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Original Article
Cognitive rehabilitation in patients with
nonamnestic mild cognitive impairment
Majid Barekatain, Maryam Alavirad1, Mahgol Tavakoli2, Golita Emsaki2, Mohammad Reza Maracy3
Department of Psychiatry, Behavioral Sciences Research Center, School of Medicine, Isfahan University of Medical Sciences, 1Department of
Psychiatry, Isfahan University of Medical Sciences, 2Department of Psychology, School of Educational Sciences and Psychology, University of
Isfahan, 3Department of Epidemiology and Biostatistics, School of Public Health, Isfahan University of Medical Sciences, Isfahan, Iran

Background: The nonamnesic type of mild cognitive impairment (na‑MCI) is predementia state with subtle decline incognitive
domains except memory. Although cognitive rehabilitation (CR) has been investigated in amnesic type of MCI, we could not find any
trial that rehabilitated na‑MCI exclusively. We studied the effectiveness of CR on na‑MCI. Materials and Methods: This study was
a blinded, randomized clinical trial. Individuals with age of 60 years or more, complete self‑directedness and diagnosis of na‑MCI,
based on Neuropsychiatry Unit Cognitive assessment tool, were selected. The 51 patients were randomly assigned into three groups:
CR, lifestyle (LS) modification, and the control group (CG). Neuropsychological tests for executive functioning were assessed at the
baseline, after the interventions, and 6 months later. Results: The mean score of the “design fluency” test increased significantly in
CR, compared to LS and CG (P = 0.007). In “five‑point” test, mean score increased significantly in CR (P = 0.03). There was higher
mean score of Behavioral Rating Inventory of Executive Function for adults in CR (P = 0.01). Conclusion: Consideration of the MCI
subtypes allows us to target specific cognitive domains, such as information processing, for better CR outcome. CR may result in
better performance of executive functioning of daily living.

Key words: Cognitive rehabilitation, mild cognitive impairment, nonamnestic

How to cite this article: Barekatain M, Alavirad M, Tavakoli M, Emsaki G, Maracy MR. Cognitive rehabilitation in patients with nonamnestic mild cognitive
impairment. J Res Med Sci 2016;21:95.

INTRODUCTION state and dementia.[3,4] The reported prevalence of MCI

in the elders has been 3–42%.[5] All of the cognitive
World’s population is experiencing aging, [1] that domains including memory, language, visuospatial
leads to serious health, economic, political, and social capacity, praxis, and executive function may be
complications. Degenerative process in aging usually impaired by MCI. MCI can be divided into amnestic
affects cognitive state negatively. The cognitive MCI (a‑MCI) and nonamnestic MCI (na‑MCI) depending
decline may result in disrupted ability to work, live on whether or not memory is impaired. [4,6] These
independently, or maintain normal social interaction, subtypes are further subdivided into “single‑domain” or
which finally will be diagnosed with dementia. It is “multi‑domain,” depending on the number of cognitive
expected that more than 16 million of elder adults will domains impaired.[7] Comprehensive diagnosis of MCI
suffer dementia until 2050 in the United States. The cost would be relied on low performances on at least two
of this developing trend in dementia will be more than neuropsychological tests within a cognitive domain.
1 trillion dollars.[2] Memory and executive functioning are considered
the main cognitive domains for a‑MCI and na‑MCI,
Mild cognitive impairment (MCI) has been established respectively.[8]
as a transitional syndrome between normal cognitive
Many clinical trials have been proposed to decrease the
Access this article online progression of MCI to dementia with pharmacological
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Address for correspondence: Prof. Majid Barekatain, Department of Psychiatry, Behavioral Sciences Research Center, School of Medicine,
Isfahan University of Medical Sciences, Nour Hospital, Ostandari Street, Isfahan, Iran. E‑mail: barekatain@med.mui.ac.ir
Received: 12‑05‑2016; Revised: 22‑06‑2016; Accepted: 18‑07‑2016

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Barekatain, et al.: Cognitive rehabilitation in na‑MCI

or nonpharmacological interventions.[9,10] Pharmacological effects on the function of the frontal lobe in patients with
treatments, such as cholinesterase inhibitors, memantine, Parkinson’s disease.[20]
huperzine A, Vitamin E, and Ginkgo biloba did not show any
benefits to decelerate progression of MCI into dementia.[9] To the best of our knowledge, all of the CR interventions
Nonpharmacological interventions have been also taken have been designed for MCI as a single entity or for a‑MCI
into consideration because of lower side effects, patients’ as a specific subtype. We could not find any rehabilitation
preference, and lack of effectiveness of the drugs. Change trial that was dedicated exclusively for na‑MCI. Thus, we
from a sedentary lifestyle to moderate physical activity has sought to evaluate the impact of CR on na‑MCI.
beneficial effects on cognitive functioning, and preliminary
evidence suggests that such change may reduce the MATERIALS AND METHODS
incidence of dementia.[10] Among the nonpharmacological
therapies in MCI, cognitive rehabilitation (CR) has been Study design and participants
highlighted.[11] CR is the process of relearning cognitive skills This study was approved by the Ethics Committee and
that have been lost due to brain impairment. If skills cannot the Research Council of the Behavioral Sciences Research
be relearned, other capacities will be used to compensate the Center, Isfahan University of Medical Sciences. All study
lost cognitive functions.[12] Some studies have shown that CR participants provided written informed consent before the
interventions may be effective on memory improvement in evaluations. The experimental principles were in accordance
a‑MCI, especially for compensatory strategies of prospective with the Declaration of Helsinki. This was a blinded,
and episodic memory deficits.[13,14] randomized clinical trial. After the announcement about
the screening of cognitive functioning for the retired staff
In many neurological conditions, CR has been shown to of public schools in Isfahan, Iran, 213 persons agreed to
be effective on executive functioning, attention, and speed be screened [Figure 1]. Through a semi‑structured clinical
of information processing. [15‑20] In multiple sclerosis, interview, a neuropsychiatrist screened 213 participants.
CR was effective on the speed of processing.[15,16] The Individuals with the age of 60 years or more, at least 5 years
effectiveness of CR in acquired brain injury was also of education, complete self‑directedness in activities of daily
reported.[17‑19] CR was effective in mild to severe head living, lack of any active or history of major psychiatric and
trauma at any time after trauma.[19] CR also had positive neurological disorders, and lack of any drug misuse were

Clinical interview, MMSE, and

NUCogfor eligibility (n = 213)

Excluded (n = 162)
♦Not meeting inclusion criteria (n = 161)
♦Declined to participate (n = 1)

Randomized allocation (n = 51)

Clinical and neuropsychological
assessments

Allocated to cognitive Allocated to lifestyle Allocated to control group

rehabilitation (n = 17) modification (n = 15) (n = 19)
Clinical and neuropsychological Clinical and neuropsychological Clinical and neuropsychological
assessments (after 8 weeks) assessments (after 8 weeks) assessments (after 8 weeks)

Lost to follow-up (n = 1) Lost to follow-up (n = 0) Lost to follow-up (n = 2)

Clinical and neuropsychological Clinical and neuropsychological Clinical and neuropsychological
assessments (n = 16, after 8 weeks) assessments (n = 15, after 8 weeks) assessments (n = 17, after
6 months)

Analyzed (n = 17) Analyzed (n = 15)

Analyzed (n = 19)
♦Excluded from analysis (n = 10) ♦Excluded from analysis (n = 0)
♦Excluded from analysis (n = 2)

Figure 1: Study assignment and outcomes

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Barekatain, et al.: Cognitive rehabilitation in na‑MCI

screened for na‑MCI. Patients with diagnosis of dementia cognitive domains of attention, visual‑spatial, memory,
and individuals who used medications that may affect executive function, and language, which has a maximum
cognitive state were excluded from the study. Based on the score of 20 for each domain. In the Persian version of
inclusion and exclusion criteria, 51 patients were recruited NUCog, the cutoff point for separating MCI from normal
to this study. The participants were assigned into three individuals and patients with dementia are 86.5, 75,
groups using block‑designed randomization that each block respectively.[23] Subjects with memory score of 16 or more in
contained of three samples. Participants in the first group the memory subscale and 11 or less in the executive function
underwent “CR,” the second trained for “Life Style” (LS) subscale were considered as na‑MCI.
modification, and the third was “Control Group” (CG) who
received only educational pamphlets after the end of the Widely accepted neuropsychological tests were selected
study [Figure 1]. Participants in each group were unaware as a battery to address executive function. The selected
of the existence of other groups. The baseline characteristics tests were: Tower of London (TOL) test to assess executive
of the groups are presented in Table 1. functioning, especially deficits in planning, [24] Color
trail test  (CTT) to measure remote divided attention and
Neuropsychological assessments sustained attention,[24,25] Five‑point test for figural fluency
Mini–mental state examination (MMSE) was used for all of function to assess divergent thinking and shifting cognitive
the 213 participants to exclude patients with dementia.[21] The set,[24] Go‑no go test for sustained attention and response
Neuropsychiatry Unit Cognitive assessment tool (NUCog) control,[24] category fluency test to evaluate self‑monitoring
was selected to confirm MCI diagnosis.[22] It contains five and working memory,[24] and design fluency test to measure
cognitive flexibility and fluency in generation of visual
Table 1: Demographic characteristics of the study patterns.[26]
participants in three groups
n (%) P Clinical assessments
CR Life style Control The Mini International Neuropsychiatric Interview was
group modification group
used to rule out major psychiatric disorders.[27] General
(n=17) group (n=15) (n=19)
Gender
Health Questionnaire was also carried out to determine
Male 1 (5.6) 3 (20) 2 (10.5) 0.45 mental health state and individuals with scores lower than
Female 16 12 17 22 were enrolled.[28]
Education
High school or less 8 (44.1) 4 (23.5) 7 (36.8) 0.59 The Behavioral Rating Inventory of Executive Function
University 9 11 12 in Adults (BRIEF‑A) was used to evaluate the behavioral
Diabetes aspects of executive functioning in daily living throughout
Yes 6 (35.3) 2 (13.3) 5 (26.3) 0.36 this study.[29]
No 11 13 14
Hypertension Health‑promoting lifestyle profile test was used to measure
Yes 7 (41.2) 6 (40) 5 (26.3) 0.58
the healthy‑promoting behaviors’ of lifestyle at 6 dimensions:
No 10 9 4
Nutrition, exercise, health responsibility, stress management,
Ischemic heart disease
interpersonal support, and self‑actualization.[30]
Yes 2 (11.8) 1 (6.7) 3 (15.8) 0.71
No 15 14 16
Hyperlipidemia Remediation programs
Yes 6 (35.3) 3 (20) 7 (36.8) 0.52 Cognitive rehabilitation group
No 11 12 12 Group sessions were conducted 2 h/week for a total of
Hypothyroidism 8 weeks. The first session was dedicated to explain the
Yes 3 (17.6) 1 (6.7) 4 (21.1) 0.5 basic elements of the protocol, obtaining information, and
No 14 14 15 gathering participants’ cognitive problems. All participants
Osteoarthritis collaboratively agreed on symptoms of attention and executive
Yes 3 (17.6) 4 (26.7) 6 (31.6) 0.62 functioning as the problem areas that they would like to
No 14 11 13
manage better. The next three sessions were matched for the
Insomnia
“attention process training” emphasized on direct attentional
Yes 2 (11.8) 1 (6.7) 1 (5.3) 0.75
training that was a hierarchical treatment protocol.[31] The
No 15 14 18
Chronic pain
fifth and sixth sessions were matched for “goal management
Ye 1 (5.9) 2 (13.3) 1 (5.3) 0.64 therapy” that used metacognitive strategies to improve
No 16 13 18 patients’ ability to organize and achieve goals in “real‑life”
CR = Cognitive rehabilitation situations. Participants learned how to use mindful attention

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Barekatain, et al.: Cognitive rehabilitation in na‑MCI

and goal setting to recognize and stop “absentmindedness” Leven’s test and Box’s test supported homogeneity of the
and “automatic pilot” to reduce daily errors and “slips.”[32,33] variances and the covariances during follow‑up times and
The last two sessions dedicated to problem‑solving therapy between the groups, respectively. Demographic data were
that facilitated identification of problems, awareness of analyzed using one‑way ANOVA. The repeated measures
various aspects of problems, generation of alternatives, ANOVA used to compare “between and within subjects”
initiation of action, and self‑monitoring.[34,35] effects. Post hoc analysis was done using Bonferroni test.
The significance level was set at 0.05. All analysis was
Lifestyle group performed by intention to treat method. Statistical analysis
Lifestyle modification has beneficial effects on quality of life, was conducted using IBM SPSS Statistics 20.0 (IBM, Somers,
and preliminary evidence suggested that such change may USA) statistical software.
reduce the incidence of dementia. However, its evidence
on cognitive benefits toward more intellectual engagement RESULTS
has been insufficient. [10] Nutritional supplements to
treat deficiency may improve cognitive performance, The average age of the study was 65.3 ± 4.8 years. The
but supplements on top of a healthy diet cannot be average age of LS, CR, and CG groups were 63.9  ±  4.0,
recommended. [36] In the lifestyle modification group, 66.2 ± 5.5, 65.7 ± 4.7 orderly, which did not show any
discussion about theoretical and practical items for healthy significant differences (P = 0.37).
LSs was explained. The role of physical activity in prevention
of cognitive problem, importance of nutrition in preserving Demographic characteristics of the three groups depicted
normal cognition, relation of biorhythms (especially quality in Table  1. In baseline, mean scores of NUCog were
and quantity of sleep) and cognition, impact of enriched 78.4 ± 2.4, 79.0 ± 3.25, 79.7 ± 2.5 for CR, LS, and CG groups,
social relationship in healthy aging, and role of stress in respectively (P = 0.37).
brain degeneration and stress management were explained
during the eight sessions of LS group. Table 2 showed comparisons of mean scores of the
neuropsychological and the clinical assessments between
Procedure the three groups through repeated measures. The interaction
Clinical interview and selection of eligible individuals were effect between time and group effects was significant for
conducted by a neuropsychiatrist. Identified goals were BRIEF test (P  <  0.01). This means that CR significantly
selected by the research team and adapted operationalized increased the quality of executive functioning of daily living
rehabilitation protocol for CR was designed. Therapy was through the time of the study.
administered in a university clinic by a Ph.D. student in
psychology who was well‑trained in CR program, had a DISCUSSION
minimum of 10 supervised hours with adult rehabilitation
clients, and completed an instructional program for using CR usually includes specific cognitive tasks or stimulus
the materials. The rehabilitation tasks chosen for each programs to improve current cognitive state or prevent
session were specific to the participants’ existing abilities more cognitive decline in MCI.[9‑14] The previous studies
and emphasize on the cognitive profile. There were written revealed that cognitive training programs may improve
materials corresponding to specific topics that could be memory performance. [37] However, there has been
modified to match each participant’s level of education and controversy about the effectiveness of rehabilitation on
comprehension. Patients were given homework to practice other cognitive domains except the memory.[37]
the skills during the consequent week. They should practice
homework and describe feedback in the next session. All Many studies reported the effectiveness of CR for
participants were evaluated at the baseline, at the end of executive functioning in healthy elders, Parkinson’s
interventions 2 months later, and at the 6th month after the disease, multiple sclerosis, and traumatic brain injury.[15‑20]
starting day by a trained resident of psychiatry (rater) with Executive function is considered like a shelter which
the neuropsychological and clinical assessment tools. The provides numbers of behavioral capabilities and related
rater was unaware of the participants’ allocation into the skills for better independent activities.[38] We proposed
3 groups. A well‑trained psychiatry resident evaluated the to evaluate the rehabilitation of executive function by
participants with MMSE and NUcog. She was not aware of “attentional training,”[31] “goal management therapy,”[32,33]
the participants’ assignment or type of intervention. and “problem‑solving”[34,35] methods.

Statistical analysis This study showed that in the field of information

The distribution pattern of the variables was checked in the processing, the mean score of “design fluency” test
study groups, using Shapiro test that supported normality. increased significantly in CR, compared to LS and

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Barekatain, et al.: Cognitive rehabilitation in na‑MCI

Table 2: Comparisons between executive function tests in the three groups within follow‑up times using analysis of
covariance repeated measures
Mean±SD P
CR Lifestyle Control Follow‑up* Group effect**
modification group
Go/no‑go
Baseline 3±0 2.8±0.4 2.7±0.6 0.231 0.2
After 8 weeks 3±0 2.9±0.3 2.9±0.2
6 months later 3±0 2.9±0.3 3±0
Color trials test
Base line 1.1±0.7 0.9±0.6 1.1±0.4 0.1 0.7
After 8 weeks 0.9±0.6 0.9±0.5 0.9±0.4
6 months later 1.2±0.6 1.1±0.5 1.2±0.8
Design fluency
After 8 weeks 9.7±4.9 12.2±4 14±5.6 <0.001 0.007
After 8 weeks 12±4 17.2±4 16.5±8.8 P (1, 2)=0.001, P (1, 3)=0.001, P (1, 2)=0.03, P (1, 3)=0.01,
6 months later 10.4±4.9 17±4.9 17.5±6.4 P  (2, 3)=1 P  (2,3)=1
Category fluency
Base line 16±4.44 18.15±3.64 19.67±3.5 0.2 0.2
After 8 weeks 18.40±4.95 19.92±2.28 18.40±2.7
6 months later 17.60±3.79 19.38±4.11 19.40±3.48
Five point
Base line 20.13±7.81 25.85±12.33 25.50±6.9 0.4 0.03
After 8 weeks 19.60±6.7 25.92±5.90 26.57±5.37 P (1,2)=0.1, P (1,3)=0.04, P (2,3)=1
6 months later 22±8.15 25.84±8.6 28±7.14
Tower of London
Base line 30.80±3.34 30.54±3.68 32.47±2.16 0.025 0.616
After 8 weeks 31.93±3.36 33.23±1.96 32.46±2.23 P (1, 2)=0.057, P (1, 3)=0.022,
6 months later 32.73±3.05 32.76±2.00 32.86±1.92 P  (2, 3)=1
MMSE
Base line 27.67±1.49 29±1.35 27.53±1.99 0.5 0.09
After 8 weeks 28.20±1.01 28.30±1.45 27.60±1.63
6 months later 28±1.96 28.92±1.44 27.86±1.72
Behavioral rating inventory of
executive function in adults
Base line 124.27±25.21 107.54±18.94 110.79±16.60 <0.001 0.145
After 8 weeks 116.20±24.86 102.23±22.92 103.57±12.41 P (1, 2) <0.001, P (1, 3)=0.001,
P  (2, 3)=0.679
6 months later 110.60±21.29 109.60±24.40 95.50±12.37
Health promoting lifestyle
profile test
Base line 138.7±21.6 135.7±30.6 144.6±24.9 0.075 0.772
After 8 weeks 142.4±33.9 151.6±28.3 144.2±21.6
6 months later 135.1±25.8 146.0±25.9 143.0±22.3
*Time, 1 = Baseline, 2 = After 8 weeks of intervention, 3 = After 6 months, **Group, 1 = Rehabilitation group, 2 = lifestyle group, 3 = Control group, Comparison between paired
groups were made with Bonferoni test. MMSE = Mini–mental state examination; CR = Cognitive rehabilitation; SD = Standard deviation

CG. This test is considered to address the assessment CR than the other two groups. The “go‑no go” test did not
of problem‑solving, planning, and organizing deals reveal any differences between the 3 groups.
as parts of executive functioning. In “five‑point” test,
mean score increased significantly in CR compared to Similar interventions in Parkinson’s disease and traumatic
CG. This result also supported rising of information brain injury revealed improvement in attention control,
processing. Alternation in attention control, which especially inhibition and shift of attention.[18,20] However, in
includes supervisory processes, self‑monitoring, and this study, CR did not improve attention control. It may due
inhibition, was assessed by “category fluency” and “go‑no to the lesser impairment of attention inhibition in MCI.[39]
go” test. The mean scores of category “fluency test” did
not increased significantly following the interventions. The CTT test that assesses flexibility and switching did not
However, an increasing trend in performance was seen in show any differences between the 3 groups. In a systematic

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Barekatain, et al.: Cognitive rehabilitation in na‑MCI

review and meta‑analysis study about the effectiveness of The limitations of this study were low sample size, which
computer‑based cognitive training in MCI, CTT test results did not permit generalization of the results. The follow‑up
also did not show any effect.[40] period was relatively short for a longstanding condition
such as MCI. Lack of brain imaging and other biomarkers
TOL test was used to assess goal setting including planning to confirm the diagnosis of MCI was another limit. We
and problem solving. No differences between the three administered same neuropsychological tests at baseline
groups were recorded. However, “goal management and at posttreatment, which might lead to learning effect.
therapy” were effective in traumatic brain injury.[19] However, we tried to overcome this problem by considering
the CG.
BRIEF‑A is sensitive to measure subtle executive changes in
MCI in real life.[29] The changes in the mean score of BRIEF‑A CONCLUSION
showed improvement of subtle executive functioning in
CR compared to LS and CG groups. Although many of Consideration of subtypes in patients with MCI could
the neuropsychological tests did not reveal any difference, allow us to target specific cognitive domains, increasing the
it was noteworthy that improvement in activities of daily likelihood of a positive response to cognitive remediation.
shown after rehabilitation. A systematic review on CR In na‑MCI, information processing would be selected as
and cognitive training for early‑stage Alzheimer’s disease the probable target for effective rehabilitation programs.
and vascular dementia showed conflicting result that Although CR did not show prominent improvement
rehabilitation interventions did not apply a significant effect in neuropsychological capacity, it could result in better
on the daily life of patients with early‑stage Alzheimer.[41] performance of executive functioning of daily living.

Several studies pointed to the effectiveness of CR in younger Acknowledgments

patients with Parkinson’s disease, multiple sclerosis, and We thank the “association of retired staff of public schools”
head trauma.[15‑20] For long‑lasting functional benefits, any CR in Isfahan, Iran.
program needs to restore the neural connections that support
the cognitive skills. In other words, brain neuroplasticity is Financial support and sponsorship
an essential element for cognitive remediation. Considering
This project was the thesis of Maryam Alavirad, which
the fact that neuroplasticity reduces with age,[6] patients with
was funded by the Isfahan University of Medical
MCI, that usually are elders, may have less potential capacity
Sciences (Research number 393560).
to obtain changes in neuronal connections. This may explain
the reason for less effectiveness of CR in MCI in comparison
Conflicts of interest
with other brain disorders.[41]
There are no conflicts of interest.
Awareness to cognitive deficits might increase the chance
AUTHORS’ CONTRIBUTION
for recovery after rehabilitation interventions. [41] Thus,
patients with na‑MCI that have less insight into their decline
MB contributed in the conception of the work, conducting
of executive functioning (in comparison to a‑MCI and
the study, supervision of data gathering, interpretation of
insight to memory decline) may obtain less benefit from
the results, writing the manuscript, and revising the draft
rehabilitation.[4,41]
of the final version of the manuscript. MA contributed in
the conception of the work, data gathering, and writing
The health‑promoting lifestyle profile test did not show any
the manuscript. MT contributed in the conception of
effectiveness between the 3 groups. Similar studies revealed
the work, planning the intervention, and supervision
results with controversies.[36]
of the interventions performance. GE contributed in
Strengths and limitations the performance of the interventions. MRM performed
The subjects of this study were selected from patients with statistical analysis and interpretations of the results. All
na‑MCI exclusively. To the best of our knowledge, this is the authors read and approved the final manuscript.
first study, which dedicated to CR interventions on na‑MCI
subtype. One of the strengths of this study was its design REFERENCES
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