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Neuropsychopharmacology Reports. 2022;42:174–182.wileyonlinelibrary.com/journal/nppr
Received: 11 November 2 021
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Revised: 29 January 2022
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Accepted: 8 February 2022
DOI: 10.10 02/n pr2 .1224 3
ORIGINAL ARTICLE
Retention and impairment of neurocognitive functions in
mild cognitive impairment and Alzheimer’s disease with a
comprehensive neuropsychological test
Lu Yao1 | Shinsuke Aoyama1 | Atushi Ouchi1 | Yasuji Yamamoto1,2 | Ichiro Sora1
This is an op en access arti cle under the ter ms of the Creative Commons Attribution- NonCommercial- NoDerivs License, which perm its use and dist ribution in
any medium, provided the original work is properly cited, the use is no n- commercial and no modifications or adaptat ions are m ade.
© 2022 The Author s. Neuropsychopharmacology Repor ts published by John Wiley & Sons Austra lia, Ltd on behalf of T he Japanese Society of
Neuropsychopharmacology.
1Depar tment of Psychiatry, Kobe
University Graduate School of Medicine,
Kobe, Japan
2Depar tment of Biosignal
Pathop hysiology, Kobe Universit y
Gradu ate Scho ol of Medicine, Kob e, Japan
Correspondence
Ichiro Sora, Professor a nd Chairpers on
of Depar tment of Psychiatry, Kobe
University Graduate School of Medicine,
7- 5- 1 Kusuno ki- cho, Chuo- ku, Kobe 650 -
0017, Japan.
Email: sora@med.kobe-u.ac.jp
Funding information
This stu dy was supported in par t by a
research grant f rom the S moking Research
Foundation
Abstract
Aim: MATRICS Consensus Cognitive Battery was developed by the National Institute
of Mental Health to establish acceptance criteria for measuring cognitive changes
in schizophrenia and can be used to assess cognitive functions in other psychiatric
disorders. We used a Japanese version of MATRICS Consensus Cognitive Battery to
explore the changes in multiple cognitive functions in patients with mild cognitive
impairment and mild Alzheimer's disease.
Methods: We administered the Japanese version of MATRICS Consensus Cognitive
Battery to 11 patients with mild cognitive impairment (MCI), 11 patients with
Alzheimer's disease, and 27 healthy controls. All Japanese versions of MATRICS
Consensus Cognitive Battery domain scores were converted to t- scores using sample
means and standard deviations and were compared for significant performance dif-
ferences among healthy control, MCI, and mild Alzheimer's disease groups.
Results: Compared with healthy controls, patients with MCI and mild Alzheimer's
disease demonstrated the same degree of impairment to processing speed, verbal
learning, and visual learning. Reasoning and problem- solving showed significant im-
pairme nts only in mild Alzheime r's disea se. Verb al and visu al abilitie s in work ing mem-
ory showed different performances in the MCI and mild Alzheimer's disease groups,
with the Alzheimer's disease group demonstrating significantly more deficits in these
domains. No significant difference was found among the groups in attention/vigilance
and social cognition.
Conclusions: The Japanese version of MATRICS Consensus Cognitive Battery can be
used to elucidate the characteristics of cognitive dysfunction of normal aging, MCI,
and mild dementia in clinical practice.
KEYWORDS
Alzheimer's disease, cognitive retention, MCCB Japanese version, mild cognitive impairment,
neurocognitive function
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1 | INTRODUC TION
Mild cognitive impairment (MCI) is a clinical condition in which cog-
nitive decline is greater than expec ted for an individual's age and
education but does not interfere with activities of daily living.1
Boundaries among normal aging, MCI, and mild dementia are dif-
ficult to distinguish.2 Although MCI as a high- risk factor for the
progression to dementia has been demonstrated,3,4 and multiple
cognitive domains decline in patients with MCI,5,6 exact causes re-
main unknown.
Patients exhibit symptoms of cognitive decline at the MCI stage,
but they are still able to perform daily living and social activities. This
is a result of the preser vation of some cognitive functions in MCI and
mild Alzheimer's disease (AD). On the other hand, MCI is a high- risk
factor for the development of AD. Therefore, elucidating the charac-
teristics of cognitive impairment in MCI and determining how these
characteristics differ from AD is impor tant.
The MATRICS Consensus Cognitive Battery (MCCB), a compre-
hensive neuropsychological measurement involving multiple cog-
nitive domains, was developed by the National Institute of Mental
Health in 20087 to establish acceptance criteria for measuring cog-
ni ti ve ch ang es in schi zo phr eni a and to be us ed in clin ic al tria ls of cog-
nitive enhancement therapy for schizophrenia. The MCCB is widely
utilized in schizophrenia research,8 - 1 0 and several studies have out-
lined its standardization in other countries.11,1 2 The MCCB is also
utilize d to as sess pe rf ormance in childre n, adol escents, and adults,13
as well as to explore the correlation between cognition and clini-
cal signs.14 In our previous study, those with chronic schizophrenia
were recruited to evaluate the MCCB Japanese version (MCCB- J).
The MCCB was significantly correlated with the Brief Assessment
of Cognition in Schizophrenia (BACS).15 The MCCB- J has good va-
lidity as a psychometric tool, and it can be used to assess cognitive
function in patients with bipolar or eating disorders in Japan.16,17
Although the basic pathologies of schizophrenia and AD are dif fer-
ent, they have similarities in the pattern of regional brain dysfunc-
tion, biochemical dysfunction, and symptomatology.18 In addition, it
is well established that impairment in the encoding of new episodic
memories is indicative of the earliest stages of AD.19 Mini- Mental
State Examination (MMSE) and Alzheimer's Disease Assessment
Scale— cognitive subscale (ADAS- cog) are usually used in clinical
practice for evaluating the cognition of MCI and AD. Visuospatial,
language, concentration, working memory, memory recall, and ori-
entation domains are covered by MMSE.20 Memory, language, and
praxis domains are covered by ADAS- cog. 21 Contrastingly, process-
ing speed, verbal learning, visual learning, working memor y, at ten-
tion/vigilance, reasoning, problem- solving, and social cognition
domains are covered by MCCB. Thus, MCCB involves the cognitive
domains that MMSE and ADAS- cog do not cover. Hence, MCCB- J
may be helpful to explore the changes in broader cognitive domains
in MCI and mild AD.
MCI and AD have been the most popular medical jargon among
the researchers and are widely used in clinical practice. In 2013,
the concept of mild neurocognitive disorders (mild NCD) and major
neurocognitive disorders due to Alzheimer's disease (major NCD
due to AD) was defined in the Diagnostic and Statistical Manual of
Mental Disorders, fifth edition (DSM- 5).22 Diagn ostic cri teria of mild
NCD are largely consistent with the previously proposed nosological
entity for MCI, 23 an d ma jo r NCD is most ly syno ny mo us with dem en -
tia.24 Because of that, the great majority of our understanding of
mild NCD and major NCD due to AD based on studies of MCI and
AD. In the present study, we aimed to use the MCCB- J to explore
and analyze the retention and impairment of these cognitive do-
mains in MCI (mild NCD) and AD (major NCD due to AD). Our study
is the first to use the MCCB- J in patients with MCI and AD.
2 | METHODS
2.1 | Subjects and procedures
Twenty- two native Japanese- speaking outpatients aged >65 years
were recruited bet ween April 2017 and December 2019 at the
memory clinic of Kobe University Hospital. 11 subjects met the
diagnostic criteria for MCI (ie, mild NCD) and 11 subjects met the
diagnostic criteria for AD (ie, major NCD due to AD), using the DSM-
5.22 Those with AD met the diagnostic criteria for mild AD (ie, stage
4) using Functional Assessment Staging.25 None of the patients in
the MCI group were receiving medication for cognitive disorder. The
mild AD group included 4 on anti- dementia treatment and 7 on non-
anti- dementia treatment. The diagnosis was supported by neuropsy-
chological examinations and brain imaging. At least one physician
specializing in dementia and one neuropsychologist were present
during the diagnosis. Subjects were also assessed by clinical inter-
view to ensure that they had no psychiatric illness (eg, depression,
bipolar disorder, brain injury, and alcohol dependence). No recruited
subjects were excluded from the analysis based on these criteria or
refusal to participate.
Age- matched healthy elderly subjects were recruited from Kobe
City, and they were all screened using the MMSE and Geriatric
Depression Scale (GDS). Twenty- seven elderly subjects met the cri-
teria of MMSE ≥26 and GDS ≤6 and comprised the healthy control
group. The exclusion criteria included an intelligence quotient below
80, as assessed using the Japanese version of the National Adult
Reading Test (JART).26
All par ticipants in the present study were right- handed. Writ ten
consent was obtained from all participants, and the study was con-
ducted according to the standards of the Declaration of Helsinki and
approved by the Hospital Ethics Committee of Kobe Universit y.
2.2 | Measures
Our neuropsychological assessment was based on the MCCB- J and
performed by clinical psychologists who had completed MCCB- J
training. The MCCB- J consists of 10 subtests that assess the follow-
ing seven cognitive domains27: trail making test (part A; TMT- A), Brief
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Assessment of Cognition in Schizophrenia Symbol Coding (BACS- SC),
Categor y Fluency— Animal Naming test to assess processing speed;
Hopkins Verbal Learning Test- Revised (HVLT- R) to assess ver-
bal learning; Brief Visuospatial Memor y Test- Revised (BVMT- R)
to assess visual learning (Trials 1, 2, and 3 were selected from the
HVLT- R and BVMT- R, and the total score of the three free recall
trials [total recall] was used to evaluate verbal and visual learning
separately); Letter– Number Span test (LNS) and Wechsler Memory
Scale III- Spatial Span test (WMS III- SS) to assess working memory;
Continuous Per formance Test— Identical Pairs (CPT- IP) to assess at-
tention/vigilance; Neuropsychological Assessment Battery- Mazes
(NAB- Mazes) to assess reasoning and problem- solving; and Mayer-
Salovey- Caruso Emotional Intelligence Test's Managing Emotions
component (MSCEIT- ME) to assess social cognition (Table 1). Each
participant completed the test in approximately 60- 90 min.
2.3 | Statistical analysis
The sample was classified into three groups by diagnostic categor y
(healthy control, MCI (ie, mild NCD), and mild AD (ie, major NCD due
to AD)), and we classified patients with mild AD into 2 groups by
drug treatment or non- drug treatment. We used the raw scores of
healthy controls and patients from each of the ten MCCB- J tests and
the MCCB scoring program to calculate t- scores of the ten MCCB- J
tests and seven domains.27 We used data from the healthy controls
as reference data in the statistical analysis.
Kruskal- Wallis test was used to compare the demographic and
clinical characteristics. Then, we performed post hoc pairwise mul-
tiple comparisons correction for significant differences with the
Bonferroni- corrected Mann- Whitney U test. To examine the differ-
ences in MCCB- J performance among the healthy control, MCI, and
mild AD groups, we performed the Kruskal- Wallis test with the seven
domain t- scores and ten MCCB- J tests as separate dependent vari-
ables and the three groups as subject variables. We then conducted
post hoc pairwise multiple comparison corrections for significant
differences using the Bonferroni- corrected Mann- Whitney U test to
adjust for domains and subtests. Effect size r was calculated among
healthy control vs MCI, healthy control vs mild AD, and MCI vs mild
AD, respectively, for the seven domains and the total score.
Mann- Whitney U test was used to compare the performance of
mild AD patients between drug treatment and non- drug treatment
in the seven domains and ten subtests. Spearman rank correlation
analysis was also performed between the total score of MMSE and
the total score of MCCB- J.
All statistical analyses were conducted using SPSS (version 11;
SPSS Inc, Chicago, IL, USA). Statistical significance was defined as
P < 0.05. To adjust for multiple comparisons (demographic, MCCB- J
domains, and subtests) using the Bonferroni correction, the signifi-
cance level was set at P ≤ 0.017.
3 | RESULTS
3.1 | Clinical and demographic features
The proportion of females in the healthy control, MCI, and mild
AD groups was 55.6%, 72.7%, and 63.6%, respec tively. Kruskal-
Wallis test revealed significant between- group differences in age
(P = 0.016), JA RT (P < 0.0 06), and MMSE (P < 0.001) . Ma nn - Wh it ne y
U test sh owe d th at the mi ld AD gr o u p was sig nif ica ntl y old er th an th e
healthy control group (P = 0.0 04), but the age of the MCI group was
not significantly different from that of the healthy control or mild AD
groups. The JART score of the mild AD group was significantly lower
than that of the healthy controls (P = 0.0 05), but the JART of the
MCI group was not significantly dif ferent from those of the healthy
control and mild AD groups. Compared with the healthy control
group, the MMSE Mann- Whitney U test for the MMSE showed that
the MCI (P < 0. 001) and mil d AD grou ps (P < 0.001) ha d signific antly
lower scores, and the mild AD group also had significantly lower
1. Processing Speed
T M T - A
Categor y Fluency: Animal Naming
B A C S - S C
5. Attention/Vigilance
C P T - I P
2. Verbal Learning
H V L T - R
6. Reasoning and Problem- Solving
NAB- Mazes
3. Visual Learning
B V M T - R
4. Working Memory
WMS III- SS
LNS
7. Social Cognition
MSCEIT- ME
Abbreviations: BACS- SC, B rief Assessment of Cognition in Schizophrenia— Symbol Coding test;
BVNT- R , Brief V isuospatial Memory Test— Revised; CPT- IP, Continuous Performance Test—
Identical Pair s; HVLT- R, Hopkins Verbal Learning Test— Revised; LNS, Letter– Number Span test;
MCCB- J, MATRICS Consensus Cognitive B atter y, Japanese version; MSCEIT- ME, Mayer- Salovey-
Caruso Emotional Intelligence Test's Managing Emotions component; NAB, Neuropsychological
Assessment Bat tery— Mazes (NAB); TMT- A , trail making test, part A; WMS III- SS, Wechsler
Memor y Scale III Spatial Span test.
TAB LE 1 MCCB- J consists of 10
subtest s assessing seven cognitive
domains
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YAO et Al.
sco re s than the MCI group (P = 0.001). No significant dif ference wa s
found in education level among the three groups ( Table 2).
3.2 | Performance between drug
treatment and non- drug treatment in mild AD
The mild AD group was further classified based on treatment as fol-
lows: anti- dementia treatment group (n = 7) and non- anti- dementia
treatment group (n = 4). The Mann- Whitney U test result s of the
MCCB- J domain and subtest scores revealed between anti- dementia
treatment group and non- anti- dementia treatment group. Because
the performance of the anti- dementia treatment group and non-
anti- dementia treatment group did not show a significant difference,
they were combined as one group for further analysis.
3.3 | MCCB- J neurocognitive function scores and
Correlation between total score of MMSE and total
score of MCCB- J
Kruskal- Wallis test of MCCB- J domain scores revealed between-
group differences in processing speed (P < 0.0 01), verbal learning
(P < 0.001), visual le arning (P < 0. 001), working memory (P < 0.001),
and reasoning and problem- solving (P = 0.004). Mann- Whitney U
test and effect size showed that compared with healthy controls,
the MCI and mild AD groups demonstrated significantly worse
performance and large or medium effect size in processing speed
(P < 0.001 r = 0.65, P < 0.001 r = 0.57), verbal learning (P < 0.001
r = 0.53, P < 0.001 r = 0.64), and visual learning (P = 0.006 r = 0.39,
P < 0.001 r = 0.61); the mild AD group had significantly worse per-
formance and large ef fect size on the working memory domain
(P < 0.001 r = 0.61), but the MCI group was not significantly dif-
ferent, with a medium effect size of r = 0.39; the mild AD group
had significantly worse performance and medium effect size in the
reasoning and problem- solving domains (P = 0.004 r = 0.41), bu t the
MCI group showed no significant difference and medium effect size
(r = 0.34). Attention/vigilance and social cognition domains showed
no significant difference and small effect size among the three
groups (Figure 1, Table S1).
Kruskal- Wallis test of MCCB- J subtest scores revealed between-
group differences on the TMT- A (P < 0.001), BACS- SC (P < 0.001),
category fluency— animal naming (P < 0.001), HVLT- R (P < 0.001),
BVMT- R (P < 0.001), LNS (P < 0.001), WMS III- SS (P = 0.001), and
NAB Maze (P = 0.004). Mann- Whitney U test showed, that com-
pared with healthy controls, the MCI and mild AD groups demon-
strated significantly worse performance on the TMT- A (P < 0.001,
P = 0.005, respectively), BACS- SC (both P < 0.001), category
fluency— animal naming (both P < 0.001), HVLT- R (both P < 0.001),
and BVMT- R (both P < 0.001); the mild AD group demonstrated
significantly worse performance on the WMS III- SS (P < 0.001) and
NAB Maze (P = 0.004), but the MCI group showed no significant
difference compared with healthy controls. A significant difference
was found among the three groups on the LNS (healthy control
>MCI, P = 0.007; healthy control >mild AD, P < 0.001; MCI >mild
AD, P = 0.004). CPT- IP and MSCEIT- ME subtests showed no signifi-
cant difference among the three groups (Figure 2, Table S2).
Based on the results of the study, however, healthy control,
MCI, and mild AD groups did not show any correlation between the
MMSE and MCCB- J total scores.
4 | DISCUSSION
We used comprehensive neuropsychological tests that are rarely
used in memory clinics to assess cognitive characteristics and
changes in patients with MCI and mild AD by utilizing the MCCB- J.
We found that, compared with the healthy control group, the patient
groups scored significantly lower and had a large or medium ef fect
size in processing speed, verbal learning, and visual learning. The
mild AD group scored significantly lower in reasoning and problem-
solving than healthy control. Verbal and visual abilities in working
memory showed different performances between the MCI and mild
AD groups. In addition, there was no significant difference and a
small effect size among the three groups in at tention/vigilance and
social cognition domains.
4.1 | Cognitive impairment in the MCI and mild
AD groups
4.1.1 | Processing speed, verbal learning, and
visual learning
Lower performance in processing speed, verbal learning, and visual
learning compared with healthy control was observed in the MCI
and mild AD groups. Processing speed is the ability to identify,
discriminate, integrate, and decide about information. It is a meas-
ure of the time required to respond to and/or process information
in one's environment.28 ,29 A previous study found that processing
speed mediates age- related memory effects but not dementia-
related memory effects.30 A decline in processing speed may occur
in the early stages of dementia, before the onset of any other clini-
cal symptoms.31 No statistically significant difference was found in
age between healthy control and MCI groups in our current study,
but a decline in processing speed was observed in the MCI group.
This may indicate that compared with the age- matched group, im-
pairment of processing speed is not caused by age- related memor y
effect in the MCI stage. Processing speed is significantly impaired
as early as the MCI stage, rather than just in the initial stages of
AD. Thus, the assessment of MCI should not only focus on episodic
memory but also processing speed as this can be used as a risk factor
to assess MCI.
As mentioned previously, trials 1, 2, and 3 were selected from
the HVLT- R32 an d BV MT- R ,33 and the to tal scor e of th e thr ee fr ee re -
call trials (total recall) was used to evaluate verbal and visual learning
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separately. Total recall from the HVLT- R can discriminate between
patients with AD and controls34 ,35 but has previously demonstrated
a relatively low discrimination capacity for distinguishing MCI from
healthy control.35 Research involving the HVLT- R and BVMT- R
combined with blood- based biomarkers of AD and a brief neuro-
psychological test revealed that, as an early prediction of risk for
developing MCI or AD, global cognitive function, episodic memory,
language fluency, and serum Aβ1 - 4 2 /A β1 - 4 0 ratio achieved an excel-
lent accuracy of 91%, but the sensitivity and specificity of verbal
learning and visual learning with blood- based biomarkers was not
apparent.36 Verba l and visu al le ar n in g dec lin ed to the sa me de gre e in
MCI and mild AD stages. Hence, whether verbal learning and visual
learning can be used as routine clinical examinations for distinguish-
ing healthy controls and MCI needs further examination.
4.1.2 | Working memory
Working memory is the ability to maintain and manipulate informa-
tion for a br ief period.37 It coordinates information in two independ-
ent domain- specific storage components for verbal and visuospatial
codes.38,39 Because of the separability of spatial and verbal working
memory,40 the LNS and WMS III- SS, which are tasks for verbal and
visuospatial ability in working memory, respectively, did not perform
TAB LE 2 Demographic and clinical characteristics
HC
n = 27
(M = 12, M/n = 44.4%)
MCI
n = 11
(M = 3, M/n = 27. 3%)
Mild AD
n = 11
(M = 4, M/n = 36.4%) P- value Post hoc comparis ons
Mean ± SD
Age (range) 75.78 ± 4.66 (66–
85 years old)
78.27 ± 5.24 (71– 85 years
old)
81.09 ± 5.26a (68– 87 years
old)
0.016 HC = MCI (P = 0.225)
HC >mild AD
(P = 0.004)
MCI = mild AD
(P = 0.21)
Education
(year s)
13.78 ± 2.40 13.0 0 ± 3.19 12.09 ± 2.55 0.193 n.s
MMSE 29 ± 1.24 25.91 ± 1.92b22.27 ± 2.37a,c <0.001 HC >MCI (P < 0.001)
HC >mild AD
(P < 0.001)
MCI >AD (P = 0.001)
F I Q - J A R T 108.96 ± 8.065 103.64 ± 11 .138 97. 82 ± 10. 515a<0.006 HC = MCI (P = 0.260)
HC >mild AD
(P = 0.005)
MCI = mild AD
(P = 0.321)
Abbreviations: AD, Alzheimer's disease; FIQ, Full scale of IQ; HC, healthy controls; JART, Japanese Adult Reading Test; M, Males; MCCB- J, MATRICS
Consensus Cognitive Battery, Japanese ver sion; MCI , mild cognitive impairment; n.s., not significant.
aSignificant pairwise differences between healthy control and mild AD (P < 0.017).
bSignificant pairwise differences between healthy control and MCI (P < 0.017).
cSignificant pairwise differences between MCI and mild AD (P < 0.017).
FIGURE 1 Kruskal- Wallis test for all
MCCB- J domains and overall cognitive
composite t- scores. Error bars show
standard deviation. MCI: mild cognitive
impairment; AD: Alzheimer's disease;
MCCB- J: MATRICS Consensus Cognitive
Batter y, Japanese version. ≈ Significant
pairwise differences between healthy
control and mild AD groups (P < 0.017);
* Significant pair wise differences
between healthy control and MCI
groups (P < 0.017); † Significant pairwise
differences bet ween MCI and mild AD
groups (P < 0.017)
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YAO et Al.
consistently in patients with MCI and mild AD. The visuospatial
ability of working memory depends principally on the right parietal
areas.41 In patie nt s wit h MCI, th e parie tal are a ha s not dem on str at ed
accelerated brain volume changes compared with that in healthy
controls,42 but this was observed in the early stages of AD.43 Hence,
this might explain why the impaired performance of visuospatial abil-
ity will appear in mild AD but not MCI. Contrastingly, we found that
the LNS was the singular subtest that showed a group difference,
suggesting that it might distinguish MCI from mild AD. Our current
results also demonstrated that verbal impairment could be observed
earlier than visual impairment in working memory in patients with
MCI. In addition, in a meta- analysis, Reger et al selected studies that
included AD- only data and showed that visuospatial skills may be
the most helpful in identifying at- risk drivers.44 This suggests that
working memory can be used not only as a clinical neuropsychologi-
cal test to distinguish healthy aging, MCI, and mild AD but also as a
basis for assessing driving fitness in the elderly.
4.2 | Cognitive retention in MCI and cognitive
impairment in mild AD
4.2.1 | Reasoning and problem- solving
NAB Mazes were selected to evaluate reasoning and problem-
solving function through the maze- tracing task, which is sensitive
to frontal lobe lesions.45 The maze task also involves inductive
reasoning, which is often used to generate a prediction or to make
forecasts. It is one of the most important and ubiquitous of all
problem- solving activities.46,47 Baghel et al determined that the in-
tegration of multiple relations between mental representations is
critical for higher- level cognition. Relational integration may be a
basic common factor that connect s various abilities that depend on
prefrontal function, including problem- solving, for which an intact
prefrontal cortex is essential.48 The present study indicates that the
integrit y of the frontal lobe is relatively preser ved in MCI but not in
mild AD as a lower performance was observed only in the mild AD
group. This suggests that obvious frontal lobe damage would not be
observed and inductive reasoning/problem- solving is preserved in
the MCI stage.
4.3 | Cognitive retention in the MCI and mild AD
4.3.1 | Attention/vigilance and social cognition
Compared with the healthy control group, worse performance of at-
tention/vigilance and social cognition domains was not observed in
MCI and mild AD groups in our current study. The attention/vigilance
domain was assessed using the CPT- IP, which measures sustained at-
tention. Sustained attention refers to the ability to maintain or focus
attention over a period of time,49 and it is typically assessed in a vigi-
lance task.50 Our result s indicate that even patients with mild AD have
a sustained attention capacity. This is likely because individuals with
AD have increased activity in the prefrontal regions during cognitive
tasks compared with that seen in age- matched healthy controls, com-
pensating for losses attributable to the degenerative disease process
in mild AD.51 Overall, sustained attention is relatively preser ved in the
early stages of AD, which has been validated in a previous study.52
The manner in which we interpret, analyze, and remember in-
formation about the social environment is a characteristic of so-
cial cognition.53 The study of information processing in a social
setting is referred to as social cognition, and it enables individu-
als to take advantage of being part of a social group.54 Managing
FIGURE 2 Kruskal- Wallis test for all MCCB- J domains and overall cognitive composite t- scores. Error bars show standard deviation.
Abbreviations: TMT- A: trail making test, Par t A; BACS- SC: Brief Assessment of Cognition in Schizophrenia— Symbol Coding test; HVLT- R:
Hopkins Verbal Learning Test— Revised; BVNT- R: Brief Visuospatial Memory Test— Revised; LNS: Letter– Number Span test; WMS- SS:
Wechsler Memory Scale III Spatial Span test; CPT- IP: Continuous Performance Test– Identical Pairs; NAB: Neuropsychological Assessment
Batter y— Mazes (NAB); MSCEIT- ME: Mayer- Salovey- Caruso Emotional Intelligence Test's Managing Emotions component; MCI: mild
cognitive impairment; AD: Alzheimer's disease; MCCB- J: MATRICS Consensus Cognitive Battery, Japanese language version. ≈ Significant
pairwise differences between healthy control and mild AD groups (P < 0.017); * Significant pairwise dif ferences between healthy control
and MCI groups (P < 0.017); † Significant pairwise dif ferences between MCI and mild AD groups (P < 0.017)
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YAO et Al .
emotions was selected from the MSCEIT to measure an individu-
al's act ion in controlling e mot ion s that ar e troubles ome and nega-
tively affect relationships.55 A previous study demonstrated that
compared with the performance of social cognitive dysfunction
in frontotemporal dementia, the degree of impairment in AD was
minimal.56 Although with the severity of social cognition, long-
term disease progression can be tracked, AD progression cannot
be predicted at the early stage using social cognition; this may
account for the relative independence between social and general
cognition.57 Ret entio n of cognit ive func tion in at tenti on/vigil ance
and social cognition may explain why patients with MCI and mild
AD are still able to perform social activities despite the general
cognitive decline.
5 | LIMITATI ON S
The present study has several limitations. First, the sample size was
small. Refusal to participate was common because the MCCB- J takes
60- 90 min to complete. Some subjects discontinued the test due to
physical exhaustion, making the test results unusable. We did not
observe much difference between those who completed the test
and those who did not complete the test (unpublished data). Further
studies may reveal detailed differences between those who have com-
pleted the test and those who have not completed the test. Second,
because of the small sample size, the correlation between MMSE and
MCCB- J total scores could not be observed among the healthy con-
trol, MCI and mild AD groups. Third, whether the poor per formance in
mild AD was correlated with age was not evaluate d. Although the data
showed that MCI and mild AD have a larger propor tion of females, we
did not assess the impact of sex on the results. A larger sample size is
necessary for future studies. More detailed classification and compari-
son should be conducted, and the relat ionships and dif feren ces amo ng
different groups should be elucidated.
6 | CONCLUSIONS
Our findings demonstrate the retention and impairment of neu-
ropsychological functions in MCI and mild AD using the MCCB- J,
suggesting that processing speed can be used as a risk factor for
assessing MCI. Whether verbal and visual learning can be used as
routine clinical examinations for distinguishing between healthy
controls and MCI requires further study. Working memor y can be
used not only as a clinical neuropsychological test to distinguish
MCI from AD but also as a basis for assessing the driving fitness
of the elderly. Notably, reasoning and problem- solving were pre-
served in MCI. Attention/vigilance and social cognition did not
demonstrate obvious impairment in the MCI and mild AD groups,
suggesting their importance in maintaining social activity. In clini-
cal practice, physicians will be able to use the MCCB- J to regularly
evaluate preserved and impaired cognitive functions and record
behavioral changes.
APPROVAL OF THE RESEARCH PROTOCOL BY AN
INSTITUTIONAL REVIEWER BOARD
The study protocol has been approved by the suitably constituted
Research Ethical Commit tee of the Kobe University Graduate
School of Medicine (No.1610), and it conforms to the provisions of
the Declaration of Helsinki.
ANIMAL STUDY
N/A .
INFORMED CONSENT
All participant s provided written consent to the study after a full
explanation of the study procedures.
ACKNOWLEDGMENTS
We would like to thank Kenichi Matsuyama for both collection of
the clinical data and assistance with statistical analysis, Mayumi
Fujiwara for the collection of the clinical data, and Masako Kuranaga
for the administration of the psychological test.
CONFLICT OF INTEREST
The authors declare no conflict of interest.
AUTHOR CONTRIBUTIONS
Lu Yao and Ichiro Sora designed the study. Lu Yao, Shinsuke Aoyama,
Yasuji Yamamoto, and Ichiro Sora collected the data. Atushi Ouchi
administered the psychological test. Lu Yao and Atushi Ouchi ana-
lyzed the data. Lu Yao wrote the draft. Lu Yao, Shinsuke Aoyama,
Yasuji Yamamoto, and Ichiro Sora wrote the final manuscript. All au-
thors approved the final manuscript .
DATA AVA ILAB ILITY STATE MEN T
Research data are not shared. This is because the participants did
not consent to open data sharing.
ORCID
Lu Yao https://orcid.org/0000-0001-6465-2209
Ichiro Sora https://orcid.org/0000-0003-0741-8373
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SUPPORTING INFORMATION
Additional suppor ting information may be found in the online
version of the article at the publisher ’s website.
How to cite this article: Yao L, Aoyama S, Ouchi A,
Yamamoto Y, Sora I. Retention and impairment of
neurocognitive functions in mild cognitive impairment and
Alzheimer’s disease with a comprehensive
neuropsychological test. Neuropsychopharmacol Rep.
2022;42:174– 182. https://doi.org/10.1002/npr2.12243
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