Abstract
Introduction: Cognitive frailty, characterized by the coexistence of cognitive impairment and physical frailty, is a significant predictor of cognitive decline. However, few studies integrate both cognitive and physical assessments alongside hormonal markers, such as cortisol, that may influence frailty and cognitive function. To address this gap, our study combines noninvasive physical, cognitive, and cortisol markers to assess frailty in aging adults. Methods: Data were collected from four sites as part of the Healthy Minds for Life (HML) longitudinal cohort, a project within the Precision Aging Network. Baseline data included cognitive evaluation using the Montreal Cognitive Assessment (MoCA); frailty assessment using a validated 20-s elbow flexion-extension test analyzed by AI under single-task (ST) and dual-task (DT) conditions; cortisol measurement in eccrine sweat samples via direct analysis in real-time mass spectrometry (DART-MS); and demographic information. Results: Of 202 participants completing all assessments, 60 were identified with mild cognitive impairment (MCI). The dual-task frailty index (FI) derived from the 20-s test significantly differentiated individuals with MCI from cognitively robust participants and correlated strongly with MoCA scores (p = 0.015). The dual-task FI showed superior model fit compared to the single-task FI when predicting cognitive function. A significant correlation between the dual-task FI and cortisol by age interaction was observed (p = 0.0042) highlighting the potential impact of cortisol to moderate the relationship between frailty and age in an otherwise healthy aging population. By contrast, no significant correlation was found between dual-task FI and aging outside of the presence of cortisol (p = 0.116) in this study. Conclusions: This study highlights practical and efficient methods for assessing frailty emphasizing the value of DT testing and cortisol measures in identifying individuals at higher risk for cognitive and physical decline. The findings underscore the importance of integrating hormonal markers with cognitive and physical assessments to enhance risk stratification and intervention planning in aging populations.
Journal Section:
Experimental Section
References
1.
Xue
Q-L
. The frailty syndrome: definition and natural history
. Clin Geriatr Med
. 2011
;27
(1
):1
–15
. 2.
Fried
LP
, Cohen
AA
, Xue
Q-L
, Walston
J
, Bandeen-Roche
K
, Varadhan
R
. The physical frailty syndrome as a transition from homeostatic symphony to cacophony
. Nat Aging
. 2021
;1
(1
):36
–46
. 3.
Kelaiditi
E
, Cesari
M
, Canevelli
M
, van Kan
GA
, Ousset
PJ
, Gillette-Guyonnet
S
, et al. Cognitive frailty: rational and definition from an (I.A.N.A./I.A.G.G.) international consensus group
. J Nutr Health Aging
. 2013
;17
(9
):726
–34
. 4.
Ruan
Q
, Yu
Z
, Chen
M
, Bao
Z
, Li
J
, He
W
. Cognitive frailty, a novel target for the prevention of elderly dependency
. Ageing Res Rev
. 2015
;20
:1
–10
. 5.
Maggio
M
, Dall’Aglio
E
, Lauretani
F
, Cattabiani
C
, Ceresini
G
, Caffarra
P
, et al. The hormonal pathway to cognitive impairment in older men
. J Nutr Health Aging
. 2012
;16
(1
):40
–54
. 6.
Lee
BK
, Glass
TA
, McAtee
MJ
, Wand
GS
, Bandeen-Roche
K
, Bolla
KI
, et al. Associations of salivary cortisol with cognitive function in the Baltimore memory study
. Arch Gen Psychiatry
. 2007
;64
(7
):810
–8
. 7.
Varadhan
R
, Walston
J
, Cappola
AR
, Carlson
MC
, Wand
GS
, Fried
LP
. Higher levels and blunted diurnal variation of cortisol in frail older women
. J Gerontol A Biol Sci Med Sci
. 2008
;63
(2
):190
–5
. 8.
Comijs
HC
, Gerritsen
L
, Penninx
BWJH
, Bremmer
MA
, Deeg
DJH
, Geerlings
MI
. The association between serum cortisol and cognitive decline in older persons
. Am J Geriatr Psychiatry
. 2010
;18
(1
):42
–50
. 9.
Reynolds
RM
, Strachan
MWJ
, Labad
J
, Lee
AJ
, Frier
BM
, Fowkes
FG
, et al. Morning cortisol levels and cognitive abilities in people with type 2 diabetes: the Edinburgh type 2 diabetes study
. Diabetes Care
. 2010
;33
(4
):714
–20
. 10.
Holanda
CMA
, Guerra
RO
, Nóbrega
PVN
, Costa
HF
, Piuvezam
MR
, Maciel
ÁCC
. Salivary cortisol and frailty syndrome in elderly residents of long-stay institutions: a cross-sectional study
. Arch Gerontol Geriatr
. 2012
;54
(2
):e146
–51
. 11.
Morley
JE
, Malmstrom
TK
. Frailty, sarcopenia, and hormones
. Endocrinol Metab Clin North Am
. 2013
;42
(2
):391
–405
. 12.
Johar
H
, Emeny
RT
, Bidlingmaier
M
, Reincke
M
, Thorand
B
, Peters
A
, et al. Blunted diurnal cortisol pattern is associated with frailty: a cross-sectional study of 745 participants aged 65 to 90 years
. J Clin Endocrinol Metab
. 2014
;99
(3
):E464
–8
. 13.
Ouanes
S
, Popp
J
. High cortisol and the risk of dementia and Alzheimer’s disease: a review of the literature
. Front Aging Neurosci
. 2019
;11
:43
. 14.
Qiu
Q
, Zhou
X
, Wu
L
, Zhang
Y
, Yu
Z
, Wang
M
, et al. Serum cortisol is associated with cerebral small vessel disease-related brain changes and cognitive impairment
. Front Aging Neurosci
. 2022
;13
:13
. 15.
Stamou
MI
, Colling
C
, Dichtel
LE
. Adrenal aging and its effects on the stress response and immunosenescence
. Maturitas
. 2023
;168
:13
–9
. 16.
Nasreddine
ZS
, Phillips
NA
, Bédirian
V
, Charbonneau
S
, Whitehead
V
, Collin
I
, et al. The Montreal Cognitive assessment, MoCA: a brief screening tool for mild cognitive impairment
. J Am Geriatr Soc
. 2005
;53
(4
):695
–9
. 17.
Luis
CA
, Keegan
AP
, Mullan
M
. Cross validation of the Montreal Cognitive Assessment in community dwelling older adults residing in the Southeastern US
. Int J Geriatr Psychiatry
. 2009
;24
(2
):197
–201
. 18.
Toosizadeh
N
, Mohler
J
, Najafi
B
. Assessing upper extremity motion: an innovative method to identify frailty
. J Am Geriatr Soc
. 2015
;63
(6
):1181
–6
. 19.
Toosizadeh
N
, Joseph
B
, Heusser
MR
, Orouji Jokar
T
, Mohler
J
, Phelan
HA
, et al. Assessing upper-extremity motion: an innovative, objective method to identify frailty in older bed-bound trauma patients
. J Am Coll Surg
. 2016
;223
(2
):240
–8
. 20.
Joseph
B
, Toosizadeh
N
, Orouji Jokar
T
, Heusser
MR
, Mohler
J
, Najafi
B
. Upper-extremity function predicts adverse health outcomes among older adults hospitalized for ground-level falls
. Gerontology
. 2017
;63
(4
):299
–307
. 21.
Lee
H
, Joseph
B
, Enriquez
A
, Najafi
B
. Toward using a smartwatch to monitor frailty in a hospital setting: using a single wrist-wearable sensor to assess frailty in bedbound inpatients
. Gerontology
. 2018
;64
(4
):389
–400
. 22.
Toosizadeh
N
, Berry
C
, Bime
C
, Najafi
B
, Kraft
M
, Mohler
J
. Assessing upper-extremity motion: an innovative method to quantify functional capacity in patients with chronic obstructive pulmonary disease
. PLoS One
. 2017
;12
(2
):e0172766
. 23.
Najafi
B
, Veranyan
N
, Zulbaran-Rojas
A
, Park
C
, Nguyen
H
, Nakahara
QK
, et al. Association between wearable device–based measures of physical frailty and major adverse events following lower extremity revascularization
. JAMA Netw Open
. 2020
;3
(11
):e2020161
. 24.
Dehghan
RM
, Lee
M
, Ouattas Phd
A
, Cay
G
, Momin
A
, Najafi
B
, et al. Quantitative biomechanical analysis in validating a video-based model to remotely assess physical frailty: a potential solution to telehealth and globalized remote-patient monitoring
. Biomed Eng Lett
. 2024
;14
:1
–11
.25.
Bazarevsky
V
, Grishchenko
I
, Raveendran
K
, Zhu
TL
, Zhang
F
, Grundmann
M
. BlazePose: on-device real-time body pose tracking
. ArXiv
. 2020
:10204
. abs/2006.26.
Joseph
B
, Pandit
V
, Rhee
P
, Aziz
H
, Sadoun
M
, Wynne
J
, et al. Predicting hospital discharge disposition in geriatric trauma patients: is frailty the answer
. J Trauma Acute Care Surg
. 2014
;76
(1
):196
–200
. 27.
Joseph
B
, Pandit
V
, Zangbar
B
, Kulvatunyou
N
, Tang
A
, O'Keeffe
T
, et al. Validating trauma-specific frailty index for geriatric trauma patients: a prospective analysis
. J Am Coll Surg
. 2014
;219
(1
):10
–7.e1
. 28.
Toosizadeh
N
, Najafi
B
, Reiman
EM
, Mager
RM
, Veldhuizen
JK
, O’Connor
K
, et al. Upper-extremity dual-task function: an innovative method to assess cognitive impairment in older adults
. Front Aging Neurosci
. 2016
;8
:167
. 29.
Zahiri
M
, Wang
C
, Gardea
M
, Nguyen
H
, Shahbazi
M
, Sharafkhaneh
A
, et al. Remote physical frailty monitoring– the application of deep learning-based image processing in tele-health
. IEEE Access
. 2020
;8
:219391
–9
. 30.
Liu
Z
, Wang
C
, Liu
G
, Najafi
B
. Deep neural network-based video processing to obtain dual-task upper-extremity motor performance toward assessment of cognitive and motor function
. IEEE Trans Neural Syst Rehabil Eng
. 2023
;31
:574
–80
. 31.
Beauchet
O
, Kressig
RW
, Najafi
B
, Aminian
K
, Dubost
V
, Mourey
F
. Age-related decline of gait control under a dual-task condition
. J Am Geriatr Soc
. 2003
;51
(8
):1187
–8
. 32.
Bahureksa
L
, Najafi
B
, Saleh
A
, Sabbagh
M
, Coon
D
, Mohler
MJ
, et al. The impact of mild cognitive impairment on gait and balance: a systematic review and meta-analysis of studies using instrumented assessment
. Gerontology
. 2017
;63
(1
):67
–83
. 33.
Runyon
JR
, Jia
M
, Goldstein
MR
, Skeath
P
, Abrell
L
, Chorover
J
, et al. Dynamic behavior of cortisol and cortisol metabolites in human eccrine sweat
. Int J Progn Health Manag
. 2023
;10
(3
). 34.
Torrente-Rodríguez
RM
, Tu
J
, Yang
Y
, Min
J
, Wang
M
, Song
Y
, et al. Investigation of cortisol dynamics in human sweat using a graphene-based wireless mHealth system
. Matter
. 2020
;2
(4
):921
–37
.35.
LaFleur
BJ
, Lee
W
, Billhiemer
D
, Lockhart
CA
, Liu
J
, Merchant
NB
. Statistical methods for assays with limits of detection: serum bile acid as a differentiator between patients with normal colons, adenomas, and colorectal cancer
. J Carcinog
. 2011
;10
:12
. 36.
Foster
KG
, Ellis
FP
, Doré
C
, Exton-Smith
AN
, Weiner
JS
. Sweat responses in the aged
. Age Ageing
. 1976
;5
(2
):91
–101
. 37.
Ezure
T
, Amano
S
, Matsuzaki
K
. Aging-related shift of eccrine sweat glands toward the skin surface due to tangling and rotation of the secretory ducts revealed by digital 3D skin reconstruction
. Skin Res Technol
. 2021
;27
(4
):569
–75
. 38.
de Souza-Talarico
JN
, Marin
M-F
, Sindi
S
, Lupien
S
. Effects of stress hormones on the brain and cognition Evidence from normal to pathological aging
. Dement Neuropsychol
. 2011
;5
(1
):8
–16
. 39.
Najafi
B
, Zhou
H
, Nguyen
H
. Gait test or No gait test: do we need walking assessment to determine physical frailty
. Gerontology
. 2019
;65
(3
):311
–2
. 40.
Schwenk
M
, Mohler
J
, Wendel
C
, D’Huyvetter
K
, Fain
M
, Taylor-Piliae
R
, et al. Wearable sensor-based in-home assessment of gait, balance, and physical activity for discrimination of frailty status: baseline results of the Arizona frailty cohort study
. Gerontology
. 2015
;61
(3
):258
–67
. © 2025 S. Karger AG, Basel
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.
2025
You do not currently have access to this content.
