Body Fat and Muscle: Relationship to Cognitive and Physical Decline

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NYU Alzheimer’s Disease Center
Silberstein Alzheimer’s Institute
Center for Cognitive Neurology
Body Fat and Muscle: Relationship
to Cognitive and Physical Decline
James E. Galvin, MD, MPH
NYU Alzheimer’s Disease Center
Supported by grants from the National Institute on Aging, Morris and Alma Schapiro Fund
and Michael J Fox Foundation
Acknowledgements
• Galvin Lab
– Magdalena Tolea, PhD
– Chaim Tarshish, PhD
– Arline Faustin, MD
– Stephanie Chrisphonte, MD
– Yael Zweig, MSN, ANP, GNP
– Licet Valois, LMSW, MPS
– Crystal Quinn, LMSW
– Katty Saravia, CCMA
• New York University
– Stella Karantzoulis, PhD
– Victoria Raveis, PhD
– Marie Boltz, PhD
– Ab Brody, PhD
– Els Fieremans, PhD
– Tim Shepard, MD, PhD
– Jean Bear-Lehman, PhD
• Washington University
– John Morris, MD
– Linda Larson-Prior, PhD
• University of Kansas
– David Johnson, PhD
Definitions
Physical Function
• Physical Functionality: physical
ability to independently carry out
activities of daily living
• Frailty: geriatric syndrome with high
risk of declines in health and
function
– 5 dimensions: weight loss, exhaustion,
weakness, slowness, and low activity
• Muscle weakness: inability to exert
force with one's skeletal muscles
• Sarcopenia: degenerative loss of
muscle mass, quality, and strength
• Functional dependence: disability in
one or more of seven basic
activities of daily living (toileting,
eating, dressing, etc.)
Cognitive Function
• Healthy brain aging: little to
no loss of memory or thinking
abilities but tend to do things
slower
• Mild Cognitive Impairment:
transitional stage between
healthy brain aging and
dementia
• Dementia: progressive decline
in memory and thinking that
interferes with everyday
function
• Alzheimer’s disease: most
common cause of dementia
What is the evidence?
• Data support a relationship between physical function
and cognition function
– Difficult to determine the causal relationship
– What comes first?
• Cognitive evaluation may be difficult for many
primary care physicians, who will be the first contact
for many patients but physical assessments are
already part of what they do
• If physical impairment can be detected before
noticeable cognitive impairment, performance-based
assessments may help identify people at-risk for
dementia
Cognitive
Physical Impairment
Faster Progression
Earlier Onset
low
low
high
high
Rajan KB et al., JGMS 67:1419-1426, 2012
Mild Physical Impairment Predicts
Future AD
HR: 1.06; 95% CI:1.01-1.12
Controlled for age, ApoE
Wilkins CH, et al JAGS 2013
Multicultural Community Dementia Screening
• Supported by grant from the National Institute on Aging
• Community-based assessment of older adults (target goal 500)
•
•
•
•
•
•
Demographics, financial resources, preferences
Cognitive-Behavioral Screening (memory, mood)
Medical Screening (blood pressure, diabetes, lung disease, obesity)
Physical assessment (balance, frailty, strength)
Anthropometric measurements
Social work follow-up
• Subset have Gold Standard testing and biomarkers collected
•
•
•
•
•
MRI scans
PET scans
EEG
Blood
Spinal fluid
• Rich dataset with over 500,000 individual data points
Body Composition
Bone
Water
Lean Muscle
Fat
Body
Visceral
Measurement Tools
Body Composition - Impedance
Dynamometer – Grip Strength
Tape Measure – Girth
Mini-PPT
• Changes in the Mini PPT scores
correlate with disability, loss of
independence, the risk of falls,
and mortality.
• Cutoff scores of less than 12
imply impaired physical
functioning
• Sensitivity: 86%
• Specificity: 90%
• Assessment takes ~7 minutes
• Range of Scores
• >12
Unimpaired
• 8-11
Mild
• 5-7
Moderate
• 0-4
Severe
MoCA
– 30 point, 10 minute
cognitive screen to detect
MCI and AD1
• Memory, constructions,
attention, executive
function, language and
orientation1
• Score less than 26
suggests impairment2
– Utility in an office setting
established1,3
– Also sensitive to PDrelated dementia2
– Sensitivity ~90%,
Specificity ~87%1
– http://www.mocatest.org
1. Nasreddine ZS et al, J Am Geriatr Soc. 2005;53:695-699. 2.
Zadikoff et al, Mov Disord. 2008;23:297-299. 3. Smith et al, Can J
Psych. 2007;52:329-332.
AD8
•
Detect change in individuals compared to
previous level of function
– No need for baseline assessment
– Patients serve as their own control
– Little bias by education, race, gender
Brief (< 2 min), Yes/No format
– 2 or more “Yes” answers highly
correlated with presence of
dementia
AUC: 0.917 (95% CI: 0.88-0.95)
Sensitivity: 92%
Positive PV: 93%
•
•
•
•
All participants Mean AD8 score (+ SD)
CDR
N
Informant
Patient
0
149
0.64 (1.19)
1.01 (1.52)
0.5
102
3.49 (2.32)
2.80 (2.19)
1
50
6.64 (1.74)
2.40 (2.51)
2
23
6.22 (2.66)
3.00 (2.66)
Only CDR 0 and 0.5 participants
Cohen’s d
ICC
1.66
0.98
.583 (95% CI: .47-68),p<.001
Biophysiological Markers of Health in
a Multicultural Community
Variable
Health
Co-morbid conditions, #
Mean Blood Pressure
Resting Heart Rate
Lung Volume (FEV1), L
HbA1c
Strength
Mini-PPT
Grip strength
Body Composition
Body Mass Index (BMI)
Bone Mass, lb
Body Water, %
Muscle Mass, lb
Body Fat, %
Visceral Fat, lb
Abdominal Girth, cm
Hip Girth, cm
Basal Metabolic Rate, kcal
Galvin and Tolea In preparation 2014
White
Black
Hispanic
P
6.2 (3.2)
117.5 (18.8)
71.3 (15.1)
3.3 (1.4)
5.7 (0.7)
6.0 (3.4)
117.5 (15.5)
71.3 (13.9)
2.3 (0.9)
6.4 (1.3)
5.0 (2.5)
114.7 (14.4)
71.4 (9.8)
2.5 (0.8)
6.1 (0.7)
0.058
0.530
0.893
<0.001
0.146
12.3 (2.6)
58.6 (24.0)
9.6 (3.7)
46.6 (16.5)
11.8 (2.4)
46.2 (19.6)
0.004
0.003
27.0 (4.5)
8.1 (13.9)
49.6 (5.7)
113.4 (27.0)
31.2 (8.2)
12.3 (4.4)
124.8 (15.8)
108.2 (9.3)
1.6 (0.4)
30.0 (6.8)
5.0 (0.9)
43.5 (6.8)
95.9 (17.6)
39.5 (9.5)
12.8 (3.1)
98.7 (14.1)
112.7 (12.7)
1.4 (0.2)
28.2 (5.0)
4.8 (0.9)
45.5 (5.9)
90.6 (17.8)
36.1 (7.9)
13.8 (12.8)
97.7 (13.6)
106.5 (10.1)
1.3 (0.2)
0.035
<0.001
<0.001
<0.001
0.004
0.307
<0.001
<0.001
<0.001
Distribution Across Community Sample
% Body Fat
Visceral Fat
Distribution Across Community Sample
% Body Water
Lean Muscle Mass
Is Sarcopenia a Risk Factor?
• Categories
– No Sarcopenia: absence of both low muscle mass and grip strength
– Pre-sarcopenia: presence of low muscle mass only
– Sarcopenia: both low muscle mass and grip strength
Age
Education, yrs.
Female, %
White race, %
BMI
Muscle mass
Grip strength
Walking speed
MoCA
AD8
Cognitive impairment and
physical impairment
None
Either
Both
62.9 (±9.7)
66.5 (±10.3) 74.3 (±7.6)
14.8 (±3.2)
14.2 (±3.9)
10.8 (±4.7)
62.7
55.9
81.8
60.3
39.0
25.9
27.6 (±6.2)
27.8 (±5.3)
29.2 (±5.3)
106.4 (±24.7) 105.8 (±22.9) 91.6 (±22.1)
64.3 (±26.7) 58.7 (±24.9) 42.3 (±13.6)
13.6 (±2.2)
14.8 (±3.9)
20.1 (±4.2)
27.8 (±1.3)
21.9 (±4.9)
19.4 (±4.2)
1.1 (±1.8)
1.8 (±1.9)
2.0 (±1.8)
P
<0.001
<0.001
0.005
0.006
0.278
<0.001
<0.001
<0.001
<0.001
0.012
Sarcopenia and Impairment
70
p<0.001
60
50
% dual impairment
% single impairment
40
% no impairment
30
20
10
0
No sarcopenia Pre-sarcopenia
Sarcopenia
Odd Ratio of having both cognitive impairment
and physical impairment
Controls
Pre-sarcopenia
Sarcopenia
Tolea and Galvin, In Preparation 2014
Unadjusted
1.0
0.94 (0.43-2.09)
5.92 (2.51-13.96)
Adjusted 1
1.0
1.29 (0.47-3.55)
4.21 (1.41-12.51)
Adjusted 2
1.0
1.89 (0.63-5.71)
3.40 (1.07-11.46)
Staging Physical Impairment as
Risk for Cognitive Impairment
• Relationship between cognitive and physical functionality is
well established at later stages of disability, however it is
less clear whether association extends to the earliest stages
of impairment
• Measurements included:
– upper extremity (UE) muscle strength (mean grip strength)
– lower extremity (LE) function (Mini Physical Performance Test),
– Cognition (Montreal Cognitive Assessment)
• Participants were categorized:
–
–
–
–
no physical impairment
UE functional impairment
LE functional impairment
both UE and LE impairment
Stage of Function and Cognition
No impairment
Age
Education
Race, %
White, non-Hispanic
Black, non-Hispanic
Hispanic
BMI
Visceral fat, %
Muscle mass
62.0 (±10.9)
14.8 (±3.0)
52.8
19.4
27.8
27.9 (±5.7)
12.7 (±4.5)
121.7 (±21.0)
*
UE
impairment
66.5 (±8.7)
13.8 (±4.6)
LE extremity
impairment
69.5 (±7.9)
13.9 (±3.2)
UE and LE P value
impairment
75.1 (±8.2)7 <0.001
11.2 (±5.0) <0.001
0.015
40.9
20.0
29.0
15.2
50.0
21.0
43.9
30.0
50.0
27.5 (5.6)
29.6 (±5.6)
28.7 (±5.4) 0.546
10.6 (±3.7)
14.6 (±3.7)
12.1 (±3.3) 0.002
91.9 (±15.5) 115.3 (±24.5) 88.4 (±17.6) <0.001
*
Relationship of BMI to Function
MoCA r=.02
Mini-PPT r=.14
Differences: Visceral and Body Fat
Body Fat
Visceral Fat
MoCA r=.19
MoCA r=.03
Mini-PPT r=.13
Mini-PPT r=.36
Worse Physical Performance
Worse Cognitive Performance
Abdomen/Hip Ratio as Proxy Marker
MoCA r=.23
Mini-PPT r=.07
Worse
Outcomes
Falls Risk
Cognitive vs. Physical Status
Cognitive Status
Physical Status
Age, y
Education, y
Female, %
White, %
Latino, %
Co-morbidities
Body Mass Index
Body Fat
Visceral Fat
Bone mass
Muscle mass
Grip strength
Falls, events (%)
Impaired
Impaired
Normal
64.4 (9.3)
74.5 (8.9)
13.89 (4.4)
11.9 (5.2)
44.8
71.9
66.1
69.6
46.6
47.3
4.3 (2.5)
6.5 (3.0)
27.5 (5.4)
28.6 (5.6)
30.2 (9.5)
36.6 (8.2)
12.1 (4.4)
12.9 (4.1)
5.8 (1.2)
5.0 (1.1)
111.6 (23.5) 96.0 (20.6)
63.9 (25.2)
43.4 (15.6)
9 (15.5)
27 (51.9)
Normal
Normal
Impaired
62.4 (9.3)
72.6 (7.2)
15.5 (3.3)
15.5 (3.4)
52.9
77.8
71.1
59.3
21.2
14.8
5.4 (2.8)
6.7 (3.1)
27.3 (5.6)
28.5 (5.1)
29.8 (9.7)
36.6 (9.0)
10.8 (4.1)
12.3 (2.7)
5.8 (1.43)
5.3 (1.2)
111.0 (24.4) 100.7 (23.3)
66.2 (25.2)
52.8 (36.9)
21 (25.0)
11 (40.7)
P value
<0.001
<0.001
0.003
0.425
<0.001
<0.001
0.543
<0.001
0.026
0.001
0.001
<0.001
<0.001
Initial Pass of Falls Risk Factor
• Demographic Variables
– Increasing age, female, living alone, self-reported
memory problems, self-reported mood problems
• Clinical/Anthropometric Variables
– Body water, fat, visceral fat, bone density, muscle
mass, pulse pressure
• Cognitive Variables
– List learning, visuoconstructive, trailmaking
• Performance Variables
– Grip strength, timed walk, flexion, progressive
Romberg
Summary
• Relationship between cognitive and physical function is complex and
bidirectional
– Physical impairments are strong risk factors for future cognitive impairment
– Once present, cognitive decline is stronger driver for further physical decline
• Loss of muscle mass and strength (sarcopenia) may be one of the earliest
detectable warning signs of impending cognitive decline
– 3 to 6-fold increased risk
– Strength testing (via dynamometer) is easy to do
– Grip strength earlier and stronger predictor than just testing mobility
• The association between cognitive and physical functionality follows a
pattern from no impairment to loss of UE muscle strength to LE functional
impairment
– May explain up to 27% of variability in performance on cognitive tests
• Falls are a significant consequence of both cognitive and physical decline
– 1st fall increases risk of 2nd fall and may further drive cognitive and physical
decline
– Our initial work developed a profile of individuals at risk for falls
Summary
• Poorly controlled medical conditions greatly increase the risk of AD
– May be multiple pathways to get to Alzheimer’s disease
– May also be multiple pathways to prevent or treat
• Interventions designed to prevent sarcopenia, increase lean muscle
mass and improve strength may help reduce the burden of cognitive and
physical impairments in community-dwelling older adults
• Efforts to prevent cognitive decline and development of dementia may
be more successful when directed to at at-risk individuals based on their
physical functional profile
• Detection of and interventions addressing physical impairments may
offer novel approaches to reducing cognitive decline and falls
• Prevention measures
- Stay mentally alert, physically fit and eat a heart-healthy diet
• AD is a disease of a lifetime; many ways to build a better brain as we age
New York University Resources
• Pearl I. Barlow Center for Memory Evaluation and Treatment
–
–
–
–
Specialty Faculty Practice
Multidisciplinary Approach
212-263-3210
www.nyulmc.org/barlow
• Alzheimer Disease Center
– Longitudinal Research Project
– 212-263-8088
– www.adc.med.nyu.edu
• Clinical Trials Center
– Study New and Exciting Treatments for Dementia
– 212-263-5708

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