AM
,
Tamnes
CK
,
Westlye
LT
,
Overbye
K
,
Aasland
HW
, et al
.
Differential longitudinal changes in cortical thickness, surface area and volume across the adult life span: regions of accelerating and decelerating change
.
J Neurosci
.
2014
;
34
(
25
):
8488
98
.
51.
Lemaitre
H
,
Goldman
AL
,
Sambataro
F
,
Verchinski
BA
,
Meyer-Lindenberg
A
,
Weinberger
DR
, et al
.
Normal age-related brain morphometric changes: nonuniformity across cortical thickness, surface area and gray matter volume
.
Neurobiol Aging
.
2012
;
33
(
3
):
617. e1
9
.
52.
Hutton
C
,
Draganski
B
,
Ashburner
J
,
Weiskopf
N
.
A comparison between voxel-based cortical thickness and voxel-based morphometry in normal aging
.
Neuroimage
.
2009
;
48
(
2
):
371
80
.
53.
Dickerson
BC
,
Feczko
E
,
Augustinack
JC
,
Pacheco
J
,
Morris
JC
,
Fischl
B
, et al
.
Differential effects of aging and Alzheimer’s disease on medial temporal lobe cortical thickness and surface area
.
Neurobiol Aging
.
2009
;
30
(
3
):
432
40
.
54.
Schwarz
CG
,
Gunter
JL
,
Wiste
HJ
,
Przybelski
SA
,
Weigand
SD
,
Ward
CP
, et al
.
A large-scale comparison of cortical thickness and volume methods for measuring Alzheimer's disease severity
.
Neuroimage Clin
.
2016
;
11
:
802
12
.
55.
Efron
B
,
Tibshirani
R
.
Bootstrap methods for standard errors, confidence intervals, and other measures of statistical accuracy
.
Stat Sci
.
1986
;
1
:
54
75
.
56.
Bortone
I
,
Zupo
R
,
Castellana
F
,
Aresta
S
,
Lampignano
L
,
Sciarra
S
, et al
.
Motoric cognitive risk syndrome, subtypes and 8-year all-cause mortality in aging phenotypes: the salus in apulia study
.
Brain Sci
.
2022
;
12
(
7
):
861
.
57.
Shim
H
,
Kim
M
,
Won
CW
.
Motoric cognitive risk syndrome is associated with processing speed and executive function, but not delayed free recall memory: the Korean frailty and aging cohort study (KFACS)
.
Arch Gerontol Geriatr
.
2020
;
87
:
103990
.
58.
Varma
AR
,
Adams
W
,
Lloyd
JJ
,
Carson
KJ
,
Snowden
JS
,
Testa
HJ
, et al
.
Diagnostic patterns of regional atrophy on MRI and regional cerebral blood flow change on SPECT in young onset patients with Alzheimer’s disease, frontotemporal dementia and vascular dementia
.
Acta Neurol Scand
.
2002
;
105
(
4
):
261
9
.
59.
Jung
WB
,
Mun
CW
,
Kim
YH
,
Park
JM
,
Lee
BD
,
Lee
YM
, et al
.
Cortical atrophy, reduced integrity of white matter and cognitive impairment in subcortical vascular dementia of Binswanger type
.
Psychiatry Clin Neurosci
.
2014
;
68
(
12
):
821
32
.
60.
Du
AT
,
Schuff
N
,
Chao
LL
,
Kornak
J
,
Ezekiel
F
,
Jagust
WJ
, et al
.
White matter lesions are associated with cortical atrophy more than entorhinal and hippocampal atrophy
.
Neurobiol Aging
.
2005
;
26
(
4
):
553
9
.
61.
Wang
N
, et al
.
Cerebral small vessel disease and motoric cognitive risk syndrome: results from the Kerala-Einstein study
.
J Alzheim Dis
.
2016
(
Preprint
):
1
9
.
62.
Chen
P-H
,
Lin
SI
,
Liao
YY
,
Hsu
WL
,
Cheng
FY
.
Corrigendum: associations between blood-based biomarkers of Alzheimer’s disease with cognition in motoric cognitive risk syndrome: a pilot study using plasma Aβ42 and total tau
.
Front Aging Neurosci
.
2022
;
14
:
1125201
.
63.
Meiner
Z
,
Ayers
E
,
Bennett
DA
,
Wang
C
,
Verghese
J
.
Risk factors for the progression of motoric cognitive risk syndrome to dementia: retrospective cohort analysis of two populations
.
Eur J Neurol
.
2021
;
28
(
6
):
1859
67
.
64.
Allali
G
,
Ayers
EI
,
Verghese
J
.
Motoric cognitive risk syndrome subtypes and cognitive profiles
.
J Gerontol A Biol Sci Med Sci
.
2016
;
71
(
3
):
378
84
.
65.
Kravatz
NL
,
Ayers
E
,
Bennett
DA
,
Verghese
J
.
Olfactory dysfunction and incidence of motoric cognitive risk syndrome: a prospective clinical-pathologic study
.
A Prospective Clinical-Pathologic Study
.
2022
;
99
(
17
):
e1886
96
.
66.
Costa
KG
,
Fontes
E
,
Menta
A
,
White
S
,
Fielding
R
,
Kowaleski
C
, et al
.
Prefrontal cortex hemodynamics during exercise in older adults with motoric cognitive risk syndrome
.
Innov Aging
.
2020
;
4
(
Suppl_1
):
189
.
You do not currently have access to this content.