You are on page 1of 20

State of the Science

Mechanism of Action for Nonpharmacological Therapies


for Individuals With Dementia
Implications for Practice and Research
Sandy C. Burgener, PhD, RN, FAAN; Ying-Ling Jao, PhD, RN; Joel G. Anderson, PhD, HTP; and
Ann L. Bossen, PhD, RN
ABSTRACT

The current review addresses the need for increased use of evidence-based, nonpharmacological therapies for individuals with dementia. To facilitate understanding of the potential efficacy of nonpharmacological therapies on cognitive functioning for individuals with dementia, the mechanisms of action for
selected therapies are described, including the assessment method used to identify the mechanism. The
strength of evidence supporting each therapy was evaluated, with some therapies demonstrating strong
support and others only moderate support for their effectiveness and mechanism of action. Therapies
with the strongest support include (a) cognitive training/stimulation, (b) physical exercise, and (c) music.
Therapies with moderate support include (a) biofield, (b) meditation, (c) engagement with a naturally
restorative environment, and (d) social engagement. Although the strength of evidence varies, together
these therapies offer treatments designed to improve cognitive functioning, have low risks and adverse
effects, and have the potential for widespread accessibility, thereby increasing the potential range of
therapies for individuals with dementia.
[Res Gerontol Nurs. 20XX; X(XX):XX-XX.]

Historically, the development of pharmacological therapies for dementia has consumed a majority of research resources and involvement of the scientific community. Concomitantly, research testing nonpharmacological therapies
has not fared well in meta-analyses assessing intervention
efficacy for dementia, as addressed in a recent review of
meta-analyses by Cohen-Mansfield et al. (2014). Yet, along
with these current and historical trends, increased evidence and theoretical understandings have evolved from
the physical sciences that offer support for nonpharma-

cological interventions designed to assist individuals with


dementia to maintain function, slow disease progression,
or both (Herring et al., 2009; Rodriguez & Verkhratsky,
2011). This increased support for nonpharmacological
therapies comes at a time when emerging drug therapies
have proven to be less effective than anticipated in ameliorating the cognitive loss inherent in dementia (Lleo,
Greenberg, & Growdon, 2006; Tschanz et al., 2011; Zec
& Burkett, 2008). Increasingly, members of the scientific
community are recognizing the need for multiple therapies

Dr. Burgener is Associate Professor Emerita, College of Nursing, University of Illinois, Urbana, Illinois; Dr. Jao is Assistant Professor, College of
Nursing, Pennsylvania State University, Philadelphia, Pennsylvania; Dr. Anderson is Assistant Professor and Roberts Scholar, School of Nursing,
University of Virginia, Charlottesville, Virginia. Dr. Jao is also Adjunct Associate Professor, and Dr. Bossen is Postdoctoral Scholar, College of Nursing,
University of Iowa, Iowa City, Iowa.
The authors have disclosed no potential conflicts of interest, financial or otherwise.
Address correspondence to Sandy C. Burgener, PhD, RN, FAAN, Associate Professor Emerita, College of Nursing, University of Illinois, 210 S. Goodwin Street, Urbana, IL 61801; e-mail: sburgenr@illinois.edu.
doi:10.3928/19404921-20150429-02

Research in Gerontological Nursing Vol. x, No. x, 20xx

Burgener et al.

to effectively treat dementia (Foster, Rosenblatt, & Kuljis,


2011; Iqbal & Grundke-Iqbal, 2011).
Many nonpharmacological therapies share common
theoretical underpinnings with evidence generated from
basic science studies. In addition, basic science has identified external factors (e.g., enriched stimulation) that influence neuropathology and, consequently, impact cognitive
function and reduce the risks of neurodegenerative disorders. However, these factors have been tested primarily
in animal models and relatively few studies have evaluated the impact in clinical trials (Briones, Suh, Hattar, &
Wadowska, 2005; Burke & Barnes, 2006; Kramer, Erickson,
& Colcombe, 2006). On the other hand, nonpharmacological therapies have been applied and evaluated in clinical
trials and have demonstrated positive outcomes at the
phenotype level. However, the mechanisms underpinning
those interventions are only beginning to be systematically
described and linked to evidence.
To enhance use of and grant support for nonpharmacological therapies, clinicians and researchers need to better
understand the state of the science regarding (a) mechanisms of action, (b) strength of evidence, and (c) current
trends in research. The most efficacious interventions are
those that target specific behaviors and identify the mechanism of action. Individually, evidence for these therapies
may have been presented in systematic reviews or metaanalyses, yet no published report was found that synthesized the evidence from multiple interventions while also
addressing the strength of evidence for the mechanism of
action for the therapy. Although many of these therapies
have multiple outcomes, the focus of the current review
centers on therapies designed to improve cognitive functioning. As such, the current report uniquely addresses
the need for further understanding of the mechanisms of
action specifically on cognitive outcomes in individuals
with dementia and the strength of evidence supporting
these effects. The current review is not intended to be a
comprehensive synthesis or meta-analysis of the research,
but rather a summary of representative studies examining
mechanisms of action for each therapy and associated cognitive outcomes.

AGING- AND DEMENTIA-RELATED


NEUROPATHOLOGY
Aging is associated with structural and functional
changes in the brain, which can lead to poor cognitive
function and neurodegenerative disorders in older adults
(Arking, 2006). Brain changes in aging related to cognitive functioning include (a) decreased brain weight, size,

and synaptic density, resulting in decreased synaptic activity and complexity; (b) decreased expression of neurotrophic factors, specifically decreased brain-derived neurotrophic factor (BDNF) in the hippocampus; (c) reduced
neurotransmitters in the hippocampus, substantia nigra,
striatal pathway, and thalamus, with changes in the hippocampus being especially apparent; and (d) decreased neurogenesis, particularly in the dentate gyrus (Arking, 2006;
Burke & Barnes, 2006; Mora, Segovia, & del Arco, 2007).
Specifically in dementia, cerebral neuropathological
changes include cerebral atrophy; decreased regional cerebral blood flow; and a decreased number of working neurons, synapses, and neurotransmitters in multiple cortical
and subcortical regions (Reisberg, Franssen, Souren, Auer,
& Kenowsky, 1998). Autopsy studies have shown that,
in individuals with dementia, the brain often displayed
cortical atrophy in the neocortex and hippocampus, which
led to cognitive dysfunction, including memory impairment, poor executive function, and a deficit in spatial
navigation (Gearing et al., 1995; Savva et al., 2009). In
addition, several neuropathological changes are associated
with Alzheimers disease, including neuritic plaques, neurofibrillary tangles, and amyloid angiopathy (Savva et al.,
2009).
With aging, the role of stress hormones (i.e., cytokines and glucocorticoids) and dysregulation of the
hypothalamicpituitaryadrenal (HPA) axis are associated with cognitive impairments, including those seen in
dementia (McEwen, 2006, 2007; Sotiropoulos et al., 2008).
The brain plays a key role in determining organ stress, with
the amygdala, hippocampus, and prefrontal cortex being
affected by chronic stress responses (McEwen, 2006). In
older adults and individuals with dementia, the stress response often becomes maladaptive due to disrupted or
failed negative feedback loops, exposing the individual
to high (i.e., toxic) levels of glucocorticoids (Sotiropoulos
et al., 2011). Glucocorticoids are associated with regulation of mood and cognition and may result in cognitive
disorders when secreted at high levels, such as those seen
in stress responses with impaired HPA axis regulation (de
Kloet, Joels, & Holsbeor, 2005). These collective changes in
function and resulting cognitive decline set the stage for an
increased understanding of the mechanisms of action for
nonpharmacological therapies directed at improving cognitive function in individuals with dementia.

THEORIES OF NEUROLOGICAL REGENERATION


Research, primarily using animal models, suggests that
the brain, despite injury, is capable of extensive reorgani-

Copyright SLACK Incorporated

Nonpharmacological Therapies for Individuals With Dementia

zation, termed brain plasticity. Plasticity is described as


the brains ability to change its structure and function to
allow the central nervous system to obtain new information, learn new skills, establish new neuronal networks in
response to environmental stimulation, and recover from
brain injuries (Mora et al., 2007; Silva et al., 2012). Results
of animal studies reported since the mid-1980s provide
evidence of plasticity and the brains capacity to respond
structurally to external stimuli (Black, Sirevaag & Greenough, 1987; Briones, 2006; Fillit et al., 2002). Although
the magnitude of plasticity in older adults is much lower
than in young individuals, current literature suggests that
neural plasticity does not disappear in aged brains (Aslan,
et al., 2012; Fillit et al., 2002). Although plasticity decreases
with age, external factors have been shown to counterbalance the effects of aging and dementia-related pathology
and consequently enhance plasticity and preserve cognitive function in older adults with dementia (Mora et al.,
2007). Enriched and varied stimulations (e.g., physical
activity, cognitive-stimulating activity, social engagement,
environmental enrichment) are widely supported behavioral and environmental factors. Specifically, theories of
neurological functioning and regeneration support many
of the therapies included in the current review.
In humans, the production of new neurons has been
shown to continue even into later years. Based on animal
studies and clinical trials in humans, plasticity theory
suggests that both rehabilitative and pharmacological
interventions may facilitate neuronal reorganization and
recovery of function (Albensi & Janigro, 2003; Bach-yRita, 2003a,b). Studies using human subjects tested the
effectiveness of enriched environments on the preservation of neuronal function, including the slowing of cell
death (Bach-y-Rita, 2003b). Robertson and Murre (1999)
reviewed human studies regarding brain plasticity and concluded that the adult brain can undergo dramatic changes
in neural structures, including dendritic and axonal
sprouting. Swaab, Dubelaar, Scherder, van Someren, and
Verwer (2003) examined evidence from a variety of studies
that indicates neurons do not die in dementia, but instead
in atrophy, indicating cells may continue to be stimulated.
An increasing body of evidence also indicates that metabolic impairment may contribute to neuronal dysfunction
and atrophy in dementia. Therefore, stimulation of neurons both pharmacologically and nonpharmacologically is
a promising strategy in the treatment of dementia.
Although some nonpharmacological therapies affect
cognitive function through neurophysiological mechanisms, some therapies require capacity of learning. Studies

Research in Gerontological Nursing Vol. x, No. x, 20xx

have shown that individuals with dementia can learn


(Bozoki, Grossman, & Smith, 2006; De Vreese, Neri,
Fiorvanti, Belloi, & Zanetti, 2001), with increased awareness of deficits being associated with an increased likelihood that an individual can benefit from cognitive rehabilitation (Clare, Wilson, Carter, Roth, & Hodges, 2004).
Evidence of brain plasticity and retained awareness and
ability for learning in dementia supports the potential benefits of nonpharmacological therapies.

NONPHARMACOLOGICAL THERAPIES
Widely used therapies that have been shown to have
a potential positive impact on cognitive functioning are
included in the current review, with most therapies being
tested specifically with individuals with dementia. For each
therapy presented, the research was reviewed if published
from the early 1990s to the present and tested the effects of
the therapy on cognitive functioning. From the reviewed
research, published reports were then examined for testing
and identification of a specific mechanism of action. The
strength of the evidence (Table 1) for effects on cognitive
functioning and identification of the mechanism of action
were reviewed and rated. The strength of the evidence
supporting each therapy is described and categorized as
demonstrating either strong or moderate support for their
effectiveness and mechanism of action. Reviewed therapies
with the strongest support include (a) cognitive training/
stimulation, (b) physical exercise, and (c) music. Therapies
with moderate support include (a) biofield, (b) meditation,
(c) engagement with a naturally restorative environment
(NRE), and (d) social engagement. These therapies have
identified mechanisms of action that support their effects
on cognitive and neuronal functioning, including potential
neurogenesis. An overview of the mechanisms of action
specific to each treatment is found in Table 2.
Therapies With Strongest Evidence
Cognitive Training/Stimulation. Cognitive training
involves individual or group activities to stimulate an
individuals cognition through association and categorization (Olazaran et al., 2010). In addition, cognitive training
often involves teaching strategies with an emphasis on
problem solving to enhance specific cognitive function
(e.g., memory, reasoning, processing speed) and has been
widely tested with individuals with dementia (Aguirre,
Woods, Spector, & Orrell, 2013; Hopper et al., 2013;
Olazaran et al., 2010; Sitzer, Twamley, & Jeste, 2006).
Cognitive stimulation refers to the characteristics of an
individuals continuous learning and adaption to environ-

Burgener et al.

TABLE 1

Scheme for Grading the Strength


and Consistency of Evidence
Grade

Evidence

A1

Evidence from well-designed meta-analysis or


well-done systematic review with results that
consistently support a specific action (e.g., assessment, intervention, treatment)

A2

Evidence from one or more randomized controlled trials with consistent results

B1

Evidence from high-quality, evidence-based


practice guideline

B2

Evidence from one or more quasi-experimental


studies with consistent results

C1

Evidence from observational studies with


consistent results (e.g., correlational, descriptive
studies)

C2

Inconsistent evidence from observational studies


or controlled trials

Evidence from expert opinion, multiple case


reports, or national consensus reports

Note. A1 and A2 = strong evidence; B1 and B2 = moderate evidence; C1, C2,


and D = weak evidence.
Reprinted with permission from The University of Iowa Nursing Interventions
Research Center Research Translation and Dissemination Core, 11/0.

mental stimuli (Yevchak, Loeb, & Fick, 2008). It is suggested


that the elements of cognitively stimulating activities
require (a) multiple function involvement, (b) attention
control, and (c) complicated tasks (Yevchak et al., 2008).
This type of activity can refer to professional work (e.g.,
driving a taxi, teaching, conducting research) or leisure
activities (e.g., travel, extensive reading, watching performances) (Frick & Benoit, 2010). Specific to individuals
with dementia, the encoding and retrieval tasks have been
most consistently examined in relation to identifying the
mechanisms underlying therapeutic responses to cognitively stimulating therapies (Schwindt & Black, 2009).
The concept of use it or lose it has been applied to
cognitive aging and suggests that specific cognitive functions are more likely to be promoted or preserved when
individuals experience more cognitive stimulation and
frequently operate that specific function (Kramer et al.,
1999; Yevchak et al., 2008). In fact, research suggests that
decreased cognitive performance in older adults is not due
to the brains inability to change, but rather a result of a
lack of stimulation (i.e., training) or insufficient interaction
with the environment (Yevchak et al., 2008). The extant
literature supports this concept, including findings that

cognitive stimulation significantly benefits cognitive function, and the benefits are seen in individuals at any age (i.e.,
older adults, individuals with dementia, nursing home residents with more advanced disease) (Frick & Benoit, 2010;
Spector et al., 2003). Recent meta-analyses indicate common outcomes of cognitive therapies include (a) improved
memory and mental ability; (b) errorless learning achievement; (c) verbal and visual learning; (d) improved executive functioning, language, and attention; (e) improved
functioning in activities of daily living; and (f) lower depression (Aguirre et al., 2013; Hopper et al., 2013; Olazaran
et al., 2010). Long-term benefits have also been described,
including improved cognitive abilities compared to controls specific to training as long as 5 years after treatment
(Willis et al., 2006). However, findings from these analyses
did not include reports of physical findings or mechanisms
of action.
Bach-y-Rita (2003a,b) reported findings that support
that the human brain can reorganize after being damaged and result in functional improvement. Mechanisms
through which this reorganization can occur have been
identified through studies of individuals with both mild
cognitive impairment (MCI) and dementia that use measures of cortical imaging (i.e., functional magnetic resonance imaging [fMRI] and positron emission tomography
[PET] scans), cerebral blood flow, and diffusion tensor
imaging for assessing white matter tracts as well as performance on measures of cognitive functioning (Aslan et al.,
2012; Belleville et al., 2011; Forster et al., 2011; Schwindt
& Black, 2009). Reported findings from imaging studies
reveal increased activation of specific brain regions,
including areas of the parietal, occipital, frontal, and temporal lobes (Belleville et al., 2011; Nyberg et al., 2003;
Schwindt & Black, 2009), prefrontal cortex, cerebellum,
and basal ganglia (Belleville et al., 2011). Increased blood
flow to specific brain regions has also been identified, including the parahippocampal gyrus and bilateral inferior
frontal gyri, as well as increased connectivity (i.e., white
matter) in the uncinate fasciculus and forceps minor
(Aslan et al., 2012). Positive cognitive outcomes reported
in these studies include facename associative encoding
(Celone et al., 2006; Diamond et al., 2007), visuospatial
paired associate learning (Gould et al., 2006), abstract pattern recall (Grn, Bittner, Schmitz, Wunderlich, & Riepe,
2002), free word recall (Becker et al., 1996), attenuated decline (Mini-Mental State Exam [MMSE] and Alzheimers
Disease Assessment Scale-cog), and word recall for patients with MCI (Belleville et al., 2011; Forster et al., 2011).
Specific to individuals with MCI, a systematic review of 20

Copyright SLACK Incorporated

Non-impaired older
adults
Adults with MCI and
mild to advanced dementia

Increased neurogenesis, specifically in the dentate gyrus and hippocampus


Increased insulin-like growth factor (IGF-1)

sol, and IGF-1 levels;

brain autopsy

Research in Gerontological Nursing Vol. x, No. x, 20xx

Neurotransmitter
secretion analysis;
cytokine, melatonin,
salivary cortisol, CgA,
and immunoglobulin levels; PET and
fMRI scans

Salivary cortisol and


IgA; EEG; heart rate
variability; natural
killer cell activity and
number; neuropsychological testing

Music therapies

Biofield therapies

MRI and fMRI scans;

Increased BDNF secretion

Serum BDNF, corti-

Increased alpha-band activity in the frontoparietal lobes

Increased immune function leading to reduction in neuroendocrine stress responses

Buffers the hyper-secretion of the corticosteroid associated with


stress and impaired HPA axis regulation

3. Activates neurotransmitter secretion

2. Buffers the hyper-secretion of the corticosteroid associated with


stress and impaired HPA axis regulation

1. Modulated immune response

Increased synaptic connectivity

Increased hippocampal volume

Diminished stress responses; decreased cortisol secretion

Anti-inflammatory effects

Increased clearance and delayed accumulation of brain amyloid


(A)

Adults with mild to


moderate dementia and
MCI

Cellular studies

Adults with mild to


advanced dementia

Non-impaired older
adults

Animal models

Non-impaired older
adults with MCI and mild
to moderate dementia

Physical exercise

Increased connectivity (white matter)

Increased blood flow to specific brain regions

basal ganglia, and prefrontal cortex

occipito-parietal, frontal, and temporal lobes, and the cerebellum,

Increased activation to brain regions, including the parietal,

MRI, fMRI, PET, and


FDG-PET scans

Population Studied

Cognitive training/
stimulation

Mechanisms of Action

Assessment Methods
for Mechanism

Nonpharmacological
Therapy

B2, A2

A2

A1

A1

Evidence
Grading

Improved mood and cognitive scores (MOCA; AMMSE),


and decreased behavioral
and psychological symptoms (RMBPC) and agitation

Improved short-term recall


and language abilities (improved MMSE scores)

Increased verbal fluency and


verbal communication, and
improved executive function

Improved word recall, face


name association encoding,
attenuating mental decline
(MCI), visuospatial paired
learning, and abstract pattern recall

Cognitive Domains of
Improvement

Mechanism of Action, Population Studied, and Effects on Cognition for Nonpharmacological Therapies

TABLE 2

Nonpharmacological Therapies for Individuals With Dementia

Assessment Methods
for Mechanism

Brain autopsy; MRI


and fMRI scans;
electrophysiology

Non-impaired adults
and older adults
Adults with mild to
advanced dementia

Animal models

Increased synaptic plasticity in the hippocampus

Non-impaired older
adults and adults with
mild to advanced dementia

Non-impaired adults and


older adults

Population Studied

Increased hippocampal neurogenesis

Restored attention capacity

Faster recovery from sympathetic activation

Decreased cortisol levels

Activation of specific neural regions including: superior and middle


frontal gyri, superior parietal gyrus, precuneus, basal ganglia,
superior occipital gyrus, anterior cingulate gyrus, superior temporal
gyrus, and insula

Increased alpha activation indicating relaxation; decreased autonomic arousal

Reduced urinary cortisol in TM practitioners

Increased antibody titers

Increased melatonin compared to controls

Increased gray matter in the left hippocampus, posterior cingulated


cortex, temporoparietal junction, cerebellum, and putamen

Thickening of the prefrontal cortex and right anterior insula

Increased left-sided anterior activation

Higher gamma-band activity in the medial frontoparietal lobes

Mechanisms of Action

A2, C1

B2, B2

A2

Evidence
Grading

Decreased risk of dementia


and improved global cognitive function, semantic and
working memory, spatial
learning, and functional level

Increased attention capacity


and speed of processing;
improved memory, calculation, semantic word fluency,
orientation, and mood; and
decreased agitation

Increased attentional performance and decreased negative affect and autonomic


arousal

Cognitive Domains of
Improvement

Note. MRI = magnetic resonance imaging; fMRI = functional magnetic resonance imaging; FDG = Fluorine-18-Fluorodeoxyglucose; PET = positron emission tomography; MCI = mild cognitive impairment; BDNF = brain-derived neurotrophic factor; HPA
= hypothalamicpituitaryadrenal; CgA = Chromogranin A; MMSE = Mini-Mental State Exam; EEG = electroencephalography; MOCA = Montreal Cognitive Assessment; AMMSE = Annotated Mini-Mental State Exam; RMBPC = Revised Memory and
Behavior Problems Checklist; TM = transcendental meditation; EKG = electrocardiogram; HR = heart rate.

Social engagement

Natural environment fMRI scans; salivary


interactions
cortisol levels; EEG
and EKG (HR); skin
conduction; neuropsychological testing

Meditation therapies EEG; MRI; serum


melatonin, serotonin, and urinary
cortisol levels

Nonpharmacological
Therapy

Mechanism of Action, Population Studied, and Effects on Cognition for Nonpharmacological Therapies

TABLE 2 (CONTINUED)

Burgener et al.

Copyright SLACK Incorporated

Nonpharmacological Therapies for Individuals With Dementia

studies revealed fMRI findings indicating changes in brain


activation specific to areas associated with memory (i.e.,
frontal, temporal, and occipital lobes), as well as increased
connectivity in the medial temporal gyrus and precuneus
(Simon, Yokomizo, & Bottino, 2012). These meta-analyses
and reports of imaging studies provide support for cognitive training and stimulation therapies as beneficial for
individuals with MCI and mild dementia, although the potential also exists for benefits for individuals at later disease
stages.
Exercise Therapies. Substantial evidence suggests that
physical activity and exercise, primarily aerobic exercise
(e.g., walking, jogging, bicycling) and activities that require
a memory for muscle movement (e.g., Tai Chi, dance), improve cognitive outcomes in older adults and individuals
with dementia. A number of epidemiological studies have
also supported the benefits of exercise for risk reduction
for dementia, with significantly lower dementia rates for
older adults who exercised more than three times per
week, controlling for dementia risk factors such as APOE
genetic predispositions (Larson et al., 2006; Podewils et
al., 2005; Scarmeas et al., 2011; Yaffe, Barnes, Nevitt, Lui,
& Covinsky, 2001). Mechanisms of action have been examined to identify the cellular and molecular pathways to
explain these positive exercise effects on the brain.
Several meta-analyses and systematic reviews describe
the effects of exercise on the brain using animal models.
The complexity of the mechanisms underlying exerciseinduced cognitive plasticity is supported by a recent review by Foster et al. (2011). Some of the basic exercise effects identified through animal studies include increased
length and number of dendritic connections (Cotman &
Berchtold, 2002); neurogenesis in the dentate gyru; increased BDNF levels in the hippocampus and dentate gyrus
(Adlard, Engesser-Cesar, & Cotman, 2011; Berchtold, Castello, & Cotman, 2010); increased brain uptake of insulinlike growth factor (IGF-1) (Trejo, Carro, & Torres-Aleman,
2001); and mediation of inflammatory processes (Nieman et al., 2006). Exercise has also been reported to delay amyloid (A) accumulation and improve memory in
transgenic mice (Lazarov et al., 2005). Although primarily
aerobic exercise has been studied, acrobatic exercise was
another exercise type with positive effects on neurogenesis
and synaptic plasticity, requiring motor learning compared to forced exercises (e.g., running, exercising on a
treadmill) (Ball & Birge, 2002). These findings suggest that
forms of exercise that require attention or motor learning,
such as Tai Chi or dance, may positively affect cognitive
functioning.

Research in Gerontological Nursing Vol. x, No. x, 20xx

A number of human studies have examined the neuropathological mechanisms of physical activity on cognitive function; however, most studies, including metaanalyses, have included older adults without dementia
(Colcombe & Kramer, 2003; Erickson et al., 2009; Foster
et al., 2011; Kramer et al., 2006; Rockwood & Middleton,
2007). Colcombe et al. (2006) examined the association
between aerobic exercise and brain structure using MRI.
Study findings included increases in the volume in gray
matter brain areas in the exercise group but not in the control group. Similar findings were reported by Erickson et
al. (2009, 2011) when testing the effects of aerobic exercise on hippocampal volume and spatial memory in older
adults. The researchers reported that a higher exercise level
was positively correlated to higher hippocampal volume
(increased by 2%) and increased BDNF serum levels after
controlling for demographic characteristics. In addition,
higher exercise and hippocampal volumes were correlated
to better spatial memory. In older adults (mean age = 67.3),
improved executive functioning was found following a
12-month walking exercise, along with increased connectivity between frontal, posterior, and temporal cortices
using fMRI data (Voss et al., 2010). Improved immune
function with exercise has also been suggested in older
adults participating in cardiovascular exercise training
(Woods et al., 2009). These protective effects suggest exercise may help preserve cognitive function in older adults
(Graff-Radford, 2011).
In studies including individuals with dementia, Heyn,
Abreu, and Ottenbacher (2004) examined the positive effects of exercise training and found a significant effect size
for cognitive performance across studies; however, none
of the studies reviewed assessed potential mechanisms of
action congruent with the cognitive outcomes. Reported
cognitive benefits were minimal, with primary outcomes
being improvements in word fluency and verbal communication (Friedman & Tappen, 1991; Molloy, Richardson,
& Crilly, 1988). In individuals with MCI, high-intensity
aerobic exercise has resulted in improved executive
functioning and glucose metabolism and reduced cortisol secretion for women only, with increased IGF-1 for
men only (Baker et al., 2010). Conversely, Podewils et al.
(2007) found no associations between physical activity and
white matter lesions using MRI data in a sample of older
adults, including individuals with dementia and MCI. Systematic studies including animals and older adults without dementia provide support for benefits of exercise on
cognitive functioning. However, the need exists for more
systematic studies that examine exercise effects and the

Burgener et al.

mechanism of action, specifically with individuals with


MCI or dementia.
Music Therapy. Music therapy is an individual or group
intervention that has the potential to affect neuropsychiatric
disorders, including organic disorders (e.g., dementia).
Music therapies have been designed to improve selfreported quality of life of individuals with dementia in various domains, including cognitive functioning and using
music experiences (e.g., singing, listening to and discussing
music, moving to music) (Simmons-Stern, Budson, & Ally,
2010). Music therapy can be performed in a group setting
or on a one-on-one basis using either relaxing music or
the individuals preferred music. The music therapy model
is based on neuroscience called neurological music therapy
(NMT). NMT is defined as the influence of music on
changes in nonmusical brain and behavior functions. In
other words, NMT (a) studies how the brain is with and
without music stimuli, (b) measures the differences, and
(c) uses these differences to document changes in the brain
through music that will eventually affect the individual
with dementia nonmusically (Boso, Politi, Barale, & Enzo,
2006).
Several reviews of the effects of music therapy have
found positive effects on older adults and individuals with
dementia (Boso et al., 2006; Fukui & Toyoshima, 2008; Lin
et al., 2011; McDermott, Crellin, Ridder, & Orrell, 2013).
Studies have been conducted with community-based older
adults (i.e., generally outpatient settings) and nursing
home residents, with most studies using randomized, controlled study designs, although sample sizes have tended
to be small (i.e., N = 20 to 87). Specific to individuals with
dementia, studies have been conducted across the disease
stages; however, no studies were found specific to individuals with MCI. Positive outcomes across studies have included (a) reductions in behavioral symptoms (Sakamoto,
Ando, & Tsutou, 2013), anxiety, and depression (Chu et
al., 2013; Raglio et al., 2010); (b) increased engagement,
socialization, attention, and verbalization (Thompson,
Moulin, Hayre, & Jones, 2005); and (c) heightened or improved hormonal and physiological parameters, including
modulated stress responses (Khalfa, Bella, Roy, Peretz, &
Lupien, 2003). Most recently, in individuals with advanced
dementia, music interventions have been shown to increase short-term parasympathetic activity and reduce
behavioral symptoms, suggesting continuing benefits of
music therapies into the later disease stages (Sakamoto et
al., 2013). One brief analysis also suggested positive cost
benefits of music therapies (Bellelli, Raglio, & Trabucchi,
2012).

In studies examining the mechanisms of action for


music therapies specifically in individuals with dementia,
positive outcomes have been documented using primarily
PET or fMRI (Fukui & Toyoshima, 2008); neurotransmitter
secretion analysis (Kumar et al., 1999; Sakamoto et al.,
2013); cytokine levels (Okada et al., 2009); melatonin
levels (Kumar et al., 1999); and salivary cortisol, immunoglobulin, and Chromogranin A measures (Chu et al., 2013;
Khalfa et al., 2003; Suzuki, Kanamori, Nagasawa, Tokiko,
& Takayuki, 2007; Takahashi & Matsushita, 2006). Findings from these studies suggest that music therapies may
benefit cognitive functioning through their modulation
of the stress response, buffering the hyper-secretion of the
corticosteroid associated with stress and impaired HPA
axis regulation, as described previously (de Kloet et al.,
2005). Increased secretion of melatonin and neurotransmitters associated with autonomic activation (i.e., norepinephrine and epinephrine) are proposed to result in both
relaxing and activating responses (Kumar et al., 1999). In
studies measuring the mechanism of action and cognitive outcomes, positive outcomes have included improved
short-term recall (Chu et al., 2013) and improved language
ability using the MMSE language subscale (Suzuki et al.,
2004) in addition to improved behavioral outcomes (Sakamoto et al., 2013; Suzuki et al., 2007). In systematic studies
conducted with individuals with dementia, findings suggest several mechanisms of action for the positive effects of
music therapies, with an identified need for further studies, including additional measures (e.g., electroencephalography [EEG]), to document specific areas of the brain
stimulated through music therapies (Boso et al., 2006).
Therapies With Moderate Evidence
Biofield Therapy. Historical accounts of hands-on
healing and energy-based interventions have been found
in numerous cultures around the world (Jain & Mills,
2010; Wang & Hermann, 2006). Termed biofield therapies, these interventions involve a practitioner using his
or her hands, either on or off an individuals body, to facilitate general health and well-being through modification of the human energy field by the direction of healing
energy (Jain & Mills, 2010). These therapies include Reiki,
Therapeutic Touch, Healing Touch, and others, many of
which are practiced by health care professionals, particularly nurses (Anderson & Taylor, 2011). Requiring no effort on the part of the patient, biofield therapies may be
an appropriate intervention for individuals with dementia
over more cognitive interventions (e.g., guided imagery,
meditation). Recent reviews have found that earlier studies

Copyright SLACK Incorporated

Nonpharmacological Therapies for Individuals With Dementia

of biofield therapies lack adequate design features, such as


appropriate controls, blinding, and sufficient sample sizes;
however, results of these studies are promising and warrant further research (Anderson & Taylor, 2011; Jain &
Mills, 2010). More recent studies of biofield therapies have
started to address these issues, enhancing study rigor (Lu,
Hart, Lutgendorf, Oh, & Schilling, 2013). Because of the
variability in methodology, the aspects of the intervention
that need to be present, including dosage and duration,
remain to be established in specific patient populations,
including those with dementia.
In vitro studies have begun to elucidate cellular mechanisms involved in mediating the effects of biofield therapies. Biofield therapy significantly reduced cytotoxicity
induced by oxidative damage in primary retinal neurons,
offering a protective effect, and increased the gene expression of IGF-1 (Yan et al., 2004). As previously discussed,
IGF-1 is believed to mediate the effects of BDNF as well
as increase the clearance of A. Studies by Kiang, Marotta,
Wirkus, and Jonas (2002) and Kiang, Ives, and Jonas (2005)
have demonstrated that biofield therapies increase intracellular Ca2+ concentrations in leukemic Jurkat cells via
L-type calcium channels (LTCCs). LTCCs are essential for
synaptic plasticity and spatial memory in the hippocampus
(Anekonda & Quinn, 2011). Aging and A promote the
influx of Ca2+ into neurons via LTCCs, leading to impaired
neuronal function, adversely affecting synaptic functions
in Alzheimers disease. Moreover, dysregulation of intracellular Ca2+ may contribute directly to the expression of
clinical symptoms in Alzheimers disease (Anekonda &
Quinn, 2011). Although speculative, biofield therapies
may positively affect the homeostatic regulation of calcium
in hippocampal neurons, thereby improving cognitive
function. In a pilot study by Uchida, Iha, Yamaoka, Nitta,
and Sugano (2012), biofield therapy increased mean power
spectral values in the alpha range versus placebo in the
frontal and central cortical regions (i.e., brain regions associated with cognitive function and the stress response)
(McEwen, 2006).
Reports of studies in other chronic disease populations measuring physiological parameters in response
to biofield therapies reflect positive changes in heart and
respiratory rates and blood pressure (Post-White et al.,
2003), and heart rate variability (Kemper, Fletcher, Hamilton, & McLean, 2009); these changes suggest relaxation
is reflected in the reduction of sympathetic tone and a
shift to a more parasympathetic response, influencing
activity of the HPA axis, which plays a role in the stress
response (as described previously), as well as in exacerbat-

Research in Gerontological Nursing Vol. x, No. x, 20xx

ing the behavioral and psychological symptoms expressed


by individuals with dementia. Biofield therapies appear to
exert effects through a psychoneuroimmunological framework by reducing stress and improving immune function.
Biofield therapies have been reported to increase salivary
immunoglobulin A (Wilkinson et al., 2002) and increase
the activity (Lutgendorf et al., 2010) and number of natural
killer cells (Coakley & Duffy, 2010). Moreover, as biofield
therapies often involve touch and nontouch techniques,
positive effects on the immune system may be secondary
to the documented beneficial effects of physical contact on
both the immune response and neuroendocrine stress hormones by manual therapies (e.g., massage) (Post-White et
al., 2003), leading to a decrease in HPA activity.
Relaxation, decreased anxiety and stress, and improved mood are the most common effects and hallmarks
of biofield therapies, and frequently have been reported
in various study populations, including individuals with
dementia (Anderson & Taylor, 2011; Jain & Mills, 2010;
Lutgendorf et al., 2010). In studies involving individuals
with dementia, biofield therapies have been shown to decrease agitation (Hawranik, Johnston, & Deatrich, 2008)
and salivary cortisol (Wang & Hermann, 2006; Woods
& Dimond, 2002). By reducing cortisol levels, biofield
therapies may have a positive impact on cognitive function. Using a quasi-experimental design, a 4-week biofield
therapy intervention improved cognitive function and behavioral and psychological symptoms of individuals with
dementia (Crawford, Leaver, & Mahoney, 2006). More
recently, a 6-month biofield therapy intervention using a
randomized controlled trial design was shown to reverse
cognitive decline and improve mood significantly in individuals with dementia (Lu et al., 2013).
Meditation Therapies. The effects of meditation on cognitive functioning have been increasingly studied in older
adults, with findings suggesting potential benefits for improved or sustained cognitive functioning, including potential benefits for individuals with dementia. Models supporting the efficacy of meditation therapies have focused
on the positive effects on attention and information processing, including activation of specific areas of the brain
(Hu, Chang, Prakash, & Chaudhury, 2011). Several types
of meditation practices have been examined in adult populations, including objectless mindfulness (Davidson et
al., 2003; Lutz, Greischar, Rawlings, Ricard, & Davidson,
2004), insight meditation (Lazar et al., 2005), Sahaja and
Vihangam yoga (Aftanas & Golosheykin, 2005; Prakash et
al., 2010; Prakash et al., 2012), Zen meditation (Pagnoni &
Cekic, 2007), and transcendental meditation (TM) (Walton

Burgener et al.

et al., 2004). As described in a review of meditation therapies, the effects on cognition have been studied across
age groups, including older adults (Xiong & Doraiswamy,
2009). These studies included both advanced and beginning practitioners, with some controlling for length of total
meditation experience (Davidson et al., 2003).
Study methods have varied and included testing
meditation interventions over 8 to 12 weeks (Alexander,
Chandler, Langer, Newman, & Davies, 1989; Davidson
et al., 2003; Holzel et al., 2011) to comparing long-term
meditation practitioners to untrained controls, with longterm practitioners often engaging in meditation daily
(Lazar et al., 2005; Walton et al., 2004). Studies have primarily taken place in community settings, although older
adults in nursing and retirement home settings have also
been included (Alexander et al., 1989). Across studies,
the cognitive benefits of meditation therapies have been
documented using a wide range of standardized tests. In
an early study, Alexander et al. (1989) demonstrated that,
in older adult participants (mean age = 81), transcendental
meditation resulted in improved cognitive flexibility and
paired associate learning. Positive cognitive outcomes for
yoga meditation practices have included increased attention, processing speed, alternation ability, and performance
on interference tests (Prakash et al., 2010; Prakash et al.,
2012), whereas Zen meditation has resulted in improved
attentional processes (Pagnoni & Cekic, 2007). Sustained
or improved attention has also been found in practitioners
of Buddhist-style concentrative meditation (Valentine &
Sweet, 1999).
A range of mechanisms of action have been identified across the types of meditation practices. Analyses of
MRIs, EEGs, and melatonin, serotonin, and cortisol levels
have been used primarily as indicators of positive effects.
Positive neurophysiological outcomes included higher
gamma-band activity in the medial frontoparietal lobes
on EEG in advanced practitioners compared to controls
(Lutz et al., 2004). In a study of an 8-week training program, mindfulness-based meditation was found to increase left-sided anterior activation on EEG (participants
mean age = 36) (Davidson et al., 2003). Using MRI, structural changes in the brain have been reported, with the
prefrontal cortex and right anterior insula being thicker
in long-term practitioners using insight meditation (mean
age = 38), with more pronounced effects in older practitioners (Lazar et al., 2005). These brain regions are associated
with attention and sensory processing, which is consistent
with findings of increased attentional capacity in meditation practitioners. In addition, the thickness of the infe-

10

rior occipitotemporal visual cortex was correlated with


years of meditation experience, controlling for age and
average thickness of the right hemisphere. More recently,
in meditation-nave participants (i.e., non-dementia),
mindfulness-based stress reduction practitioners (8-week
treatment) demonstrated MRI structural changes, including increased gray matter concentrations in the left hippocampus, posterior cingulated cortex, temporo-parietal
junction, cerebellum (Holzel et al., 2011), and putamen
(Pagnoni & Cekic, 2007) compared to controls.
Metabolic stressors have also been examined, with
melatonin secretion being greater in TM practitioners
compared to controls; however, melatonin secretion began
to decline in TM practitioners after long meditation
an effect that was not explained (Solberg et al., 2004). In
post-menopausal women (mean age = 75), following an
administered metabolic stressor (glucose), long-term
TM practitioners displayed significantly lower cortisol
levels compared to non-practicing, age-matched controls
(Walton et al., 2004). Interestingly, along with activation of
specific brain regions, increases in antibody titer following
an influenza vaccination were also found in practitioners
compared to controls, suggesting positive effects on immune functioning (Davidson et al., 2003).
Although studies are lacking meditation specifically
with individuals with dementia, these findings have identified mechanisms of action with the potential to positively
impact cognitive functioning, including changes in brain
structure and stress responses. As cortical thinning occurs
with aging and more aggressively in dementia, the preservation of cortical thickness in specified brain regions
may buffer or attenuate this thinning in individuals with
dementia (Hu et al., 2011). The positive effects of TM on
cortisol response and melatonin secretion may reduce the
well-documented harmful effects of stress-induced cortisol
secretion in the hippocampus, including atrophy. EEG
findings suggest a second, positive effect on improved attentional capacity and the ability to regulate negative emotions, further lowering autonomic arousal and decreasing
the cortisol response. Although cost-effectiveness studies
have not been conducted, one study reported higher levels
of mindbody therapies in adults with neurological conditions, including dementia, supporting the potential acceptance of these therapies by individuals with dementia
(Wells, Phillips, & McCarthy, 2011).
Interacting With the Natural Environment. Multiple
studies have shown that interacting with the natural environment produces attention-restoration effects, thus improving cognitive function (Hartig, Evans, Jamner, Davis,

Copyright SLACK Incorporated

Nonpharmacological Therapies for Individuals With Dementia

& Garling, 2003; Kaplan, 1995, 2001). Interactions with nature may include any activity that stimulates one or more
of the senses either through natural or man-made stimuli
(Gibson, Chalfont, Clarke, Torrington, & Sixsmixth, 2007;
Herzog, Chen, & Primeau, 2002). Natural environments
have been shown to improve attention and memory more
effectively than built environments (Korpela & Hartig,
1996; Lauman, Garling, & Stormark, 2003). The NRE
can be experienced indoors or outdoors and can include
gardening, aromatherapy, light therapy, a walk in nature,
viewing nature through windows, and listening to bird or
water sounds. NRE interactions provide cognitive, physical, and emotional stimulation and spiritual enhancement
(Cox, Burns, & Savage, 2004; Lee & Kim, 2008; Ottosson
& Grahn, 2005). NRE elements are a rich source of multisensory stimulation and range from physically passive
to active engagement and individual or social stimulation
(Bengtsson & Carlsson, 2005; Sugiyama & Ward-Thompson, 2007).
As noted previously, studies demonstrate that attention
control is an important mechanism in cognition, especially
for individuals with dementia (Baddeley, Baddeley, Bucks,
& Wilcock, 2001; Gorus, De Raedt, Lambert, Lemper, &
Mets, 2006; Perry & Hodges, 1999). Attention has been
correlated with memory, executive functions (e.g., planning, decision making), motor function, and way-finding
(Baddeley et al., 2001; Parasuraman & Haxby, 1993; Perry
& Hodges, 1999). Selective or directed attention is the
ability that allows directing responses to salient stimuli
and processing information without interference from
irrelevant stimuli (Perry & Hodges, 1999). The control of
cognition (i.e., executive functioning) and emotions (i.e.,
self-regulation) share limited resources (Baumeister, Vohs,
& Tice, 2007; Kaplan & Berman, 2010). This finding is supported by neuroimaging data in that both executive functioning and self-regulation are heavily reliant on the functioning of the anterior cingulate cortex (Posner, Rothbart,
Sheese, & Tang, 2007).
In studies using attention restoration therapy (ART),
which is theory-based interventions involving interactions
with NRE, the authors found that by spending time in or
being exposed to the natural environment, a soft fascination occurs that promotes relaxation and allows for restoration of attention capacity (versus hard fascination [e.g.,
sirens, bright and flashing lights], which requires attention
to process) (Kaplan, 1995). Using fMRI, Kim et al. (2010)
showed differential brain activation patterns between natural and urban scenic views. The predominant activation
areas stimulated by natural scenery were contrasted with

Research in Gerontological Nursing Vol. x, No. x, 20xx

urban views and less aversively arousing and more pleasant


(Kim et al., 2010). For example, the precuneus, activated by
natural scenery, is related to regulation of tasks with cognitive and affective components (e.g., episodic memory).
Neural mediation of stress promotes cognitive reserve,
thus enhancing task performance and cognitive capacity
(Petrosini et al., 2009; Stern, 2009). NRE therapies have
been demonstrated to mitigate the effects of stress, specifically the hypersecretion of glucocorticoids common in
older adults and individuals with dementia (Kemperman,
Gast, & Gage, 2002; Rodiek, 2002). The natural environment, specifically gardening, was shown to decrease salivary cortisol levels, self-reported stress, and increased positive mood in a population of middle- to old-age healthy
adults (Van den Berg & Custers, 2011). Van den Berg and
Custers (2011) found that levels of salivary cortisol returned to normal levels when participants were allowed
30 minutes of gardening activities after having been intentionally stressed (Stroop test with social comparison), providing support acute stress reduction from NRE activities.
Research findings suggesting physiological stress reduction include galvanic skin response and electromyogram,
and decreases in heart rate and blood pressure (Ulrich et
al., 1991). This study showed increases in alpha activity
when viewing nature scenes. High alpha activity is associated with lower levels of physiological arousal and feelings
of wakeful relaxation (Teplan, 2002).
Other studies not using a dementia sample have found
correlations between improved attention capacity and interventions using nature with use of backward digit span
testing or attention network task tests (Berman, Jonides,
& Kaplan, 2008; Cimprich, 1993; Cimprich & Ronis, 2001,
2003; Herzog et al., 2002; Tennessen & Cimprich, 1995).
Lauman et al. (2003) demonstrated decreased autonomic
arousal by viewing natural versus urban settings by measuring inter-beat intervals (via EKG) and improved
orienting task performance.
There have been fewer studies for populations with
dementia, but they still show evidence of cognitive benefits. Using indoor gardening activities, Lee & Kim (2008)
demonstrated significant improvements in cognitive
scores on the Revised Hasegawa Dementia Scale. Support
for positive cognitive effects in individuals with dementia
was demonstrated in a quasi-experimental study by Tse
(2010). NRE therapies have demonstrated a variety of additional benefits for individuals with dementia, including
decreases in agitation (Cohen-Mansfield, 2007; Detweiler, Murphy, Kim, Myers, & Ashai, 2009; La Garce, 2002;
Mather, Nemecek, & Oliver, 1997; Mooney & Nicell, 1992;

11

Burgener et al.

Riemersma-van der Lek et al., 2008; Whall et al., 1997); decreased psychotropic drug use and falls (Detweiler, Murphy, Myers, & Kim, 2008; Detweiler et al., 2009); circadian
rhythm normalization (i.e., sleep patterns and quality)
(Lee & Kim, 2008); as well as increased socialization, life
satisfaction, and positive affect (Heyn et al., 2004; Jarrott &
Gigliotti, 2010; Rappe & Topo, 2007; Tse, 2010).
In summary, growing evidence supports NRE therapies as having benefits for cognitive functioning for older
adults, including individuals with dementia. The mechanism showing the most robust support is that of stress
mediation, although due to the multidimensionality of
NRE interventions, other mechanisms may contribute to
the overall effects. Components of chronobiology, physical
activity, social interactions, sensory stimulation, practicing
remembered skills/hobbies, and sense of accomplishment
and meaningfulness may play a role in the influence of
NRE on cognition. NRE interventions are multidimensional activities; therefore, identifying the precise mechanisms of action for NRE need to be viewed in light of the
overall impact.
Social Engagement. Social engagement is conceptually
defined as staying socially connected, frequently participating in social activities, and a feeling of being socially
supported (Cacioppo & Hawkley, 2009). It is generally accepted that individuals with higher social engagement have higher cognitive function and are less likely
to have dementia, whereas social isolation and loneliness
contribute to impaired learning and executive functions
and increased risks for cognitive decline and dementia
(Cacioppo & Hawkley, 2009). The positive effects of social engagement have been supported in both animal and
human studies.
In animal models, rats housed in groups performed
better on spatial learning tasks compared to socially isolated rats (Lu et al., 2003). In addition, the study by Lu et
al. (2003) revealed that group-housed rats had significantly
increased neuron proliferation in the dentate gyrus of the
hippocampus and synaptic plasticity in the hippocampus.
Some recovery of cognitive function also was found, with
the rats previously isolated for 4 weeks and then subsequently reared in groups for another 4 weeks, showing
recovered performance in spatial learning tasks (Lu et al.,
2003). These early findings were supported by a later study
by Madroal et al. (2010), in which increased hippocampal
neurogenesis was observed in young mice (age = <3
months) caged in groups, providing social engagement.
However, this same effect was not found in adult mice,
suggesting the benefit of social engagement on associative

12

learning and related hippocampal neurogenesis is more


pronounced at younger ages (Madroal et al., 2010).
The benefit of social engagement on brain functioning
has been further supported by evidence generated from
multiple large-scale human studies (Amieva et al., 2010;
Bennett, Schneider, Tang, Arnold, & Wilson, 2006). An
early longitudinal, 12-year study of 2,812 home-dwelling
older adults revealed that individuals with more social ties
had a lower incidence of cognitive decline compared to
their less socially connected counterparts (Bassuk, Glass,
& Berkman, 1999). Similarly, another longitudinal study
found that older adults with poor social connections, lower participation in social activities, and social disengagement were at high risk for cognitive decline (Zunzunegui,
Alvarado, Del Ser, & Otero, 2003). Moreover, Bennett et
al. (2006) reported that social network size can modify the
association between dementia pathology and cognitive
function; individuals with a larger network size showed
higher cognitive function despite having more severe
dementia pathology. This effect was especially pronounced
for semantic and working memory, controlling for relevant mediating factors (e.g., depression). In a later crosssectional study, Krueger et al. (2009) examined 838 institutionalized older adults without dementia and found that
a higher frequency of social activity and perceived social
support were significantly associated with higher global
cognitive function, including memory, perception speed,
and visuospatial ability.
Taken together, evidence (from animal and human
studies) supports that social engagement is associated with
higher cognitive function (including learning, executive
function, and hippocampus-related memory), as well as
improved neurogenesis and synaptic plasticity in the hippocampus (animal studies only). Moreover, the possibility
exists that decreased cognitive functioning resulting from
isolation may be reversed through later social interaction.
These collective findings are promising; however, there is
a lack of intervention trials testing social engagement as
therapy for individuals with dementia (Flicker, 2009).

DISCUSSION
Although not exhaustive, the current review includes
a variety of nonpharmacological therapies with evidence
of the underlying mechanism of action on cognitive functioning from cellular, animal, and human studies (Table 2).
A conceptual view of the various mechanisms of action on
cognitive functioning is included (Figure), providing an
overview of the mechanisms of action identified from the
reviewed research. From this conceptual model, it is clear

Copyright SLACK Incorporated

Nonpharmacological Therapies for Individuals With Dementia

Figure. Mechanisms for action for selected nonpharmacological therapies for individuals with dementia.
Note. BDNF = brain-derived neurotrophic factor; IGF-1 = insulin-like growth factor-1; neurogenesis = social engagement, cognitive training,
and exercise therapies; hormonal changes = natural environment intervention, music, biofield, exercise, and meditation therapies; brain
regions and activity affected = music, meditation, cognitive training, and biofield therapies; amyloid B-related changes = exercise therapies;
neurotrophic factor changes = exercise and music therapies.

that a variety of mechanisms from nonpharmacological


interventions impact cognition, with many addressing
age- and dementia-related neuropathic changes described
previously. For example, increases in actual brain size and
cortical thickness were demonstrated in studies testing
the effects of cognitive training, physical exercise, and social engagement, whereas neurotrophic factors, including
increased BDNF, were found to be modulated following
physical exercise and music therapies. Changes (i.e., increases) in cerebral blood flow have also been found following cognitive therapies. Impaired HPA axis function
was also positively affected by a number of therapies, including music, biofield, physical exercise, meditation, and
interacting with a natural environment. The current review
identifies the links between nonpharmacological therapies
and their effects on specific mechanisms of action and cognitive function, many of which have been identified as being associated with aging and cognitive decline (Arking,
2006; Burke & Barnes, 2006; Mora et al., 2007). These findings underscore the understanding that many nonpharmacological interventions designed to improve cognitive
functioning are theory-driven and supported by empirical
research findings.
Findings from the current review also have relevance
for clinical practice. By increasing our understanding of
the potential benefits of nonpharmacological therapies, the
implicit hope is to advance support for combined therapies
for individuals with dementia, using drug and non-drug

Research in Gerontological Nursing Vol. x, No. x, 20xx

therapies with identified positive effects on neuronal functioning. Although medication therapies have been available to treat dementia for approximately two decades, the
limits of these drugs have been well-established, increasing
the potential importance of adding non-drug therapies to
treatment plans (Tschanz et al., 2011; Zec & Burkett, 2008).
As many of these therapies (i.e., cognitive training,
exercise, and meditation) have preventive actions, they
provide the older adult with choices for self-care actions,
with benefits for disease prevention as well as maintenance
of cognitive functioning. For those newly diagnosed with
dementia, these therapies provide the opportunity to select treatment options that fit with the individuals preferences and previous activities. Clinically, recommending
dual therapies allows the patient more treatment options,
including therapies that can be individualized, based on an
individuals domain of cognitive impairment and preferences, with a possible non-drug treatment plan (Table 3).
As most non-drug therapies have no or few adverse effects
and can be made available in many community settings,
the potential benefits of incorporating non-drug therapies
may far exceed the potential costs, as many of these therapies are also considered pleasant activities (e.g., music,
social engagement, interacting with the natural environment).
The implications of these findings for research are
evident, including the need for head-to-head studies
examining the effects of dual therapies compared to

13

Burgener et al.

Physical exercise

Preferably aerobic exercises if tolerated, including walking. If


walking or aerobic exercises cannot be tolerated, then exercises
that are less strenuous yet require a memory for muscle movement, such as Tai Chi or dance, are recommended.

Cognitive therapies

Preferably diverse therapies that use cognitive training and


stimulation as the focus of the training.

Mediation therapies

May include: transcendental meditation, mindfulness meditation,


insight meditation, Sahaja yoga

Biofield therapies

May include: Healing Touch, Therapeutic Touch, Reiki, polarity


therapy

to the growing body of research identifying protective or preventive factors


and therapies that may be
beneficial prior to the onset of memory loss or dementia. Findings may also
point to the importance of
future research testing nonpharmacological therapies
to ameliorate pathology
and potentially improve
cognitive functioning in
individuals with dementia.

Environmental/recreational
therapies

May include: social engagement, interacting with the natural


environment, music therapy

REFERENCES

TABLE 3

Treatment Plan for Nonpharmacological Therapies


Therapy

Treatment Plan

medication-only therapies, especially in individuals with


MCI or early-stage dementia. Research that includes
samples of individuals with MCI or early-stage dementia
diagnoses are especially lacking in biofield and meditation therapies, indicating the need to increase controlled,
randomized trials testing these two therapies. Studies
examining combined therapies (i.e., multi-modal studies)
are also indicated as suggested by the rather unique mechanisms of action found for some therapies. For example,
the mechanisms of action identified for cognitive therapies
have little overlap with those identified for music therapies,
suggesting that these combined therapies may produce a
synergistic effect on cognitive functioning. Cost-effectiveness studies are indicated as well, given the potential
to improve overall functioning and decrease the need for
assistive care. These findings also suggest the importance
of examining the mechanism of action underlying any
nonpharmacological therapy to better understand the effects on the brain and assure the therapy has the potential
to positively impact cognitive functioning in older adults,
especially individuals with cognitive impairment.

CONCLUSION
The current analysis and overview provides a beginning understanding of the potential positive effects of a
variety of nonpharmacological interventions on neuropathology and cognitive function. Collectively, the variety of
therapies reviewed allows for tailoring of a treatment plan
based on individual strengths and preferences, providing
a guide for health care providers to use in recommending
nonpharmacological therapies. The current findings add

14

Adlard, P.A., Engesser-Cesar, C.,


& Cotman, C.W. (2011). Mild
stress facilitates learning and exercise improves retention in aged mice. Experimental Gerontology, 46, 53-59. doi:10.1016/j.exger.2010.10.001
Aftanas, L., & Golosheykin, S. (2005). Impact of regular meditation
practice on EEG activity at rest and during evoked negative emotions. International Journal of Neuroscience, 115, 893-909.
Aguirre, E., Woods, R.T., Spector, A., & Orrell, M. (2013). Cognitive
stimulation for dementia: A systematic review of the evidence for
effectiveness from randomized controlled trials. Ageing Research
Reviews, 12, 253-262. doi:10.1016/j.arr.2012.07.001
Albensi, B.C., & Janigro, D. (2003). Traumatic brain injury and
its effects on synaptic plasticity. Brain Injury, 17, 653-663.
doi:10.1080/0269905031000107142
Alexander, C.N., Chandler, H.M., Langer, E.J., Newman, R.I., &
Davies, J.L. (1989). Transcendental meditation, mindfulness, and
longevity: An experimental study with the elderly. Journal of Personality and Social Psychology, 57, 950-964.
Amieva, H., Sotykova, R., Matharan, F., Helmer, C., Antonucci, T.C.,
& Dartigues, J.-F. (2010). What aspects of social network are protective for dementia? Not the quantity but the quality of social
interactions is protective up to 15 years later. Psychosomatic Medicine, 72, 905-911. doi:10.1097/PSY.0b013e3181f5e121
Anderson, J.G., & Taylor, A.G. (2011). Effects of Healing
Touch in clinical practice: A systematic review of randomized clinical trials. Journal of Holistic Nursing, 29, 221-228.
doi:10.1177/0898010110393353
Anekonda, T.S., & Quinn, J.F. (2011). Calcium channel blocking
as a therapeutic strategy for Alzheimers disease: The case for
isradipine. Biochimica et Biophysica Acta, 1812, 1584-1590.
doi:10.1016/j.bbadis.2011.08.013
Arking, R. (2006). The biology of aging: Observations and principles
(3rd ed.). New York, NY: Oxford University Press.
Aslan, S., Chapman, S.B., Kanter-Bartz, E., Mudar, R., Keebler, C.,
Bardner, J.,Hart, J. (2012, October). Neural mechanisms of
brain plasticity with complex mental activity in adults. Paper presented at the Annual Meeting of the Society for Neuroscience,
New Orleans, LA.
Bach-y-Rita, P. (2003a). Theoretical basis for brain plasticity after TBI.
Brain Injury, 17, 643-651.

Copyright SLACK Incorporated

Nonpharmacological Therapies for Individuals With Dementia

Bach-y-Rita, P. (2003b). Late postacute neurologic rehabilitation:


Neuroscience, engineering, and clinical programs. Archives of
Physical Medicine and Rehabilitation, 84, 1100-1108. doi:10.1016/
S0003-9993(03)00312-5
Baddeley, A.D., Baddeley, R.S., Bucks, R.S., & Wilcock, G.K. (2001).
Attentional control in Alzheimers disease. Brain, 124, 1492-1508.
Baker, L.D., Frank, L.I., Foster-Schubert, K., Green, P.S., Wilkinson,
C.W., McTiernan, A.,Craft, S. (2010). Effects of aerobic exercise on mild cognitive impairment: A controlled trial. Archives of
Neurology, 67, 71-79. doi:10.1001/archneurol.2009.307
Ball, L.J., & Birge, S.J. (2002). Prevention of brain aging and dementia.
Clinical Geriatric Medicine, 18, 485-503.
Bassuk, S.S., Glass, T.A., & Berkman, L.F. (1999). Social disengagement and incident cognitive decline in community-dwelling
elderly persons. Annals of Internal Medicine, 131, 165-173.
doi:10.7326/0003-4819-131-3-199908030-00002
Baumeister, R.F., Vohs, K.D., & Tice, D.M. (2007). The strength model
of self-control. Current Directions in Psychological Science, 16,
351-355. doi:10.1111/j.1467-8721.2007.00534.x
Becker, J.T., Mintun, M.A., Aleva, K., Wiseman, M.B., Nichols, T., &
DeKosky, S.T. (1996). Compensatory reallocation of brain resources supporting verbal episodic memory in Alzheimers disease. Neurology, 46, 692-700. doi:10.1212/WNL.46.3.692
Bellelli, G., Raglio, A., & Trabucchi, M. (2012). Music interventions
against agitated behaviors in elderly persons with dementia: A
cost-effective perspective. International Journal of Geriatric Psychiatry, 27, 327. doi:10.1002/gps.2775
Belleville, S., Clement, F., Mellah, S., Gilbert, B., Fontaine, F., &
Gauthier, S. (2011). Training-related brain plasticity in subjects
at risk of developing Alzheimers disease. Brain, 135, 1623-1634.
Bengtsson, A., & Carlsson, G. (2005). Outdoor environments at three
nursing homes: Focus groups interviews with staff. Journal of
Housing for the Elderly, 19, 49-69. doi:10.1016/j.ufug.2013.03.008
Bennett, D.A., Schneider J.A., Tang, Y., Arnold S.E., & Wilson, R.S.
(2006). The effect of social networks on the relation between
Alzheimers disease pathology and level of cognitive function in
old people: A longitudinal cohort study. Lancet Neurology, 5, 406412. doi:10.1016/S1474-4422(06)70417-3
Berchtold, N.C., Castello, N., & Cotman, C.W. (2010). Exercise and
time-dependent benefits to learning and memory. Neuroscience,
167, 588-597. doi:10.1016/j.neuroscience.2010.02.050
Berman, M.G., Jonides, J., & Kaplan, S. (2008). The cognitive benefits
of interacting with nature. Psychological Science, 19, 1207-1212.
doi:10.1111/j.1467-9280.2008.02225.x
Black, J.E., Sirevaag, A.M., & Greenough, W.T. (1987). Complex
experience promotes capillary formation in young rat visual
cortex. Neuroscience Letters, 83, 351-355. doi:10.1016/03043940(87)90113-3
Boso, M., Politi, P., Barale, F., & Enzo, E. (2006). Neurophysiology and
neurobiology of the musical experience. Functional Neurology,
21, 187-191.
Bozoki, A., Grossman, M., & Smith, E.E. (2006). Can patients with
Alzheimers disease learn a category implicitly? Neuropsychologia,
44, 816-827. doi:10.1016/j.neuropsychologia.2005.08.001
Briones, T.L. (2006). Environment, physical activity, and neurogenesis: Implications for prevention and treatment of
Alzheimers disease. Current Alzheimer Research, 3, 49-54.
doi:10.2174/156720506775697197
Briones, T.L., Suh, E., Hattar, H., & Wadowska, M. (2005). Dentate gyrus neurogenesis after cerebral ischemia and behavioral
training. Biological Research in Nursing, 6, 167-179.

Research in Gerontological Nursing Vol. x, No. x, 20xx

Burke, S.N., & Barnes, C.A. (2006). Neural plasticity in the ageing
brain. Nature Reviews Neuroscience, 7, 30-40. doi:10.1038/
nrn1809
Cacioppo, J.T., & Hawkley, L.C. (2009). Perceived social isolation and cognition. Trends in Cognitive Sciences, 13, 447-454.
doi:10.1016/j.tics.2009.06.005
Celone, K.A., Calhoun, V.D., Dickerson, B.C., Atri, A., Chua, E.F.,
Miller, S.I.,Sperling, R.A. (2006). Alterations in memory networks in mild cognitive impairment and Alzheimers disease: An
independent component analysis. Journal of Neuroscience, 26,
10222-10231. doi:10.1523/JNEUROSCI.2250-06.2006
Chu, H., Yang, C.Y., Lin, Y., Ou, K.L., Lee, T.Y., O-Brien, A.P., & Chou,
K.R. (2013). The impact of group music therapy on depression
and cognition in elderly persons with dementia: A randomized
controlled study. Biological Research for Nursing, 14, 209-217.
doi:10.1177/1099800413485410
Cimprich, B. (1993). Development of an intervention to restore attention in cancer patients. Cancer Nursing, 16, 83-92.
Cimprich, B., & Ronis, D.L. (2001). Attention and symptom distress
in women with and without breast cancer. Nursing Research, 50,
86-94.
Cimprich, B., & Ronis, D.L. (2003). An environmental intervention to
restore attention in women with newly diagnosed breast cancer.
Cancer Nursing, 26, 284-292.
Clare, L., Wilson, B.A., Carter, G., Roth, I., & Hodges, J.R. (2004).
Awareness in early-stage Alzheimers disease: Relationship to
outcome of cognitive rehabilitation. Journal of Clinical Experimental Neuropsychology, 26, 215-226.
Coakley, A.B., & Duffy, M.E. (2010). The effect of therapeutic touch
on post-operative patients. Journal of Holistic Nursing, 28, 193200. doi:10.1177/0898010110368861
Cohen-Mansfield, J. (2007). Outdoor wandering parks for persons
with dementia. Journal of Housing for the Elderly, 21, 35-53.
doi:10.1300/J081v21n01_03
Cohen-Mansfield, J., Buckwalter, K., Beattie, E., Rose, K., Neville, C.,
& Kolanowski, A. (2014). Expanded review criteria: The case
of nonpharmacological interventions in dementia. Journal of
Alzheimers Disease, 41, 15-28. doi:10.3233/JAD-132357
Colcombe, S.J., Erickson, K.I., Scalf, P.E., Kim, J.S., Prakash, R.,
McAuley, E.,Kramer, A.F. (2006). Aerobic exercise training increases brain volume in aging humans. Journals of Gerontology.
Series A, Biological Sciences and Medical Sciences, 61, 1166-1170.
Colcombe, S.J., & Kramer, A.F. (2003). Fitness effects on the cognitive
function of older adults: A meta-analytic study. Psychological Sciences, 14, 125-130. doi:10.1111/1467-9280.t01-1-01430
Cotman, C.W., & Berchtold, N.C. (2002). Exercise: A behavioral intervention to enhance brain health and plasticity. Trends in Neuroscience, 25, 295-301. doi:10.1016/S0166-2236(02)02143-4
Cox, H., Burns, I., & Savage, S. (2004). Multisensory environments
for leisure: Promoting well-being in nursing home residents
with dementia. Journal of Gerontological Nursing, 30(2), 37-45.
doi:10.3928/0098-9134-20040201-08
Crawford, S.E., Leaver, V.W., & Mahoney, S.D. (2006). Using Reiki
to decrease memory and behavior problems in mild cognitive
impairment and mild Alzheimers disease. Journal of Alternative
and Complementary Medicine, 12, 911-913.
Davidson, R.J., Kabat-Zinn, J., Schumacher, J., Rosenkranz, M.,
Muller, D., Santorelli, S.F.,Sheridan, J.F. (2003). Alterations
in brain and immune function produced by mindfulness meditation. Psychosomatic Medicine, 65, 564-570. doi:10.1097/01.
PSY.0000077505.67574.E3

15

Burgener et al.

de Kloet, E.R., Joels, M., & Holsboer, R. (2005). Stress and the brain:
From adaptation to disease. National Review of Neuroscience, 6,
463-475. doi:10.1038/nrn1683
Detweiler, M.B., Murphy, P.F., Kim, K.Y., Meyers, L.C., & Ashai,
A. (2009). Scheduled medications and falls in dementia
patients utilizing a wander garden. American Journal of
Alzheimers Disease and Other Dementias, 24, 322-332.
doi:10.1177/1533317509334036
Detweiler, M.B., Murphy, P.F., Meyers, L.C., & Kim, K.Y. (2008). Does
a wander garden influence inappropriate behaviors in dementia
residents? American Journal of Alzheimers Disease & Other Dementias, 23, 31-45. doi:10.1177/1533317507309799
De Vreese, L.P., Neri, M., Fiorvanti, M., Belloi, L., & Zanetti, O.
(2001). Memory rehabilitation in Alzheimers disease: A review
of progress. International Journal of Geriatric Psychiatry, 16, 794809. doi:10.1002/gps.428
Diamond, E.I., Miller, S., Dickerson, B.C., Atri, A., DePeau,
K., Fenstermacher, E.,Sperling, R.A. (2007). Relationship of fMRI activation to clinical trial memory measures in
Alzheimer disease. Neurology, 69, 1331-1341. doi:10.1212/01.
wnl.0000277292.37292.69
Erickson, K.I., Prakash, R.S., Voss, M.W., Chaddock, L., Hu, L.,
Morris, K.S.,Kramer, A.F. (2009). Aerobic fitness is associated
with hippocampal volume in elderly humans. Hippocampus, 19,
1030-1039. doi:10.1002/hipo.20547
Erickson, K.I., Voss, M.W., Prakash, R.S., Basak, C., Szabo, A.,
Chaddock, L.,...Kramer, A.F. (2011). Exercise training increases
size of hippocampus and improves memory. Proceedings of the
National Academy of Sciences of the United States of America, 108,
3017-3022. doi:10.1073/pnas.1015950108
Fillit, H.M., Butler, R.N., OConnell, A.W., Albert, M.S., Birren, J.E.,
Cotman, C.W.,Tully, T. (2002). Achieving and maintaining
cognitive vitality with aging. Mayo Clinic Proceedings, 77, 681696. doi:10.4065/77.7.681
Flicker, L. (2009). Life style interventions to reduce the risk of dementia.
Maturitas, 63, 319-322. doi:10.1016/j.maturitas.2009.06.008
Forster, S., Buschert, V.C., Teipel, S.J., Friese, U., Buchholz, H.-G.,
Drzezga, A.,Buerger, K. (2011). Effects of a 6-month cognitive
intervention on brain metabolism in patients with amnestic MCI
and mild Alzheimers disease. Journal of Alzheimers Disease, 26,
337-348. doi:10.3233/JAD-2011-0025
Foster, P.P, Rosenblatt, K.P., & Kuljis, R.O. (2011). Exercise-induced
cognitive plasticity, implications for mild cognitive impairment and Alzheimers disease. Frontiers in Neurology, 2, 1-12.
doi:10.3389/fneur.2011.00028
Frick, K.M., & Benoit, J.D. (2010). Use it or lose it: Environmental
enrichment as a means to promote successful cognitive aging.
Scientific World Journal, 10, 1129-1141. doi:10.1100/tsw.2010.111
Friedman, R., & Tappen, R.M. (1991). The effect of planned walking
on communication in Alzheimers disease. Journal of the
American Geriatrics Society, 39, 654-670.
Fukui, H., & Toyoshima, K. (2008). Music facilitates the neurogenesis,
regeneration and repair of neurons. Medical Hypotheses, 71, 765769. doi:10.1016/j.mehy.2008.06.019
Gearing, M., Mirra, S.S., Hedreen, J.C., Sumi, S.M., Hansen, L.A., &
Heyman, A. (1995). The consortium to establish a registry for
Alzheimers Disease (CERAD): Part X: Neuropathology confirmation of the clinical diagnosis of Alzheimers disease. Neurology,
45, 461-466. doi:10.1212/WNL.45.3.461
Gibson, G., Chalfont, G.E., Clarke, P.D., Torrington, J.M., & Sixsmith,
A.J. (2007). Housing and connection to nature for people with

16

dementia: Findings from the INDEPENDENT project. Journal of


Housing for the Elderly, 21, 55-72.
Gorus, E., De Raedt, R., Lambert, M., Lemper, J.C., & Mets, T. (2006).
Attentional processes discriminate between patients with mild
Alzheimers disease and cognitively healthy elderly. International
Psychogeriatrics, 18, 539-549. doi:10.1017/S1041610205002723
Gould, R.I., Arroyo, B., Brown, R.G., Owen, A.M., Bullmore, E.T., &
Howard, R.J. (2006). Brain mechanisms of successful compensation during learning in Alzheimer disease. Neurology, 67, 10111017. doi:10.1212/01.wnl.0000237534.31734.1b
Graff-Radford, N.R. (2011). Can aerobic exercise protect against
dementia? Alzheimers Research & Therapy, 3, 6. doi:10.1186/
alzrt65
Grn, G., Bittner, D., Schmitz, B., Wunderlich, A.P., & Riepe, M.W.
(2002). Subjective memory complaints: Objective neural markers
in patients with Alzheimers disease and major depressive disorder. Annals of Neurology, 51, 491-498.
Hartig, T., Evans, G.W., Jamner, L.D., Davis, D., & Garling, T. (2003).
Tracking restoration in natural and urban field settings. Journal
of Environmental Psychology, 23, 109-123. doi:10.1016/S02724944(02)00109-3
Hawranik, P., Johnston, P., & Deatrich, J. (2008). Therapeutic Touch and
agitation in individuals with Alzheimers disease. Western Journal
of Nursing Research, 30, 417-434. doi:10.1177/0193945907305126
Herring, A., Ambree, O., Tomm, M., Habermann, H., Sachser, N.,
Paulus, W., & Keyvani, K. (2009). Environmental enrichment enhances cellular plasticity in transgenic mice with Alzheimer-like
pathology. Experimental Neurology, 216, 184-192. doi:10.1016/j.
expneurol.2008.11.027
Herzog, T.R., Chen, H.C., & Primeau, J.S. (2002). Perception of the
restorative potential of natural and other settings. Journal of Environmental Psychology, 22, 295-306. doi:10.1006/jevp.2002.0235
Heyn, P., Abreu, B.C., & Ottenbacher, K.J. (2004). The effects of exercise training on elderly persons with cognitive impairment and
dementia: A meta-analysis. Archives of Physical & Medical Rehabilitation, 85, 1694-1704.
Holzel, B.K., Carmody, J., Vangel, M., Congleton, C., Yerramsetti,
S.M., Gard, T., & Lazar, S.W. (2011). Mindfulness practice leads
to increases in regional brain gray matter density. Psychiatry Research, 191, 36-43. doi:10.1016/j.pscychresns.2010.08.006
Hopper, T., Bourgeois, M., Pimentel, J., Qualls, C.D., Hickey, E.,
Frymark, T., & Schooling, T. (2013). An evidence-based systematic review on cognitive interventions for individuals with dementia. American Journal of Speech & Language Pathology, 22,
126-145. doi:10.1044/1058-0360(2012/11-0137)
Hu, X., Chang, F., Prakash, R., & Chaudhury, S. (2011). A theoretical
model of efficacy of concentrative meditation for cognitive rehabilitation of dementia. Medical Hypotheses, 77, 266-269.
doi:10.1016/j.mehy.2011.04.031
Iqbal, K., & Grundke-Iqbal, I. (2011). Opportunities and challenges in
developing Alzheimer disease therapeutics. Acta Neuropathology,
122, 543-549. doi:10.1007/s00401-011-0878-z
Jain, S., & Mills, P.J. (2010). Biofield therapies: Helpful or full of hype?
A best evidence synthesis. International Journal of Behavioral
Medicine, 17, 1-16. doi:10.1007/s12529-009-9062-4
Jarrott, S.E., & Gigliotti, C.M. (2010). Comparing responses to
horticulture-based and traditional activities in dementia care
programs. American Journal of Alzheimers Disease and Other
Dementias, 25, 657-665. doi:10.1177/1533317510385810
Kaplan, S. (1995). The restorative benefits of nature: Towards an integrative framework. Journal of Environmental Psychology, 15, 169-

Copyright SLACK Incorporated

Nonpharmacological Therapies for Individuals With Dementia

182. doi:10.1016/0272-4944(95)90001-2
Kaplan, S. (2001). Meditation, restoration, and the management
of mental fatigue. Environment and Behavior, 33, 480-506.
doi:10.1177/00139160121973106
Kaplan, S., & Berman, M.G. (2010). Directed attention as a common resource for executive function and self-regulation. Perspectives on
Psychological Science, 5, 43-57. doi:10.1177/1745691609356784
Kemper, K.J., Fletcher, N.B., Hamilton, C.A., & McLean, T.W. (2009).
Impact of healing touch on pediatric oncology outpatients: Pilot
study. Journal of the Society for Integrative Oncology, 7, 12-18.
Kemperman, G., Gast, D., & Gage, F.H. (2002). Neuroplasticity in old
age: Sustained fivefold induction of hippocampal neurogenesis
by long-term environmental enrichment. Annals of Neurology,
52, 135-143. doi:10.1002/ana.10262
Khalfa, S., Bella, S.D., Roy, M., Peretz, I., & Lupien, S.J. (2003). Effects
of relaxing music on salivary cortisol level after psychological
stress. Annuals of the New York Academy of Sciences, 999, 374376. doi:10.1196/annals.1284.045
Kiang, J.G., Ives, J.A., & Jonas, W.B. (2005). External bioenergyinduced increases in intracellular free calcium concentrations are
mediated by Na+/Ca2+ exchanger and L-type calcium channel.
Molecular and Cellular Biochemistry, 271, 51-59.
Kiang, J.G., Marotta, D., Wirkus, M., & Jonas, W.B. (2002). External
bioenergy increases intracellular free calcium concentration and
reduces cellular response to heat stress. Journal of Investigative
Medicine, 50, 38-45. doi:10.2310/6650.2002.33516
Kim, G.-W., Jeong, G.-W., Kim, T.-H., Baek, H.-S., Oh, S.-K., Kang,
H.-K.,Song, J.-K. (2010). Functional neuroanatomy associated
with natural and urban scenic views in the human brain: 3.0T
functional MR imaging. Korean Journal of Radiology, 11, 507
513. doi:10.3348/kjr.2010.11.5.507
Korpela, K., & Hartig, T. (1996). Restorative quality of favorite places.
Journal of Environmental Psychology, 16, 221-233.
Kramer A.F., Erickson, K.I., & Colcombe, S.J. (2006). Exercise, cognition, and the aging brain. Journal of Applied Physiology, 101,
1237-1242. doi:10.1152/japplphysiol.00500.2006
Kramer, A.F., Hahn, S., Cohen, N.J., Banich, M.T., McAuley, E.,
Harrison, C.R.,Colcombe, A. (1999). Ageing, fitness and neurocognitive function. Nature, 400, 418-419. doi:10.1038/22682
Krueger, K.R., Wilson, R.S., Kamenetsky, J.M., Barnesm, L.L., Bienia,
J.L., & Bennett, D.A. (2009). Social engagement and cognitive
function in old age. Experimental Aging Research, 35, 45-60.
doi:10.1080/03610730802545028
Kumar, A.M., Tims, F., Cruess, D.G., Mintzer, M.J., Ironson, G.,
Loewenstein, D.,Kumar, M. (1999). Music therapy increases
serum melatonin levels in patients with Alzheimers disease.
Alternative Therapies in Health & Medicine, 5, 49-57.
La Garce, M. (2002). Control of environmental lighting and its effects
on behaviors of the Alzheimers type. Journal of Interior Design,
28, 15-25. doi:10.1111/j.1939-1668.2002.tb00375.x
Larson, E.B., Wang, I., Bowen, J.D., McCormich, W.C., Teri, L., Crane,
P.,Kukull, W. (2006). Exercise is associated with reduced risk
for incident dementia among persons 65 years of age and older.
Annals of Internal Medicine, 144, 73-81. doi:10.7326/0003-4819144-2-200601170-00004
Lauman, K., Garling, T., & Stormark, K.M. (2003). Selective attention and heart rate responses to natural and urban environments.
Journal of Environmental Psychology, 23, 125-134. doi:10.1016/
S0272-4944(02)00110-X
Lazar, S.W., Kerr, C.E., Wasserman, R.H., Gray, J.R., Greve, D.N.,
Treadway, M.T.,Fischl, B. (2005). Meditation experience is as-

Research in Gerontological Nursing Vol. x, No. x, 20xx

sociated with increased cortical thickness. Neuroreport, 16, 18931897.


Lazarov, O., Robinson, J., Tang, Y.P., Hairston, I.S., Korade-Mirnics,
A., Lee, V.M.,Sisodia, S.S. (2005). Environmental enrichment
reduces A-beta levels and amyloid deposition in transgenic mice.
Cell, 120, 701-713. doi:10.1016/j.cell.2005.01.015
Lee, Y., & Kim, S. (2008). Effects of indoor gardening on sleep, agitation, and cognition in dementia patients: A pilot study. International Journal of Geriatric Psychiatry, 23, 483-489. doi:10.1002/
gps.1920
Lin, S.T., Yang, P., Lai, C.Y., Su, Y.Y., Yeh, Y.C., Huang, M.F., & Chen,
C.C. (2011). Mental health implications of music: Insight from
neuroscientific and clinical studies. Harvard Review of Psychiatry,
19, 34-46. doi:10.3109/10673229.2011.549769
Lleo, A., Greenberg, S.M., & Growdon, J.H. (2006). Current pharmacotherapy for Alzheimers disease. Annual Review of Medicine,
57, 513-533.
Lu, D.F., Hart, L.K., Lutgendorf, S.K., Oh, H., & Schilling, M. (2013).
Slowing progression of early stages of AD with alternative
therapies: A feasibility study. Geriatric Nursing, 34, 457-464.
doi:10.1016/j.gerinurse.2013.07.003
Lu, L., Bao, G., Chen, H., Xia, P., Fan, X., Zhang, J.,Ma, L. (2003).
Modification of hippocampal neurogenesis and neuroplasticity
by social environments. Experimental Neurology, 183, 600-609.
doi:10.1016/S0014-4886(03)00248-6
Lutgendorf, S.K., Mullen-Houser, E., Russell, D., DeGeest, K.,
Jacobson, G., Hart, L.,Lubaroff, D.M. (2010). Preservation of
immune function in cervical cancer patients during chemoradiation using a novel integrative approach. Brain, Behavior, and Immunity, 24, 1231-1240. doi:10.1016/j.bbi.2010.06.014
Lutz, A., Grieschar, L.L., Rawlings, N.B., Ricard, M., & Davidson,
R.J. (2004). Long-term meditators self-induce high-amplitude
gamma synchrony during mental practice. Proceedings of the
National Academy of Science, 101, 16369-16373. doi:10.1073/
pnas.0407401101
Madroal, N., Lopez-Aracil, C., Rangel, A., del Rio, J.A., DelgadoGarcia, J.M., & Gruart, A. (2010). Effects of enriched physical
and social environments on motor performance, associative
learning, and hippocampal neurogenesis in mice. PloS One, 5,
e11130. doi:10.1371/journal.pone.0011130
Mather, J.A., Nemecek, D., & Oliver, K. (1997). The effect of a
walled garden on behavior of individuals with Alzheimers disease. American Journal of Alzheimers Disease, 12, 252-257.
doi:10.1177/153331759701200603
McDermott, O., Crellin, N., Ridder, H.M., & Orrell, M. (2013).
Music therapy in dementia: A narrative synthesis systematic review. International Journal of Geriatric Psychiatry, 28, 781-794.
doi:10.1002/gps.3895
McEwen, B.S. (2006). Protective and damaging effects of stress mediators: Central role of the brain. Dialogues in Clinical Neuroscience,
8, 367-381.
McEwen, B.S. (2007). Physiology and neurobiology of stress and adaptation: Central role of the brain. Physiology Review, 87, 873904. doi:10.1152/physrev.00041.2006
Molloy, D.W., Richardson, L.D., & Crilly, R.G. (1988). The effects of a
three-month exercise program on neuropsychological function
in elderly institutionalized women: A randomized controlled
trial. Age & Ageing, 17, 303-310. doi:10.1093/ageing/17.5.303
Mooney, P., & Nicell, P.L. (1992). The importance of exterior environment for Alzheimers residents: Effective care and risk management. Healthcare Management Forum, 5, 23-29.

17

Burgener et al.

Mora, F., Segovia, G., & del Arco, A. (2007). Aging, plasticity and environmental enrichment: Structural changes and neurotransmitter
dynamics in several areas of the brain. Brain Research Reviews,
55, 78-88. doi:10.1016/j.brainresrev.2007.03.011
Nieman, D.C., Henson, D.A., Davis, J.M., Dumke, C.I., Utter, A.C.,
Murphy, E.A.,McAnulty, L.S. (2006). Blood leukocyte mRNA
expression for IL-10, IL-1Ra, and IL-8, but not IL-6, increases
after exercise. Journal of Interferon Cytokine Research, 26, 668674.
Nyberg, L., Sandblom, J., Jones, S., Neely, A.S., Peterson, K.M., Ingvar,
M., & Backman, L. (2003). Neural correlates of training-related
memory improvement in adulthood and aging. Proceedings of the
National Academy of Sciences of the United States of America, 100,
13728-13733. doi:10.1073/pnas.1735487100
Okada, K., Kurita, A., Takase, B., Otsuka, T., Kodani, E., Kusama, Y.,
Mizuno, K. (2009). Effects of music therapy on autonomic nervous system activity, incidence of heart failure events, and plasma
cytokine and catecholamine levels in elderly patients with cerebrovascular disease and dementia. International Heart Journal,
50, 95-110.
Olazaran, J., Reisberg, B., Clare, L., Cruz, I., Pena-Casanova, J.,
Del Ser, T.,...Muniz, R. (2010). Nonpharmacological therapies in Alzheimers disease: A systematic review of efficacy.
Dementia and Geriatric Cognitive Disorders, 30, 161-178.
doi:10.1159/000316119
Ottosson, J., & Grahn, P. (2005). A comparison of leisure time spent in
a garden with leisure time spent indoors: On measures of restoration in residents in geriatric care. Landscape Research, 30, 23-55.
doi:10.1080/0142639042000324758
Pagnoni, G., & Cekic, M. (2007). Age effects on gray matter volume
and attentional performance in Zen meditation. Neurobiology of
Aging, 28, 1623-1627. doi:10.1016/j.neurobiolaging.2007.06.008
Parasuraman, R., & Haxby, J.V. (1993). Attention and brain function
in Alzheimers disease: A review. Neuropsychology, 7, 242-272.
doi:10.1037/0894-4105.7.3.242
Perry, J.R., & Hodges, J.R. (1999). Attention and executive deficits
in Alzheimers disease: A critical review. Brain, 122, 383-404.
doi:10.1093/brain/122.3.383
Petrosini, L., De Bartolo, P., Foti, F., Gelfo, F., Cutuli, D., Leggio, M.G.,
& Mandolesi, L. (2009). On whether the environmental enrichment may provide cognitive and brain reserves. Brain Research
Reviews, 61, 221-239. doi:10.1016/j.brainresrev.2009.07.002
Podewils, L.J., Guallar, E., Beauchamp, N.H., Lyketsos, C.G., Kuller,
L.H., & Scheltens, P. (2007). Physical activity and white matter
lesion progression. Neurology, 68, 1223-1227. doi:10.1212/01.
wnl.0000259063.50219.3e
Podewils, L.J., Guallar, E., Kuller, L.H., Fried, L.P., Carlson, O.M., &
Lyketsos, C.G. (2005). Physical activity, APOE genotype, and dementia risk: Findings from the CHS Cognition Study. American
Journal of Epidemiology, 161, 639-651. doi:10.1093/aje/kwi092
Posner, M.I., Rothbart, M.K., Sheese, B.E., & Tang, Y.Y. (2007). The
anterior cingulate gyrus and the mechanism of self-regulation.
Cognitive Affective & Behavioral Neuroscience, 7, 391-395.
Post-White, J., Kinney, M.E., Savik, K., Gau, J.B., Wilcox, C., & Lerner,
I. (2003). Therapeutic massage and healing touch improve
symptoms in cancer. Integrative Cancer Therapies, 2, 332-344.
doi:10.1177/1534735403259064
Prakash, R., Dubey, I., Abhishek, P., Gupta, S.K., Rastogi, P., &
Siddiqui, S.V. (2010). Long-term Vihangam yoga meditation
and scores on tests of attention. Perceptual and Motor Skills, 110,
1139-1148.

18

Prakash, R., Rastogi, P., Dubey, I., Abhishek, P., Chaudhury, S., &
Small, B.J. (2012). Long-term concentrative meditation and cognitive performance among older adults. Aging Neuropsychology
& Cognition, 19, 479-494. doi:10.1080/13825585.2011.630932
Raglio, A., Oasi, O., Gianotti, M., Manzoni, V., Bolis, S., Ubezio,
M.C.,Stramba-Badiale, M. (2010). Effects of music therapy
on psychological symptoms and heart rate variability in patients
with dementia: A pilot study. Current Aging Science, 3, 242-246.
Rappe, E., & Topo, P. (2007). Contact with outdoor greenery can
support competence among people with dementia. Journal of
Housing for the Elderly, 21, 229-248. doi:10.1300/J081v21n03_12
Reimersma-van der Lek, R.F., Swaab, D.F., Twisk, J., Hol, E.M.,
Hoogendijk, W.J., & Van Someren, E.J. (2008). Effect of bright
light and melatonin on cognitive and noncognitive function in elderly residents of group care facilities. Journal of the
American Medical Association, 299, 2642-2655. doi:10.1001/
jama.299.22.2642
Reisberg, B., Franssen, E.H., Souren, L.E., Auer, S., & Kenowsky, S.
(1998). Progression of Alzheimers disease: Variability and consistency: Ontogenic models, their applicability and relevance.
Journal of Neural Transmission Supplement, 54, 9-20.
Robertson, I.H., & Murre, J.M. (1999). Rehabilitation of brain damage:
Brain plasticity and principles of guided recovery. Psychological
Bulletin, 125, 544-575. doi:10.1037/0033-2909.125.5.544
Rockwood, K., & Middleton, L. (2007). Physical activity and the
maintenance of cognitive function. Alzheimers & Dementia, 3,
S38-S44. doi:10.1016/j.jalz.2007.01.003
Rodiek, S. (2002). Influence of an outdoor garden on mood and stress
in older adults. Journal of Therapeutic Horticulture, 8, 14-21.
Rodriguez, J.J., & Verkhratsky, A. (2011). Neurogenesis in Alzheimers
disease. Journal of Anatomy, 219, 78-89. doi:10.1111/j.14697580.2011.01343.x
Sakamoto, M., Ando, H., & Tsutou, A. (2013). Comparing the effects
of different individualized music interventions for elderly individuals with severe dementia. International Psychogeriatrics, 25,
775-784. doi:10.1017/S1041610212002256
Savva, G.M., Wharton, S.B., Ince, P.G., Forster, G., Matthews, F.E.,
& Brayne, C. (2009). Age, neuropathology, and dementia. New
England Journal of Medicine, 360, 2302-2309. doi:10.1056/
NEJMoa0806142
Scarmeas, N., Luchsinger, J.A., Brickman, A.M., Cosentino, S.,
Schupf, N., Xin-Tang, M.,Stern, Y. (2011). Physical activity and
Alzheimer disease course. American Journal of Geriatric Psychiatry, 19, 471-481. doi:10.1097/JGP.0b013e3181eb00a9
Schwindt, G.C., & Black, S.E. (2009). Functional imaging studies
of episodic memory in Alzheimers disease: A quantitative meta-analysis. NeuroImage, 45, 181-190. doi:10.1016/j.
neuroimage.2008.11.024
Silva, S.G., Unsain, N., Masco, D.H., Toscano-Silva, M., Amorim,
H.A., Araujo, B.H.S.,...Arida, R.M. (2012). Early exercise promotes positive hippocampal plasticity and improves spatial
memory in the adult life of rats. Hippocampus, 22, 347-358.
doi:10.1002/hipo.20903
Simmons-Stern, N.R., Budson, A.E., & Ally, B.A. (2010). Music
as a memory enhancer in patients with Alzheimers disease. Neuropsychologia, 48, 3164-3167. doi:10.1016/j.
neuropsychologia.2010.04.033
Simon, S.S., Yokomizo, J.E., & Bottino, C.M.C. (2012). Cognitive intervention in amnestic mild cognitive impairment: A systematic
review. Neuroscience and Biobehavioral Reviews, 36, 1163-1178.
doi:10.1016/j.neubiorev.2012.01.007

Copyright SLACK Incorporated

Nonpharmacological Therapies for Individuals With Dementia

Sitzer, D.I., Twamley, E.W., & Jeste, D.V. (2006). Cognitive training in
Alzheimers disease: A meta-analysis of the literature. Acta Psychiatrica Scandinavica, 114, 75-90.
Solberg, E.E., Holen, A., Ekeberg, O., Osterud, B., Halvorsen, R., &
Sandvik, L. (2004). The effects of long meditation on plasma
melatonin and blood serotonin. Medical Science Monitor, 10,
CR96-CR101.
Sotiropoulos, I., Catania, C., Pinto, L.G., Silva, R., Pollerberg, G.E.,
Takashima, A.,...Almeida, O.F. (2011). Stress acts cumulatively
to precipitate Alzheimers disease-like tau pathology and cognitive deficits. Journal of Neuroscience, 31, 7840-7847. doi:10.1523/
JNEUROSCI.0730-11.2011
Sotiropoulos, I., Catania, C., Riedemann, T., Fry, J.P., Breen, K.C.,
Michaelidis, T.M., & Almeida, O.F. (2008). Glucocorticoids
trigger Alzheimer disease-like pathobiochemistry in rat neuronal
cells expressing human tau. Journal of Neurochemistry, 107, 385397. doi:10.1111/j.1471-4159.2008.05613.x
Spector, A., Thorgrimsen, L., Woods, B., Royan, L., Davies, S.,
Butterworth, M., & Orrell, M. (2003). Efficacy of an evidencebased cognitive stimulation therapy programme for people with
dementia. British Journal of Psychiatry, 183, 248-254. doi:10.1192/
bjp.183.3.248
Stern, Y. (2009). Cognitive reserve. Neuropsychologia, 47, 2015-2028.
doi:10.1016/j.neuropsychologia.2009.03.004
Sugiyama, T., & Ward-Thompson, C. (2007). Outdoor environments,
activity and the well-being of older people: Conceptualizing
environmental support. Environment and Planning, A39, 19431960. doi:10.1068/a38226
Suzuki, M., Kanamori, M., Nagasawa, S., Tokiko, I., & Takayuki, S.
(2007). Music therapy-induced changes in behavioral evaluations, and saliva chromogranin A and immunoglobulin A
concentrations in elderly patients with senile dementia. Geriatrics & Gerontology International, 7, 61-71. doi:10.1111/j.14470594.2007.00374.x
Suzuki, M., Kanamori, M., Watanabe, M., Nagasawa, S., Kojima, E.,
Ooshiro, H., & Nakahara, D. (2004). Behavioral and endocrinological evaluation of music therapy for elderly patients with
dementia. Nursing Health Science, 6, 11-18. doi:10.1111/j.14422018.2003.00168.x
Swaab, D.F.., Dubelaar, E.J., Scherder, E.J., van Someren, E.J., &
Verwer, R.W. (2003). Therapeutic strategies for Alzheimer disease: Focus on neuronal reactivation of metabolically impaired
neurons. Alzheimer Disease & Associated Disorders, 17(Suppl. 4),
S114-S122.
Takahashi, T., & Matsushita, H. (2006). Long-term effects of music
therapy on elderly with moderate/severe dementia. Journal of
Music Therapy, 43, 317-333. doi:10.1093/jmt/43.4.317
Tennessen, C.M., & Cimprich, B. (1995). Views to nature: Effects
on attention. Journal of Environmental Psychology, 15, 77-85.
doi:10.1016/0272-4944(95)90016-0
Teplan, M. (2002). Fundamentals of EEG measurement. Measurement
Science Review, 2(2), 1-11.
Thompson, R.G., Moulin, C.J.A., Hayre, S., & Jones, R.W. (2005).
Music enhances category fluency in healthy older adults and
Alzheimers disease patients. Experimental Aging Research, 31,
91-99. doi:10.1080/03610730590882819
Trejo, J.I., Carro, E., & Torres-Aleman, I. (2001). Circulating insulinlike growth factor I mediates exercise-induced increases in the
number of new neurons in the adult hippocampus. Journal of
Neuroscience, 21, 1628-1634.
Tschanz, J.T., Corcoran, C.D., Schwartz, S., Treiber, K., Green, R.C.,

Research in Gerontological Nursing Vol. x, No. x, 20xx

Norton, M.C.,Lyketsos, C.G. (2011). Progression of cognition, functional, and neuropsychiatric symptom domains in a
population cohort with Alzheimer dementia: The Cache County
Dementia Progression study. American Journal of Geriatric Psychiatry, 19, 532-542. doi:10.1097/JGP.0b013e3181faec23
Tse, M.M. (2010). Therapeutic effects of an indoor gardening programme for older people living in nursing homes. Journal of Clinical Nursing, 19, 949-958. doi:10.1111/j.1365-2702.2009.02803.x
Uchida, S., Iha, T., Yamaoka, K., Nitta, K., & Sugano, H. (2012).
Effect of biofield therapy in the human brain. Journal of Alternative and Complementary Medicine, 18, 875-879. doi:10.1089/
acm.2011.0428
Ulrich, R.S., Simons, R.F., Losito, B.D., Fiorito, E., Miles, M.A., &
Zelson, M. (1991). Stress recovery during exposure to natural
and urban environments. Journal of Environmental Psychology,
11, 201-230. doi:10.1016/S0272-4944(05)80184-7
Valentine, E.R., & Sweet, P.L.G. (1999). Meditation and attention: A
comparison of the effects of concentrative and mindfulness meditation on sustained attention. Mental Health, Religion, & Culture,
2, 59-70. doi:10.1080/13674679908406332
Van den Berg, A.E., & Custers, H.G. (2011). Gardening promotes
neuroendocrine and affective restoration from stress. Journal of
Health Psychology, 16, 3-11. doi:10.1177/1359105310365577
Voss, M.W., Prakash, R.S., Erickson, K.I., Chandramallika, B.,
Chaddock, L., Kim, J.S.,Kramer, A.F. (2010). Plasticity of
brain networks in a randomized intervention trial of exercise
training in older adults. Frontiers in Aging Neuroscience, 2, 1-16.
doi:10.3389/fnagi.2010.00032
Walton, K.G., Fields, J.Z., Levitsky, D.K., Harris, D.A., Pugh, N.D.,
& Schneider, R.H. (2004). Lowering cortisol and CVD risk in
postmenopausal women: A pilot study using the Transcendental
Meditation program. Annals of the New York Academy of Sciences,
1032, 211-215. doi:10.1196/annals.1314.023
Wang, K.L., & Hermann, C. (2006). Pilot study to test the effectiveness
of Healing Touch on agitation in people with dementia. Geriatric
Nursing, 27, 34-40. doi:10.1016/j.gerinurse.2005.09.014
Wells, R.E., Phillips, R.S., & McCarthy, E.P. (2011). Patterns of mindbody therapies in adults with common neurological conditions.
Neuroepidemiology, 36, 46-51. doi:10.1159/000322949.
Whall, A.L., Black, M.E., Groh, C.J., Yankou, D.J., Kupferschmid,
B.J., & Foster, N.L. (1997). The effect of natural environments
upon agitation and aggression in late stage dementia patients. American Journal of Alzheimers Disease, 12, 216-220.
doi:10.1177/153331759701200506
Wilkinson, D.S., Knox, P.L., Chatman, J.E., Johnson, T.L., Barbour, N.,
Myles, Y., & Reel, A. (2002). The clinical effectiveness of healing
touch. Journal of Alternative and Complementary Medicine, 8, 3347.
Willis, S.L., Tennstedt, S.L., Marsiske, M., Ball, K., Elias, J., Koepke,
K.M.,Wright, E. (2006). Long-term effects of cognitive training
on everyday functional outcomes in older adults. Journal of the
American Medical Association, 296, 2805-2814. doi:10.1001/
jama.296.23.2805
Woods, D.L., & Dimond, M. (2002). The effect of Therapeutic
Touch on agitated behavior and cortisol in persons with
Alzheimers disease. Biological Research for Nursing, 4, 104-114.
doi:10.1177/1099800402238331
Woods, J.A., Keylock, K.T., Lowder, T., Vieira, V.J., Zelkovich, W.,
Dumich, S.,McAuley, E. (2009). Cardiovascular exercise
training extends influenza vaccine seroprotection in sedentary
older adults: The immune function intervention trial. Journal
of the American Geriatrics Society, 57, 2183-2191. doi:10.1111/

19

Burgener et al.

j.1532-5415.2009.02563.x
Xiong, G.L., & Doraiswamy, P.M. (2009). Does meditation enhance
cognition and brain plasticity? Annals of the New York Academy
of Sciences, 1172, 63-69. doi:10.1196/annals.1393.002
Yaffe, K., Barnes, D., Nevitt, M., Lui, L.Y., & Covinsky, K. (2001). A
prospective study of physical activity and cognitive decline in elderly women: Women who walk. Archives of Internal Medicine,
161, 1703-1708. doi:10.1001/archinte.161.14.1703
Yan, X., Shen, H., Zaharia, M., Wang, J., Wolf, D., Li, F.,Cao, W.
(2004). Involvement of phosphatidylinositol 3-kinase and insulinlike growth factor-1 in YXLST-mediated neuroprotection. Brain
Research, 1006, 198-206. doi:10.1016/j.brainres.2004.01.068
Yevchak, A.M., Loeb, S.J., & Fick, D.M. (2008). Promoting cognitive
health and vitality: A review of clinical implications. Geriatric
Nursing, 29, 302-310. doi:10.1016/j.gerinurse.2007.10.017
Zec, R.F., & Burkett, N.R. (2008). Non-pharmacological and pharmacological treatment of the cognitive and behavioral symptoms of
Alzheimer disease. Neurology Rehabilitation, 23, 425-438.
Zunzunegui, M.V., Alvarado, B.E., Del Ser, T., & Otero, A. (2003).
Social networks, social integration, and social engagement determine cognitive decline in community-dwelling Spanish older
adults. Journals of Gerontology. Series B, Psychological Sciences
and Social Sciences, 58, S93-S100.

20

Copyright SLACK Incorporated