C li nic al A d van c es i n

G e r i a t r i c Ps y c h i a t r y
A Focus on Prevention of Mood and
Cognitive Disorders

Harris Eyre, MBBSa,b, Bernhard Baune, MD, PhD

a
,
Helen Lavretsky, MD, MSc,*

KEYWORDS
 Late life  Psychiatry  Cognitive decline  Mood disorder  Depression
 Prevention  Treatment

KEY POINTS
 World population aging in the twenty-first century is unprecedented in human history, and
will place substantial pressure on health systems across the world with concurrent rises in
chronic diseases, particularly cognitive disorders and late-life affective disorders.
 Prevention of mood and cognitive disorders is of utmost importance to reduce morbidity
and mortality and the high costs of health care for both patients and society.
 Recent data and innovative preventive interventions involving lifestyle, resilience building,
and complementary, alternative, and integrative medicine for treatment and prevention of
geriatric mood and cognitive disorders are discussed.
 Current clinical challenges and future directions for research are addressed.

INTRODUCTION

The world’s population is aging in the twenty-first century at a rate unprecedented in

human history, and this will place substantial pressure on health systems across the
world along with concurrent rises in chronic diseases. In particular, rates of cognitive
disorders and late-life affective disorders are expected to increase. A recent global
report1 suggests that the proportion of older people (aged 60 years) increased

a
Discipline of Psychiatry, University of Adelaide, 55 Frome Road, Adelaide, South Australia
5005, Australia; b Semel Institute for Neuroscience, University of California, Los Angeles, 760
Westwood Boulevard, Los Angeles, CA 90095, USA; c Late Life Mood Stress and Wellness
Research Program, Semel Institute for Neuroscience, University of California, Los Angeles,
760 Westwood Plaza, Room 37-465, Los Angeles, CA 90077, USA
* Corresponding author.
E-mail address: [email protected]

Psychiatr Clin N Am 38 (2015) 495–514

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496 Eyre et al

from 9.2% in 1990% to 11.7% in 2013, and will continue to grow as a proportion of the
world population, reaching 21.1% by 2050. In tandem with aging, there are robust pre-
dictions suggesting that rates of age-related cognitive decline, dementia, and geriatric
depression will increase, with serious consequences. As of 2013, there were an esti-
mated 44.4 million people worldwide with dementia.2 This number will increase to an
estimated 75.6 million in 2030 and 135.5 million in 2050. The most recent data on geri-
atric depression3 identified depressive disorders as a leading cause of burden interna-
tionally, and suggested major depressive disorder was also a contributor of burden
allocated to suicide and ischemic heart disease. Depressive disorders were the sec-
ond leading cause of years lived with disability in 2010.3
These large burdens of disease are met by modest efficacies of current therapies
and poor access for many. Unfortunately for those with Alzheimer disease (AD), phar-
macological agents temporarily treat symptoms without having an effect on the under-
lying pathophysiology of the disease.4 In geriatric depression, a recent meta-analysis
of clinical trials suggests a response rate of 48% and a remission rate of 33.7%, both
very similar to response and remission rates found in adult patients.5 Clearly innova-
tive prevention and treatment strategies are needed.
Throughout health care, everything clinicians do should be aimed toward preven-
tion. This approach ranges from preventing the onset of disease in those who are
well, through preventing chronicity, disability, and other consequences of disease,
to preventing relapses in those in recovery. When conceptualizing approaches in pre-
vention science, the most commonly used models are those of the Institute of Medi-
cine (IOM)6 and the World Health Organization (WHO) framework of levels of
prevention (ie, primary, secondary, and tertiary prevention).7 A report from the IOM6
suggests prevention may be directed toward the whole population (universal preven-
tion), high-risk groups (selective prevention), or those with subsyndromal symptoms
(indicated prevention). The WHO prevention framework7 suggests primary prevention
involves strategies aimed at preventing the development of disease; secondary pre-
vention involves strategies to diagnose and treat existent disease in early stages
before significant morbidity occurs; and tertiary prevention involves strategies to
reduce the negative impact of existent disease by restoring function and reducing
disease-related complications.
Fortunately, there are several innovative prevention and treatment strategies being
developed. This article focuses on several key strategies that include preventive and
treatment strategies coming from resilience-building interventions, and complemen-
tary, alternative and integrative therapies. Platforms such as telepsychiatry and
Internet-based interventions are also promising mechanisms to enhance access to
therapies. The latest clinical advances in geriatric psychiatry for the prevention and
treatment of mood disorders and cognitive decline are outlined, followed by an explo-
ration of clinically relevant scientific advances under way at present.

CLINICAL ADVANCES IN GERIATRIC DEPRESSION

Preventive Interventions for Geriatric Depression
This review focuses on the IOM framework of prevention comprising universal, selec-
tive, and indicated prevention.6 A critique of prevention in geriatric psychiatry should
focus on (1) feasibility, (2) effectiveness, and (3) ethical and economic considerations.8
Table 1 outlines these conceptual frameworks of preventive science, and gives clin-
ical examples for the fields of geriatric psychiatry.
With respect to universal prevention, any universal preventive action for geriatric
depression should be a “light” intervention in terms of cost, effort for patients, and
 Geriatric Mood and Cognitive Disorders 497

Table 1
Clinical implications of preventive science frameworks in geriatric psychiatry

Preventive Definition and Clinical Examples for Clinical Examples for

Approach Explanation Geriatric Depression Cognitive Decline
Universal Strategies that involve Environmental design and modification (eg, green
the whole space development, walkway modification, food
population. Provided access, health communities); cross-governmental
without screening initiatives; Internet-based promotions;
informational programs for the general public
Selective Strategies that involve Risk factors:
targeted Preexisting disease: psychiatric illness (eg, anxiety
subpopulations disorder, age-related cognitive dysfunction,
whose risk of substance-related disorders); general medical
developing a disorder conditions (eg, cardiovascular disease, obesity,
is above average. diabetes)
Involves identified Health-related behaviors: eg, psychological stress;
exposure to specific physical inactivity; alcohol, tobacco and other
risk factors drugs; sleep disruption; dietary factors
Biological factors
Indicated Strategies aimed at Subthreshold; early intervention
subjects who have
early and
subthreshold
symptoms and signs
of illness. Involves a
screening process
Primary Strategies to avoid As per universal and selective approaches
occurrence of disease
Secondary Strategies to diagnose Relapse prevention; Early intervention to
and treat existent attenuation of prevent conversion to
disease in early stages episode duration and tertiary
before significant severity of episode;
morbidity occurs early intervention
Tertiary Strategies to reduce Prevention of cognitive decline; prevention of
negative impact of psychotropic drug use and therefore reduced side
existent disease by effects; prevention of catatonia; prevention of
restoring function adverse effects of illness on social and
and reducing disease- occupational functioning
related complications

Data from Refs.4,6,7,72–75

impact (reviewed extensively elsewhere8). An example is a public awareness

campaign. Cuijpers9 has described that, even in a disorder such as depression which
has a relatively high incidence, studies testing universal prevention are not likely to be
feasible. Such a study would require too many participants and be too costly to be
run.8 Cuijpers suggests “this does not imply that universal prevention may not be use-
ful, but it does suggest that universal prevention is probably best seen as a ‘primer’—a
way to prepare the public that depression is a disorder that can be managed, to
reduce stigma.”9 Fortunately, given technological advances and the widespread ac-
cess to electronic media globally, electronic health preventive interventions for older
people are in development.8 These developments may drive down costs of programs,
and increase opportunities for and scales of preventive interventions, hence shifting
preventive action toward universal programs.
498 Eyre et al

With respect to selective prevention, several tested interventions are available (for
review see Ref.8). These interventions usually involve a way of identifying those at
risk, and creating engagement with the intervention itself. Identification of older people
at risk and engaging them effectively depends very much on local socioeconomic and
cultural factors.8 In high-resource settings with well-developed health services, the
more prudent point of contact for selective prevention may be community health ser-
vices. Encouragingly, epidemiological data show that most older people with risk fac-
tors for depression do contact their family physician regularly and that these doctors
have reliable data about many known risk factors.8 Engaging older people who are not
clinically depressed in an intervention is not easy. Complicated factors include a lack
of awareness of mental health; lack of trust in interventions; lack of time, trained
personnel, and resources to engage in an intervention; and the societal stigma sur-
rounding mental illness.8 Beekman and colleagues8 suggest “it is possible from an
intrapersonal psychological perspective, humans tend to dislike doing things now to
avoid harm later—ie, there is no immediate benefit.” From the intervention perspec-
tive, the interventions that have been designed are mostly “light” versions of robust
clinical interventions, such as cognitive therapy, interpersonal therapy, reminiscence,
and problem solving.8 Often these are modified to cater for persons exposed to spe-
cific risk factors and circumstances.8 Other ingredients involve engaging in pleasant
activities, physical activity, using nutritional supplements such as vitamin D and fish
oils, and exposure to bright light (see for review Ref.10).
Indicated prevention engages older people who do have symptoms of depression
but who have not developed a diagnosable major mood disorder. These individuals
do have symptoms, and these symptoms interfere with their well-being and daily func-
tioning. Indeed, older people with subthreshold depressive symptoms are at very high
risk for developing diagnosable major mood disorders.11 A drawback of indicated pre-
vention is that participants need to be diagnosed with “symptoms but no disorder.”8
The trials that have been conducted in this area mostly recruited participants through
screening.11 A positive screen implies that some significant symptoms are present. In
a next diagnostic step, the outcome may either (1) a diagnosable major mood disorder
or (2) no such disorder. The patient is then referred for treatment or offered a preven-
tive intervention, respectively. A study in the Netherlands by van’t Veer-Tazleer and
colleagues12 tested a program that was organized along the lines of “stepped
care.” In this program all the older participants with “symptoms but major disorder”
were offered a choice of educational and self-help interventions first, slowly stepping
up the intensity of the intervention if the symptoms remained present. The intervention
halved the 12-month incidence of depressive and anxiety disorders, from 0.24 in the
usual care group to 0.12 in the stepped-care group (relative risk, 0.49; 95% confi-
dence interval [CI], 0.24–0.98).

Resilience-Building Interventions
Advancing age is often associated with increased vulnerability to a unique set of
stressors including retirement, medical comorbidity, loss of loved ones, and the threat
of loss of independence. As such, there has been a surge of interest in exploring fac-
tors that contribute to older adults aging more successfully. One such aspect of suc-
cessful aging is the concept of resilience.13
The critical role of resilience in successful aging has been well documented.14–16
Positive constructs such as resilience may be thought of as being complements to
traditional medicine in that they emphasize personal strength rather than disease or
deficits.17 The study of resilience coincides with the rising trend toward a strengths-
based approach to aging, which is slowly starting to replace, or at least complement,
 Geriatric Mood and Cognitive Disorders 499

the traditional negative deficits view of aging (see for review Ref.18). One of the goals of
positive aging is for individuals to evolve, adapt, and find meaning and purpose in life
events. One study found that older adults who were more resilient tended to report
fewer adversities and were more likely to use adaptive, solution-driven coping rather
than avoidant coping strategies in the face of challenge.19 Additional individual char-
acteristics that have been viewed as being important contributors to resilience include
commitment, dynamism, humor in the face of adversity, optimism, faith, altruism, and
perceiving adversity as an opportunity to learn and grow.20
To the authors’ knowledge, there are no published interventions specifically target-
ing resilience in geriatric mood and cognitive disorders, but there are some data in
adult populations. Padesky and Mooney21 describe a 4-step strengths-based cogni-
tive behavioral therapy model designed to enhance resilience. The 4 steps to resil-
ience include: a search for strengths; construction of a personal model of resilience;
applying the personal model of resilience to areas of life difficulties; and practicing
resilience. In this treatment approach, individuals are supported to search for areas
of competence such as good health, positive relationships with others, self-efficacy,
emotion regulation skills, and the belief that one’s life has meaning. The purpose of
this search is based on the notion that all individuals possess resilience traits, however
much they have been unaware of same. A personal model of resilience is created that
may then be used by the individual in life situations.
When exploring resilience in older participants, a recent observational study by
Jeste and colleagues18 found significant associations between resilience and self-
rated successful aging in a sample of more than 1000 community-dwelling older
adults. The magnitude of these effects was reportedly comparable in size with that
of physical health. This finding was supported by Manning and colleagues22 who re-
ported another observational study, finding high levels of resilience protect against the
psychological impact of chronic new conditions in older adults. Some research has
suggested that high levels of resilience significantly contribute to longevity and that
this becomes even more significant at very advanced ages, centenarians being
more resilient than any other age group.23 In a cohort of middle- to older-aged women
with breast cancer, Loprinzi and colleagues24 demonstrated the possible efficacy of
the Stress Management and Resiliency Training (SMART) program in increasing the
quality of life. In this intervention, participants attended two 90-minute group sessions
in which they were taught relaxation techniques, in addition to skills to delay judgment
and attend to novel aspects of the environment rather than one’s thoughts. Partici-
pants also learned to adopt a flexible disposition and practice gratitude, compassion,
and acceptance. The investigators found that relative to the wait-list control group,
women who received the SMART intervention reported improved resilience, quality
of life, anxiety, stress, and fatigue. The evidence of the feasibility of such a brief inter-
vention is promising in the context of adapting programs for older adults.

Complementary, Alternative, and Integrative Therapies for Geriatric Depression

Complementary and alternative medicine “is a group of diverse medical and health
care systems, practices, and products that are not presently considered part of con-
ventional medicine.”25 Some of these therapies provide promise as novel and effective
therapies for treatment and prevention of geriatric psychiatric disorders with generally
more modest side-effect profiles.10 “Complementary” generally refers to using a
nonmainstream approach together with conventional Western medicine. “Alternative”
refers to using a nonmainstream approach in place of conventional Western medicine.
“Integrative medicine” is another term often used when strategy combines alternative
and complementary medicine with evidence-based Western medicine. In this article
500 Eyre et al

such therapies are referred to as complementary, alternative, and integrative medicine

(CAIM). CAIM interventions have varying levels of efficacy and evidence; they can
include mind-body practices, conventional physical activity, dietary interventions,
and natural products, in addition to body-based practices and other medical system
practices.
Mind-body practices refer to practices whereby there is both physical and mental
activity that may be combined during training. These activities can be more
exercise-focused (ie, yoga, tai chi, qigong) or more focused on practice and stress
reduction (ie, mindfulness and relaxation). Physical activity refers to any bodily move-
ment produced by skeletal muscles that requires energy expenditure, and may include
aerobic, resistance, stretching and toning, or combination activities. Dietary interven-
tions explore the effect of dietary patterns on health and illness, and may include,
among others, Western, traditional, and Mediterranean dietary patterns, and caloric
restriction. Natural products may include herbs, vitamins, minerals, natural supple-
ments, and probiotics. Body-based practices may include spinal manipulation (eg,
chiropractic, osteopathic medicine), aromatherapy, and massage therapy. Other
medical systems include traditional Chinese medicine (including acupuncture), ayur-
vedic medicine, or homeopathy. These CAIM interventions are largely based on ther-
apies that have been used in many civilizations and religions for hundreds and
thousands of years. It is not since the past 50 to 100 years that empirical science
has begun to explore the evidence behind these therapies.

Clinical importance
There are several major reasons why geriatric mental health providers need to recog-
nize the importance of these interventions. (1) CAIM therapy use is high and rising.
Research suggests 12-month prevalence of any CAIM usage (excluding prayer) in
the United States is around 35% to 50%; Baby Boomers (adults born from 1946 to
1964) report significantly higher rates of use than the Silent Generation (born from
1925 to 1945) for chronic conditions.26 (2) The global population is aging. See earlier
discussion. (3) CAIM therapies are increasingly cited in clinical guidelines. It is now
commonplace to note the use of therapies such as conventional exercise in the man-
agement of psychiatric conditions. (4) CAIM therapies are a source for innovative in-
terventions and have a growing, quality empirical research basis. Empirical research
into these therapies is exploring their clinical efficacy in trials and the neurobiological
mechanism underlying their effects. (5) CAIM therapies can help to lower utilization of
conventional medicines. CAIM therapies may be used in replacement of conventional
medicines for the management of mild illnesses (eg, relaxation techniques for mild
anxiety instead of benzodiazepines, which are known to have adverse effects in
elderly populations).10 (6) CAIM therapies can have significant side effects and
CAIM-drug interactions. With the high use in geriatric populations, this is an important
reason why clinicians need to better understand CAIM therapies.10

Conventional physical activity

Conventional physical exercise has received attention for its potential role in the treat-
ment of geriatric depression. The effects of aerobic exercise on depressed adults
(50 years) was examined and compared with either monotherapy with sertraline
as a standard antidepressant or a combination.27 The study found that after 16 weeks,
all groups demonstrated significant and equivalent reductions in depressive symp-
toms. Furthermore, a 10-month follow-up study showed that participants in the exer-
cise group (who improved to the point of remission during the initial study) had lower
rates of relapse with sertraline versus antidepressants. Another study of exercise in
 Geriatric Mood and Cognitive Disorders 501

older adults found that 10 weeks of strength-training exercises classes, provided as

an adjunctive treatment, lessened depressive symptoms in a group of older adults
who failed antidepressant response alone when compared with a health education
course.28 A systematic review29 examining the role of exercise in the treatment of
depression in older adults was published in 2009. This study noted 11 randomized
controlled trials (RCTs) with a total of 641 participants older than 60 years. The study
noted short-term (0–3 months) positive outcomes in 9 studies, although there was
variation in the type, intensity, and duration of exercise. The efficacy of exercise in
the medium- and long-term (3–12 months and >12 months, respectively) was less
clear. Methodological issues were noted, with only 5 studies showing appropriate allo-
cation of concealment, 5 studies with intention-to-treat analysis, and 7 studies with
blinding. From a more real-world perspective, the effectiveness of several lifestyle in-
terventions promoting increases in conventional physical exercise were recently
reviewed.30 Interventions were relatively successful in initiating increased levels of
physical activity in the short term; however, maintenance of these gains were dimin-
ished over time, and there was no convincing evidence that behavioral reinforcement
strategies were beneficial; therefore, adherence is a major concern. Another review of
exercise interventions found that although many older adults increase activity levels in
response to a wide variety of interventions, the amount of increase is seldom enough
to affect health outcomes in a positive manner.30
In conclusion, preliminary evidence points to exercise as having a significant poten-
tial to lessen symptoms in depressed older adults and, furthermore, to prevent relapse
of depression and/or development of depressive symptoms in older adults experi-
encing acute stressors associated with aging. Therefore, the authors recommend
physical exercise as a stand-alone therapy in the treatment of mild depression, and
as an adjunct in moderate depression.
Currently, the American College of Sports Medicine31 recommends that exercise
programs for older adults include both aerobic and nonaerobic physical activities,
such as resistance training, balance training, and stretching, for optimal general
health. See Box 1 for the latest clinical guidelines on physical activity for older adults.

Mind-body practices
Mindful exercise interventions have shown promise in addressing depressive symp-
toms in older adults. For example, a study of 82 older adult participants with depres-
sion randomized to either 16 weeks of qigong practice or newspaper reading groups
found that qigong participants showed significantly greater improvements in mood,
self-efficacy, and personal well-being.32 Practice of yoga typically benefits from in-
struction by expert instructors, and requires the dedication by participants to multiple
weekly sessions and continual use for maximal benefit. Prior review of published RCTs
of yoga for depression in adults revealed that although all trials found benefit, trial
methodologies have generally been weak with lack of blinding, short duration of the
intervention, variable outcome measures, and limited information about subjects,
randomization procedures, compliance, and dropout rates.33 Comparative studies
of yoga have likewise been limited, with one trial demonstrating that yoga was as effec-
tive as tricyclic antidepressants and another showing that yoga may provide benefit as
an augmentation strategy for antidepressant treatment.34 Yoga is commonly used in
combination with other treatments for depression, anxiety, and stress-related disor-
ders. Data on use of yoga for anxiety and depression in older adults are more limited;
however, one significant study of 69 older adults in India did compare the impact of
yoga with Ayurveda or a wait-list control condition on sleep and depressive symp-
toms.35 Participants in the yoga group practiced physical postures, relaxation
502 Eyre et al

Box 1
Clinical suggestions for geriatric populations

If 65 years or older, generally fit, and have no limiting health conditions.

 At least 150 minutes of moderate-intensity aerobic activity (ie, brisk walking) every week and
muscle-strengthening activities on 2 or more days a week that work all major muscle groups
(ie, legs, hips, back, abdomen, chest, shoulders, and arms) OR
 75 minutes of vigorous-intensity aerobic activity (ie, jogging or running) every week and
muscle-strengthening activities on 2 or more days a week that work all major muscle
groups OR
 An equivalent mix of moderate- and vigorous-intensity aerobic activity and muscle-
strengthening activities on 2 or more days a week that work all major muscle groups
Other comments:
 If there is a limiting condition, it is recommended that the health professional and patient
consult a qualified exercise physiologist
 10 minutes at a time is fine for physical activity
 The following activities count as muscle-strengthening activities: yoga, heavy gardening

Adapted from the Centers for Disease Control and Prevention Report ‘Physical activity is essen-
tial to healthy aging’. How much physical activity do older adults need? 2014. Available at:
http://www.cdc.gov/physicalactivity/everyone/guidelines/olderadults.html. Accessed October
28, 2014.

techniques, regulated breathing, and devotional songs, and attended lectures for
more than 7 hours a week during the course of the 6-month trial. Practice of yoga
significantly affected the quality of sleep and level of depressive symptoms when
compared with the 2 control conditions, neither of which demonstrated significant ef-
fects. In particular, depressive symptoms, as measured by the short form of the Geri-
atric Depression Scale, decreased in the yoga group from a baseline average of 10.6 to
8.1 by 3 months and 6.7 by 6 months. The average time to fall asleep decreased in the
yoga group by 10 minutes while the total number of hours slept increased by 60 mi-
nutes, and resulted in a greater feeling of being rested after 6 months. A recent study
by Shahidi and colleagues36 compared the effectiveness of laughter yoga, group ex-
ercise therapy, and a control arm in decreasing depression in older adult women (60–
80 years). In this study, 70 depressed women were chosen if their Geriatric Depression
Score was greater than 10. This study went for 10 sessions and found a significant
improvement in depression score with both yoga and group exercise therapy in com-
parison with control activity. Although the evidence supporting the use of these ther-
apies in the treatment of late-life mental illnesses is not strong, there are some
interesting early results that require further high-quality research.37
The authors recommend the use of mind-body therapies as a stand-alone or
adjunctive antidepressant treatment in the management of geriatric depression,
based on individual preference and the severity of depression. Further high-quality
data are needed to further inform these recommendations.

Dietary interventions
Dietary interventions are seen as a promising method to both treat and prevent geri-
atric depression. When considering the diet composition of older depressed adults,
some concerning findings come from a recent cross-sectional study.38 In this study
of 278 older adults (144 with depression; 134 without depression), vitamin C, lutein,
and cryptoxanthin intakes were significantly lower among depressed individuals
 Geriatric Mood and Cognitive Disorders 503

than in controls. In addition, fruit and vegetable consumption, a primary determinant of

antioxidant intake, was lower in depressed individuals. This type of dietary intake may
indeed be a risk factor for depression. A recent systematic review39 addressed asso-
ciations between dietary patterns and depression in community-dwelling adult popu-
lations. A total of 21 studies were identified. Results from 13 observational studies
were pooled, from cross-sectional to 15 years prospective. Two dietary patterns
were identified. The healthy diet pattern was significantly associated with a reduced
odds of depression (odds ratio [OR], 0.84; 95% CI, 0.76–0.92; P<.001). No statistically
significant association was observed between the Western diet and depression (OR,
1.17; 95% CI, 0.97–1.68; P 5 .094); however, the studies were too few for a precise
estimate of this effect. The results suggest that high intakes of fruit, vegetables,
fish, and whole grains may be associated with a reduced risk of depression.
The authors are aware of only one RCT, currently under way in Australia, to explore
the effect of dietary interventions on adult depression,40 not specifically in an older-
age population. This study is enrolling participants with a current major depressive
episode who are randomized to a dietary intervention group or a social support group.
The dietary intervention consists of 7 individual nutrition consulting sessions (60 mi-
nutes each) delivered by a dietician. Data will be explored across the 3-month trials
and a 6-month follow-up. Data on the potential benefits of dietary coaching in the pre-
vention of incident depression for older adults has recently been drawn from a larger
randomized depression prevention trial that ran over 2 years.41 Older adults (n 5 122)
receiving dietary coaching experienced a low incidence of major depressive episodes
and exhibited a 40% to 50% decrease in depressive symptoms, and enhanced well-
being, during the initial 6-week intervention; these gains were sustained over 2 years.42
Clearly the role of dietary intervention is intriguing.

CLINICAL ADVANCES IN COGNITIVE DECLINE AND DEMENTIA

Prevention of Cognitive Decline and Dementia
The rising burden globally of mental, cognitive, and substance use disorders2,43 sup-
ports the need for improved methods to aid prevention and early intervention.44
Classic risk factor studies in dementia are hampered by the difficult phenotyping of
the disease with large heterogeneity in severity and presentation, and by the fact
that once symptomatic, irreversible brain damage is already present. The paradigm
shift in medicine toward prevention calls for identification of potentially modifiable fac-
tors that affect disease at an earlier stage. The rising burden of cognitive disorders is
occurring as our wider understanding of preventive lifestyle modifications and our un-
derstanding of the neurobiological underpinnings is rapidly evolving. For example,
with AD, a recent study has highlighted the important role of risk factor reduction
for reducing AD prevalence.44 Barnes and Yaffe44 explored the role of 7 potentially
modifiable AD risk factors: diabetes, mid-life hypertension, mid-life obesity, smoking,
depression, low educational attainment, and physical inactivity. The investigators
determined that these factors contributed to up to half of AD cases globally
(17.2 million), and that a 10% to 25% reduction in all risk factors could potentially pre-
vent as many as 1.1 to 3.0 million cases. There is now an emerging body of literature
exploring the effect of these risk factors on neurobiological factors. Other lifestyle fac-
tors that have been found to reduce the risk of AD include mind-body exercise (eg,
yoga, tai chi, qi gong45), conventional physical activity (eg, aerobic, strength
training45), supplements (eg, U3 fatty acids, flavanols46), stress-reduction techniques
(eg, mindfulness-based stress reduction47), sleep modification strategies,48 and die-
tary interventions (eg, fish consumption, Mediterranean diet).49
504 Eyre et al

Complementary, Alternative, and Integrative Therapies for Cognitive Decline and

Dementia
Conventional physical activity
Conventional physical activity is one of the most promising therapies for the treatment
and prevention of cognitive decline and dementia.4 There is a variety of subtypes of
physical activity, from aerobic activity, to resistance, to stretching and toning.
A recent RCT50 examined the efficacy of resistance and aerobic training in the
improvement of cognitive functions in subjects with subjective mild cognitive impair-
ment (MCI). The study occurred over 6 months and involved 86 community-dwelling
women aged 70 to 80 years.
 Physical activity protocols included twice-weekly resistance training, twice-
weekly aerobic training, or twice-weekly balance and toning (BAT) training (ie,
control).
 Resistance training improved selective attention, conflict resolution, and associ-
ated memory compared with BAT.
 By contrast, aerobic physical activity improved general balance and mobility and
cardiovascular capacity.
 The study also found that aerobic physical activity improved verbal memory, and
both resistance and aerobic physical activity improved spatial memory.
A recent stringent meta-analysis51 has examined the efficacy of exercise on cogni-
tion in older adults with MCI. MCI was diagnosed on documented criteria or via the
Mini-Mental State Examination (MMSE). Fourteen RCTs with 1695 participants aged
65 to 95 years were analyzed, with a duration of 6 to 52 weeks. Overall, 42% of effect
sizes (ESs) were potentially clinically relevant (ES >0.20) with only 8% of cognitive out-
comes statistically significant. The meta-analysis revealed negligible but significant ef-
fects of exercise on verbal fluency (ES, 0.17; 95% CI, 0.04–0.30). No significant benefit
was found for additional executive measures, memory, or information processing. The
investigators critically appraised RCT methods and concluded on a moderate quality,
with most trial samples being too small for sufficient power. There is clearly some ef-
fect for exercise at moderate to high levels of exertion. In addition, nowadays there is
emerging evidence for the effect of low levels of physical activity or “sedentary behav-
iors” such as sitting. Physical inactivity may increase the risk of AD by 82%.52 Approx-
imately 13% of AD cases worldwide may be attributable to sedentary behaviors.44 A
25% reduction in sedentary behavior could potentially prevent more than 1 million AD
cases globally.44 Sedentary behaviors may contribute to risk of AD and dementia by
increased risk of cardiometabolic risk factors (diabetes, hypertension, obesity) asso-
ciated with increased risk of dementia.53
Our clinical recommendation is that physical activity should be encouraged for all
older adults. More work is required to discern whether physical activity recommenda-
tions or dementia prevention are the same as generic “healthy aging” recommenda-
tions (as in Table 1). Although shorter-term interventions are useful in the research
setting, care must be taken to ensure a sustained engagement in physical activity.
Care must also be taken to create an age-appropriate and physical function–appro-
priate prescription, given the risks of adverse health effects (eg, falls, cardiovascular
events).

Mindful exercise
A recent meta-analysis54 critically evaluated the effects of tai chi on individuals aged
60 and older with and without cognitive impairment. In this study, 20 eligible studies
with a total of 2553 participants were identified who met inclusion criteria for the
 Geriatric Mood and Cognitive Disorders 505

systematic review; 11 of the 20 eligible studies were RCTs, 1 was a prospective non-
randomized controlled study, 4 were prospective noncontrolled observational studies,
and 4 were cross-sectional studies. Overall quality of RCTs was modest, with 3 of 11
trials categorized as being at high risk of bias. Meta-analyses of outcomes related to
executive function in RCTs of cognitively healthy adults indicated a large ES when tai
chi participants were compared with nonintervention controls (Hedges g 5 0.90;
P 5 .04) and a moderate effect size when compared with exercise controls
(g 5 0.51; P 5 .003). Meta-analyses of outcomes related to global cognitive function
in RCTs of cognitively impaired adults, ranging from MCI to dementia, showed smaller
but statistically significant effects when tai chi was compared with nonintervention
(g 5 0.35; P 5 .004) and other active interventions (g 5 0.30; P 5 .002).
There is a relative dearth of studies examining yoga and its effects on memory
enhancement. One main study of which the authors are aware explores the effects
of yoga and exercise in 135 healthy men and women aged 65 to 85 years.55 In this
study, subjects were exposed to 6 months of Hatha yoga classes, walking classes,
or wait-list control; subjects were screened with a variety of mood and cognition tests
(eg, Stroop test). After the intervention there were no effects from either of the active
interventions on any of the cognitive and alertness outcome measures. The yoga inter-
vention produced improvements in physical measures (eg, timed 1-legged standing,
forward flexibility) and several quality-of-life measures related to sense of well-
being, energy, and fatigue compared with control activity. This type of study needs
to be replicated in populations with MCI to better understand the potential effects.

Mind-body practices and stress-reduction techniques

Relaxation techniques, such as breathing exercises, guided imagery, and progressive
muscle relaxation, are designed to produce the body’s natural relaxation response.
These relaxation therapies are proved to lower stress levels in elderly subjects, and
so are recommended for clinical use. A recent pilot randomized trial47 with
mindfulness-based stress reduction (MBSR) aimed to test the safety and feasibility
of MBSR in older adults with MCI. The investigators found that adults with MCI can
safely participate and adhere to an MBSR program. The qualitative interviews
revealed that most enjoyed the program and described improved mindfulness skills,
well-being, interpersonal skills, acceptance/awareness of MCI, and decreased stress
reactivity. Most data suggest a trend toward improvement for measures of cognition
and well-being. Nevertheless a more formal, large-scale RCT is needed.
Firm clinical recommendations for these activities are not possible given the paucity
of sufficient evidence at this stage. However, the authors would recommend mind-
body therapies as useful stand-alone or adjunctive therapies for the management of
mild neuropsychiatric symptoms (eg, cognitive impairment and psychological
distress) and physical health (eg, balance, strength, coordination). Care must be taken
to create an age-appropriate, physically appropriate, and mental function–appropriate
prescription.56 The recommendations are based on clinical experience, emerging ev-
idence, and the safe nature of these activities.

Dietary interventions
Examining the effect of nutrition on cognitive decline is a new area of research showing
favorable results. Two significant studies are outlined here to illustrate the latest and
most significant developments in this area. A recent analysis of the Australian Imaging,
Biomarkers and Lifestyle Study of aging explores the association of 3 well-recognized
dietary patterns with cognitive change over a 3-year follow-up period. In this study,
527 healthy older participants (age 69.3  6.4 years) were enlisted and underwent
506 Eyre et al

dietary analysis using a food frequency question, in addition to neuropsychological

analyses at baseline, 18 months, and 36 months. Three dietary patterns were delin-
eated: the Australian-style Mediterranean diet (AusMeDi), the Western diet, and the
prudent diet. The principal aspects of the AusMeDi diet include proportionally high
consumption of olive oil, legumes, unrefined cereals, fruits, and vegetables, moderate
to high consumption of fish, moderate consumption of dairy products (mostly as
cheese and yogurt), moderate consumption of wine, and low consumption of meat
and meat products. Western diets are characterized by high intakes of red meat, sug-
ary desserts, high-fat foods, and refined grains. It also typically contains high-fat dairy
products, high-sugar drinks, and higher intakes of processed meat. The prudent diet
was characterized by high intakes of green leafy vegetables, fruits, nuts, grains, low-
fat foods, and protein. Higher baseline adherence to the AusMeDi was associated with
better performance in the executive function cognitive domain after 36 months in
apolipoprotein E (APOE) ε4 allele carriers (P<.01). Higher baseline Western diet adher-
ence was associated with greater cognitive decline after 36 months in the visuospatial
cognitive domain in APOE ε4 allele noncarriers (P<.01). All other results were not sig-
nificant. Systematic reviews of observation studies show similar results.57
The authors are aware of only one RCT exploring the role of diet in the prevention of
cognitive impairment. This study was a multicenter, randomized, primary prevention
trial named Prevención con Dieta Mediterránea (PREDIMED),58 which assessed the
effects of a nutritional intervention using the MeDi (supplemented with either extra-
virgin olive oil [EVOO] or mixed nuts) in comparison with a low-fat control diet. This
study assessed 522 participants at high vascular risk (age 74.6  5.7) and examined
cognitive performance (MMSE and Clock Drawing Test [CDT]) after 6.5 years of nutri-
tional intervention. After full adjustment, the MeDi EVOO group showed higher mean
MMSE and CDT scores versus control (adjusted differences: 10.62, 95% CI 10.18
to 11.05, P 5 .005 for MMSE; and 10.51, 95% CI 10.20 to 10.82, P 5 .001 for
CDT). Similarly, the MeDi 1 nuts group showed higher mean MMSE and CDT scores
(adjusted differences: 10.57, 95% CI 10.11 to 11.03, P 5 .015 for MMSE; and 10.33,
95% CI 10.003 to 10.67, P 5 .048 for CDT) versus control. Clearly, further RCTs are
needed in this area of research to improve the quality.
From a clinical perspective, the authors recommend that the population in general
adheres as closely as possible to the Mediterranean and healthy diets. Further clinical
trials are needed to discover the best diet(s) for maintaining brain health.

Natural products
Natural products may include herbs, minerals, natural supplements, vitamins, and
probiotics. A range of these products has been explored with regard to the treatment
and prevention of cognitive impairment. There are too many of these products to thor-
oughly review here, so only the main products, with a larger body of research or epide-
miological use, are reviewed, with further reading recommended.
U3 polyunsaturated fatty acid supplements One of the most widely used therapies is
U3 polyunsaturated fatty acids (PUFAs). More than 37% of individuals who reported
using a nonvitamin, nonmineral natural product in the 2007 National Health Interview
Survey reported using U3 PUFAs.59 Oily fish, such as salmon, mackerel, herring, and
sardines, are a rich source of U3 PUFAs, which are essential for brain development. It
is thought that U3 PUFAs may benefit neurodegenerative disorders owing to their anti-
oxidant and anti-inflammatory effects.60 Previous research from observational studies
has suggested that increased consumption of fish oils rich in U3 PUFAs may reduce
the chance of developing dementia. A recent Cochrane Database systematic review60
 Geriatric Mood and Cognitive Disorders 507

explored the effects of U3 PUFAs on the prevention of dementia and cognitive decline
in cognitively healthy older people. Information was available from 3 RCTs including
3536 participants in total. This meta-analysis found no evidence to support a preven-
tive effect following 24 or 40 months of intervention. RCTs suggest that selected pa-
tients with an MMSE score greater than 27 were more likely to identify a positive effect
of U3 PUFA supplementation. It would seem that studies of longer duration are
required to further explore this area. The authors’ clinical recommendation empha-
sizes clinician-patient discussions of evidence. Care must be taken with potential
side effects of mild nausea, mild increased bleeding, and a fishy aftertaste.
Table 2 lists further details on other CAIM therapies for the treatment and prevention
of cognitive decline.
Potential side effects and complementary, alternative, and integrative medicine-drug
interactions
As alluded to earlier, when encountering natural products in a clinical environment, it is
important to consider potential side effects and CAIM-drug interactions. Table 3 out-
lines an array of clinical findings and potential pitfalls of natural products. Of impor-
tance is that CAIM use may exacerbate polypharmacy in the elderly, which is a risk
factor for drug interactions, medication errors, and hospitalization. A survey of 271
British seniors found a mean of 5.91 (range 4–7) herbal and nutritional supplements
and 2.26 prescription drugs.61

TELEPSYCHIATRY AND INTERNET-BASED APPROACHES FOR OLDER ADULTS

Because of the low rates of receiving adequate treatment among older adults, and the
intrinsic and extrinsic barriers to mental health care, it is important to develop evidence-
based treatments that are easily accessible to patients, and which keep time and costs
low.62 Telemedicine and Internet-based treatments have been proposed as interven-
tions helpful for these issues.63–65 Internet-guided and telepsychiatry interventions
may save costs and time for patients and therapists, reach depressed older adults
who are not reachable with traditional therapies, solve transportation problems, stimu-
late empowerment of patients, and reduce the stigma associated with mental illness.62
Internet-based therapies can be seen as a specific type of guided self-help interven-
tion (for review see Ref.62). A self-help intervention can be defined as a psychological
treatment whereby the patient or client takes home a standardized treatment and
works through it more or less independently.66,67 In the standardized psychological
treatment, the patient can follow step-by-step instructions on what to do in applying
a generally accepted psychological treatment. The standardized psychological treat-
ment can be written down in hard-copy print, but can also be made available through
other media such as a personal computer, television, video, or the Internet. Contact
with therapists is not a necessity for the completion of the self-help therapy; if contact
with a therapist takes place, it should only be for support or facilitation. Contact is not
aimed at developing a traditional relationship between therapist and patient, and is
only meant to support the carrying out of the psychological treatment. Interaction be-
tween patient and therapist can take place through face-to-face contact, telephone,
email, or any other communication method.
Although a growing number of studies have examined the effects of Internet-based
interventions and telephone-supported interventions, few have examined these in
older adults.67 However, research shows that these interventions are promising,
and there is no reason to assume that they are not effective in older adults. Concerns
may include lesser proficiency with information technology in old age and lesser visual
acuity. More research is needed, especially as technological developments continue
 508
Eyre et al
Table 2
Other natural products and supplements suggested for the treatment of cognitive impairment

Suggested
Herb/Supplement Dose Possible Mechanism of Action Evidence Base Side Effects
Bacopa monnieri 300 mg/d An ayurvedic medicinal plant that No convincing evidence: 9 RCTs; GI upset
acts as a free radical scavenger 518 subjects in meta-analysis.
and in animal models reduces Limited evidence given poor
Ab; may also boost cholinergic study design
function
Curcumin (yellow curry) 2000–8000 mg/d Antioxidant, anti-inflammatory, Mixed results; no convincing GI upset
induces heat-shock proteins; evidence: 2 studies find no
antiamyloid effects in animals effect; 1 study finds beneficial
effect
Dehydroepiandrosterone 100 mg/d Adrenal steroid that declines with No convincing evidence of benefit. Acne, balding, insulin resistance,
(DHEA) aging, is lower in AD patients, 3 RCTs dyslipidemia, mood changes,
and is neurotrophic in animals hepatic dysfunction, possible
effects on hormone-sensitive
cancers
Hydergine 3 mg/d Combination of 4 ergot derivatives A 2000 Cochrane meta-analysis of GI upset, psychosis, flushing, blood
with vasodilatory effects and 19 trials found some evidence of pressure changes
possible effect on monoamine modest efficacy but many trials
and cholinergic transmission conducted before standardized
criteria for diagnosing dementia
Lecithin 3600 mg/d Acetylcholine precursor Review of 11 randomized trials GI upset, rash, headache, dizziness
showed no consistent benefit
Resveratrol Unknown (phase Polyphenol in the skin of red Clinical trial linking to increased Possible estrogen-like effects, as its
1 trials 2500– grapes and red wine with cerebral blood flow. Needs chemical structure is similar to
5000 mg/d) antioxidant and antiamyloid further study on cognitive phytoestrogens
properties in animals effects
Vitamin E 800–2000 IU/d Free radical scavenging No convincing evidence. Cochrane High dose increases all-cause
review of 3 studies mortality

Abbreviations: AD, Alzheimer disease; GI, gastrointestinal; RCT, randomized controlled trial.
Data from Refs.76–82
 Geriatric Mood and Cognitive Disorders 509

Table 3
Potential CAIM-drug interactions between natural products and prescription medications

Herb/Supplement Prescription Drug(s) Possible Interaction

Chamomile Sedatives (or alcohol) Oversedation
Garlic extract Protease inhibitors Decreased efficacy against HIV
Ginkgo biloba Anticoagulants Excessive bleeding
Omeprazole (CYP2C19 Decreased drug levels (2C19
substrates) induction)
Antipsychotic Priapism
Ginseng Anticoagulants Excessive bleeding
Monoamine oxidase inhibitors Mania, hypertension, headache
Sulfonylureas, insulin Hypoglycemia
Stimulants Insomnia, anxiety, mania
Kava Sedatives (or alcohol) Oversedation
Levodopa Increased parkinsonism
Omega-3 fatty Warfarin Excessive bleeding
acids
St John’s wort Protease inhibitors Decreased efficacy against HIV
cyclosporine Organ rejection
Serotonergic antidepressants Serotonin syndrome
Oral contraceptives Ineffective contraception
Tetracycline Photosensitivity
Valerian Sedatives (or alcohol) Oversedation
CYP3A4 substrates Increased drug levels (3A4 inhibition)
Vitamin E Anticoagulants Excessive bleeding

Abbreviation: HIV, human immunodeficiency virus.

rapidly, and innovative types of intervention and new possibilities to reduce the dis-
ease burden are required.

PROMISING RESEARCH AGENDAS

In addition to these current clinical advances, there is a range of research advances

that may pave the way for future clinical innovations.

Geroscience
Geroscience is an interdisciplinary field that aims to understand the relationship be-
tween aging and age-related diseases.68 In geroscience, researchers in a variety of dis-
ciplines may work together, sharing data and ideas, with a common goal of explaining
and intervening in age-related diseases. “Compression of morbidity,” a major focus of
geroscience research, is a concept whereby scientists discover ways to decrease the
period of an individual’s life in which there is poor health. With this aim, individuals hope
to postpone and reduce disease onset, disability, dependency, and suffering. The exact
mechanisms of aging are still under debate, although there are several mechanisms
which are generally agreed on (see for discussion Ref.69). These mechanisms include
genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, mito-
chondrial dysfunction, cellular senescence, and chronic inflammation.

Health Neuroscience
Health neuroscience was coined by Erickson and colleagues,70 and is at the interface
of health psychology and neuroscience. It is concerned with the interplay between the
510 Eyre et al

brain and physical health over the life span. A chief goal of health neuroscience is to
characterize bidirectional and dynamic brain-behavior and brain-physiology relation-
ships that are determinants, markers, and consequences of physical health states
across the life span. The motivation behind this goal is that a better understanding
of these relationships will provide mechanistic insights into how the brain links multi-
level genetic, biological, psychological, behavioral, social, and environmental factors
with physical health, especially vulnerability to and resilience against clinical illnesses.

Convergence Medicine
Convergence medicine is a novel derivative of convergence science, and refers to the
discipline of how societal health can be optimized by the cross-pollination of clinical
medical practice with nonclinical fields (eg, engineering, information technology,
entrepreneurship, public health, business, finance, management, journalism, politics,
law, and the arts).71 The aim is for health innovation based on interdisciplinary team
work and multidisciplinary mind-sets.

SUMMARY

Major problems are faced in geriatric psychiatry, and this article reviews the latest clin-
ical advances that hold promise for assisting the prevention and treatment of depres-
sion, cognitive decline, and dementia. Several major factors coalesce to drive the
need for innovation in geriatric psychiatry. First, the global population is aging. Sec-
ond, age-related cognitive decline, dementia, and depression have a large burden.
Third, the current treatment options for these conditions are modest. Finally, there
is a relatively poor lack of access in low- and middle-income environments. Promising
advances in geriatric psychiatry include preventive resilience-building interventions,
complementary, alternative, and integrative therapies, and brain-stimulation tech-
niques. Platforms such as telepsychiatry and Internet-based interventions are also
promising mechanisms to enhance access to therapies.

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