NIA BedsidetoBench Conference

1
NIA Bedside-to-Bench Conference

• Cognition, mood and movement disorders in older
  Mexican Americans
• Mukaila A. Raji, MD, MSc
• Associate Professor, Internal Medicine-Geriatrics
• Director, Memory Loss Clinics
• University of Texas Medical Branch
• Galveston, Texas, USA

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Objectives

• Recognize high rates of cardiovascular risk
  factors (metabolic syndrome, diabetes, physical
  inactivity) in older Mexican Americans
• Recognize the association of vascular risk
  factors with cognitive, depressive and gait
  disorders in this population

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Hispanics as of U.S. Population
Source U.S. Bureau of the Census
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POPULATION PROJECTIONS TO 2050

• Non-Hispanic Whites 210 million
• Hispanics 103 million (25)
• African Americans (Blacks) 61 million
• Asian Origin 33 million

Source U.S. Bureau of the Census (2004)
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FIGURE 1. Hispanics by Origin 2002 (In
percent)
Mexican American 66.9
Central and
South American 14.3
Puerto Rican 8.6
Cuban 3.7
Other Hispanic 6.5
Source U.S. Census Bureau, Annual Demographic
Supplement to the March 2002 Current Population
Survey. (Adapted from U.S. Bureau of the Census,
2003)
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Older Mexican Americans Risk factor profiles

• Markides Coreil, 1986 Ford, 2002 Dergance,
  2005 Ostir, 2000 Barcelo, 2007 Blaum, 2007
  Martins, 2007 Crespo, 1996 Kirali, 2006
  Kivipelto, 2005

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Prevalence of the metabolic syndrome among US
adults findings from the third National Health
and Nutrition Examination Survey. Ford ES, Giles
WH, Dietz WH

• Metabolic syndrome defined as 3 of
• ? waist circumference
• serum trig 150 mg/dL
• BP 130/85 mm Hg
• serum glucose level 110 mg/dL
• low HDL
• Mexican Americans had highest age-adjusted
  prevalence of metabolic syndrome (32)

JAMA, 2002
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Leisure-time physical activity among U.S. adults
Results from the Third National Health and
Nutrition Examination Survey
Crespo CJ, Keteyian SJ, Heath GW, Sempos CT

• highest rates of physical inactivity
• Mexican-American men (33)
• Mexican-American women (46)
• non-Hispanic black women (40)

Arch Intern Med. 1996
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Changes in Blood Pressure and Risk Factors for
Cardiovascular Disease among Older Mexican
Americans from 1982-1984 to 1993-1994
Stroup-Benham, C.A., Markides, K.S., Espino, D.V.
Goodwin, J. S.

• Prevalence of obesity and diabetes rose
  significantly
• Mean diastolic pressure increased significantly

Journal of the American Geriatric Society, 1999
10
Prevalence of cardiovascular risk factors and the
serum levels of 25-hydroxyvitamin D in the United
States data from the Third National Health and
Nutrition Examination Survey.
Martins D, Wolf M, Pan D et al.

• Prevalence of 25-hydroxyvitamin D levels lt30
  ng/mL highest in the elderly, non-Hispanic blacks
  and Mexican Americans
• Increased risk of hypertension, diabetes
  obesity in persons with lowest serum 25(OH)D
  levels

Arch Intern Med. 2007
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Epidemiological evidence linking vascular risk
factors to cognition, mood movement disorders
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Diabetes mellitus, glycemic control, and incident
depressive symptoms among 70- to 79-year-old
persons the health, aging, body composition
study Maraldi C, Volpato S, Penninx BW. et al.

• 6-year prospective cohort study of 2500
  community-residing elders
• Uncontrolled diabetes predicts new onset
  depression over the 6-year period
• Obesity also predicts incident depression
• Arch Intern Med. 2007

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Metabolic syndrome and cognitive decline in
elderly Latinos findings from the Sacramento
Area Latino Study of Aging study. Yaffe K,
Haan M, Blackwell T et al.
Metabolic syndrome in elderly Latinos is
associated with greater 3-year decline on
Modified Mini-Mental State Examination (3MS)
the Delayed Word-List Recall tests
J Am Geriatr Soc. 2007
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Predictors of decline in MMSE scores among older
Mexican Americans Findings from Hispanic EPESE
Nguyen HT, Black SA, Ray LA et al.

• Physician diagnosed diabetes is an independent
  predictor of increased risk of MMSE decline over
  5 years in older Mexican Americans

J Gerontol Medical Sciences, 2002
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Diabetes mellitus and incidence of lower body
disability among older Mexican Americans. Al
Snih S, Fisher M, Raji MA et al.

• Diabetes is independently associated with
  increased risk of developing new limitations in
  mobility tasks and lower body disability over a
  7-year follow-up

J. of Gerontology Medical Sciences, 2005
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Is the metabolic syndrome, with or without
diabetes, associated with progressive disability
in older mexican americans? Blaum CS, West NA,
Haan MN.

• Baseline metabolic syndrome is associated with
  high risk of developing limitation of mobility
  strength over 3-year follow-up, regardless of
  presence of diabetes

J. of Gerontology Medical Sciences, 2007
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The microvascular frontal-subcortical syndrome of
aging. Pugh KG, Lipsitz LA

• Frontal-sub-cortical regions modulate cognition,
  affect motor control
• Ischemic lesions in these regions may lead to
  cognitive, mood and movement disorders
• Interventions to reduce midlife cardiovascular
  risk factors
• Neurobiol Aging. 2002

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Implication of shared risk factors One
disorder may be a risk factor for others

• Shared risk factors may cause disorders in
  cognition, mood and mobility
• Any of the disorders (e.g., depression) could be
  initial presentation in a patient
• Over time with persistence of risk factors,
  other disorders (e.g., cognitive decline) may
  emerge

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Evidence linking cognition, mood movement
disordersRaji MA Ostir GV, Markides KS, Goodwin
JS, J Gerontol 2002
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Cognitive Function, Gait Speed Decline,
Comorbidities The Health ABC study H.
Atkinson, C. Rosano, E. Simonsick et al.

• Global executive cognition tests are strong
  independent predictors of declines in gait speed
  over 3-yr period
• Depression attenuates association of executive
  cognition with gait-speed decline
• J. of Gerontology Medical Sciences, 2007

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Depression, Gait Speed and Cognitive Decline in
Older Mexican Americans

• Eight foot walk time
• high depressive symptoms
• Independent predictors of dev of cognitive
  decline over 7 yrs among initially
  cognitively-intact elders

Raji et al. J Geriatric Psychiatr Neurol
2007 Alfaro-Acha et al. J Am Geriatr Soc. 2007
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Data from Health, Aging, and Body Composition
Study Maraldi C, Volpato S, Penninx BW. et al.

• Slow walking speed
• cognitive impairment
• independent predictors of risk of new onset
  depression in elderly over 6-year period
• Arch Intern Med. 2007

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Mechanisms Implications

• Vascular e.g. frontal cortical regions ischemia
• Inflammation
• Nutrition
• Metabolic
• Endocrine
• Genetics
• Treatment implications new ways to treat
  cognitive, mood and mobility disorders
• Diagnostic implications proteomics, genomics,
  metabolomics, etc.

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CONCLUSIONS

• Obesity, diabetes, metabolic syndrome, low
• physical activity, low serum vitamin D are
  common conditions in older Mexican Americans
• These conditions predict co-occurrence of
  cognitive, mood and movement disorders
• Understanding the underlying mechanisms is key to
  developing culturally appropriate tests to
  prevent mental and mobility disorders in Mexican
  American elders, a rapidly growing segment of US
  population

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ACKNOWLEDGEMENTS

• P30 AG-024832-01. UTMB Claude Pepper Older
  American Independence Center, from the National
  Institute of Health. (James Goodwin, Principal
  Investigator)
• R01-AG -10939-11. A Longitudinal Study of
  Mexican-American Elderly Health, from the
  National Institute on Aging (Kyriakos Markides,
  Principal Investigator)
• R01-AG-017638-04. Disablement Process in Mexican
  American Older Adults, from the National
  Institute on Aging (Kenneth Ottenbacher,
  Principal Investigator)

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References

• Raji, MA, Ostir GV, Markides KS, Goodwin JS. The
  interaction of cognitive and emotional status on
  subsequent physical functioning in older Mexican
  Americans Findings from the Hispanic-EPESE. J
  Gerontol Med Sci. 200257AM1-M5.
• Ford ES, Giles WH, Dietz WH. Prevalence of the
  metabolic syndrome among US adults findings from
  the third NHANES. JAMA. 2002287356-359
• Dergance JM, Mouton CP, Lichtenstein MJ et al.
  Potential mediators of ethnic differences in
  physical activity in older Mexican Americans and
  European Americans results from the San Antonio
  Longitudinal Study of Aging. J Am Geriatr Soc.
  2005 531240-7.
• Barcelo A, Gregg EW, Pastor-Valero M, et al Waist
  circumference, BMI and the prevalence of
  self-reported diabetes among the elderly of the
  United States and six cities of Latin America and
  the Caribbean. Diabetes Res Clin Pract. 2007 Jul
  30 Epub ahead of print 17669541
• Blaum CS, West NA, Haan MN. Is the metabolic
  syndrome, with or without diabetes, associated
  with progressive disability in older mexican
  americans? J Gerontol A Biol Sci Med Sci.
  200762766-73.
• Martins D, Wolf M, Pan D, Prevalence of
  cardiovascular risk factors and the serum levels
  of 25-hydroxyvitamin D in the United States data
  from the Third National Health and Nutrition
  Examination Survey. Arch Intern Med.
  20071671159-65.

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References

• Nguyen HT, Black SA, Ray LA et al Predictors of
  decline in MMSE scores among older Mexican
  Americans. J Gerontol Biol Sci Med Sci.
  200257M181-5.
• Yaffe K, Haan M, Blackwell T et al. Metabolic
  syndrome and cognitive decline in elderly
  Latinos findings from the Sacramento Area Latino
  Study of Aging study. J Am Geriatr Soc.
  200755758-62
• Alfaro-Acha A, Al Snih S, Raji MA et al.. Does
  8-foot walk time predict cognitive decline in
  older Mexicans Americans? J Am Geriatr Soc.
  55245-251, 2007
• Rotkiewicz-Piorun, AM, Al Snih S, Kuo YF, Raji MA
  et al.. Cognitive decline in older Mexican
  Americans with diabetes. J Natl Med Assoc,
  200698(11)1840-7.
• Arvanitakis Z, Wilson RS, Bienias JL, Bennett DA.
  Diabetes and parkinsonian signs in older
  persons. Alzheimer Dis Assoc Disord.
  200721144-9.
• Al Snih S, Fisher M, Raji MA, Markides KS et al.
  Diabetes mellitus and incidence of lower body
  disability among older Mexican Americans. J
  Gerontol A Biol Sci Med Sci. 2005601152-6.

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References

• Pugh KG, Lipsitz LA The microvascular
  frontal-subcortical syndrome of aging. Neurobiol
  Aging. 200223421-31
• Maraldi C, Volpato S, Penninx BW. et al. Diabetes
  mellitus, glycemic control, and incident
  depressive symptoms among 70- to 79-year-old
  persons the health, aging, and body composition
  study. Arch Intern Med. 20071671137-44.
• Raji MA, Reyes-Ortiz CA, Kuo YF et al. Depressive
  symptoms and cognitive change in older Mexican
  Americans. J Geriatric Psychiatry and Neurol
  200720145-152.
• Raji MA, Kuo YF, Al Snih S, Markides KS, Peek MK,
  Ottenbacher KJ. Cognitive status, muscle strength
  and subsequent disability in older Mexican
  Americans. J Am Geriatr Soc. 2005531462-8.
• Ostir GV, Markides KS, Freeman DH Jr, Goodwin JS.
  Obesity and health conditions in elderly Mexican
  Americans the Hispanic EPESE. Established
  Population for Epidemiologic Studies of the
  Elderly. Ethn Dis. 20001031-8.
• Crespo CJ, Keteyian SJ, Heath GW . Leisure-time
  physical activity among U.S. adults Results from
  the Third National Health and Nutrition
  Examination Survey. Arch Intern Med 1996 9398.
  

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References

• Kivipelto M, Ngandu T, Fratiglioni L, et al.
  Obesity and vascular risk factors at midlife and
  the risk of dementia and Alzheimer disease. Arch
  Neurol. 2005 62(1556-60.
• Kiraly SJ, Kiraly MA, Hawe RD, Makhani N. Vitamin
  D as a neuroactive substance review.
  ScientificWorldJournal. 2006 Jan 266125-39.
• Wu JH, Haan MN, Liang J, et al. Impact of
  diabetes on cognitive function among older
  Latinos. A population-based cohort study. J Clin
  Epidemiol. 200356686-693.
• United States Bureau of the Census.  The Hispanic
  population in the United States March 2002.
  Current Population Reports, p 20-545, U.S.
   Bureau of the Census, Washington, D.C. 2003.
• Markides Coreil. The health of Hispanics in the
  southwestern United States an epidemiologic
  paradox. Public Health Rep. 1986101253-65.
• Atkinson HH, Rosano C, Simonsick EM et al.
  Cognitive function, gait speed decline, and
  comorbidities the health, aging and body
  composition study. J Gerontol A Biol Sci Med Sci.
  2007 62844-50.

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NIA Bedside-to-Bench Conference

• Cognition, mood and movement disorders in older
  Mexican Americans
• Mukaila A. Raji, MD, MSc
• Associate Professor, Internal Medicine-Geriatrics
• Director, Memory Loss Clinics
• University of Texas Medical Branch
• Galveston, Texas, USA