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C International Psychogeriatric Association 2015

International Psychogeriatrics: page 1 of 11 


doi:10.1017/S1041610215001556

Disturbance of attention network functions in Chinese healthy


older adults: an intra-individual perspective
...........................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Hanna Lu, Ada W. T. Fung, Sandra S. M. Chan and Linda C. W. Lam


Department of Psychiatry, the Chinese University of Hong Kong, G/F, Multi-Centre, Tai Po Hospital, Hong Kong, SAR China

ABSTRACT

Background: Intra-individual variability (IIV) and the change of attentional functions have been reported to
be susceptible to both healthy ageing and pathological ageing. The current study aimed to evaluate the IIV of
attention and the age-related effect on alerting, orienting, and executive control in cognitively healthy older
adults.
Method: We evaluated 145 Chinese older adults (age range of 6580 years, mean age of 72.41 years) with
a comprehensive neuropsychological battery and the Attention network test (ANT). A two-step strategy of
analytical methods was used: Firstly, the IIV of older adults was evaluated by the intraindividual coefficient
of variation of reaction time (ICV-RT). The correlation between ICV-RT and age was used to evaluate
the necessity of subgrouping. Further, the comparisons of ANT performance among three age groups were
performed with processing speed adjusted.
Results: Persons correlation revealed significant positive correlations between age and IIV (r = 0.185, p =
0.032), age and executive control (r = 0.253, p = 0.003). Furthermore, one-way ANOVA comparisons among
three age groups revealed a significant age-related disturbance on executive control (F = 4.55, p = 0.01), in
which oldest group (group with age >75 years) showed less efficient executive control than young-old (group
with age 6570 years) (Conventional score, p = 0.012; Ratio score, p = 0.020).
Conclusion: Advancing age has an effect on both IIV and executive attention in cognitively healthy older
adults, suggesting that the disturbance of executive attention is a sensitive indicator to reflect healthy ageing.
Its significance to predict further deterioration should be carefully evaluated with prospective studies.
Key words: healthy ageing, attention network, intra-individual variability, executive control

Introduction
According to the latest World Alzheimer Report, 44
million adults now suffer from dementia worldwide,
and the projected number will double the current
brunt of disease by 2,030, even trebling the existing
number by 2,050 (Alzheimers Association, 2014).
Because there is no effective treatment to halt
the disease process and treatment outcomes are
unfavourable when the disease progresses to a later
stage, it is crucial to identify the specific cognitive
characteristics and markers that differentiate
cognitive ageing from conditions associated with
high risk of progressive neurodegeneration. The
potential clinical implications of these markers may
help to lay platforms for early intervention. Among
Correspondence should be addressed to: Linda C. W. Lam, MD, Department of
Psychiatry, The Chinese University of Hong Kong, G/F Multicenter, Tai Po
Hospital, Tai Po, Hong Kong. Phone: +(852) 2607-6027; Fax: +(852) 26675464. Email: cwlam@cuhk.edu.hk. Received 15 Apr 2015; revision requested
8 May 2015; revised version received 20 Aug 2015; accepted 26 Aug 2015.

all the cognitive domains, complex attention plays


a fundamental role (Grady, 2008) and serves as
a main diagnostic item of mild neurocognitive
disorders (MND) in Diagnostic and Statistical
Manual of Mental Disorders, 5th edition (DSM5) (American Psychiatric Association, 2013), which
includes selective attention, sustained attention,
and processing speed (Blazer, 2013). Hence, the
composite role of complex attention as a sensitive
marker for healthy ageing warrants exploration.
Based on attention network theory, attention
is described as a set of integrated processes with
differentiated functions, which includes alerting,
orienting, and executive control (Petersen and
Posner, 2012b; Posner and Petersen, 1990).
Alerting provides the capacity to achieve and
maintain vigilance to an impending stimulus, and
has been associated with functioning in frontal lobe,
parietal lobe and thalamus. Orienting is defined as
the selection of relevant stimuli to attend to and the
shifting of attention. The brain regions involved in

H. Lu et al.

orienting are the superior parietal lobe, temporal


parietal junction, frontal eye fields, and superior
colliculus (Posner, 2014). Executive control refers
to a variety of abilities ranging from planning,
manipulating, and the inhibition of behavioral
responses. It involves conflict resolution and control
over decision-making, error detection, and response
inhibition. The brain regions involved in this final
and highest order of attentional process are the
anterior cingulate cortex (ACC) and lateral ventral
prefrontal cortex (VLPFC) along with the basal
ganglia (Matsumoto and Tanaka, 2004).
The ANT is used to quantitatively and
simultaneously evaluate alerting, orienting, and
executive control (Fan et al., 2002a), and has
been widely used across various participants (Rueda
et al., 2004; Dennis et al., 2008; Mullane et al.,
2011; Weaver et al., 2013). As to its application
in the study of ageing, a handful of studies
focusing on healthy adults with different age ranges
have reported some consistent and inconsistent
results. For instance, compared to young adults, a
diminished alerting effect during conflict resolution
has been found in healthy older adults (FernandezDuque and Black, 2006; Jennings et al., 2007).
Later, Gamboz also found that alerting was
significantly reduced in old age, while orienting and
executive control between young and older adults
were equivalent (Gamboz et al., 2010). When comes
to a relatively large sample across the adulthood, a
significant age-related decline has been found on
executive control (Waszak et al., 2010; Zhou et al.,
2011). Moreover, the negative correlation between
age and executive control is still significant within
older adults. In a relatively large sample of older
adults, the age differences have been found in three
attention network functions. Besides, the old-old
adults (80+ years old) have demonstrated worse
performance on executive control than the youngold adults (7079 years old) (Mahoney et al., 2010).
Given the evidence summarized above, it
seems that age has an effect on attention
network functions, particularly on executive control
function. However, two things should be noted
may contribute to the inconsistent results between
studies: The first is slowing processing speed:
processing speed is the basic component of
information processing, and is conceived as a
general resource related to higher-level cognition
(Salthouse, 1996). Moreover, slowing processing
speed is strongly tied to healthy ageing (Hedden and
Gabrieli, 2004). Except for Mahoney et al.s study
(Mahoney et al., 2010), the previous comparisons
of ANT performance did not adjust for processing
speed. Considering ANT scores are calculated by
the subtractions of reaction time under specific
experimental conditions, an immediate concern is

whether the worse performance of ANT is due


to the slowing RT? The second is increased IIV:
IIV represents the facet of within-person variability,
and is regarded as a measure of moment-tomoment fluctuations in an individuals performance
(Martin and Hofer, 2004; Hilborn et al., 2009;
Shin et al., 2013). Throughout the adulthood, IIV
is a stable individual characteristic that appears
to progressively increase with chronological age,
especially with older age (Bielak et al., 2014).
Studies have confirmed that IIV measured by
processing speed could differentiate young adults
from older adults and has been served as a sensitive
biomarker of ageing (MacDonald et al., 2009).
As the spectrum of cognitive abilities has become
diversified in old age, it should be noted that
except for the slowing processing speed, the higher
within-person variability might cause mixed results
as well (Nelson and Dannefer, 1992; Christensen,
2001). Indeed, one recent study has reported
that increased IIV is correlated with the decline
of cognitive performance (Kennedy et al., 2013).
Therefore, it may lead to the concern that whether
the age difference of cognitive function was an
artifact associated with increased IIV? Considering
together, these findings provide the critical insight to
investigate the possible influence of within-person
variability on cognitive functions in older adults.
Thus, in this study we aimed to detect the
disturbance of attention network functions in
healthy Chinese older adults, with both processing
speed and within-person variability considered. To
achieve these objectives, we proposed a two-step
strategy based on two analytical methods. In the first
step, the older adults were considered as one group.
The relationship of age and IIV would provide
evidence to evaluate the necessity of subgrouping.
In the second step, we would compare the ANT
performance among different age groups, with
processing speed considered. We hypothesized that:
(1) The within-person variability would increase
with advancing age; (2) The adults with older age
would demonstrate poorer performance on ANT,
especially under the conditions of high demand on
executive control.

Methods
Study participants
A total of 145 right-handed Chinese older adults
aged from 65 to 80 years (mean age 72.41 years)
participated in this study. All participants were
recruited from another cohort study that aims to
establish a detailed characterization of cognitive
and healthy profiles of Chinese older adults and
to determine the diagnostic markers for preclinical

Attention network function in healthy older adults

dementia. Potential participants 65 and older,


identified from the communities in Hong Kong,
were first contacted and invited to participate by
telephone. The eligible participants were scheduled
for a 1.5-hour in-person interview at the research
center.
During the on-site interview, the participants
received comprehensive assessments, including
cognitive, psychological, medical, everyday activity
as well as attention network functions. The
inclusion criteria were as follows: (1) aged 65 years
and older; (2) no significant cognitive impairment
(presented with Clinical dementia rating scale
(CDR) score equal to 0 and Cantonese version of
Mini-Mental State Examination (CMMSE) score
of larger than 28; (3) absence of mood disorder,
sleep disorder, and psychiatric disorders. Exclusion
criteria were as follows: (1) cognitive impairment
based on CMMSE score of less that 24; (2) mild or
major neurocognitive disorders as defined by DSM5 (American Psychiatric Association, 2013).
Ethics approval
Ethics approval was obtained from the Joint Chinese
University of Hong Kong New territories East
Cluster Clinical Research Ethics Committee (The
Joint CUHK-NTECCREC). Written informed
consent from all participants was obtained before
assessment.
Cognitive assessment and clinical evaluation
A standardized neuropsychological battery was used
to evaluate the global cognition and major domains
of cognition (Lam et al., 2008). The battery was
administered by trained research assistants and the
scores were calculated by two independent raters.
Cornell scale for depression in dementia (CSDD)
is used to assess the depression symptom, with
a cut-off of five (global score) (Schreiner et al.,
2003). Chinese version of the Pittsburgh sleep
quality index (PSQI) is used to evaluate the sleep
problem, with a cut-off of eight (total score) (Beck
et al., 2004). Activity of daily living scale (ADL)
is used to assess the everyday functioning (Lam
et al., 2009). CDR, CMMSE, Alzheimers Disease
Assessment Scale (ADAS), Montreal Cognitive
Assessment Hong Kong version (HK MoCA) (Chu
et al., 2000) are used as a global measure of
cognitive function. Delayed recall of words: the
number of recalled words is used as the performance
of episodic memory. Trail making tests (TMT):
the participants connect either numbers (A), or
numbers and letters in an alternate fashion (B) as
fast as possible; the time of completing in seconds
is used as a measure of attention (TMT-A) and
a measure of general executive function (TMT-

B). Digit span tests: the participants repeat the


numbers they heard, either forward or backward;
the number of correct repeated numbers is used
as a measure of attention (DSF) and a measure
of working memory (DSB). All the measures were
conducted with Chinese instructions.
Attention network test (ANT)
PARADIGM AND PROCEDURE

We used the standard ANT paradigm developed


by Fan Jin and his team (Fan et al., 2002a)
(Download from: https://www.sacklerinstitute.org/
cornell/assays_and_tools/ant/jin.fan/), and ran the
paradigm on E-Prime 2.0 (Psychology Software
Tools, Pittsburgh, PA). Within ANT paradigm,
there are four types of cue: no cue, center cue,
double cue, and spatial cue; and three types of
flanker: neutral, congruent, and incongruent. In a
given trial, a central cross-fixation point presents
for 400 to 1,600 ms (randomized), subsequently is
replaced for 100 ms by one of four warning cues.
The target, a central arrow could appear above or
below the cross-fixation and was surrounded by two
flankers on each side (Figure 1).
None of the participants had practiced the
ANT previously. All participants were seated
approximately 53 cm from the computer screen
with corrected vision by their glasses if needed.
Before the test, participants were instructed to
play the practice trials of ANT and required to
decide whether a central arrow pointed to left
or right, and press a left button if the central
arrow was pointing to left, or right button if it
was pointing to right. Following the illustration, all
participants were instructed to respond as rapidly
and as accurately as possible to the direction of the
flanker stimulus by clicking the left or right button.
After completing 24 practice trials with accuracy
feedback, all participants would take part in three
test blocks without feedback, which contained 288
trials in total. There was a short break between each
of the test block.
EVALUATION OF ATTENTION NETWORK
FUNCTIONS

There are two indices used to evaluate the


performance of ANT, which are accuracy and
reaction time (RT). Accuracy is the degree of
correctness of making a decision and is also
used for the quality control of ANT data. An
accuracy of experimental condition less than 70% is
considered as unqualified data (Fan et al., 2002a).
RT, measured in milliseconds (ms), refers to the
processing speed for a defined stimulus, and is also
used to assess the within-person variability (Dixon
et al., 2007; Wojtowicz et al., 2014).

H. Lu et al.

Figure 1. (Colour online) The schematic diagram of attention network test (ANT).

MEASURE OF INTRA-INDIVIDUAL
VARIABILITY

As described above, IIV represents the withinperson fluctuation of performance in a repeated


task. The ANT consists of 288 trials for collecting
response speed and is suitable for measuring IIV. To
adjust the effect of slowing processing speed, ICVRT (Stuss et al., 2003; Phillips et al., 2013) is used
to evaluate the IIV enumerated with the formula:
ICV-RT = (standard deviation of processing speed
/ mean of processing speed) 100 (Tractenberg
and Pietrzak, 2011).
MEASURES OF ATTENTION NETWORK
FUNCTIONS

Two scoring methods were performed to evaluate


the attention network functions:
(1) Conventional score: the score of each attention
function is defined as a subtraction of the
RT between one condition and the appropriate
reference condition, resulting in scores for the
attention network functions (Fan et al., 2002a;
Galvao-carmona and Izquierdo, 2014; Wang et al.,
2014). Alerting is calculated by subtracting the
mean RT of the condition with center cue from the

mean RT of the condition with no cue. Orienting


is calculated by subtracting the mean RT of the
conditions with spatial cue from the mean RT of
the condition with center cue. Executive control
is calculated by subtracting the mean RT of the
condition with congruent flanker from the mean
RT of the condition with incongruent flanker.
The formulae of conventional scoring are as
follows:
Alerting = RTno-cue RTcenter-cue
Orienting = RTcenter-cue RTspatial-cue
Executive control (conflict) = RTincongruent
RTcongruent
(2) Ratio score: to adjust the effect of slowing
processing speed, the ratio score is equal to
the conventional score divided by the RT of
reference condition (Westlye et al., 2011; Yin et al.,
2012; Galvao-carmona and Izquierdo, 2014). The
formulae of ratio scoring are as follows:
Alerting
ratio
=
(RTno-cue

RTcenter-cue )/RTcenter-cue
Orienting
ratio
=
(RTcenter-cue

RTspatial-cue )/RTspatial-cue
Executive control ratio = (RTincongruent
RTcongruent )/RTcongruent

Attention network function in healthy older adults


STATISTICAL ANALYSES
In the first step: median values of RT averaged
across blocks for each condition were used to
avoid the influence of outliers. The scores of
attention network components were calculated
using the formulae described above. Persons
correlation coefficients were performed to examine
the relationships between age, ICV-RT, and ANT
indices, controlled for the effects of gender,
education, and processing speed. Linear regression
was used to estimate the relationship between age,
ICV-RT, and ANT indices. Significance levels were
set at p values less than 0.05.
In the second step: The differences of
demographics and cognitive performance and ANT
among different age groups were tested either
with 2 test for categorical variables or with oneway analysis of variance (ANOVA) for continuous
variables. When appropriate, the Tukey method
was used to do the post hoc multiple comparisons.
The effect size was evaluated using the partial
eta squared ( 2 ). Persons correlation coefficients
were used to measure the associations of ANT
indices and cognitive functions. Significance levels
were set at p values less than 0.05. The quality
checking, accuracy, RT, and standard deviation of
RT were calculated by E-Data Aid embedded in EPrime 2.0. The 2 test, one-way ANOVA, Pearsons
correlation, and linear regression were performed by
IBM SPSS Statistics 20.

Results
Quality control and ANT performance
According to the quality control standard
suggested by Fan Jin (Fan et al., 2002a), an accuracy
of ANT less than 70% indicates that the participate
does not well understand how to perform the
ANT. Thus, under this circumstances, the ANT
indices, including processing speed, and attentional
components calculated by subtractions of RTs,
are considered unqualified as well. To evaluate
the attention network functions with caution, eight
participants were excluded from the dataset. Thus,
a final sample of 137 healthy older adults was used
for further analysis. The group-level performance of
ANT was as follows: accuracy was higher than 99%;
the processing speed was 687.49 105.97 ms; the
ICV-RT was 19.99 4.57 ms; alerting score was
3.95 31.88; orienting score was 19.76 28.65;
executive control score was 59.86 45.86.
Age-related change of attention network
functions
Persons correlation analysis revealed that the
alerting score (r = 0.011, p = 0.895) and orienting

score (r = 0.019, p = 0.828) did not correlate with


age. A significant positive correlation was found
between the executive control score (r = 0.253,
p = 0.003) and age, which indicates adults with
older age spend more time to detect the conflict and
make a decision. Linear regression demonstrated
that age (controlled for gender, education) was the
significant factor determining the executive control
( = 0.252, t = 3.01, p = 0.003).
As to the within-person variability, a significant
relationship was found between age and the ICVRT (r = 0.185, p = 0.032), which indicates
that adults with older age demonstrate the greater
within-person fluctuation of performance, even in
the context of healthy ageing. This result indicates
that the heterogeneity of attentional performance
within older adults has become noticeable. Thus, in
the second step, we divided 137 healthy older adults
into subgroups.
Investigations among three age groups
DEMOGRAPHICS AND COGNITIVE
PERFORMANCE

As suggested (Hester et al., 2004; Verhaeghen,


2013), we divided the healthy older adults into
three groups: age of 6570 years, age of 7175
years, and age of >75 years, with an age range of
5 years. As Table 1 shows, the basic demographics
in terms of gender and years of education among
the groups were similar. The global cognition,
episodic memory, and general attention were also
comparable. However, a significant difference was
found in executive function measure by TMT-B (F
(2, 134) = 3.282, p = 0.041). Moreover, the group
with age > 75 years showed poorer performance
of TMT-B than the group with age of 6570 years
(p = 0.041).
ANT PERFORMANCE
Accuracy: As Table 2 shows, the accuracy of ANT

among the three age groups was similar.


REACTION TIME AND WITHIN-PERSON
VARIABILITY

The RT and ICV-RT among the three age groups


were similar (Table 3). Although the correlation
between age and processing speed did not reach
the significance (r = 0.067, p = 0.442), there was
a trend that the processing speed was progressively
slowed down with advancing age under various cue
and flanker conditions.
SCORES OF ATTENTION NETWORK
FUNCTIONS

There was no age difference of alerting (F (2, 134) =


0.23, p = 0.78) and orienting (F (2, 134) =

H. Lu et al.

Table 1. Demographics and cognitive proles among three age groups


AGE

6570 (N = 54)

AGE

7175 (N = 56)

AGE

>75 (N = 27)

P VALUE

............................................................................................................................................................................................................................................................................................................................

Gender (F/M)
Education (years)
Systolic BP
Diastolic BP
CSDD
PSQI
ADL
CDR-SOB
CMMSE
HK MoCA
ADAS
Delayed recall
Digit span backward (DSB)
Trail making test B (time)
Trail making test A
Digit span forward (DSF)

21/33
8.59 4.26
138.51 20.98
79.85 10.99
0.63 2.12
5.98 3.16
0.990 0.025
0.47 0.63
28.54 1.13
27.46 2.02
4.69 2.19
7.91 1.46
3.65 1.28
57.35 30.94
12.57 5.96
7.78 1.13

27/29
10.05 4.10
140.39 18.90
77.14 10.89
0.11 0.41
6.57 3.83
0.996 0.015
0.44 0.59
28.70 1.21
27.18 1.72
5.17 2.06
7.45 1.31
3.98 1.46
69.40 35.73
12.37 6.03
7.54 1.11

13/14
9.30 4.55
136.67 17.50
76.96 9.64
0.33 0.96
5.30 2.60
0.989 0.036
0.54 0.10
28.74 1.63
27.00 1.73
4.79 1.94
7.56 1.72
3.48 1.09
81.34 61.72
14.64 7.67
7.52 1.16

0.516
0.177
0.704
0.332
0.161
0.261
0.321
0.668
0.605
0.634
0.489
0.265
0.199
0.041
0.283
0.550

Note. Data are raw scores and presented as meanSD. CSDD = The Cornell Scale for Depression in Dementia; PSQI = Pittsburgh Sleep
Quality Index; CDR-SOB = Clinical dementia rating-sum of box; ADL = Activity of daily living scale.

Table 2. Accuracy under different cue/anker conditions among three age groups
AGE

6570 (N = 54)

AGE

7175 (N = 56)

AGE

>75 (N = 27)

P VALUE

............................................................................................................................................................................................................................................................................................................................

NoCue_Neutral
NoCue_Congruent
NoCue_Incongruent
CenterCue_Neutral
CenterCue_Congruent
CenterCue_Incongruent
DoubleCue_Neutral
DoubleCue_Congruent
DoubleCue_Incongruent
SpatialCue_Neutral
SpatialCue_Congruent
SpatialCue_Incongruent

0.9891 0.0194
0.9908 0.0132
0.9887 0.0160
0.9893 0.0170
0.9910 0.0118
0.9889 0.0162
0.9896 0.0185
0.9914 0.0122
0.9894 0.0168
0.9889 0.0190
0.9906 0.0132
0.9886 0.0178

0.9879 0.0225
0.9907 0.0193
0.9871 0.0176
0.9853 0.0261
0.9881 0.0227
0.9845 0.0209
0.9884 0.0214
0.9913 0.0178
0.9876 0.0180
0.9858 0.0216
0.9886 0.0179
0.9849 0.0171

0.9879 0.0154
0.9887 0.0150
0.9844 0.0190
0.9876 0.0131
0.9883 0.0129
0.9841 0.0169
0.9885 0.0154
0.9893 0.0156
0.9850 0.0210
0.9873 0.0144
0.9880 0.0144
0.9838 0.0199

0.057
0.176
0.573
0.515
0.438
1.041
0.064
0.195
0.520
0.359
0.346
0.865

0.945
0.839
0.565
0.598
0.646
0.356
0.938
0.823
0.596
0.699
0.708
0.424

Note. Data are raw scores and presented as meansSD. NoCue_Neutral represents the ANT trial with no cue as cue type and neutral as
flanker type.

Table 3. ICV-RT and reaction time among three age groups


AGE

6570 (N = 54)

AGE

7175 (N = 56)

AGE

>75 (N = 27)

VALUE

............................................................................................................................................................................................................................................................................................................................

ICV-RT
NoCue_Neutral
NoCue_Congruent
NoCue_Incongruent
CenterCue_Neutral
CenterCue_Congruent
CenterCue_Incongruent
DoubleCue_Neutral
DoubleCue_Congruent
DoubleCue_Incongruent
SpatialCue_Neutral
SpatialCue_Congruent
SpatialCue_Incongruent

20.72 7.75
657.36 101.05
664.66 102.07
688.14 103.97
656.49 104.33
663.78 105.33
687.26 107.39
658.67 102.64
665.96 104.08
689.44 106.04
666.46 105.50
673.75 106.86
697.23 109.19

20.55 7.03
665.22 108.91
673.86 113.93
705.66 107.17
662.31 108.27
670.94 113.59
702.74 107.72
667.29 112.93
675.93 118.18
707.73 111.72
671.68 109.64
680.32 115.02
712.12 109.06

22.44 8.23
698.97 102.12
701.24 98.58
740.19 99.09
696.76 96.84
699.03 93.41
737.98 95.27
698.64 102.14
700.91 100.04
739.86 101.07
707.49 97.94
709.76 95.28
748.72 95.99

0.626
1.480
1.076
3.238
1.422
1.014
2.092
1.291
0.923
1.984
1.459
1.039
2.103

0.536
0.231
0.344
0.111
0.245
0.366
0.127
0.279
0.400
0.142
0.236
0.357
0.126

Note. Data are raw scores and presented as meansSD. NoCue_Neutral represents the ANT trial with no cue as cue type and neutral as
flanker type.
ICV-RT = Intra-individual coefficient of variation (ICV) of Reaction Time.

Attention network function in healthy older adults

Table 4. Scores of attention network functions among three age groups


AGE

6570 (N = 54)

AGE

7175 (N = 56)

AGE

>75 (N = 27)

P VALUE

............................................................................................................................................................................................................................................................................................................................

1.76 27.28
19.94 26.64
46.96 38.41
0.0048 0.0425
0.0283 0.0374
0.07 0.06

Alerting
Orienting
Executive control
Alerting ratio
Orienting ratio
Executive control ratio

5.83 34.71
18.75 27.23
63.59 48.54
0.0101 0.0517
0.03 0.04
0.10 0.08

4.43 35.12
21.47 35.69
77.91 47.94
0.0060 0.5009
0.03 0.05
0.12 0.78

0.799
0.922
0.011
0.837
0.964
0.020

Note. Data are raw scores and presented as meansSD.

Table 5. Associations of ANT indices and cognitive functions


EXECUTIVE
ICV-RT

ALERTING

ORIENTING

CONTROL

............................................................................................................................................................................................................................................................................................................................

CDR-SOB
CMMSE
HK MoCA
ADAS
Delayed Recall
DSB
TMT-B
TMT-A
DSF

0.007
0.039
0.288
0.078
0.062
0.093
0.191
0.139
0.081

0.937
0.654
0.001
0.373
0.479
0.287
0.028
0.112
0.358

0.022
0.059
0.060
0.055
0.007
0.076
0.018
0.066
0.143

0.804
0.498
0.492
0.530
0.936
0.385
0.838
0.451
0.102

0.167
0.131
0.092
0.058
0.028
0.024
0.016
0.046
0.125

0.055
0.134
0.295
0.505
0.747
0.784
0.858
0.601
0.154

0.068
0.043
0.033
0.025
0.020
0.027
0.122
0.000
0.127

0.437
0.621
0.709
0.780
0.816
0.760
0.164
0.997
0.147

Figure 2. Scores of attention network functions across three age groups.

0.08, p = 0.92) among the three age groups. An


age-related decline was found in executive control
(Conventional score: F (2, 134) = 4.648, p =
0.011, 2 = 0.06; Ratio score: F (2, 134) = 3.884,
p = 0.023, 2 = 0.051) (Table 4). Moreover, the
group with age > 75 years demonstrated poorer
performance of executive control than the group
age 6570 years (Conventional score: p = 0.011;
Ratio score: p = 0.020) (Figure 2).

CORRELATIONS BETWEEN ANT INDICES


AND COGNITIVE FUNCTIONS

There was no significant correlation between


ANT scores and the scores of major cognitive
functions (controlled for age, gender, education,
and processing speed). As to the within-person
variability, there was a negative correlation between
ICV-RT and HK MoCA (r = 0.288, p
= 0.001, 95% CI [0.501, 0.125]), and a

H. Lu et al.

positive correlation between ICV-RT and TMTB (r = 0.191, p = 0.028, 95% CI [0.021,
0.359]). Within ANT indices, no relationship was
found between ICV-RT and ANT scores. The
results indicated that attention network functions
measured by ANT were relatively independent from
other cognitive functions. However, the declined
cognitive functions might have an effect on the
within-person variability, or vice versa.

age differences of executive function might be


influenced by the increased IIV, or vice versa.
The age differences in IIV seem to have profound
effects on many cognitive functions, particularly
on executive function. Alternatively, an absence
of correlation between the ICV-RT and executive
control measured by ANT implicated that the
attention network functions measured by ANT
seems to be less influenced by the IIV. Therefore,
it may provide a more convincing evaluation of the
age differences in attention network functions.

Discussion
To the best of our knowledge, this is the first
work to detect both IIV and attention network
functions in community-dwelling Chinese healthy
older adults. With advancing age, increased withinperson variability and declined executive control
function have been found in current study.
Meanwhile, the oldest group (age > 75 years)
showed less efficient executive control function than
the group with age 6570 years. These findings
suggest that executive control measured by ANT,
rather than processing speed, alerting and orienting,
is a sensitive marker of healthy ageing, even in the
context of relatively normal cognition.
Age and intra-individual variability (IIV)
Until recently, variability has been considered
as an important individual difference measure
relevant to understanding age differences in brain
function (Garrett et al., 2013). Indeed, inspired
by previous attempts (MacDonald et al., 2003;
Bunce et al., 2004; Salthouse et al., 2006; Kennedy
et al., 2013), our observations demonstrate that the
within-person variability increased in old age, and
appeared to highlight the necessity of subgrouping
in a sample of older adults (Rabbitt et al., 2001;
Tractenberg and Pietrzak, 2011; Phillips et al.,
2013). The increased within-person variability in
old age suggests that older adults have more
difficulty on keeping the consistency of performance
across the experimental trials.
Given the declined brain functions in late
adulthood, it is applaudable to assume that withinperson variability maybe affected by the declined
executive functions (Bellgrove et al., 2004). As
outlined nicely by MacDonald et al. (2009), greater
IIV is associated with the reduced functional MRI
(fMRI) activities in the regions related to executive
functions (MacDonald et al., 2009). A further
question emerges from this work is whether poorer
executive control and decision-making function
in older adults are reflected by within-person
variability of neuropsychological measure as well?
Interestingly, the positive correlations between
age, ICV-RT, and TMT-B supported that the

Age and attention network functions


AGE, ALERTING, AND ORIENTING

Age difference on alerting is quite inconsistent.


Some studies (Festa-Martino et al., 2004; Jennings
et al., 2007; Zhou et al., 2011) found a decreased
alerting effect in older adults. In contrast, an
increased alerting effect also was found in old age
(Fernandez-Duque and Black, 2006). One thing
should be noted is that among these studies, the
researchers recruited the adults with a wide age
range, such as young adults, middle-age adults,
and older adults. However, when focusing on older
adults, no significant relationship has been found
between age and alerting, exactly in line with the
results found by Mahoney et al. (Mahoney et al.,
2010). As to orienting, no significant relationship
has been found between age and orienting as
well, which is consistent with previous attempts
(Mahoney et al., 2010; Waszak et al., 2010).
AGE AND EXECUTIVE CONTROL

As expected, adults with old age demonstrate


poorer performance on ANT, particularly on
executive control. Additionally, the group with
older age (age >75 years) has less efficient
executive control function than the group with
younger age (age: 6570 years). And the results
are consistent under both conventional and ratio
scoring methods. Given the age-related decline in
executive function, it is not surprising that our
results are aligned with the studies focusing on late
life (Fisk and Sharp, 2004, Mahoney et al., 2010;
Zhou et al., 2011). Interestingly, an unexpected
result, that is insignificant relationship between age
and processing speed encourages us to rethink the
coexisting of slowing processing speed and declined
executive control in older adults.
Based on attention network theory, executive
control associated anatomical units are mostly
located in prefrontal cortex (PFC) and embedded
with dopaminergic networks (Posner, 2012). The
PFC is the hub of information processing and
decision making, also participates in synthesizing a
wide range of external and internal stimuli to exert

Attention network function in healthy older adults

control (van den Heuvel and Sporns, 2013). As


frontal ageing hypothesis proposed (Greenwood,
2000; Salat, 2011), the close relationship of the PFC
and healthy ageing has been explored in a number of
studies by means of structural MRI (Raz et al., 1999;
Resnick et al., 2003; Yao et al., 2012) and positron
emission tomography (PET) (Hazlett et al., 2010).
Supporting an association between neuroanatomy and neurotransmitter, the PFC regions are
highly related to the executive functions, and with
the dominant neuromodulator as dopamine (DA).
Besides, this association also plays a key role
in healthy ageing process. A body of work have
exhibited that through the adulthood, the changes
of cognitive functions occur gradually, and are
accompanied with the decreasing dopamine D2
receptor (Volkow et al., 1998; Drag et al., 2010).
Additionally, a decrease of 513% per decade of
D2/3R receptor has been found in the extrastriatal
brain regions (Kaasinen et al., 2000), especially in
the PFC regions (Li et al., 2001). Interestingly, DA
is also the dominant neuromodulator of executive
control described in attention network theory
(Petersen and Posner, 2012b).
Taken together with the aforementioned evidence, it is reasonable to infer that the disturbance
of executive control in older adults found in this
study may enrich the neuropsychological evidence
supporting the frontal ageing hypothesis, and
highlight a sensitive and early sign of healthy ageing
before the detectable changes of brain function
occurred. It is also important to note that the
findings need to be interpreted with its limitation.
First, this is a cross-sectional study and the
results could not imply ageing effect. Second, only
older adults with a relatively restricted age range
participate. Third, multiple correlations between
ANT indices and the cognitive performance may
inflate the rate of false positives. A predefined
hypothesis and a confidence interval around a
difference without overlap zero may help for
declaring the significant results.
In the light of the preceding discussion, our
findings are aligned with a growing body of evidence
that healthy ageing is accompanied by several
dynamic changes, such as increased within-person
variability, slowing processing speed, and declined
executive function (Hedden and Gabrieli, 2004).
At this point, we summarize two major thrusts of
our results based on ANT: (1) With advancing age,
the IIV measured by ICV-RT has become greater,
which highlights the necessity of subgrouping in the
older participants; and (2) The executive control
function, rather than processing speed, alerting, and
orienting, is a sensitive marker of healthy ageing,
even in the context of relatively normal cognition.
Therefore, it would be intriguing to evaluate if

executive control component would be a sensitive


marker to predict cognitive deterioration and the
progression to dementia.

Conict of interest
None.

Description of authors roles


Hanna Lu, Sandra S.M. Chan and Linda C.W.
Lam conceived and designed this study. Ada W.T.
Fung coordinated the development of this study.
Regarding to this paper, Hanna Lu drafted, Ada
W.T. Fung, Sandra S.M. Chan and Linda C.W.
Lam discussed and agreed the final version.

Acknowledgments
This research was supported by Lui Che Woo
Institute of Innovation Medicine grant at The
Chinese University of Hong Kong. The authors
would like to thank all the participants and their
relatives that kindly agreed to participate in the
study. And we also want to thank the reviewers
for their valuable comments and suggestions to
improve the quality of the paper.

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