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Rationale and Design of a Clinical Trial of Adapted Tango to Improve Negative Health Impacts in Middle Aged African-American Female Caregivers of Persons with Alzheimer’s Disease (ACT Trial)



Alzheimer's disease (AD) is a devastating progressive neurodegenerative disease resulting in memory loss and a severe reduction in ability to perform activities of daily living. The role of caring for someone with AD frequently falls to female family members, often daughters. The burden of caregiving can increase stress and anxiety and cause health decline in the caregiver. The combination of ethnicity-related genetic factors promoting the development of dementias among African-Americans (AA) and the increased risk among women for developing AD means that AA women who are caregivers of a parent with AD are at great risk for developing dementias including AD. The proposed study would compare the cognitive, motor, and psychosocial benefits of a well-established 12 week, 20-lesson adapted Argentine Tango intervention (N=30) to a no-contact control group (N=10) in middle-aged (45-65 years) AA women who are caregivers of a parent with AD in the metro Atlanta area.
Journal of Alzheimer’s Disease 68 (2019) 767–775
DOI 10.3233/JAD-181130
IOS Press
Rationale and Design of a Clinical Trial of
Adapted Tango to Improve Negative Health
Impacts in Middle Aged African-American
Female Caregivers of Persons with
Alzheimer’s Disease (ACT Trial)
Madeleine E. Hackneya,b,c,, Lauren E. McCulloughd, Allison A. Baya, Hayley A. Silversteina,
Ariel R. Harta, Ryan J. Shineand Whitney Whartonf
aDepartment of Medicine, Division of General Medicine and Geriatrics, Emory School of Medicine,
Atlanta, GA, USA
bAtlanta VA Center for Visual and Neurocognitive Rehabilitation, Decatur, GA, USA
cDepartment of Rehabilitation Medicine, Emory School of Medicine, Atlanta, GA, USA
dEmory University Rollins School of Public Health, Atlanta, GA, USA
eEmory University College of Arts and Sciences, Atlanta, GA, USA
fDepartment of Neurology, Atlanta, Emory University School of Medicine, GA, USA
Accepted 16 January 2019
Abstract. Alzheimer’s disease (AD) is a devastating progressive neurodegenerative disease resulting in memory loss and a
severe reduction in ability to perform activities of daily living. The role of caring for someone with AD frequently falls to
female family members, often daughters. The burden of caregiving can increase stress and anxiety and cause health decline in
the caregiver. The combination of ethnicity-related genetic factors promoting the development of dementias among African-
Americans (AA) and the increased risk among women for developing AD means that AA women who are caregivers of a
parent with AD are at great risk for developing dementias including AD. The proposed study would compare the cognitive,
motor, and psychosocial benefits of a well-established 12 week, 20-lesson adapted Argentine Tango intervention (N= 30) to
a no-contact control group (N =10) in middle-aged (45–65 years) AA women who are caregivers of a parent with AD in the
metro Atlanta area.
Keywords: African American, Alzheimer’s disease, caregiver, clinical trial, dance, inflammation
As of 2018, 16.1 million Americans provide unpaid
care for people with Alzheimer’s disease (AD) and
Correspondence to: Dr. Madeleine E. Hackney, PhD, Division
of General Medicine and Geriatrics, Department of Medicine,
Emory School of Medicine, 1841 Clifton Rd NE, #553; Atlanta,
GA 30307, USA. Tel.: +1 404 321 6111/Ext. 5006; E-mails: and E-mail:
other dementias [1]. Compared to non-caregivers,
caregivers experience more depressive symptoms and
anxiety, lower levels of perceived health, more sleep
problems, and worse physical health. Overall, higher
stress is reported by caregivers compared to non-
caregivers, correlating to increased risk of negative
health outcomes [2]. Furthermore, in an older pop-
ulation, simply being a familial caregiver who is
experiencing physical or psychological strain has
ISSN 1387-2877/19/$35.00 © 2019 IOS Press and the authors. All rights reserved
768 M.E. Hackney et al. / Rationale and Design of ACT Trial
been identified as an independent risk factor for mor-
tality [3]. As such, caregivers often have considerable
health needs and require interventions for reducing
stress and improving health.
Dementia caregivers have increased risk for
psychological and physiological illness including
depression, hypertension, diabetes mellitus, dimin-
ished quality of life (QOL), disruption of profession,
and increased mortality [4, 5]. AD caregiving has
unique challenges including mood fluctuations, per-
sonality changes, agitation, impaired language and
reasoning, poor safety awareness, and impaired mem-
ory, which interfere with activities of daily living [6].
Stress and depression are independent risk factors for
developing AD [7–9], and caregivers are more prone
to cognitive impairment than healthy controls [10].
As a result, caregivers of those with AD may be at
greater risk for developing AD themselves due to the
increased burden of caring for a person with these
Although the current literature on biomarkers
of stress in caregivers is mixed, certain studies
show that AD caregiving is associated with higher
subjective levels of stress and higher quantita-
tive levels of low-grade inflammation, as indicated
by elevated plasma C-reactive protein (CRP) and
inflammatory cytokines [11, 12]. Furthermore, lower
satisfaction with leisure activities was associated
with higher inflammation, pointing to the impor-
tance of interventions which improve quality of life
[13]. Further research is needed to elucidate the
biological consequences of caregiver stress. What
we do know is that inflammation is crucial to the
development of AD pathophysiology, as evidenced
by reactive microglia on autopsy studies and ele-
vated inflammatory-binding on positron emission
tomography (PET) imaging in patients who progress
from mild cognitive impairment (MCI) to AD [14].
Recent literature suggests that an initial inflamma-
tory stimulus triggers activation of microglia and
astrocytes which secrete inflammatory cytokines and
chemokines which lead to further accumulation of
amyloid and further production of pro-inflammatory
cytokines [15]. Inflammation is thought to eventually
lead to increased blood brain barrier permeability,
hypoperfusion, and eventual neuronal damage [16].
Family history of AD increases risk due to both
overrepresentation of the apolipoprotein E type 4
(APOE 4) allele and psychosocial variables such
as caregiver-related stress [17]. Ethnicity also plays
a role in the risk for developing AD. African-
Americans (AA) are 1.6 times more likely than
Whites to develop dementia by age 85. Among rel-
atives of White (CC) persons with AD, those with
the APOE 4 allele have twice the risk of develop-
ing AD, whereas those of AA ethnicity who have
at least one APOE 4 allele have triple the risk of
developing AD. Thus, ethnicity may be very pow-
erful in determining risk of AD [18]. Middle aged
AA female family caregivers who are the children of
AD patients are particularly at risk for developing AD
due to ethnicity, gender, and age. According to a CDC
report on depression in the U.S., minorities including
non-Hispanic blacks, Hispanics, and non-Hispanics
of other races experience higher levels of depression
compared to non-Hispanic whites [19]. Females have
an increased risk of AD due to menopause related
hormonal changes, longer lifespan, and propensity
for caregiving [20]. Adult children are commonly
caught between caring for their children and/or
grandchildren in addition to their parents, while also
maintaining employment. These demands often leave
little time for self-care, including exercise.
This situation is problematic, as exercise may be
preventative to the development of AD secondary to
its effects on inflammation and the pathophysiology
of AD. Exercise has already been shown to improve
cognitive performance and functionality in patients
with AD [21]. Namely, exercise reduces resting heart
rate and blood pressure, increases myocardial oxy-
gen utilization, and in the case of long-term exercise,
prevents endothelial dysfunction and oxidative dam-
age, which contribute to neuronal degeneration in
AD [22]. Reductions in blood pressure, particularly
those that act on the renin-angiotensin system, have
beneficial effects on cognition and can slow con-
version from MCI to AD [23]. Similarly, mid-life
hypertension and cardiovascular disease are linked
to development of dementia in later life [24]. For the
targeted population, lack of exercise may be an addi-
tional contributor to increased risk of developing AD.
Adapted tango is an adapted form of Argentine
tango, and an intervention that has been researched
in individuals with Parkinson’s disease (PD), as
well as in older adults [25–28]. Adapted tango is
a challenging dual-tasking activity promoting social
interaction, cognitive engagement, musical interpre-
tation, and creative thinking along with the physical
demands of coordination, timing of movement, and
balance [28]. While the physical effects of a dance
intervention have yet to be investigated in this popu-
lation, it is known that music alone has some potential
in improving anxiety and depression and in reducing
caregiver burden [29].
M.E. Hackney et al. / Rationale and Design of ACT Trial 769
Here we describe the design and rationale of a
pilot clinical trial to evaluate whether AD risk factors
can be mitigated using an adapted tango interven-
tion versus control. The trial will determine whether
adapted tango is efficacious in improving quality of
life (QOL), mood, cognitive and physical function,
plasma inflammatory cytokines, and blood pressure
within AA caregivers. We hypothesize that adapted
tango will be a safe, enjoyable, and effective inter-
vention that will reduce stress, and improve quality
of life, balance, walking, and mobility, with a positive
effect on inflammation and blood pressure.
This is a 12-week, randomized, placebo-controlled
Phase I clinical trial. Thirty participants will be ran-
domized in a 2:1 ratio to treatment (N = 20) and
control (N = 10) conditions with controls frequency
matched to cases based on two age stratifications
(45–55 years and 56–65 years of age). Participants
undergo blood biomarker, cognitive, physical/motor,
and mood testing pre and post intervention or con-
trol conditions. Participants will attend two clinical
visits (pre and post intervention/control). Clinic vis-
its will last approximately 2 h and will entail: 1) a 1 h
cognitive testing battery; 2) blood draw for inflamma-
tory cytokines, rapid blood glucose level, homeostatic
model assessment for insulin resistance (HOMA-IR),
and ApoE4 genotyping; 3) height, weight, and blood
pressure measurement. Cognitive testing includes
a comprehensive pre/post battery in domains of
memory [30, 31], spatial ability [32, 33], executive
function [34–36], language [37], quantitative mea-
sures that assess mood, and positive and negative
aspects of caregiving [38–42]; and 4) physical func-
tion testing includes a pre/post battery in the domains
of balance [43, 44], walking [45, 46], and motor
function [44, 47]. Details of the physiological and
cognitive measures are described below.
Informed consent will be obtained prior to ran-
domization at the first clinic visit. Thirty AA women
family caregivers (aged 45–65 years) from the Emory
Alzheimer’s Disease Research Center (ADRC) and
Dr. Wharton’s studies of AD caregivers will be
asked to participate in the proposed trial. The par-
ticipants’ parents will have a diagnosis of probable
AD as defined by National Institute of Neurological
Disorders and Stroke-Alzheimer’s Disease and
Related Disorders Association (NINDS-ADRDA)
criteria and will be verified using the validated
Dementia Questionnaire [48] and medical records,
when available. Participants with a parental diagno-
sis have increased risk for AD and overrepresentation
of the ApoE4 allele, a genetic risk factor for AD. In
Dr. Wharton’s previous studies, we have reported that
50–67% of the AD adult child sample is ApoE4 pos-
itive [49, 50]. Participants will be compensated $50
for their participation in the form of gift cards.
Adapted tango dance intervention (N = 20)
Participants randomized to the experimental group
will take part in 20, 1.5 h long adapted tango dance
sessions over 12 weeks. Participants will be encour-
aged to participate in classes two times per week.
Dance interventions will take place at the Atlanta VA
Medical Center in the Movement Studies Laboratory
(MSL) of the Center for Visual and Neurocognitive
Rehabilitation (CVNR), which Dr. Hackney (Co-PI,
CVNR) has used in previous studies. We will use a
program previously tested in people with PD, visual
impairment and older adults with cognitive impair-
ment: an adapted Argentine tango (adapted tango)
program. Adapted tango has benefitted spatial cog-
nition, gait, balance, and disease severity in PD [51].
Classes taught by trained and experienced instructors
will be offered four times per week for a total of
12 weeks in a movement studies laboratory at the
VA. Our prior studies showed offering 4 class times
per week allowed schedule flexibility for the partici-
pants, which increased the likelihood of participants
completing 20 classes. Therefore, classes in the cur-
rent study will be offered at four times per week. The
classes will follow methods outlined in an adapted
tango manual, which has been developed empirically
through several studies [27]. The manual delineates
older adult motor impairments and challenges,
fall risk and prevention, partnering enhancement
exercises, rhythmic entrainment, and a structured
syllabus and format. Classes will begin with a 20 min
standing warm-up followed by partnering and
rhythmic exercises. Next, novel step elements will
be introduced and participants will be taught how to
combine the new steps with previously learned steps
via improvisational. Caregivers will dance with each
other or student volunteers. Music will be played
throughout classes. Artistic expression, i.e., attention
to aesthetics, and improvisation, will be encouraged.
Adapted tango classes improve spatial cognition in
770 M.E. Hackney et al. / Rationale and Design of ACT Trial
PD patients [51] and motor-cognitive integration in
older adults [28], which we reported can last up to
3 months post treatment. Adapted tango has been
introduced in AA communities successfully: in 2012,
18 retired AA participants began a 20-lesson adapted
tango program and 14 of these participants com-
pleted 20 lessons within 12 weeks and were satisfied.
Our prior data show also that a 12-week intervention
is an acceptable period to show cognitive benefits
of adapted tango in an AA population. Moreover,
12-week dance interventions have successfully
improved inflammatory, vascular, and subjective
mood measures in younger populations [52].
Non-intervention control group (N = 10)
Ten participants will take part in the pre-
assessment and blood draw followed by the post
assessment and blood draw 12 weeks later. Partici-
pants in this group will be instructed not to change
anything from their daily routine during the time
between appointments.
Trial description summary
Figure 1 shows the timeline and detailed visit
Screening performed as a phone screen.
Inflammatory, cognitive, motor, and mood indices
collected pre and post intervention:
Biological and clinical data
Participants will undergo blood draw for E4 sta-
tus and inflammatory cytokines before and after
the trial using well-established research procedures.
All blood samples will be collected after an 8 h
overnight fast by a member of the research team.
Participants will complete medical and medica-
tion questionnaires, anthropometric measures, and 2
resting blood pressure reads. Biomarkers include tar-
geted, inflammatory, and depression indices that have
been linked to AD family caregiver stress [12] and
have been shown to change over a 3-month period,
the same duration of this trial [53]. Moreover, these
inflammatory and stress markers are easily obtained,
affordable, and likely measurable at a large number
of clinics and research institutions.
Inflammatory and depression blood biomarkers
will be batched and assayed at Emory University.
Four panels of biomarkers will be measured in plasma
using commercially available singleplex or multiplex
assays in a Luminex 200 platform: Cytokines and
chemokines (including interleukin-7, interleukin-8,
interleukin-9, interleukin-10, interferon induced pro-
tein 10, macrophage derived chemokine, monocyte
chemoattractant protein 1, transforming growth fac-
tor alpha, and tumor necrosis factor alpha); C-reactive
protein and serum amyloid protein; stress-related
cortisol; endothelial markers ICAM-1 and VCAM-
1; metabolic variables including homeostasis model
assessment for insulin resistance index (HOMA-IR)
and rapid blood glucose homeostasis.
Cognitive data
Cognitive testing will last 1.5 h and will take place
at the Memory Disorders Clinic at Emory University.
To determine the extent to which the dance interven-
tion affects cognition, we will use a comprehensive
battery in cognitive domains of memory, spatial abil-
ity, executive function and language, with a focus on
executive function. Testing will be conducted by a
trained Research Coordinator during the same clin-
ical visit that blood and vitals are collected. Tests
include but are not limited to: the Montreal Cogni-
tive Assessment [54], the Tower of London [55], the
Stroop Color Word Interference test [56], Trails B
[57], Digit Span [58], the Buschke Selective Remind-
ing Test [59], the Reverse Corsi Blocks [33], the
Brooks spatial memory test [60], and the body posi-
tion spatial task [61].
Motor and physical function data
To determine the extent to which the dance inter-
vention affects physical function, we will use a
comprehensive battery in motor domains of balance,
walking, and lower body strength. Motor and phys-
ical function testing will be conducted by a trained
Research Coordinator during the same clinical visit
that blood and vitals are collected. Tests include but
are not limited to the 30 s chair stand [47], four-square
step test [43], 6 min walk [46], Miniature Balance
Evaluation Systems Test (mini-BEST) [44], and gait
speed tests (preferred, fast, backward) [45].
M.E. Hackney et al. / Rationale and Design of ACT Trial 771
Fig. 1. Study tasks and timeline.
772 M.E. Hackney et al. / Rationale and Design of ACT Trial
Mood and stress data
In light of recent literature linking caregiver stress
to increased inflammation and cognitive decline, we
have compiled a battery of stress measures that assess
both positive and negative aspects of caregiving. We
also include measures to assess the physical and
cognitive status of the care recipient, which likely
contributes to caregiver stress. Measures include:
Positive Aspects of Caregiving Scale (11 item) [38,
39], Pearlin Caregiver Stress Scale [62], The Zarit
Burden Interview [40], Center for Epidemiologic
Studies Depression Scale (CES-D) [41], Dementia
Quality of Life measure (DEMQOL) (Carer v4) [42].
Evaluations and data collection timelines
Figure 1 shows the timeline and detailed visit pro-
We will assess the biological, cognitive, and mood
outcomes pre and post intervention for both experi-
mental and control groups. All tests will be two-tailed
and use a 0.05 significance level. Models will be
adjusted for age, education, and other covariates,
as appropriate, based on a priori knowledge, and
directed acyclic graph analyses. While we will use
inferential statistics to compare function before treat-
ment with after treatment, this pilot trial has been
primarily designed to provide information about the
feasibility of a dance intervention among AA female
caregivers, appropriate clinical and patient reported
outcomes, as well as clinically meaningful effect
sizes. Feasibility will be determined by a conserva-
tive estimate of attrition rate less than 30% in both
groups based on Dr. Wharton’s and Hackney’s previ-
ous studies and documented adherence tendencies in
caregiver interventions which literature suggests may
be as high as 70% in a similar population after 15
months [63]. Appropriateness of clinical and patient-
reported outcomes will be determined by number
of refusals to perform the tests, all of which will
be documented. This population, which consists of
AA female caregivers, has an overrepresentation of
diabetes and high blood pressure, symptoms which
are exacerbated by caregiver physiological and psy-
chological stress, all of which will be measured and
assessed in this trial. We will also observe all tests
for ceiling effects in determining appropriateness.
Literature has shown that interventions and pharma-
ceutical therapies have made clinically meaningful
reductions on inflammation and blood pressure in less
than 12 weeks; therefore, the data we gather related to
the effect of the dance intervention will be compared
to these studies’ findings and effect sizes.
Several studies have examined the relationship
between caregiving and cognitive, motor, and psy-
chosocial measures. A comprehensive literature
review by Vitaliano et al. found that people who
are caregivers of a spouse with dementia are at an
increased risk for cognitive impairment than non-
caregivers [64]. Similarly, Caswell et al. (2003) found
evidence that caregivers of spouses with demen-
tia may also have negative impacts on cognitive
and psycho-social health as a result of caregiv-
ing [65]. Another study by Canonici et al. (2012)
found evidence that motor interventions for peo-
ple with probable AD improved motor function for
AD patients and decreased caregiver burden among
the caregivers of the patients involved in the motor
intervention [66]. The body of previous literature
suggests that caregiving increases risk for negative
cognitive, mood, and psycho-social indicators among
caregivers, while motor interventions improve cog-
nition among individuals with cognitive impairment
including dementias. However, no study has exam-
ined the impact of a neuro-cognitive intervention on
a population consisting of AA women who are also
caregivers for a parent with probable AD, and there-
fore at greater risk for developing AD themselves.
Given the multi-faceted nature of the increased risk
for cognitive impairment in this population, our pro-
posed study would fill a gap in existing knowledge
about the relationship between caregiving and AD.
With the increasing incidence and prevalence of
AD, research efforts should target high-risk groups to
prevent or slow disease progression in tandem with
cure-driven research directives in established disease.
Interventions that may impart physiological, cogni-
tive, physical and mood related benefits, including
adapted tango intervention, is a cost-effective way
of slowing AD, particularly in high-risk individuals,
and allow for more rapid research trajectories over
conventional drug discovery approaches [67]. While
longer interventions are optimal, early intervention
is critical and assessing the impact on biomarkers
in addition to cognitive changes is also of great
M.E. Hackney et al. / Rationale and Design of ACT Trial 773
importance. Because we know that inflammation and
vascular health are implicated in AD neuropathol-
ogy, and exercise is beneficial in preventing AD,
research should clinically investigate the extent to
which adapted tango interventions could confer AD-
related benefits in African Americans at high risk for
AD, during middle age. This pilot clinical trial will
provide data to address these issues.
A Department of Veterans Affairs Career Devel-
opment award supported ME Hackney (N0780W).
W Wharton is supported by NIH-NIA grants:
K01AG042498. This trial is supported by the Emory
Goizueta Alzheimer’s Disease Research Center and
the Atlanta VA Center for Visual and Neurocognitive
Authors’ disclosures available online (https://
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... Our results contrast with those of two recently published trials (Note: Wharton and colleagues results were an Alzheimer's Association published poster presentation with the clinical trial design published by Hackney et al., 2019) that did focus on middle aged/older African American adults (Hackney et al., 2019;Fausto et al., 2021;Wharton et al., 2021). These interventions utilized dance-based physical activity (i.e., cardio dance routines and adapted tango) and reported domainspecific cognitive improvements over time in the exercise condition in comparison to control. ...
... Our results contrast with those of two recently published trials (Note: Wharton and colleagues results were an Alzheimer's Association published poster presentation with the clinical trial design published by Hackney et al., 2019) that did focus on middle aged/older African American adults (Hackney et al., 2019;Fausto et al., 2021;Wharton et al., 2021). These interventions utilized dance-based physical activity (i.e., cardio dance routines and adapted tango) and reported domainspecific cognitive improvements over time in the exercise condition in comparison to control. ...
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Introduction Regular physical activity lowers risk for cognitive decline and neurodegenerative disorders. Older African Americans (AAs) have been underrepresented in trials that increased physical activity to improve cognitive outcomes. Methods 56 sedentary, older, cognitively healthy AAs (avg. 69.2 ± 3.4 yrs. old) were randomized in 1:1 ratio into either a 12-week successful aging group (SAG) or a 12-week physical activity group (PAG). Participants in SAG attended weekly 60-min educational sessions in which healthy aging topics were discussed. Participants in PAG attended supervised physical activity sessions twice per week at local YMCAs (90–120 min/week) and were prescribed 2–3 days per week of home-based activity. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) assessed cognitive function. ANCOVA models compared mean 12-week change in global cognition and subdomain scores between groups with secondary analyses for sex differences. Effect sizes for RBANS were calculated. Results The RBANS global cognition score (SAG Est. 5.6 ± 1.8, effect size = 0.37, p = 0.003) and several subdomain scores (one-sample T tests, all p < 0.05) increased significantly within the SAG. Scores for global cognition increased more in SAG than in PAG (Change Estimate, PAG minus SAG: –4.6 ± 2.5 points, effect size = 0.31) at a trend level ( p = 0.072). SAG females increased their global cognition score more than PAG females and more than males in either PAG or SAG (all p < 0.035). Discussion A 12-week physical activity intervention (PAG) did not improve cognitive functioning among older AAs but a comparator healthy aging education program did. Inadequate physical activity dosage or duration, SAG members acting on health-related information from educational sessions, and/or social stimulation within the SAG may have contributed to these results. Future studies should combine socially engaging activities with vigorous physical activity for cognitive enhancement among cognitively healthy older African Americans. Clinical Trial Registration , identifier NCT03474302.
... In this study, women who had professional support in order to encourage their self-care felt less overloaded. (18) Women's health care, in addition to reproductive demands, has required professionals to change practices and provide more humanized and qualified care. Knowing women's health conditions and psychosocial needs has become a priority for healthier female aging with better quality of life, in addition to favoring self-care. ...
... Thirty-one middle-aged (45-65 years old) AA women taking part in a larger clinical trial were included in the present study (Hackney et al., 2019). Participants were recruited from the Emory Alzheimer's Disease Research Center and from ongoing studies of individuals with parental history of AD. ...
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Background Alzheimer’s disease (AD) is a devastating, progressive neurodegenerative disease resulting in memory loss and a severe reduction in ability to perform activities of daily living. Ethnicity‐related genetic factors promoting the development of dementias among African Americans (AA) and increased risk among females for developing AD indicates that AA female with a parent with AD are at great risk for developing dementias. Method This phase I study assessed the impact of a 12 week, 20‐lesson adapted Argentine Tango intervention (N=24) vs. a no‐contact control group (N=10) on measures of cognition, motor and psychosocial performance, and plasma inflammatory markers in middle‐aged (45‐65 years) AA females who are at increased risk for AD by virtue of parental history. Result Some females (n=17) were also caregivers, and thus the impact of the program on caregiving burden was examined in this subset. Preliminary analysis of efficacy was conducted with significance tests on biomarkers and key measures of balance, strength, and cognition, including visuospatial and executive function. After 12 weeks, Tango participants had significantly decreased inflammatory cytokine levels: IL‐7 (p=.003), IFN‐γ (p=.011), and TNFα (p=.011), compared to controls. Participants in Tango improved on the Fullerton Advanced Balance Scale, which measures both dynamic and static balance (p=.023), the 30 second chair stand, which assesses functional lower body strength in older adults (p=.018), and inhibition of the color word interference test, which measures to ability to inhibit cognitive interference (p=0.031). Large effects were noted for the Tango group from pre to postintervention in the Trails B test score, which measures executive control and functioning. Other non‐significant, yet large effects were noted in gait speed, spatial cognition, and executive function. Moderate effects were noted in caregiving burden measures among the subset of caregivers. Conclusion These data show substantial cognitive and motor improvements and reduction in inflammatory biomarkers through a non‐pharmacologic and affordable intervention among a small cohort of AA females with a parental history of AD.
... There were no significant differences between excluded and included participants on key demographics and clinical characteristics (Age Participants were at least 40 years of age and selfidentified as African American (AA) and a woman. The participants' parents had a diagnosis of probable AD as defined by National Institute of Neurological Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINDS-ADRDA) criteria, which was verified using the validated Dementia Questionnaire and medical records when available [24]. Because these women had a parent with likely AD, these women were considered to be at greater risk for developing AD. ...
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Background: Alzheimer's disease (AD) is a prevalent neurodegenerative disease. Treatments are necessary to target people at high risk for AD. Inflammation, particularly tumor necrosis factor alpha (TNFα), appears to be an important marker associated with the development of AD pathophysiology. Consuming a high-fat diet induces tissue expression of TNFα. Objective: This study investigates the relationship between nutrition, circulating inflammation, and cognition in African American women (age: M = 59.5 (±8.20) [42-73] years) at risk for developing AD. Methods: Participants were split into high-fat and low-fat groups based on total dietary fat consumption self-reported on the Lower Mississippi Delta Nutrition Intervention Research Initiative Food Frequency Questionnaire (Delta NIRI FFQ). Results: A high-fat diet was associated with increased blood serum TNFα (p = 0.02) compared to the low-fat diet. In addition, global cognition scores were 9.0% better in those who consumed a higher fat diet (p = 0.04). No significant differences across groups were noted for executive function, dual-tasking, and visuospatial performance. Conclusion: These results indicate that there may be multiple biological pathways involved in AD development, suggesting the need for more holistic approaches to mitigate AD-development risk.
... p=0.02). Similarly, many of the recent trials done by various researchers such as Borges-Machado F, Ribeiro Ó, Hackney ME, McCullough LE, Ptomey LT, Vidoni ED, Lu X, Moeini M all concluded that exercise is a very vital component in slowing the progression of cognitive decline in AD patients [47][48][49][50]. A review of the various clinical trials is listed in Table 1 ...
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Alzheimer's disease (AD) is a progressive disorder that causes brain cells to slowly degenerate and die. This leads to a continuous decline in thinking, behavioral and social skills that disrupts a person's ability to function independently. AD is the most common cause of dementia globally. Neuroinflammation caused by intracellular neurofibrillary tangles and extracellular amyloid deposits leads to atrophy of brain cells especially the hippocampus, which is associated with memory formation. This atrophy leads to dementia and cognitive decline. Among the many preventive factors being studied, exercise is thought to play a vital role in not only preventing the pre-clinical stage of AD but also slowing the clinical progression of AD. It is also deployed as a treatment option for late-stage AD along with pharmacological treatment options. Various studies and clinical trials in both human and animal models are of the opinion that exercise slows the onset and progression of cognitive decline in AD patients. Some studies suggest that this effect is due to a decrease in neurofibrillary tangles and amyloid deposits in brain parenchyma. Others suggest that exercise causes an increase in angiogenesis, neurogenesis, and synaptogenesis mainly due to an increase in blood flow, brain-derived neurotrophic factor (BDNF), insulin-like growth factor 1 (IGF-1), hormones, and second messengers.
Background: As the Hispanic/Latino (HL) population grows, so too does the need for HL family caregivers for persons with dementia. HL caregivers tend to have less education, lower health literacy, and lower income, each uniquely compounding burden. Research is needed to appropriately tailor interventions for this population. Objective: A systematic review and meta-analysis was conducted to 1) provide an updated review of non-pharmacologic intervention studies for HL dementia caregivers, 2) characterize promising interventions, and 3) highlight opportunities for future research. Methods: Databases were searched for articles evaluating non-pharmacologic interventions for HL dementia caregivers. Studies were excluded if target populations did not include HLs or if no intervention was delivered. Data were extracted and random effects meta-analysis was performed on two primary outcomes: caregiver depression and burden. Effect sizes were calculated as pre- and post-intervention standardized mean differences (SMD), and further depression subgroup meta-analysis was performed. Other secondary outcome measures (e.g., perceived social support, caregiver knowledge, anxiety) were evaluated qualitatively. Results: Twenty-three studies were identified. Most included multiple components pertaining to psychosocial support, caregiver education, and community resource facilitation. Many studies were successful in improving caregiver outcomes, though intervention design varied. Meta-analysis revealed minimal to moderate heterogeneity and small effect size in improving depressive symptoms (SMD = -0.31, 95% CI -0.46 to -0.16; I2 = 50.16%) and burden (SMD = -0.28, 95% CI -0.37 to -0.18; I2 = 11.06%). Conclusion: Although intervention components varied, many reported outcome improvements. Future studies may benefit from targeting physical health, addressing sociocultural and economic contexts of caregivers, and leveraging technology.
People with parental history (PH) of Alzheimer's Disease (AD) and Alzheimer's Disease and related dementias (ADRD) are themselves at risk of developing dementia. ADRD are more prevalent in African Americans and women. A decline in executive function and motor-cognitive integration can cause an impaired performance of functional skills. The monitoring of cognitive and psychosocial function in individuals with a PH of ADRD is important for implementing interventions to delay or prevent ADRD diagnosis. This study compared 58 African American women (M age = 63.2 ± 7.2 years) with PH of ADRD (n = 34) versus without PH (NPH; n = 24) on the performance of motor-cognitive and executive function tasks, and mental and physical quality of life (QOL) using point biserial correlations and linear regression. Linear regression revealed no difference between participants with and without PH on motor-cognitive tests. However, compared to participants with NPH, participants with PH of ADRD performed significantly worse on the DKEFS (Delis Kaplan Executive Function System) Tower Test (PH: M = 9.9 ± 2.0; NPH: M = 11.5 ± 4.3; p = 0.046), had poorer mental QOL (PH: M = 46.8 ± 10.7; NPH: M = 52.8 ± 7.8 l; p = 0.007); and physical QOL (PH: M = 40.9 ± 9.3; NPH: M = 44.7 ± 8.6; p = 0.023). African American women at risk for ADRD may exhibit deficiencies in executive function and physical and mental quality of life before memory deficits meet the criterion for ADRD diagnosis. Motor-Cognitive tasks may be preserved. Executive function and mental and physical health-related QOL may be important targets for identifying individuals at increased risk for ADRD and developing appropriate rehabilitative interventions.
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Background: 10%to 20%of Americans aged 65 and older have mild cognitive impairment (MCI) with 10%progressing to Alzheimer's disease (AD) each year. Underserved groups, including African Americans (AAs), are among the most vulnerable to MCI and AD. Although evidence continues to amass, the benefits of exercise and movement for AD is still understudied in AD. Objective: Understanding the attitudes, perceptions, and beliefs about motor-cognitive integration and examining the physical activity of a sample of predominantly Black women community members with self-reported memory problems will allow improved recruitment and refinement of multimodal interventions designed to improve motor-cognitive and cognitive function. Methods: We conducted focus groups with older adults who reported subjective memory complaints (n = 15; Black: n = 12, White: n = 3, mean age 71.7±5.8). Results: Findings from thematic analysis showed most participants knew of benefits of exercise. However, most participants reported not getting adequate exercise due to factors such as pain, increased responsibilities, and fears of injury. Despite barriers, participants expressed enthusiasm for multimodal interventions designed to target body and brain health and provided several suggestions to improve or enhance the proposed interventions. Conclusion: Results provide useful insights regarding improving participation among historically under-represented groups in clinical movement-based research. Participants' discussion focused primarily on the way motor-cognitive integration prevents falls, maintains memory, and provides a social benefit. The reported perceived benefits and limitations of exercise, as this population understands it, can help researchers and physicians better engage the community for lifestyle changes that will support greater motor-cognitive health.
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Alzheimer's disease (AD) is a devastating, progressive neurodegenerative disease resulting in memory loss and a severe reduction in the ability to perform activities of daily living. Ethnicity-related genetic factors promoting the development of dementias among African Americans (AA) and increased risk among women for developing AD indicates that AA women with a parental history of AD are at great risk for developing AD. This phase I study assessed the impact of a 12 week, 20-lesson adapted Argentine Tango intervention (n = 24) to a no-contact control group (n = 10) on measures of plasma inflammatory markers, cognition, and motor and psychosocial performance in middle-aged AA woman at increased risk for AD by virtue of parental history. Some woman (n = 16) were also caregivers; thus, the impact of the intervention on caregiving burden was examined in this subset. Preliminary analysis of efficacy was conducted with significance tests on biomarkers and key measures of cognition, including visuospatial and executive function, balance, and strength. After 12 weeks, Tango participants had significantly decreased inflammatory cytokine, including reductions in IL-7 (p = 0.003), IFN-γ (p = 0.011), TNFα (p = 0.011), and MCP-1 (p = 0.042) compared to controls. Large effects were noted for the Tango group on tests of executive functioning (d = 0.89), and inhibition (p = 0.031). Participants in Tango improved in dynamic and static balance (p = 0.018) and functional lower body strength (p = 0.023). Secondary assessment revealed trends favoring the intervention group were noted in spatial cognition and executive function. Moderate effects were noted in caregiving burden measures among the subset of caregivers. These data demonstrate substantial reductions in inflammatory biomarkers along with cognitive and motor improvements through a non-pharmacologic, affordable intervention among a small, well-characterized cohort of AA women with a parental history of AD.
Introduction African-Americans (AAs) are 64% more likely to be diagnosed with AD than non-Hispanic Whites. AAs with elevated AD biomarkers exhibit greater neurodegeneration in AD signature regions compared to non-Hispanic Whites with elevated AD biomarkers. This pilot trial examined whether normal or elevated plasma levels of interleukin (IL)-10 are associated with changes in executive function and short-term memory in AA women at risk for developing AD due to parental history. Method Observational study comparing groups with elevated and normal plasma IL-10 levels. Study included 31 AA women (age=58.9±8 years) with parental history of AD. Measures included inflammatory blood biomarkers, executive function and visuospatial short-term memory tests. Multivariate linear regression with adjustment for comorbidities, and Bonferroni corrections for multiple comparisons were used to compare groups. Effect sizes (Cohen’s d) were generated. Using endpoints with moderate-large effects between groups, Pearson correlations determined associations between biomarker levels and cognitive performance. Results The elevated IL-10 group performed worse on the Trail-Making Test proportional score ((B-A)/A) (effect size (d =-0.87 (−1.6, −.1)). Moderate effects with large confident intervals were noted in inhibition, set-switching, and body position spatial memory. Significant differences between groups in levels of other inflammatory markers were noted, including IL-7 (p=0.002) and interferon γ (p=0.02). IL-7 remained significant after Bonferroni correction. Correlation matrices revealed moderate-large, significant correlations (yet with wide confidence intervals) between levels of IL-10 and IL-9 with BPST total correct trials, and between interferon γ and delayed recall. Conclusions Interleukins may incite inflammation, leading to impaired aspects of executive function and short-term memory in this sample of African American women at risk for developing AD. This research provides effect sizes that will be used to power future research that will further investigate the relationship between inflammation, AD biomarkers, and cognitive function in an understudied population.
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Background The four square step test (FSST) was first validated in healthy older adults to provide a measure of dynamic standing balance and mobility. The FSST has since been used in a variety of patient populations. The purpose of this systematic review is to determine the validity and reliability of the FSST in these different adult patient populations. Methods The literature search was conducted to highlight all the studies that measured validity and reliability of the FSST. Six electronic databases were searched including AMED, CINAHL, MEDLINE, PEDro, Web of Science and Google Scholar. Grey literature was also searched for any documents relevant to the review. Two independent reviewers carried out study selection and quality assessment. The methodological quality was assessed using the QUADAS-2 tool, which is a validated tool for the quality assessment of diagnostic accuracy studies, and the COSMIN four-point checklist, which contains standards for evaluating reliability studies on the measurement properties of health instruments. ResultsFifteen studies were reviewed studying community-dwelling older adults, Parkinson’s disease, Huntington’s disease, multiple sclerosis, vestibular disorders, post stroke, post unilateral transtibial amputation, knee pain and hip osteoarthritis. Three of the studies were of moderate methodological quality scoring low in risk of bias and applicability for all domains in the QUADAS-2 tool. Three studies scored “fair” on the COSMIN four-point checklist for the reliability components. The concurrent validity of the FSST was measured in nine of the studies with moderate to strong correlations being found. Excellent Intraclass Correlation Coefficients were found between physiotherapists carrying out the tests (ICC = .99) with good to excellent test-retest reliability shown in nine of the studies (ICC = .73–.98). Conclusions The FSST may be an effective and valid tool for measuring dynamic balance and a participants’ falls risk. It has been shown to have strong correlations with other measures of balance and mobility with good reliability shown in a number of populations. However, the quality of the papers reviewed was variable with key factors, such as sample size and test set up, needing to be addressed before the tool can be confidently used in these specified populations.
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Objectives Older familial caregivers of Alzheimer’s disease patients are subjected to stress-related cognitive and psychophysiological dysfunctions that may affect their quality of life and ability to provide care. Younger caregivers have never been properly evaluated. We hypothesized that they would show qualitatively similar cognitive and psychophysiological alterations to those of older caregivers. Method The cognitive measures of 17 young (31–58 years) and 18 old (63–84 years) caregivers and of 17 young (37–57 years) and 18 old (62–84 years) non-caregiver controls were evaluated together with their salivary cortisol and dehydroepiandrosterone (DHEA) levels, as measured by radioimmunoassays and ELISA assays of brain-derived neurotrophic factor (BDNF) in serum. Results Although younger caregivers had milder impairments in memory and executive functions than older caregivers, their performances fell to the same or lower levels as those of the healthy older controls. Decreases in DHEA and BDNF levels were correlated with the cognitive dysfunctions observed in the older and younger caregivers, respectively. Cortisol at 10PM increased in both caregiver groups. Discussion Younger caregivers were prone to cognitive impairments similar to older caregivers, although the degree and the neuropsychological correlates of the cognitive dysfunctions were somewhat different between the two groups. This work has implications for caregiver and care-recipient health and for research on the neurobiology of stress-related cognitive dysfunctions.
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Background: This study assessed how family caregivers for patients with Alzheimer's disease (AD) or dementia in Japan differed from non-caregivers in characteristics and health outcomes (i.e., comorbidities, health-related quality of life [HRQoL], productivity, and resource use). Caregivers were hypothesized to experience significantly poorer outcomes than non-caregivers. Methods: Data were combined from the 2012 and 2013 National Health and Wellness Survey in Japan (n = 60000). Caregivers for adult relatives with AD or dementia were compared with non-caregivers on: comorbidities (including Patient Health Questionnaire (PHQ-9) cutoff scores suggesting presence/absence of major depressive disorder (MDD)), Work Productivity and Activity Impairment (WPAI), SF-36v2-based HRQoL, and healthcare resource utilization. Sociodemographic characteristics, health characteristics and behaviors, and Charlson comorbidity index (CCI) scores were compared across groups. Propensity matching, based on scores generated from a logistic regression predicting caregiving, was used to match caregivers with non-caregivers with similar likelihood of being caregivers. Bivariate comparisons across matched groups served to estimate outcomes differences due to caregiving. Results: Among 55060 respondents, compared with non-caregivers (n = 53758), caregivers (n = 1302) were older (52.6 vs. 47.5 years), more frequently female (53 % vs. 49 %), married/partnered, frequent alcohol drinkers, current smokers, exercisers, and not employed, and they averaged higher CCI scores (0.37 vs. 0.14), all p < 0.05. Propensity scores incorporated sex, age, body mass index (BMI), exercise, alcohol, smoking, marital status, CCI, insured status, education, employment, income, and children in household. A greedy matching algorithm produced 1297 exact matches, excluding 5 non-matched caregivers. Health utilities scores were significantly lower among caregivers (0.724) vs. non-caregivers (0.764), as were SF-36v2 Physical and Mental Component Summary scores. Caregivers vs. non-caregivers had significantly higher absenteeism, presenteeism-related impairment, overall work impairment (25.8 % vs. 20.4 %, respectively), and activity impairment (25.4 % vs. 21.8 %), more emergency room and traditional provider visits (7.70 vs. 5.35) in the past six months, and more frequent MDD (14 % vs. 9 %), depression, insomnia, anxiety, and pain. Conclusions: Those providing care for patients with AD or dementia in Japan experienced significantly poorer HRQoL and greater comorbid risk, productivity impairment, and resource use. These findings inform the need for greater support for caregivers and their patients.
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Introduction: Because of the growing number of caregivers and the awareness of related health and quality-of-life issues, caregiving has emerged as an important public health issue. We examined the characteristics and caregiving experiences of caregivers of people with and without cognitive impairment. Methods: Participants (n = 668) were adults who responded to the 2005 North Carolina Behavioral Risk Factor Surveillance System. Caregivers were people who provided regular care to a family member or friend aged 60 years or older either with or without cognitive impairment (ie, memory loss, confusion, or Alzheimer's disease). Results: Demographic characteristics of caregivers of people with cognitive impairment were similar to those of caregivers of people without cognitive impairment. However, compared with caregivers of people without cognitive impairment, caregivers of people with cognitive impairment reported higher levels of disability, were more likely to be paid, and provided care for a longer duration. Care recipients with cognitive impairment were more likely than care recipients without cognitive impairment to be older, have dementia or confusion, and need assistance with memory and learning. Conclusion: State-level caregiving surveillance is vital in assessing and responding to the needs of the growing number of caregivers.
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[Purpose] The main objective of this study was to determine the contributions and extent to which certain physical measurements explain performance in the 6-minute walk test in healthy older adults living in a geriatric nursing home and for older adults dwelling in the community. [Subjects] The subjects were 122 adults aged 65 and older with no cognitive impairment who were independent in their daily activities. [Methods] The 6-minute walk test, age, body mass index, walking speed, chair stand test, Berg Balance Scale, Timed Up-and-Go test, rectus femoris cross-sectional area, Short Physical Performance Battery, and hand-grip strength were examined. [Results] Strong significant associations were found between mobility, lower-limb function, balance, and the 6-minute walk test. A stepwise multiple regression on the entire sample showed that lower-limb function was a significant and independent predictor for the 6-minute walk test. Additionally, lower-limb function was a strong predictor for the 6-minute walk test in our nursing home group, whereas mobility was found to be the best predictor in our community-dwelling group. [Conclusion] Better lower-limb function, balance, and mobility result in a higher distance covered by healthy older adults. Lower-limb function and mobility appeared to best determine walking performance in the nursing home and community-dwelling groups, respectively.
We highlight the important differences between the concepts of capacity and performance and highlight the development of measures and their application in common conditions encountered in health care practice with older people. A number of expert consensus projects have concluded that mobility, balance, muscle strength and dexterity are core domains for capacity measurement in older people. Instruments with evidence of adequate psychometric properties for the evaluation of capacity in response to intervention programmes include the Short Physical Performance Battery, hand grip strength, mini-BEST and 9-hole pegboard test. Measures that can track individual change and convey information that can be used to inform clinical decision-making, individual prognosis or prediction of events require greater precision. However, few such measures are available. Performance measurement usually focuses on basic or instrumental (advanced) Activities of Daily Living performed by people in their usual environments. Finally, we discuss the limitations of physical performance and capacity measures and future developments that may enhance the use of these measures in health and clinical care.
The apolipoprotein E type 4 allele (APOE-epsilon 4) is genetically associated with the common late onset familial and sporadic forms of Alzheimer's disease (AD). Risk for AD increased from 20% to 90% and mean age at onset decreased from 84 to 68 years with increasing number of APOE-epsilon 4 alleles in 42 families with late onset AD. Thus APOE-epsilon 4 gene dose is a major risk factor for late onset AD and, in these families, homozygosity for APOE-epsilon 4 was virtually sufficient to cause AD by age 80.