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JADXXX10.1177/1087054717730609Journal of Attention DisordersLin and Gau

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Journal of Attention Disorders

Comparison of Neuropsychological
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DOI: 10.1177/1087054717730609
https://doi.org/10.1177/1087054717730609

Early- and Late-Onset DSM-5 ADHD journals.sagepub.com/home/jad

Yu-Ju Lin1,2 and Susan Shur-Fen Gau2

Abstract
Objective: We aimed to compare the visually dependent neuropsychological functioning among adults with Diagnostic
and Statistical Manual of Mental Disorders (5th ed.; DSM-5) ADHD who recalled symptom onset by and after age 7 and
non-ADHD controls. Method: We divided the participants, aged 17 to 40 years, into three groups—(a) ADHD, onset
<7 years (early-onset, n = 142); (b) ADHD, onset between 7 and <12 years (late-onset, n = 41); (c) non-ADHD controls
(n = 148)—and compared their neuropsychological functioning, measured by the Cambridge Neuropsychological Testing
Automated Battery. Results: Both ADHD groups had deficits in attention and signal detectability, spatial working memory,
and short-term spatial memory, but only the early-onset group showed deficits in alertness, set-shifting, and planning after
controlling for age, sex, and psychiatric comorbidities. There was no statistical difference between the two ADHD groups
in neuropsychological functioning. Conclusion: DSM-5 criteria for diagnosing adult ADHD are not too lax regarding
neuropsychological functioning. (J. of Att. Dis. XXXX; XX(X) XX-XX)

Keywords
ADHD, DSM-5, age-of-onset, neuropsychological functioning, comorbidities

Introduction of individuals with ADHD developed after 7 years old

ADHD is a well-known neurodevelopmental disorder that
persists into adulthood (Barkley, Fischer, Smallish, &
Fletcher, 2006). Literature has clearly documented neuro-
psychological deficits in children (Willcutt, Doyle, Nigg,
Faraone, & Pennington, 2005) as well as in adults (Alderson,
Kasper, Hudec, & Patros, 2013; Schoechlin & Engel, 2005)
with ADHD. Although not all individuals with ADHD have
neuropsychological deficits (Seidman, 2006), some neuro-
psychological deficits, especially those subserved by pre-
frontal brain regions (Sonuga-Barke, 2005), are viewed as
endophenotypes (Castellanos & Tannock, 2002) of ADHD
and might play a valuable role in validating the psychiatric
diagnosis (Hyman, 2007).
Since long ago, there had been criticisms about the arbi-
trary decision of the age-of-onset criterion for diagnosing
ADHD (Barkley & Biederman, 1997; Kieling et al., 2010)
and the developmentally inappropriate symptoms as well as
symptom threshold in adult populations (Faraone et al.,
2000; Tannock, 2013). Longitudinal studies gave conflict-
ing data about the general age range of emerging ADHD
symptoms: Some showed that only a small proportion of
individuals developed impairing ADHD symptoms after 7
years old (Polanczyk et al., 2010; Todd, Huang, &
Henderson, 2008), while others found that more than 10%
(Applegate et al., 1997; Todd et al., 2008). Diagnosing adult
ADHD requires a recall of childhood symptoms (Adler &
Chua, 2002) and inevitably suffers from recall bias (Barkley,
Fischer, Smallish, & Fletcher, 2002). Individuals with
ADHD and their parents frequently reported later ages of
onset during the follow-up interviews than their initial
reports (Todd et al., 2008). Only half of adults with ADHD
recalled their symptom onset before 7 years (Kessler et al.,
2005). Therefore, even only a small number of individuals
develop ADHD after 7 years old, the possible recalled bias
of ADHD onset for adolescents and young adults (Todd
et al., 2008) will also result in underrecognition of ADHD
in the adult population (Kieling et al., 2010). Adults with
unrecognized ADHD often experience various negative life
events and have adverse outcomes (Barkley et al., 2006).
Several studies provided evidence to support the revi-
sion of ADHD age-of-onset criterion by showing
1
Far Eastern Memorial Hospital, New Taipei City, Taiwan
2
National Taiwan University, Taipei, Taiwan
Corresponding Author:
Susan Shur-Fen Gau, Department of Psychiatry, National Taiwan
University Hospital and College of Medicine, No. 7, Chung-Shan South
Road, Taipei 10002, Taiwan.
Email: gaushufe@ntu.edu.tw
2 Journal of Attention Disorders 00(0)
comparable familial transmission, comorbidity pattern
(Faraone, Biederman, Spencer, et al., 2006), functional
impairment (Rohde et al., 2000; Willoughby, Curran,
Costello, & Angold, 2000), impaired neuropsychological
functions (Faraone, Biederman, Doyle, et al., 2006), and
treatment response (Biederman et al., 2006; Reinhardt
et al., 2007) between groups of different ages of onset, nam-
ing, by and after 7 years old, of ADHD. Therefore, the
Diagnostic and Statistical Manual of Mental Disorders (5th
ed.; DSM-5; American Psychiatric Association, 2013) crite-
ria for ADHD elevate the age-of-onset threshold from 7 to
12 years and lower the symptom threshold from 6 to 5 at
each symptom domain for individuals aged 17 years and
older (American Psychiatric Association, 2013). After
DSM-5 formally published, Chandra, Biederman, and
Faraone (2016) reported comparable impairments in quality
of life and social adjustment, and similar patterns of psychi-
atric comorbidity and familial transmission between late-
onset ADHD and Diagnostic and Statistical Manual of
Mental Disorders (4th ed.; DSM-IV; American Psychiatric
Association, 1994) ADHD. Vande Voort, He, Jameson, and
Merikangas (2014) reported that using DSM-5 criteria
caused a moderate increase of prevalence (from 7.38% to
10.84%) as compared with DSM-IV criteria despite no sig-
nificant difference in severity and comorbidity between the
earlier and later onset groups. Concerns about overinflating
ADHD diagnosis by DSM-5 (Batstra & Frances, 2012;
Prosser & Reid, 2013) still call for further studies to vali-
date the new criteria.
Following our previous findings of no difference in
functional impairment, quality of life (Lin, Lo, Yang, &
Gau, 2015), and psychiatric comorbid conditions (Lin,
Yang, & Gau, 2016) between the early- and late-onset adult
ADHD groups, this work intended to compare neuropsy-
chological functioning between adults with early- and late-
onset ADHD diagnosed by DSM-5. Although such an issue
had been investigated by Faraone, Biederman, Doyle, et al.
(2006), their work did not address the influence of psychiat-
ric comorbidities on the neuropsychological performance,
and most of their neuropsychological tasks were verbally
dependent. Visuospatial memory and central executive
functions are more closely related to ADHD behavioral
symptoms than verbal memory (Alderson et al., 2013).
Functional neuroimaging studies also demonstrated that
frontoparietal network and visual system subserving visuo-
spatial (working) memory (Klingberg, 2006) and attention
(Hart, Radua, Nakao, Mataix-Cols, & Rubia, 2013) have
altered activity in adults with ADHD in addition to the fron-
tostriatal network (Cortese et al., 2012; Vaidya, 2012).
Therefore, we believe visual tasks are highly correlated to
ADHD diagnosis with the level of correlation no less than
the verbal ones.
There are several overlapping symptoms between
depressive disorders, anxiety disorders, and ADHD, such as
inattention, forgetfulness, restlessness, and impulsiveness.
Besides, neuropsychological deficits frequently found in
ADHD, including deficits in executive functions, working
memory, visuospatial memory, psychomotor processing
speed, and verbal fluency, are also found in major depres-
sive disorder (Baune, Fuhr, Air, & Hering, 2014) and oppo-
sitional defiant disorder (ODD)/conduct disorder (CD; Lin
& Gau, 2017; Sergeant, Geurts, & Oosterlaan, 2002).
Previous studies either excluded individuals with psychiat-
ric comorbidity (Schoechlin & Engel, 2005) or only
adjusted for overall psychiatric comorbidity (Gau & Huang,
2014; Seidman, Biederman, Weber, Hatch, & Faraone,
1998) while investigating neuropsychological functioning
in ADHD. Given that adults with ADHD frequently have
psychiatric comorbidities (Biederman et al., 1993) which
may cloud the diagnosis of adult ADHD (Shaffer, 1994),
controlling for a specific comorbidity one at a time is sug-
gested to remove the influences of comorbidities on the
neuropsychological deficits found in ADHD (Hervey,
Epstein, & Curry, 2004; Schoechlin & Engel, 2005).
The Cambridge Neuropsychological Test Automated
Battery (CANTAB) is a widely used measure to assess vari-
ous nonverbal neuropsychological functioning (Levaux
et al., 2007) with good reliability and validity (Luciana,
2003). Combining our previous studies and others’ studies,
we found that many tasks in CANTAB could differentiate
children (Fried, Hirshfeld-Becker, Petty, Batchelder, &
Biederman, 2015; Rhodes, Coghill, & Matthews, 2005) and
adolescents (Gau, Chiu, Shang, Cheng, & Soong, 2009) with
ADHD from typically developing youths, including high-
executive demand tasks, such as Spatial Working Memory
(SWM), Stocking of Cambridge (SOC), Intradimensional
and Extradimensional Shifting (IED), and low-executive
demand tasks, such as Rapid Visual Information Processing
(RVP), Reaction Time, and Spatial Span. Besides, previous
studies suggested that neuropsychological functions mea-
sured by SWM, SOC, IED, Spatial Span (Gau & Shang,
2010), and RVP (Gau & Huang, 2014) in CANTAB might
be the endophenotypes of ADHD. Therefore, if adults with
late-onset ADHD also have similar neuropsychological defi-
cits measured by the CANTAB as adults with early-onset
ADHD and these deficits are independent of any specific
psychiatric comorbidity, late-onset ADHD might be within
the spectrum of ADHD.
In this study, we selected the neuropsychological tasks
assessing visual sustained attention (RVP), short-term spa-
tial memory (Spatial Span), spatial working memory
(SWM), set-shifting (IED), and visual planning (SOC),
which were sensitive to frontal lobe dysfunction (Owen,
Doyon, Petrides, & Evans, 1996), for analysis. To investi-
gate the neuropsychological performance of ADHD regard-
ing age-of-onset, we divided participants into three groups:
(a) ADHD with early-onset (onset by 7 years old); (b)
ADHD with late-onset (onset between 7 and 12 years old);
Lin and Gau 3
(c) non-ADHD controls. We expected that adults with
ADHD would have significant neuropsychological deficits
regardless of the recalled age of onset and the psychiatric
comorbidity.
Method
Participants and Procedure
We recruited adults (aged 17 years and older) who met the
Diagnostic and Statistical Manual of Mental Disorders (4th
ed., text rev.; DSM-IV-TR; American Psychiatric
Association, 2000) diagnostic criteria for ADHD and sub-
threshold ADHD (five symptoms out of nine inattention or/
and hyperactivity/impulsivity symptoms or age of onset
after 7 years) during 2010-2014 at Department of Psychiatry,
National Taiwan University Hospital (NTUH), Taipei,
Taiwan. There were two sources of the participant recruit-
ment. First, new cases of adult ADHD were recruited by
advertisement or referred by psychiatrists or family physi-
cians (new recruitment sample). They first received tele-
phone interview by a trained psychologist using the
modified adult ADHD supplement of the Chinese versions
of the Kiddie Schedule for Affective Disorder and
Schizophrenia–Epidemiological Version (K-SADS-E; Gau
& Chang, 2013). After the telephone interview, those who
were suspected of having the diagnosis of ADHD and their
parents and/or partners were invited. Second, adults with
medical documents of childhood ADHD at NTUH who
possibly met the DSM-5 criteria for adult ADHD at the time
of recruitment were invited (clinical follow-up sample).
These adults first came to our clinic when they were 6-10
years old, and they and their parents received clinical evalu-
ation and a formal diagnostic interview. All of them were
followed up in the Department of Psychiatry, NTUH with a
medical document of their psychopathology, treatment, dif-
ficulties, and improvements.
After signing the informed consent, all the participants
received formal psychiatric diagnostic interview as well as
the Conners’ Adult ADHD Diagnostic Interview (Conners,
Erhardt, & Sparrow, 1999) by the corresponding author.
Then they received the modified adult version of the ADHD
supplement (Gau & Chang, 2013; Lin et al., 2015; Lin et al.,
2016) of the K-SADS-E (Gau, 2007) and SADS (Ni, Lin,
Gau, Huang, & Yang, 2017) for childhood/current diagnosis
of ADHD and other psychiatric disorders, respectively, by
the trained interviewers. The interviewers were all blind to
the sources of referral. Among adults with ADHD, 93
(43.5%) had been diagnosed with ADHD at childhood with
valid medical records at the same hospital, and 121 (56.5%)
were recruited by advertisement and referral. Through
advertisement on the Internet, newspaper, and posters at the
colleges and public places, we recruited adult controls
according to the age and sex distributions of the ADHD
group. Participants in the control group received the same
clinical and psychiatric evaluations as adults with ADHD to
ensure that they did not have lifetime or current diagnosis of
ADHD.
Participants were excluded if they had any systemic
medical illness such as cardiovascular disease, learning dis-
ability, autism spectrum disorder, and full-scale IQ < 80.
Considering the possibility of cognitive decline, we
excluded participants who were older than 40 years. After
excluding individuals with incomplete data and those older
than 40 years, there were 183 adults with DSM-5 ADHD
left in the study. Adults with DSM-5 ADHD were classified
into two groups by recalled age-of-onset: early-onset group
(onset <7 years old) and late-onset group (onset between 7
and <12 years old). Finally, there were 142, 41, and 148
individuals in the early-onset ADHD, late-onset ADHD,
and control groups, respectively. In the late-onset group, six
were from the clinical follow-up sample.
All participants, after clinical and diagnostic interviews,
were assessed by the Wechsler Adult Intelligence Scale−III
for the intelligence, followed by the CANTAB for neuro-
psychological functioning in a fixed order of the tasks. We
asked the participants who currently received medication (n
= 77) for ADHD to hold medication at least 48 hr before the
neuropsychological assessment. All the psychologists
applying the IQ test and CANTAB were blinded for group
status. This study was approved by the Research Ethics
Committee of NTUH, Taiwan (IRB ID, 2010003087R;
ClinicalTrials.gov number, NCT01247610), before the
study implementation.
Interviewer Training
The corresponding author was responsible for training
interviewers for the psychiatric interview including the
Chinese K-SADS-E and SADS interviews (including the
modified adult ADHD supplement). The details of inter-
viewer training were described in the supplementary
material.
Agreement of Age-of-Onset at Two-Time Points
Only 40 individuals in the clinical follow-up sample had
complete data on age-of-onset and ADHD symptoms at
both baseline and follow-up. According to the parental
reports, all the 40 individuals had the age of onset of ADHD
before 7 years at baseline. Of these 40 individuals with
ADHD, 34 individuals reported that their age-of-onset of
ADHD was before 7 years old at adulthood and six between
7 and 12 years old. All the adults with ADHD retrospec-
tively reported later age-of-onset of ADHD at follow-up—
M (SD), 5.51 (1.29) years old in the early-onset group, and
9.17 (1.03) in the late-onset group—than that reported by
their parents to the participants with ADHD at baseline—M
4 Journal of Attention Disorders 00(0)
(SD) 4.19 (1.53) years old in the early-onset group and 4.33
(1.72) in the late-onset group. The result is compatible with
the reports of Todd et al. (2008). For the details of age-of-
onset and ADHD symptom agreement, please refer to the
supplementary material.
Measures
Six CANTAB tasks were selected in this study and classi-
fied into low-executive function (low-EF) tasks and execu-
tive function (EF) tasks according to the EF demands (Lin,
Chen, & Gau, 2013), as described by Rhodes et al. (2005).
The descriptions of neuropsychological tasks are summa-
rized in Table 1.
Statistical Analyses
We conducted analyses by SAS 9.3 (SAS Institute Inc.,
Cary, NC). For demographic data, we used chi-square for
categorical variables and linear regression for continuous
variables. All the results of neuropsychological tasks were
calculated and presented with raw scores. For group com-
parisons of neuropsychological functions, we tested three
models using multiple analyses. In the first model (Model
1), we controlled age, sex, and any psychiatric comorbid-
ity (1 for any psychiatric comorbidity and 0 for none). In
the second model (Model 2), we added current ADHD
medication use (1 for any ADHD medication use and 0 for
none), participant’s education, marital status, job, and
parental marital status into the first model as the covari-
ates, because these demographic variables were signifi-
cantly different between groups. The third model was
similar to the first model, but the overall “any psychiatric
comorbidity” was replaced by the specific psychiatric
comorbidity. In the third model (Model 3), a specific psy-
chiatric comorbidity was controlled one at a time, includ-
ing “depressive disorder,” “anxiety disorder,” “sleep
disorder,” “lifetime oppositional defiant disorder (ODD)”
and “lifetime conduct disorder (CD),” respectively. We
did not control IQ in our analysis because there was no IQ
difference between groups (Table 3). Besides, some
authors thought factors leading to decreased IQ perfor-
mance might be the same factors contributing to neuropsy-
chological dysfunction in ADHD. Therefore, controlling
for IQ may remove part of the variance of neuropsycho-
logical dysfunction associated with ADHD (Nigg, 2001).
The Bonferroni correction method was applied to adjust
for multiple comparisons in the post hoc analysis. The
effect size was calculated for group comparisons of neuro-
psychological functioning based on Cohen’s definition
and was divided into low (0.2-0.5), medium (0.5-0.8), and
high (> 0.8) levels. The significant level was preselected
as p < .05.
Results
Basic Data and ADHD Symptoms
Table 2 summarizes the demographics of the three groups.
Adults with ADHD were significantly older than controls,
and there was no group difference in the distributions of
sex, and parental occupation and education. More partici-
pants in the ADHD groups were married/living with the
couple, did not attend college and more parents were
divorced or separated as compared to the control group.
There were significantly more symptoms of hyperactivity
in the early- than in the late-onset ADHD group and no dif-
ference in inattention and impulsivity symptoms between
two ADHD groups (Table 3). There was no difference in the
proportion of ADHD medication use between early-onset
and late-onset ADHD groups (Table 3).
Comparisons of Neuropsychological Functioning
Among Groups (Table 4)
Cognitive alertness (Reaction Time).  The early-onset ADHD
group had longer reaction time than the control group in the
simple analysis. No group difference was noted in the mul-
tiple analysis.
Sustained attention/signal detectability (RVP).  Both the early-
and late-onset ADHD groups were impaired in the probabil-
ity of hit (sustained attention), A′, and mean latency (signal
detectability) of RVP in both the simple analysis and the
first model of multiple analysis. Only the early-onset ADHD
group showed significant impairment in the probability of
hit, and A′ and both ADHD groups showed impairment in
mean latency in the second model of multiple analysis.
Short-term spatial memory (Spatial Span). For the span
lengths, adults in both ADHD groups had shorter span
length than controls in the simple analysis and only adults
in the late-onset ADHD group had fewer span lengths than
controls in the first model of the multiple analysis. In all
analyses, adults in both ADHD groups made more errors
than those in the control group.
Spatial working memory (SWM).  Both early- and late-onset
groups showed poor strategy utilization and more between
errors in the simple analysis. In the multiple analysis, there
was no group difference in strategy utilization in both two
models and in between errors in the second model of mul-
tiple analysis.
Spatial planning (SOC). Only the early-onset group had
fewer problems solved in minimum moves in the simple
analysis and more mean moves in the five-move problem in
both simple and multiple analyses than the control group.
Lin and Gau 5

Table 1.  Neuropsychological Tasks and the Corresponding Functions.

Neuropsychological tasks Functions measured Descriptions

Low-EF tasks
  Reaction Time
   Simple reaction time Alertness This task assesses alerting stage of arousal (including stages of alerting, phasic responding,
   Five-choice reaction time and signal/noise ratio enhancing) in arousal/activation theory (Pribram & McGuinness,
1975), by recording the reaction time in response to a stimulus with minimal influence
by the movement speed. The participants are asked to press a button on the table and
touch the screen while seeing the stimulus presented in the simple circle (simple-
choice) or one of five circles (five-choice) on the screen. The task lasts for 3 min.
Reaction time (i.e., the mean of time taken to release the button after the presence of
the stimulus) of the simple-choice and five-choice tasks was presented.
  Rapid Visual Information Processing (RVP)
   Probability of hit Sustained attention This task, a 7-min visual continuous performance test (CPT) modified, is used to measure
  A′ Signal detectability sustained attention capacity. Digits (ranging from 2 to 9) appear one at a time (100 digits
(signal/noise per minute) in a random order. The participants are asked to press a response pad
discrimination) when they note any of three number sequences: 3-5-7, 2-4-6, 4-6-8. Three indices were
   Mean latency (ms) Alertness and sustained reported: (a) probability of hits (h): total hits divided by the sum of total hits and total
attention misses; (b) A′: sensitivity to the target, regardless of response tendency, which ranges
from 0 to 1, calculated as A′ = 0.5 + [(h – f) + (h – f) 2] / [4 × h × (1 – f)], and higher
score indicating higher sensitivity of signal/noise discrimination of arousal (Sahgal, 1987)
(f: probability of false alarm: total false alarms divided by the sum of total false alarms and
total correct rejections); and (c) mean latency: mean time taken to respond in correct
responses.
  Spatial Span
  Span length Spatial short-term This task is the visuospatial analogue of the digit span test and lasts for 5 min. Similar to
  Total errors memory the Corsi blocks task (Milner, 1971), it requires the ability to remember the order of
   Total usage errors visual stimuli presented. There are 9 white boxes presented in fixed locations on the
screen. The color of the boxes are changed one after the other in a predetermined
sequence. The end of the sequence is indicated by a sound. The participants are asked
to point to the boxes on the screen in the order as previously presented on the
screen. The task begins with a level of 2-box then gradually up to a level of 9-box. If
the participant fails in all the three sequences in a particular level, the test terminates.
Three indices were presented: (a) span length, the longest sequence successfully
recalled; (b) total errors, the number of times an incorrect box selected across the
whole task; (b) total usage errors, the number of times a box not in the sequence
selected across the whole task.
EF tasks
  Spatial Working Memory (SWM)
  Strategy utilization Strategy usage It is constructed based on a self-ordered search test (Petrides & Milner, 1982), an
  Between errors Spatial working adaptation of Olton’s radial arm maze (Olton, 1987). It takes 4 min to complete the
memory task. Participants are asked to search through the covered box presented on the
screen to find the blue token hidden inside. Only one single token is hidden in one
of the boxes in each trial and the box that had been found to have the token inside
would not have a token again in the subsequent trials. The SWM includes three
difficulty levels (4-box, 6-box, and 8-box), each included four tests. Two indices were
presented: (a) strategy utilization: the number of search sequences starting with a
novel box in both 6- and 8-box; (b) Between errors: total times the participant opens
a box without a blue token because of ever having a token inside in previous trial
across three difficulty levels.
  Stocking of Cambridge (SOC)
   Problems solved in This task assesses spatial planning based on the Tower of London and takes 10 min. At
minimum moves the beginning of each trial, three suspended vertical stockings and three colored balls
   Mean move, 5-move Spatial planning are presented on the screen. Participants are asked to move the colored balls, one
problems in a single move at a time, between stockings to accomplish a goal position within a
specified number of moves in the problem-solving condition, and then they are asked
to copy each move by following the identical sequence of moves played back by the
computer, based on their employment of problem solving in the control condition.
The SOC comprises of four problem sets (2, 3, 4, and 5 moves) to reflect increasing
demands on planning. Two major indices were presented to tap the thinking accuracy:
(a) problems solved in minimum moves: the number of occasions which were
successfully completed in the minimum possible number of moves; (b) mean moves
of the 5-move task: the mean of the number of moves taken in excess of minimum
moves (5 moves) but within the maximum allowed.

(continued)
6 Journal of Attention Disorders 00(0)

Table 1. (continued)
Neuropsychological tasks Functions measured Descriptions

  Intradimensional/Extradimensional Shifts (IED)

  Extradimensional shift
errors
  Pre-extradimensional
shift errors
  Completed stages
Set-shifting This task assesses set-shifting, the ability to learn new problem and shift to a new
Sustained attention
Set-shifting and
sustained attention
strategy from the feedback. It takes 7 min to complete the task. There are two
artificial dimensions: white line and color-filled shapes. Simple followed by compound
(combination of line and shape) stimuli are presented and the participant has to select
which stimulus is right by the feedback. When the participant reaches the criterion
(six consecutive correct responses) at a given stage, the task progresses to the next
stage and the stimuli/rules change. If the participant fails to reach 50 trials at any
stage, the test terminates. There are nine stages. During Stages 1 to 7, the participant
has to selectively maintain attention on the rule based on the color-shape dimension,
i.e., intradimensional shift, and then at Stages 8 and 9, the participant has to shift
attention to the rule based on the white line dimension, i.e., extradimensional shift
(Luciana & Nelson, 1998). Three indices were presented: (a) extradimensional shift
errors: the number of errors in the extradimensional stages; (b) pre-extradimensional
errors: the number of errors made prior to the extradimensional shift (Stages 1 to 7)
of the task, i.e., failing to keep current rule; (c) completed stage: the number of stages
that were completed.

Note. EF = executive function.

Table 2.  Demographic Data.

1. ADHD 2. ADHD Statistics
Onset < 7 Onset 7 to <12 3. Control
  (n = 142) (n = 41) (n = 148) F P Comparison
Age, M (SD) 27.60 (6.23) 28.74 (6.12) 24.74 (5.03) 13.73 <.0001 1,2>3
Gender, n (%) χ2  
 Male 85 (69.86) 26 (63.41) 85 (57.43) 0.52 .77  
Education  
  Postgraduate and above 34 (23.94) 8 (19.51) 48 (32.43) 10.78 .03  
 College 84 (59.15) 28 (68.29) 91 (61.49)  
  Senior high school and below 24 (16.90) 5 (12.20) 9 (6.08)  
Job
 Professional 7 (5.93) 2 (4.88) 6 (4.05) Fisher’s exact test .01  
  Technical personnel 66 (46.48) 18 (43.90) 42 (28.38)  
  Nontechnical personnel 69 (48.59) 21 (51.22) 100 (67.57)  
Marital status (n = 140) (n = 41) (n = 131) χ2  
 Singlea 113 (80.71) 27 (73.17) 119 (90.84) 10.57 .03  
  Married or living with couple 27 (19.29) 8 (26.83) 12 (9.16) (df = 4)  
Parental education (n = 133) (n = 40) (n = 138)  
  College and above 79 (59.40) 19 (47.50) 74 (57.81) χ2 (df = 4) = 9.03 .06  
  Senior high school 36 (27.07) 8 (20.00) 36 (28.13)  
  Junior high school and below 18 (13.53) 13 (32.50) 18 (14.06)  
Parental jobb (n = 132) (n = 40) (n = 130)  
 Professional 16 (12.12) 4 (10.00) 17 (13.08) Fisher’s exact test .16  
  Technical personnel 87 (65.91) 20 (50.00) 87 (66.92)  
  Nontechnical personnel 29 (21.97) 16 (40.00) 26 (20.00)  
Parental marital status (n = 138) (n = 40) (n = 132)  
  Married or living with couple 105 (76.09) 32 (80.00) 117 (88.64) Fisher’s exact test .02  
  Separated or divorced 26 (18.84) 5 (12.50) 8 (6.06)  
 Others 7 (5.07) 3 (7.50) 7 (5.30)  
a
Including divorced or separated (two in early-onset group and one in the control group).
b
If both parents had jobs, we presented the category of expected higher income here.

Set-shifting (IED).  Adults with early- and late-onset ADHD simple analysis, but not in the multiple analyses. Only the
had more extradimensional shift errors than controls in the early-onset ADHD group had more pre-extradimensional
Lin and Gau 7

Table 3.  ADHD Symptoms, Intelligence, and Psychiatric History Among Groups.
1. ADHD 2. ADHD Statistics
Onset <7 Onset 7 to <12 3. Control
  (n = 142) (n = 41) (n = 148) F P Comparison
ADHD symptoms_K-SADS
 Past
  Inattention 8.61 (0.76) 8.54 (0.64) 0.34 (0.78) 1755.15 <.0001 1,2>3
  Hyperactivity 4.10 (1.87) 3.34 (2.01) 0.14 (0.45) 235.25 <.0001 1>2>3
  Impulsivity 2.16 (1.07) 1.08 (1.05) 0.09 (0.32) 217.08 <.0001 1,2>3
 Current
  Inattention 8.18 (1.15) 7.80 (1.05) 0.12 (0.4) 2966.04 <.0001 1,2>3
  Hyperactivity 3.04 (1.83) 2.37 (1.74) 0.03 (0.22) 180.26 <.0001 1>2>3
  Impulsivity 1.73 (1.13) 1.44 (1.05) 0.04 (0.24) 155.10 <.0001 1,2>3
Intelligence, M (SD)
  Full IQ 110.95 (11.61) 109.97 (12.58) 112.01 (10.95) 0.88 .42  
  Performance IQ 110.51 (13.20) 109.54 (12.89) 112.29 (12.08) 1.41 .24  
  Verbal IQ 110.13 (11.76) 109.43 (13.29) 110.64 (10.60) 0.31 .73  
History of ADHD medication use, χ2 (df = 2) value  
n (%)a
 Overall 97 (68.31) 24 (58.54) 0 (0.0) 1.36 (1) .24  
 Methylphenidate 81 (57.04) 19 (46.34) 0 (0.0) 1.46 (1) .23  
 Atomoxetine 20 (14.08) 8 (27.59) 0 (0.0) 0.72(1) .40  
Current ADHD medication use, χ2 (df = 1) value  
n (%)a
 Overall 62 (43.66) 15 (36.59) 0 (0.0) 0.65 .42  
 Methylphenidate 62 (43.66) 15 (36.59) 0 (0.0) 0.65 .42  
 Atomoxetine 0 (0) 0 (0) 0 (0.0) — —  
Psychiatric comorbidity χ2 (df = 2) value  
  Any psychiatric disorder 107 (72.35) 30 (73.17) 11 (7.43) 150.56 <.0001 1,2>3
  Major depression 9 (6.34) 3 (7.32) 0 (0.0) Fisher exact test .001 1,2>3
  Dysthymia 25 (17.61) 5 (12.20) 1 (0.68) <.0001 1,2>3
  Bipolar disorder 2 (1.41) 0 (0.0) 0 (0.0) .54 1,2>3
   Any anxiety disorder 51 (35.92) 16 (30.02) 6 (4.05) <.0001 1,2>3
  Sleep disorders 42 (29.58) 9 (21.95) 1 (0.68) <.0001 1,2>3
  ODD (lifetime) 71 (50.71) 22 (53.66) 5 (3.38) χ2 (df = 2) 89.84 <.0001 1,2>3
  CD (lifetime) 50 (35.71) 14 (34.15) 5 (3.38) 50.29 <.0001 1,2>3

Note. Anxiety disorders did not include obsessive-compulsive disorder in this study. K-SADS = Kiddie Schedule for Affective Disorders and Schizo-
phrenia; ODD = oppositional defiant disorder; CD = conduct disorder.
a
Only two ADHD groups were compared. History of medication use = current and ever use of medication.

shift errors in the simple analysis, and fewer completed
stages in the simple analysis and the first model of multiple
analysis.
For the neuropsychological functions which were
impaired in ADHD, the effect size of two ADHD groups
over the control group ranged from 0.4 to 0.9, referring a
medium to large effect size (Supplementary Table S1).
There was no significant difference of neuropsychological
functions between the two ADHD groups in the simple and
multiple analyses.
Influence of the Specific Psychiatric Comorbidity
When we performed the multiple analysis that controlled
for age, sex, and the psychiatric comorbidity one at a time
(Model 3), neuropsychological tasks with significant group
difference were the same as what was revealed in the simple
analyses (Supplementary Table S2).
Influence of ADHD Medication Use
Adding the current medication treatment for ADHD and
demographic variables into the multiple analyses models
(Model 2), we found that the statistical difference of SWM
between errors, IED extradimensional shift errors, and RVP
probability of hit and A′ between adults with late-onset
ADHD and the controls did not reach the significant level
(p > .05; Table 4). Becuase current ADHD medication treat-
ment was reversely correlated with the performance in sim-
ple Reaction Time (Pearson correlation, r = .22, p < .001),
RVP probability of hit, (r = −.14, p = .01), RVP A′ (r = −.14,
p = .01), total usage errors in Spatial Span (r = .21,
8 Journal of Attention Disorders 00(0)

Table 4.  Comparison of Neuropsychological Functioning Among Adults With Early-Onset, Late-Onset ADHD, and Controls.
Multiple analysis
1. ADHD onset 2. ADHD onset 7 3. Control
<7 (n = 142) to <12 (n = 41) (n = 148) Simple analysis Model 1a Model 2b

Neuropsychological tasks M (SD) F Comparison F Comparison F Comparison

Reaction Time
  Simple reaction time (ms) 337.2 (67.54) 320.47 (43.52) 312.01 (43.47) 7.66*** 1>3 2.14 1.88  
  Five-choice reaction time (ms) 354.36 (57.72) 336.68 (36.91) 329.07 (47.12) 9.09*** 1>3 3.56 2.28  
Rapid Visual Information Processing
  Probability of hit 0.69 (0.19) 0.7 (0.14) 0.79 (0.16) 14.48*** 1,2<3 6.86** 1,2<3 5.36** 1<3
  A′ 0.92 (0.05) 0.92 (0.04) 0.95 (0.04) 14.86*** 1,2<3 6.86** 1,2<3 5.40** 1<3
  Mean latency (ms) 426.86 (90.63) 427.26 (84.67) 386.71 (66.23) 10.37*** 1,2>3 5.48** 1,2>3 6.21** 1,2>3
Spatial Span
  Span length 7.1 (1.38) 7.24 (1.22) 7.91 (1.16) 15.83*** 1,2<3 3.51* 1<3 1.76  
  Total errors 13.22 (6.3) 14.76 (5.91) 10.99 (6.91) 7.24*** 1,2>3 5.37** 1,2>3 6.44** 1,2>3
  Total usage errors 1.53 (1.4) 1.63 (1.32) 0.8 (0.97) 15.69*** 1,2>3 8.23*** 1,2>3 4.80** 1,2>3
Spatial Working Memory
  Strategy utilization 32.06 (5.91) 32.8 (5.16) 29.92 (5.85) 6.76*** 1,2>3 0.81 0.55  
  Between errors 21.49 (16.95) 21.71 (14.58) 11.57 (12.92) 18.11*** 1,2>3 5.10** 1,2>3 2.41  
Stocking of Cambridge
  Problems solved in minimum moves 9.05 (1.76) 9.32 (2.11) 9.82 (1.68) 6.90** 1<3 1.85 0.84  
  Mean move, 5-move problem 6.41 (1.27) 6.04 (1.13) 5.82 (1.08) 9.27*** 1>3 4.74** 1>3 3.87* 1>3
Intradimensional/Extradimensional Shift
  Extradimensional shift errors 5.78 (7.41) 6.53 (7.61) 3.56 (3.32) 6.77** 1,2>3 3.40* 1.11  
  Pre-extradimensional shift errors 6.52 (4) 6.55 (3.21) 5.32 (2.42) 5.49** 1>3 2.38 1.19  
  Completed stages 8.77 (0.85) 8.78 (0.62) 8.98 (0.18) 4.88** 1>3 3.83* 1>3 1.36  

a
Adjusting for age, sex, and any psychiatric disorder.
b
Adjusting for age, sex, any psychiatric disorder, participant’s education, job, marital status, current medication use for ADHD, and parental marital status.
*p < .05. **p < .01. ***p < .001.

p < .001), SWM between errors (r = .27, p < .001), IED
extradimensional shift errors (r = .17, p = .006), and com-
pleted stages (r = −.12, p = 0.03), ADHD medication treat-
ment might share the variance of the correlation between
neuropsychological deficits and ADHD. Adults with poorer
neuropsychological performance were more likely to
receive medication treatment in this naturalistic study,
implying a self-selection bias.
Discussion
Main Findings
With the intention to validate the DSM-5 adult ADHD age-
of-onset criterion by neuropsychological functioning, this
study found that adults with DSM-5 ADHD, regardless of
age-of-onset, had significant deficits in sustained attention
(RVP probability of hit), signal detectability (RVP A′), spa-
tial working memory (SWM between errors), and set-shift-
ing (IED extradimensional shift errors) after considering
the influences of age, sex, and any psychiatric comorbidity,
but deficits in alertness (Reaction Time) and planning (SOC
five-move task) were only noted in adults with early-onset
ADHD. Current medication was correlated with poorer
neuropsychological performance, implying a self-selection
bias in this study.
Psychiatric Comorbidity and Neuropsychological
Functioning in ADHD
Following our previous findings of no difference in func-
tional impairment, quality of life (Lin et al., 2015), and psy-
chiatric comorbidity (Lin et al., 2016) between the early- and
late-onset adult ADHD groups, this work further revealed
comparable neuropsychological dysfunctions between
adults with early- and late-onset ADHD diagnosis accord-
ing to the DSM-5 criteria. Although this was not the first
study to validate the age-of-onset criterion by neuropsycho-
logical functioning, this was the first study controlling for
each psychiatric comorbidity one at a time. We found no
other psychiatric disorder could explain the neuropsycho-
logical deficits in adults with ADHD. Under a comprehen-
sive psychiatric interview, adult ADHD diagnosis, even
with recalled onset between 7 and 12 years and possible
recall bias, would be valid. Late-onset adult ADHD is not a
pseudodiagnosis that just coincidentally presents the symp-
toms of other psychiatric disorders.
Neuropsychological Deficits in Early- and Late-
Onset ADHD
In this study, we tested two models of multiple analyses,
which revealed similar results. When we looked into the
Lin and Gau 9
differences of the results between Models 1 and 2, we found
that spatial working memory was an important neuropsy-
chological function that made participants decide to use
medication, because, in Model 2, current ADHD medica-
tion use was associated with worse SWM function (p = .04)
independent of group, age, sex, and other demographic
variables. Therefore, the loss of group differences of SWM
at Model 2 was largely due to the share of the variance of
medication use and ADHD. The loss of significant differ-
ence between the late-onset and the control groups in RVP
might be due to small sample size of the late-onset ADHD
group and lack of power to detect the differences when
there were many variables in the analysis. The demographic
variables had nonsignificant effects on the results. The fol-
lowing discussion is therefore mainly based on the results
of the first model of the multiple analyses.
Adults in both early- and late-onset ADHD groups had
a longer latency of correct response in RVP, suggesting
impaired psychological processes involving sustained
attention (van der Meere, Shalev, Borger, & Gross-Tsur,
1995). Meanwhile, our finding that only adults with
early-onset ADHD had longer reaction time in both sim-
ple and five-choice reaction time tasks suggested that
alertness, which was important in the attentional process
(Nigg, 2005), was impaired only in early-onset ADHD, or
that adults with late-onset ADHD had milder impairment
in the attentional network than those with early-onset
ADHD. Inattentive symptoms of late-onset ADHD might
emerge through neuropsychological mechanisms other
than alertness, such as impaired signal detectability of
attention, sustained attention, and/or other executive
dysfunctions.
We had an intriguing finding that adults with late-onset
ADHD had the noninferior performance of SOC as com-
pared with controls despite that they had significant deficits
in spatial working memory (SWM) and short-term spatial
memory (Spatial Span). During the process of planning,
one has to organize response sequences and to monitor exe-
cution which places a load on working memory (Owen
et al., 1996). The dissociated correlation of late-onset
ADHD with spatial (working) memory and spatial planning
might be explained by a different load of working memory
in CANTAB. SOC in the CANTAB, with the maximum
five-move task, required less load of (working) memory
than the Spatial Span, with maximum nine digits, and
SWM, with maximum eight-box tasks. It was possible that
adults with late-onset ADHD had deficits in spatial (work-
ing) memory but not planning in the lab setting, and a load
of spatial (working) memory in the SOC task did not pro-
voke impaired performance in the late-onset ADHD.
Further studies with well-controlled tasks for the divided
neuropsychological mechanisms with different loads are
needed to verify our hypothesis.
In this study, adults with early-onset ADHD had signifi-
cantly more previous and current hyperactive symptoms
than those with late-onset ADHD, but there was no correla-
tion of hyperactive symptom count and reaction time (sim-
ple task, F = 0.01, p = .90, five-choice task, F = 0.58, p =
.45) and SOC (five-move tasks, F = 0.02, p = .90) after
controlling for the inattentive symptom count. Higher
hyperactive symptom count did not explain the differential
neuropsychological presentations of early- and late-onset
ADHD in this study.
ADHD is a heterogeneous disorder with a various com-
bination of neuropsychological deficits across different
affected persons, and the presentations and emergence of
symptoms are also correlated to individual adaptation to
environmental and developmental constraints (Sonuga-
Barke, 2005). Our finding that these late-onset ADHD
adults had relatively preserved planning ability implies that
they may have fewer dysfunctional brain circuits and thus
developed symptoms later or their preserved abilities could
compensate for ADHD symptoms during their early child-
hood. Nevertheless, when ADHD persisted into adulthood,
adults with ADHD who recalled onset between 7 and 12
years showed no less functional impairment and had a com-
parable decrease of life quality as that recalled onset by 7
years (Faraone, Biederman, Spencer, et al., 2006; Lin et al.,
2015). More recently, Moffitt et al. (2015) found in their
longitudinal study that individuals with adult-onset ADHD,
despite subjective complaints of cognitive deficits, had
fewer tested cognitive deficits than those with childhood-
onset regardless of current ADHD status. Although the
symptoms of adult-onset ADHD might be explained by
substance dependence and other psychiatric disorders, their
findings implied that neuropsychological functions might
be correlated to the timing of emergence of ADHD symp-
toms, that is, late-onset ADHD might be a minor form of
ADHD as compared with early-onset ADHD. The author
also suggested a possibility that adult-onset ADHD might
be an independent disorder etiologically different from
childhood-onset ADHD (Moffitt et al., 2015). Further lon-
gitudinal and imaging studies are needed to elucidate the
role of the Brain Function × Environment interaction in the
onset of ADHD in a developmental view.
Limitations
The findings shall be interpreted with some limitations.
First, the participants were either clinic-based subjects or
recruited via advertisement from the same university hospi-
tal. Thus, the generalization of the results is questionable.
Second, the intelligence level was relatively high in our
sample, and therefore our results could not be generalized
to the population of lower intelligence. Third, this study
might suffer from recall bias of age-of-onset. Fourth,
although we asked the participants who were currently
10 Journal of Attention Disorders 00(0)
treated with medication to hold it for more than 48 hr before
they received CANTAB tests, we could not rule out the pos-
sibility of residual or withdrawal effect of medication. Fifth,
the sample size of the late-onset ADHD group was rela-
tively small and might lack the statistical power to detect
the small group difference, especially between early- and
late-onset ADHD. Further longitudinal study with a larger
sample size of the late-onset group would be helpful to elu-
cidate the difference between early- and late-onset ADHD
and eliminate the recall bias.
Conclusion
Our study showed that adults with late-onset ADHD had
comparable neuropsychological deficits, including sus-
tained attention, signal detectability, spatial working mem-
ory, short-term spatial memory, and set-shifting as their
early-onset counterparts and these deficits could not be
explained by the presence of other psychiatric comorbidi-
ties. Therefore, extending the age-of-onset criterion for
adults did not overdiagnose ADHD in adults, even based on
the recalled information. Adults with late-onset ADHD had
no deficits in spatial planning and alertness, and the preser-
vation of these neuropsychological abilities might postpone
the true or recall of occurrences of ADHD-related difficul-
ties during the development. Further longitudinal studies
are warranted to elucidate the role of the interactions
between brain functions and the environment in the onset of
ADHD at a developmental perspective.
Acknowledgments
We would like to express our thanks to Ms. Yu-Lun Lin for data
management and psychiatric interviews, and all participants for
their time and efforts.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
article.
Funding
The author(s) disclosed receipt of the following financial support
for the research, authorship, and/or publication of this article: This
work was supported by National Health Research Institute (NHRI-
EX100-10008PI, NHRI-EX101-10008PI, NHRI-EX102-10008PI;
NHRI-EX103-10008PI), Taiwan.
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Author Biographies
Yu-Ju Lin, MD, MS in epidemiology, is a board-certificated child
psychiatrist. She has worked as child psychiatrist in Far Eastern
Memorial Hospital, a medical center in North Taiwan and is the
adjunct visiting physician in National Taiwan University Hospital
and a lecturer in National Taiwan University. Her research interest
is in epidemiology, symptomatology, and neuropsychological
functioning of ADHD across life span.
Susan Shur-Fen Gau, MD, PhD, is the director of Department of
Medical Genetics and ex-director of Department of Psychiatry,
National Taiwan University Hospital and the professor of the
Department of Psychiatry, Department of Psychology, School of
Occupational Therapy, Graduate Institute of Brain and Mind
Sciences, Graduate Institute of Epidemiology and Preventive
Medicine, and Graduate Institute of Clinical Medicine, National
Taiwan University, Taiwan. She has been conducting the clinical,
follow-up, neuropsychological, treatment, neuroimage, and
genetic studies on ADHD and autism spectrum disorder as well as
national survey of mental disorders in children and adolescents in
Taiwan.