Introduction: Subjective cognitive decline (SCD) is considered a preclinical manifestation of Alzheimer’s disease (AD). Recent research suggests that subtle cognitive changes in SCD are linked to an increased risk of clinical decline. This study investigates the longitudinal trajectories of both objective and self-reported cognitive functions in individuals with SCD, with a focus on the impact of subtle cognitive impairment (SCI). Methods: A total of 107 individuals with SCD, with at least two annual follow-ups, were included in this study. We analyzed the trajectories of both objective and subjective cognitive functions, assessed changes in medial temporal lobe regional volumes, and compared baseline AD biomarkers between SCD individuals with SCI (n = 22, SCI group) and without SCI (n = 85). Results: SCD individuals with SCI showed a faster decline in objective cognitive function over time compared to those without SCI, who exhibited cognitive improvement. Self-reported cognitive complaints showed no differences between groups at baseline or in annual changes over time. The SCI group had lower baseline entorhinal cortical volumes and greater volume reductions over time and also exhibited more abnormalities in AD biomarkers, including higher amyloid PET positivity, a lower Aβ 42/40 ratio, and elevated p-tau181. Conclusion: SCI status in SCD individuals is associated with significant cognitive decline, along with more abnormal AD biomarkers. These findings suggest that early identification of SCI status in individuals with SCD may improve the prediction of cognitive decline. However, self-reported cognitive complaints may have a limited role in monitoring clinical changes in SCD.

1.
Jessen
F
,
Amariglio
RE
,
van Boxtel
M
,
Breteler
M
,
Ceccaldi
M
,
Chetelat
G
, et al
.
A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer’s disease
.
Alzheimers Dement
.
2014
;
10
(
6
):
844
52
.
2.
Hong
YJ
,
Lee
JH
.
Subjective cognitive decline and Alzheimer’s disease spectrum disorder
.
Dement Neurocogn Disord
.
2017
;
16
(
2
):
40
7
.
3.
Mitchell
AJ
,
Beaumont
H
,
Ferguson
D
,
Yadegarfar
M
,
Stubbs
B
.
Risk of dementia and mild cognitive impairment in older people with subjective memory complaints: meta-analysis
.
Acta Psychiatr Scand
.
2014
;
130
(
6
):
439
51
.
4.
Slot
RER
,
Sikkes
SAM
,
Berkhof
J
,
Brodaty
H
,
Buckley
R
,
Cavedo
E
, et al
.
Subjective cognitive decline and rates of incident Alzheimer’s disease and non-Alzheimer’s disease dementia
.
Alzheimers Dement
.
2019
;
15
(
3
):
465
76
.
5.
Jessen
F
,
Amariglio
RE
,
Buckley
RF
,
van der Flier
WM
,
Han
Y
,
Molinuevo
JL
, et al
.
The characterisation of subjective cognitive decline
.
Lancet Neurol
.
2020
;
19
(
3
):
271
8
.
6.
Ebenau
JL
,
Timmers
T
,
Wesselman
LMP
,
Verberk
IMW
,
Verfaillie
SCJ
,
Slot
RER
, et al
.
ATN classification and clinical progression in subjective cognitive decline: the SCIENCe project
.
Neurology
.
2020
;
95
(
1
):
e46
58
.
7.
Loewenstein
DA
,
Greig
MT
,
Schinka
JA
,
Barker
W
,
Shen
Q
,
Potter
E
, et al
.
An investigation of PreMCI: subtypes and longitudinal outcomes
.
Alzheimers Dement
.
2012
;
8
(
3
):
172
9
.
8.
Toledo
JB
,
Bjerke
M
,
Chen
K
,
Rozycki
M
,
Jack
CR
Jr
,
Weiner
MW
, et al
.
Memory, executive, and multidomain subtle cognitive impairment: clinical and biomarker findings
.
Neurology
.
2015
;
85
(
2
):
144
53
.
9.
Thomas
KR
,
Edmonds
EC
,
Eppig
J
,
Salmon
DP
,
Bondi
MW
;
Alzheimer’s Disease Neuroimaging Initiative
.
Using neuropsychological process scores to identify subtle cognitive decline and predict progression to mild cognitive impairment
.
J Alzheimers Dis
.
2018
;
64
(
1
):
195
204
.
10.
Shen
XN
,
Kuo
K
,
Yang
YX
,
Li
HQ
,
Chen
SD
,
Cui
M
, et al
.
Subtle cognitive impairment as a marker of Alzheimer’s pathologies and clinical progression in cognitively normal individuals
.
Alzheimers Dement
.
2021
;
13
(
1
):
e12198
.
11.
Stark
M
,
Wolfsgruber
S
,
Kleineidam
L
,
Frommann
I
,
Altenstein
S
,
Bartels
C
, et al
.
Relevance of minor neuropsychological deficits in patients with subjective cognitive decline
.
Neurology
.
2023
;
101
(
21
):
e2185
96
.
12.
Stricker
NH
,
Lundt
ES
,
Albertson
SM
,
Machulda
MM
,
Pudumjee
SB
,
Kremers
WK
, et al
.
Diagnostic and prognostic accuracy of the cogstate brief battery and auditory verbal learning test in preclinical Alzheimer’s disease and incident mild cognitive impairment: implications for defining subtle objective cognitive impairment
.
J Alzheimers Dis
.
2020
;
76
(
1
):
261
74
.
13.
Thomas
KR
,
Bangen
KJ
,
Weigand
AJ
,
Edmonds
EC
,
Wong
CG
,
Cooper
S
, et al
.
Objective subtle cognitive difficulties predict future amyloid accumulation and neurodegeneration
.
Neurology
.
2020
;
94
(
4
):
e397
406
.
14.
Bangen
KJ
,
Thomas
KR
,
Weigand
AJ
,
Edmonds
EC
,
Clark
AL
,
Solders
S
, et al
.
Elevated plasma neurofilament light predicts a faster rate of cognitive decline over 5 years in participants with objectively-defined subtle cognitive decline and MCI
.
Alzheimers Dement
.
2021
;
17
(
10
):
1756
62
.
15.
Sperling
RA
,
Aisen
PS
,
Beckett
LA
,
Bennett
DA
,
Craft
S
,
Fagan
AM
, et al
.
Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease
.
Alzheimers Dement
.
2011
;
7
(
3
):
280
92
.
16.
Chipi
E
,
Salvadori
N
,
Farotti
L
,
Parnetti
L
.
Biomarker-based signature of Alzheimer’s disease in pre-MCI individuals
.
Brain Sci
.
2019
;
9
(
9
):
213
.
17.
Ryu
SY
,
Hong
YJ
,
Ho
S
,
Jeong
JH
,
Park
KH
,
Kim
S
, et al
.
Subtle cognitive deficits are associated with amyloid-β positivity, but not severity of self-reported decline: results from the CoSCo study
.
Dement Geriatr Cogn Disord
.
2022
;
51
(
2
):
159
67
.
18.
Ho
S
,
Hong
YJ
,
Jeong
JH
,
Park
KH
,
Kim
S
,
Wang
MJ
, et al
.
Study design and baseline results in a cohort study to identify predictors for the clinical progression to mild cognitive impairment or dementia from subjective cognitive decline (CoSCo) study
.
Dement Neurocogn Disord
.
2022
;
21
(
4
):
147
61
.
19.
Kang
YW
,
Na
DL
,
Hahn
SH
.
A validity study on the Korean Mini-Mental State Examination (K-MMSE) in dementia patients
.
J Korean Neurol Assoc
.
1997
;
15
:
300
8
.
20.
Kang
Y
,
Jahng
SM
,
Na
DL
.
Seoul neuropsychological screening battery II (SNSB-II) Seoul, Korea: human brain research & consulting Co
;
2012
.
21.
Edmonds
EC
,
Delano-Wood
L
,
Galasko
DR
,
Salmon
DP
,
Bondi
MW
;
Alzheimer’s Disease Neuroimaging Initiative
.
Subtle cognitive decline and biomarker staging in preclinical Alzheimer’s disease
.
J Alzheimers Dis
.
2015
;
47
(
1
):
231
42
.
22.
Wolfsgruber
S
,
Molinuevo
JL
,
Wagner
M
,
Teunissen
CE
,
Rami
L
,
Coll-Padros
N
, et al
.
Prevalence of abnormal Alzheimer’s disease biomarkers in patients with subjective cognitive decline: cross-sectional comparison of three European memory clinic samples
.
Alzheimers Res Ther
.
2019
;
11
(
1
):
8
.
23.
Farias
ST
,
Mungas
D
,
Reed
BR
,
Cahn-Weiner
D
,
Jagust
W
,
Baynes
K
, et al
.
The measurement of everyday cognition (ECog): scale development and psychometric properties
.
Neuropsychology
.
2008
;
22
(
4
):
531
44
.
24.
Song
M
,
Lee
SH
,
Jahng
S
,
Kim
SY
,
Kang
Y
.
Validation of the Korean-everyday cognition (K-ECog)
.
J Korean Med Sci
.
2019
;
34
(
9
):
e67
.
25.
Hong
YJ
,
Park
KW
,
Kang
DY
,
Lee
JH
.
Prediction of Alzheimer’s pathological changes in subjective cognitive decline using the self-report questionnaire and neuroimaging biomarkers
.
Dement Neurocogn Disord
.
2019
;
18
(
1
):
19
29
.
26.
Noh
Y
,
Lee
Y
,
Seo
SW
,
Jeong
JH
,
Choi
SH
,
Back
JH
, et al
.
A new classification system for ischemia using a combination of deep and periventricular white matter hyperintensities
.
J Stroke Cerebrovasc Dis
.
2014
;
23
(
4
):
636
42
.
27.
Lee
M
,
Kim
J
,
Ey Kim
R
,
Kim
HG
,
Oh
SW
,
Lee
MK
, et al
.
Split-attention U-net: a fully convolutional network for robust multi-label segmentation from brain MRI
.
Brain Sci
.
2020
;
10
(
12
):
974
.
28.
Becker
GA
,
Ichise
M
,
Barthel
H
,
Luthardt
J
,
Patt
M
,
Seese
A
, et al
.
PET quantification of 18F-florbetaben binding to β-amyloid deposits in human brains
.
J Nucl Med
.
2013
;
54
(
5
):
723
31
.
29.
Barthel
H
,
Gertz
H-J
,
Dresel
S
,
Peters
O
,
Bartenstein
P
,
Buerger
K
, et al
.
Cerebral amyloid-β PET with florbetaben (18F) in patients with Alzheimer’s disease and healthy controls: a multicentre phase 2 diagnostic study
.
Lancet Neurol
.
2011
;
10
(
5
):
424
35
.
30.
Sabri
O
,
Sabbagh
MN
,
Seibyl
J
,
Barthel
H
,
Akatsu
H
,
Ouchi
Y
, et al
.
Florbetaben PET imaging to detect amyloid beta plaques in Alzheimer’s disease: phase 3 study
.
Alzheimers Dement
.
2015
;
11
(
8
):
964
74
.
31.
Kang
SK
,
Kim
D
,
Shin
SA
,
Kim
YK
,
Choi
H
,
Lee
JS
.
Fast and accurate amyloid brain PET quantification without MRI using deep neural networks
.
J Nucl Med
.
2023
;
64
(
4
):
659
66
.
32.
Jessen
F
,
Wolfsgruber
S
,
Kleineindam
L
,
Spottke
A
,
Altenstein
S
,
Bartels
C
, et al
.
Subjective cognitive decline and stage 2 of Alzheimer disease in patients from memory centers
.
Alzheimers Dement
.
2023
;
19
(
2
):
487
97
.
33.
Kuhn
E
,
Perrotin
A
,
La Joie
R
,
Touron
E
,
Dautricourt
S
,
Vanhoutte
M
, et al
.
Association of the informant-reported memory decline with cognitive and brain deterioration through the alzheimer clinical continuum
.
Neurology
.
2023
;
100
(
24
):
e2454
65
.
34.
Braak
H
,
Braak
E
.
Neuropathological stageing of Alzheimer-related changes
.
Acta Neuropathol
.
1991
;
82
(
4
):
239
59
.
35.
Bangen
KJ
,
Weigand
AJ
,
Thomas
KR
,
Delano-Wood
L
,
Clark
LR
,
Eppig
J
, et al
.
Cognitive dispersion is a sensitive marker for early neurodegenerative changes and functional decline in nondemented older adults
.
Neuropsychology
.
2019
;
33
(
5
):
599
608
.
You do not currently have access to this content.