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

2. 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

3. Hispanics as % of U.S. Population
Source: U.S. Bureau of the Census

4. POPULATION PROJECTIONS TO 2050
Non-Hispanic Whites 210 million
Hispanics million (25%)
African Americans (Blacks) 61 million
Asian Origin million
Source: U.S. Bureau of the Census (2004)

5. 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)

6. 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

7. Metabolic syndrome defined as ≥3 of: ↑ waist circumference
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

8. Crespo CJ, Keteyian SJ, Heath GW, Sempos CT
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

9. Changes in Blood Pressure and Risk Factors for Cardiovascular Disease among Older Mexican Americans from to
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. Martins D, Wolf M, Pan D et al.
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 <30 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

11. Epidemiological evidence linking vascular risk factors to cognition, mood & movement disorders

12. 6-year prospective cohort study of ~ 2500 community-residing elders
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

13. 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

14. 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

15. 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

16. 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

17. The microvascular frontal-subcortical syndrome of aging
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

18. 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

19. Evidence linking cognition, mood & movement disorders Raji MA Ostir GV, Markides KS, Goodwin JS, J Gerontol 2002

20. 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

21. 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

22. 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

23. 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.

24. 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

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

26. 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. 2002;57A:M1-M5.
Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third NHANES. JAMA. 2002;287:
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 ;53:
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 Jul 30; [Epub ahead of print] :
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. 2007;62:
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. 2007;167:

27. 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. 2002;57:M181-5.
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. 2007;55:758-62
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. 55: , 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, 2006;98(11):
Arvanitakis Z, Wilson RS, Bienias JL, Bennett DA. Diabetes and parkinsonian signs in older persons. Alzheimer Dis Assoc Disord. 2007;21:144-9.
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. 2005;60:

28. References
Pugh KG, Lipsitz LA The microvascular frontal-subcortical syndrome of aging. Neurobiol Aging. 2002;23:421-31
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. 2007;167:
Raji MA, Reyes-Ortiz CA, Kuo YF et al. Depressive symptoms and cognitive change in older Mexican Americans. J Geriatric Psychiatry and Neurol 2007;20:
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. 2005;53:
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. 2000;10:31-8.
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;: 93–98.

29. 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 ;62(:
Kiraly SJ, Kiraly MA, Hawe RD, Makhani N. Vitamin D as a neuroactive substance: review. ScientificWorldJournal Jan 26;6:
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. 2003;56:
United States Bureau of the Census.  The Hispanic population in the United States: March Current Population Reports, p , U.S.  Bureau of the Census, Washington, D.C
Markides & Coreil. The health of Hispanics in the southwestern United States: an epidemiologic paradox. Public Health Rep. 1986;101:
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 ;62:

30. 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