Journal of Clinical and Diagnostic Research. 2015 Jul, Vol-9(7): VE01-VE06 1
DOI: 10.7860/JCDR/2015/13392.6186 Review Article
Keywords: Ageing, Cognitive impairment, Dementia,Neuro-psychiatric disorders
Cognition refers to the higher mental functions of the brain and
includes thinking, language, memory, attention, perception,
planning, intelligence and problem solving [1]. They are subjective in
nature and may be affected by number of factors including ageing,
stress, various medical conditions such as hypertension, dementias,
Parkinson’s disease (PD) and psychiatric illnesses like schizophrenia,
bipolar disorders [2,3]. All these disorders have some components
of or predispose to cognitive decline or dysfunction.
Cognitive dysfunction is the decline in intellectual functions such
as thinking, reasoning and remembering, which interferes with daily
functioning. Considering the ever increasing population of the elderly
and stress related problems, cognitive decline is an epidemic in the
making [4]. Thus, memory enhancers are predicted to play a great
role in the near future. Cognitive Enhancers (CE) are molecules (drugs,
supplements, nutraceuticals, and functional foods) or various brain
stimulation methods that improve some aspect of brain function or
cognition [5]. They may be Pharmacological Cognitive Enhancers
(PCE) or Non-Pharmacological Cognitive Enhancers (NPCE). PCE
include herbal medicines (asparagus, gingko biloba, and ginseng)
and pharmaceutical drugs. Only a few PCE are approved for
enhancing cognition, most do not have established effiacy, have
out of label use or are under research. Also, the ethical issues of
using PCE in healthy ageing subjects are of great concern. These
concerns have promoted the use and research for NPCE.
NPCE include physical exercise, sleep, meditation, computer
training, brain stimulation, yoga and music. These are largely
ignored and neglected, despite being relatively safe and culturally
accepted. Cochrane Reviews on non-pharmacological interventions
have found relative paucity of evidence regarding the effects of
these interventions. This review describes various NPCE, the role
of NPCE in ageing and various neuro-psychiatric disorders, and
the current status of Cochrane database recommendations. We
searched the Pubmed database for all articles and reviews having
the terms ‘non pharmacological and cognitive’ in the title, published
till 2014 since the year 2000. A total of 11 results displayed, out of
Psychiatry Section
Non Pharmacological Cognitive
Enhancers – Current Perspectives
Cognition refers to the mental processes involved in thinking, knowing, remembering, judging, and problem solving. Cognitive dysfunctions
are an integral part of neuropsychiatric disorders as well as in healthy ageing. Cognitive Enhancers are molecules that help improve
aspects of cognition like memory, intelligence, motivation, attention and concentration. Recently, Non Pharmacological Cognitive
Enhancers have gained popularity as effective and safe alternative to various established drugs. Many of these Non Pharmacological
Cognitive Enhancers seem to be more effiacious compared to currently available Pharmacological Cognitive Enhancers. This review
describes and summarizes evidence on various Non Pharmacological Cognitive Enhancers such as physical exercise, sleep, meditation
and yoga, spirituality, nutrients, computer training, brain stimulation, and music. We also discuss their role in ageing and different
neuro-psychiatric disorders, and current status of Cochrane database recommendations. We searched the Pubmed database for the
articles and reviews having the terms ‘non pharmacological and cognitive’ in the title, published from 2000 till 2014. A total of 11 results
displayed, out of which 10 were relevant to the review. These were selected and reviewed. Appropriate cross-references within the
articles along with Cochrane reviews were also considered and studied.
AnKur SAchdevA1, KuldiP KumAr2, Kuljeet Singh AnAnd3
which 10 were relevant to the review. Appropriate cross-references
within the articles were also considered and studied. Cochrane
review database was searched for the terms ‘exercise’, ‘sleep’,
‘yoga’, ‘computer training’, and ‘music therapy’. Appropriate results
pertinent to review were selected.
A range of strategies from environmental stimulation to exercise
have been tested and developed to enhance cognition. Most
interventions target either underlying disease pathologies or the
processes underlying normal cognition.
Physical exercises, especially aerobic exercises, are documented
to enhance and preserve cognitive functions. Hillman suggested
that regular aerobic exercises improve cognition and have benefiial
effects on brain functions [6]. Exercise is thought to enhance
production and release of neurotrophins specially, brain-derived
neurotrophic factor (BDNF) and also induces a cascade of molecular
and cellular processes that favor angiogenesis, neurogenesis and
synaptogenesis [7]. Physical activity is also hypothesized to improve
mood and cognition by increasing the synaptic transmission of
monoamines as well as enhancing the release of endorphins.
The effect of exercise has been studied across different age groups.
Physical exercise was demonstrated to benefi intelligence and
academic functions in school age children [8] as well as improve
different aspects of cognition in older adults with and without
pathological cognitive decline [9]. A recent meta-analysis [10]
demonstrated that aerobic exercise improves cognitive functions
such as memory, processing speed, attention, and executive
functions. It may be concluded that physical activity helps to preserve
mental abilities throughout aging and across all age groups.
Exercise also benefis subjects suffering from Mild Cognitive
Impairment (MCI) or early-stage dementia [10]. Evidence suggests
that exercising in young leads to better cognitive output in elderly
and it follows dose-response effect [11]. The prefrontal and medial
temporal cortices, particularly hippocampus, are sensitive to
exercise with trophic responses leading to increased volume and
Ankur Sachdeva et al., Non Pharmacological Cognitive Enhancers – Current Perspectives
2 Journal of Clinical and Diagnostic Research. 2015 Jul, Vol-9(7): VE01-VE06
exposure therapy was followed by sleep [29]. A study found sleep
problems to be associated with cognitive errors seen in anxiety and
depression [30]. Depressed patients treated with olanzapine showed
improvement in sleep quality and it correlated with improvement in
cognition and illness severity [31].
Sleep disturbances appear even before cognitive symptoms in
the preclinical phase of AD. Poor quality sleep has been linked
with greater cognitive decline and increased risk of mild cognitive
impairment and dementia. Cognition declines faster in older adults
who have disturbed sleep than those who sleep well [32]. Lee et
al., concluded that patients with ADHD have more sleep problems
compared with controls, which positively correlated with the
cognitive functions [33]. In conclusion, sleep enhances some
aspects of cognition but future research is needed to establish its
role as a cognitive enhancer and to evaluate the timeframe for which
the benefis persist.
MEdItAtIon And yogA
Meditation has been emphasized to promote mental well-being,
enhance attention and other cognitive capacities. Traditional
approaches like Buddhist mindfulness meditations and Zen
meditations have resurged along with several modern group-based
standardized meditations. Meditation practice has been associated
with increased attention performance and cognitive flxibility in
experienced meditators as compared to control subjects [34].
A systematic review found preliminary positive effects of meditation
on attention, memory, executive function, processing speed, and
general cognition in age related cognitive decline and degenerative
disorders [35]. Cochrane database review found no signifiant
benefis of meditation therapy in children or adults diagnosed
with ADHD [36]. Another cochrane database review found that
transcendental meditation is comparable and as effective in
reducing anxiety as other relaxation therapies [37]. Mind fulness
interventions have been found moderately effective in treating
negative symptoms in Schizophrenia and can be useful adjunct to
pharmacotherapy [38].
Yoga has its origins in Indian culture and is the oldest known form of
meditation. Yoga based interventions appear to signifiantly improve
several cognitive domains in elderly such as immediate and delayed
recall, verbal and visual memory, attention, working memory, verbal
flency, executive function and processing speed [39]. Yoga has
emerged as an effective and feasible add on therapy in schizophrenia,
with special benefis in improving social cognition and negative
symptoms [40]. However, a review comparing yoga to exercise found
no short term evidence of effects on positive symptoms, negative
symptoms, quality of life and social function [41]. Yoga was found to
benefi individuals with depressive symptoms, including quality of life
and cognition [42]. Some of the consistent effects of yoga practice
include stress reduction, emotion regulation, improved mood and
well being. It can be concluded that yoga and meditation are safe
and effective traditional methods for enhancing cognition and their
use should be encouraged. Considering the multiple benefis of
Yoga, the World Health Organization has declared 21 st June as the
‘International Yoga Day’ [43].
Spirituality is considered as an important component of overall wellbeing. Spirituality helps an individual cope with stressors in the world
and strives towards his potential. Inspite of growing recognition of
religion and spirituality as part of the treatment/rehabilitation plan for
cognitively impaired patients, there are limited studies that focus on
its role for enhancing cognition.
Studies suggest that a few aspects of spirituality may assist in
decreasing depressive symptoms, including cognitive errors [44].
Evidence shows that religious beliefs and spirituality may lead to
enhanced levels of psychological well being, coping capacities,
increases in hippocampal cerebral blood flw [12]. Exercise is
considered protective for Alzheimer’s Disease. Several studies have
reported reduced incidence of dementia or cognitive deterioration
with physical activity [13]. Daily physical training of 30 minutes
reduces the number of hospitalizations in AD patients [14]. Exercise
is considered as an adjunctive treatment and a preventive measure
in Parkinson’s Disease (PD). Specifi core areas for physical exercise
therapy in PD includes cueing strategies to improve gait, cognitive
movement strategies to improve transfers, special exercises to
improve balance and training of joint mobility and muscle power in
order to improve physical capacity [15].
Patients with serious mental illnesses may also benefi with exercise.
Exercise has been shown to effectively treat depression and anxiety
disorders along with enhancing cognition [16,17]. Physical exercise
is an important component of stress reduction programs and has
shown on psychological well-being [18]. Exercise also improves
symptoms such as reduced self esteem and social withdrawal. A
cochrane systematic review found exercise to signifiantly improve
negative symptoms of mental state along with quality of life [19].
No effect on positive symptoms was noted. However, one recent
review found that exercise programs had no signifiant effect on
symptoms of mental health [20]. We can conclude that there is
converging evidence on several levels that physical exercise benefis
and preserves cognition throughout the lifespan and across various
neuropsychiatric disorders.
Sleep is considered important for effective functioning of brain
and cognition. Researchers have suggested that wide variety of
cognitive functions ranging from attention and memory, to language
and reasoning, are affected due to lack of adequate sleep [21].
Sleep-specifi manipulations have been found to effectively enhance
cognitive functions [22].
Sleep facilitates several cognitive functions such as working
memory, language processing, creativity and decision making [23].
Short periods of day time naps benefi memory performance and
concentration, even in subjects who are not sleep deprived. Sleep
facilitates memory consolidation as well as subsequent acquisition
of new learning material [23]. Sleep also promotes the integration
and reprocessing of fresh memories into the existing reservoir of
long-term memories [24].
Surprisingly, inspite of so much research on sleep and its role
in memory enhancement, it is usually neglected in therapeutic
aspects. The sleep state might be particularly well suited as a target
for the enhancement of memory capacities. First, sleep can be
timed in relation to learning so that it optimally supports encoding
and memory consolidation. This may be possible by introducing
short naps before learning of new information [25]. The second way
to augment memory during sleep is to manipulate memory and/or
sleep directly in such a selective way that it targets the processing
of specifi memory functions during sleep [22]. Pharmacological
agents can also be used to modulate the processing of memories
during sleep. However, new learning of declarative and procedural
memories during sleep is still out of question [22].
One of the clinical applications of sleep may be in restoring normal
cognitive functioning. Many neuro psychiatric and degenerative
disorders are accompanied by changes in sleep patterns and
dysfunctions of memory. Memory for words improved in patients
with schizophrenia following stimulation of slow oscillations with
transcranial direct stimulation during sleep [26]. However, it was
observed that administration of olanzapine (which increases slow
wave sleep), and GABA agonist eszopiclone, failed to normalize
memory consolidation in schizophrenia patients [27,28]. This
calls for further research to clarify and establish the role of sleep
for enhancing cognition in these patients. In the treatment of
spider phobia, increase therapeutic effectiveness was found if Ankur Sachdeva et al., Non Pharmacological Cognitive Enhancers – Current Perspectives
Journal of Clinical and Diagnostic Research. 2015 Jul, Vol-9(7): VE01-VE06 3
fewer symptoms of distress, depression, anxiety and more positive
affect [45]. Individuals with strong religious convictions often utilize
positive religious coping behaviours to assist with stress reduction
and emotion regulation. Kaufman et al., [46] found that spirituality
and religious practices, such as prayer, Bible reading, and
devotions, may decrease the rate of cognitive decline of Alzheimer’s
patients. Religion and spirituality benefi participants in psychosocial
rehabilitation programs.
In general, spirituality strengthens a sense of self and self-esteem and
helps in countering stigma and shame with positive self-attributions
[47]. Higher spiritual inclination are found to have positive effects for
persons diagnosed with Schizophrenia [48] and are associated with
optimism and resiliency against stress among individuals recovering
from substance abuse [49]. Spirituality empowers confience,
presents a sense of purpose and opportunities for growth and
positive change.
However, spirituality in itself is not free of negative consequences.
Negative religious coping activities such as expressing anger at God,
attributing negative events to God‘s punishment has been linked
to greater affective distress, including greater anxiety, depression,
suicidality and lower self-esteem. Furthermore, emotional struggles
and feelings of rejection can be reinforced by religious communities
who see mental disorders as signs of moral or spiritual failure. Hence,
caution needs to be taken while using spirituality in neuropsychiatric
disorders and enhancing cognition.
Music has been recently emphasized as an alternative way of
enhancing cognition. Music therapy and other musical activities
like listening to music, singing and playing a musical instrument
have shown promise in neuropsychiatric disorders, especially in
Two main types of music therapy are described: receptive and active
music therapy. “Receptive music therapy consists of listening to
music by the therapist who sings or selects recorded music for the
recipients. In active music therapy, recipients are actively involved
in the music-making and playing instruments. The participants are
encouraged to participate and improvise with instruments or voice,
and with dance, music or singing” [50].
In Alzheimer’s patients, music part of memory seems interestingly
spared by the disease [51]. Elderly adults who frequently play a
musical instrument are less likely to develop dementia. Positive
effects on scores on working memory, perceptual speed, and
motor skills were noted in elderly population after piano lessons
[52]. Music, amongst other cognitive exercises like puzzles and
crosswords, was proposed to have the strongest neuro-protective
effect [52]. A study showed the effectiveness of group music therapy
on depression and cognitive functions, particularly short term recall
function among elderly persons with mild and moderate dementia
[53]. Choir music was found to reduce depression, increase levels
of motivation, purpose, wellbeing and quality of life in people with
dementia [54].
Music therapy may have a role in psychosocial rehabilitation
in enduring mental illnesses. It helps improve an individual’s
psychological and physiological well-being, social cohesiveness and
emotional expressions [55]. It helps in reducing social isolation, and
improves participation in external events. Music therapy signifiantly
improved aggression/hostility in pre adolescents with emotional,
learning, and behavioural problems. A randomized trial of music
therapy for in patients with Schizophrenia found benefis in negative
and cognitive domains but not so in positive symptoms [55]. Gold
et al., concluded that music therapy sessions help improve mental
state and global functioning in Schizophrenia. Therefore, it adds to
the standard care of treatment [56]. A Cochrane review suggested
that music therapy improves mood, is accepted by people with
depression and acts as a protective factor in clients with suicidal
ideation [57]. We can conclude that initial results of including music
in cognitive training are encouraging. However, quantitative research
based evidence is lacking in this fild.
cognItIvE tRAInIng
Techniques of stimulating brain and cognition are widely practiced
in areas of sports and rehabilitation. There have been studies and
debates about different types of techniques involved in cognitive
enhancement in ageing population, dementia and neuropsychiatric
Visualization techniques require users to vividly imagine themselves
performing a task (running a race, going to a store), repeatedly
imagining every movement and the associated feelings [58]. These
exercises are hypothesized to work by activating the neural networks
which are involved in skill execution simultaneously as the task is
held, optimizing neural reorganization.
The concept of enhancing working memory (WM) through targeted
training has mounting evidence. Training related increase in WM
capacity can improve a range of important cognitive skills. The
training paradigms usually teach effective approaches to encode,
register, and retrieve from WM [59]. Such methods of ‘strategy
training’ have been successfully used in children with Down
syndrome [60] to supplement specifi WM defiits. Strategy
training was reported to slow the decline of, and perhaps improve,
WM in older adult populations [61]. Self-report measures indicating
improved everyday memory in trained older adults suggest utility
of this training module. ‘Core training methods’ are designed to
target ‘domain-general WM mechanisms’. These involve repetition
of cognitively stimulating high intensity WM tasks, which improves
WM [59]. Core training programme found benefis in cognition and
intelligence in young healthy adults, in cohort of children diagnosed
with ADHD [62], quality of life improvements in patients with
multiple sclerosis [63], and patients with stroke and Schizophrenia
patients [64].
Memory therapy in the mild to moderate stages of AD can be
successful, provided it is individualized based on patient’s daily
problems and their residual cognitive capacities. Cognitive training
is an effiient method to delay cognitive decline in persons with MCI.
Some techniques of cognitive stimulation make use of ecological or
virtual environments to compensate age related cognitive decline.
Several types of cognitive trainings are available aimed at improving
memory, learning, attention, executive functions, mnemonic
techniques, or global cognition [65].
Mnemonic strategies can be seen as strong and reliable enhancers
of learning and memory capacity. The ability to cope with verbal
or numerical information becomes increasingly important and
complex as age progresses. Mnemonics have been shown to be
effective for retaining easy-to-learn material with small effect sizes.
For diffiult tasks, effect sizes may be as high as Cohen’s d of 3 or
4. But mnemonics have not proved effective in age-related cognitive
decline [66].
Cognitive Remediation therapy (CRT) aims to improve cognitive
processes in dementias and neuropsychiatric disorders. CRT
expects that changes will maintain over follow up period and
will translate into real world benefi. A meta analysis of cognitive
remediation in Schizophrenia by McGurk et al., found that CRT
resulted in signifiant improvements in most domains of cognition
[67]. Cognitive adaptation training is a structured program that
utilizes measures such as mobile phone reminders and medication
administration aids that help with daily functioning [68]. Similarly,
social cognition remediation programs have been developed
especially in regard to improving emotional perception, and facial
affect recognition.
Ankur Sachdeva et al., Non Pharmacological Cognitive Enhancers – Current Perspectives
4 Journal of Clinical and Diagnostic Research. 2015 Jul, Vol-9(7): VE01-VE06
Brain stimulation techniques were developed for therapeutic
purposes in psychiatry or neurology. They act by inflencing regions
of the brain non-specifially rather than by some physiological
alterations. Some of these methods are non invasive, while other
achieves greater selectivity by placing electrodes inside or on the
brain. Non invasive techniques include Transcranial Direct Current
Stimulation (tDCS) and Transcranial Magnetic Stimulation (TMS).
Invasive methods include Deep Brain Stimulation (DBS) and direct
vagus nerve stimulation (dVNS). Some of these techniques exhibited
cognition enhancing effects on healthy individuals [69].
While most of these methods help in encoding of memory and
learning, a few like DBS may directly modulate and affect memory
systems [70]. tDCS and TMS are the most researched. Anterior
temporal lobe tDCS and paired pulse TMS stimulation during
encoding help enhance speed of recall [71,72]. Studies have found
tDCS to enhance performance on working memory tasks, learning
and recall of words on stimulation of left dorso-lateral prefrontal
cortex (DLPFC) during encoding [73]. TMS and tDCS have been
found to enhance procedural skills by inflencing brain plasticity
and learning motor tasks by stimulation of the motor areas useful
in rehabilitation and therapy. fMRI guided studies have shown
stimulation of the right cortical region to be most successful. The
most common side effects reported are headaches, local pain and
confusion. The most serious risk is the occurrence of seizure.
There is limited data on cognitive restoration or enhancement in
neuropsychiatric disorders. Effiacy of rTMS on cognitive performance in depressed individuals has yielded mixed results. Among 13
trials comparing active and sham rTMS, 8 did not report signifiant
differences in regards to cognitive functions [74]. However, some
studies did report improvement in cognitive functions after rTMS over
the left DLPFC. Many studies found benefis in psychomotor speed
and concentration, mood, executive functions and visuospatial
ability, procedural learning, verbal learning, working memory and
language in depressive disorders, post stroke depression and
depression with PD [75,76]. tDCS in depression has also shown
cognitive improvements in different domains [77]. Signifiant effect
of rTMS in cognitive functions in schizophrenia has been observed
[78]. However, one study did not fid any cognitive improvement
[79]. Ahmed et al., found signifiant improvement in global cognitive
functioning by rTMS applied over the bilateral DLPFCs in Alzheimer
dementia [80] which was replicated in other RCTs [74]. In ADHD,
a recent cross over study found benefiial effects of right DLPFC
rTMS in attention [81]. rTMS has been proposed as a potential tool
that may improve the symptoms of autism spectrum disorders,
specially error monitoring and post-error response correction [82].
We can conclude that these methods have benefiial effects on
cognitive enhancement, although extensive research is needed to
evaluate long term benefis.
coMPutER BASEd IntERvEntIonS
The rapid popularity and the concept of internet gaming addiction
in adolescents have generated concern among practitioners and
policy makers. However, Computer based repetitive stimulation
allows training of various cognitive tasks, which promotes
cognitive well being. Computer based training programs have
shown improvements of memory, attention, executive function
and processing speed along with working memory and episodic
memory in young and older adults [83]. There has been focus on
enhancing long term memory or brain plasticity to prevent dementia
and age related cognitive decline [84]. There have been variable
effect sizes of computerized training on the cognitive domains.
Processing speed and perceptual measures show medium to large
effect sizes, while memory domains are only in the small or medium
range [83]. It has been shown that improved cognitive performances
maintained for 6 months after suspension of training, supporting
the idea that age-related decline cannot be only halted, but actually
reversed. However, Whitlock et al., reported no effects of gamebased cognitive training on visuo spatial navigational abilities and
memory [85]. Moreover, increased aggression and reduction of
empathy have been reported for violent computer games [86].
Intensive, computer based cognitive training has showed improvement in verbal learning and memory in MCI subjects [87]. A
cognition-specifi computer based cognitive training program in PD
patients found improvement in attention and memory [88]. Cognitive
remediation therapy, delivered via computerized programs, of
varying length and complexity has been found effective in people
with severe, chronic mental illnesses such as Schizophrenia, bipolar
disorders and depression. Still, better study designs are needed
to develop and individualize computer based therapies for different
neuropsychiatric disorders.
concluSIon And FutuRE RESEARch
We summarized the effects of non pharmacological interventions
on cognition in healthy individuals, ageing population as well as in
neuropsychiatric disorders. All the non pharmacological interventions
can be envisioned to be somewhat effective in maintaining and
perhaps improving optimal levels of cognitive capabilities. Some of
the NPCE such as sleep, meditation, exercise, music, spirituality,
are based on widely accepted traditional habits. Others like, brain
stimulation, cognitive training and computer based interventions are
modern and complex.
Most of these are cost effective and relatively free of adverse
effects. Still, many issues are unresolved and need clarifiation. The
most important is of ethical concerns. Voices have been raised on
possible issues of doctors “playing Gods” by trying to enhance what
is inherited, interference in nature, autonomy of patients, selective
improvements in cognitive domains, and improper use of NPCE for
competition in today’s world.
These methods are still evolving and need strong research based
evidence before being conclusively used in clinical setting. They
may well be used as adjuvant therapeutic tools in the early stage
of neurodegenerative conditions. Comparative research on the
variety of currently existing NPCE is strongly needed to evaluate the
similarities and differences amongst them, so as to individualize the
therapy based on specifi cognitive profie of the patient.
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PArticulArS OF cOntriButOrS:
1. Senior Resident, Department of Psychiatry and Drug De-addiction, Post Graduate Institute of Medical Education and Research,
Dr Ram Manohar Lohia Hospital, New Delhi, India.
2. Associate Professor, Department of Psychiatry, Vardhman Mahavir Medical College and Safdarjang Hospital, New Delhi, India.
3. Professor, Head of the Department, Department of Neurology, Post Graduate Institute of Medical Education and Research, Dr Ram Manohar Lohia Hospital,
New Delhi, India.
nAme, AddreSS, e-mAil id OF the cOrreSPOnding AuthOr:
Dr. Ankur Sachdeva,
Senior Resident, Department of Psychiatry and Drug De-addiction, Post Graduate Institute of Medical Education and Research,
Dr Ram Manohar Lohia Hospital, Park Street, New Delhi-110001, India.
FinAnciAl Or Other cOmPeting intereStS: None.
Date of Submission: Feb 11, 2015
Date of Peer Review: Apr 28, 2015
Date of Acceptance: may 23, 2015
Date of Publishing: jul 01, 2015