framingham study

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Framingham Heart Study The Pre-Clinical Stage of Alzheimer’s The Pre-Clinical Stage of Alzheimer’s Disease: A 30-year Prospective Study of Disease: A 30-year Prospective Study of the Framingham Cohort the Framingham Cohort Rhoda Au, Ph.D. Rhoda Au, Ph.D. March 6, 2010 March 6, 2010

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Page 1: Framingham Study

Framingham Heart Study

The Pre-Clinical Stage of Alzheimer’s The Pre-Clinical Stage of Alzheimer’s Disease: A 30-year Prospective Study of Disease: A 30-year Prospective Study of

the Framingham Cohortthe Framingham Cohort

Rhoda Au, Ph.D.Rhoda Au, Ph.D.March 6, 2010March 6, 2010

Page 2: Framingham Study

Disclosures

NoneNone

Page 3: Framingham Study

Educational Objectives

Present data from 3 different Present data from 3 different points of longitudinal follow-uppoints of longitudinal follow-up

Revisit the concept of “pre-Revisit the concept of “pre-clinical”clinical”

Examine the idea of age-specific Examine the idea of age-specific definitions of “pre-clinical” and definitions of “pre-clinical” and impact on measurement toolsimpact on measurement tools

Page 4: Framingham Study

Framingham Heart StudyFramingham Heart Study Longitudinal Community-Based Family StudyLongitudinal Community-Based Family Study

Gen 1 Original cohort

Gen 2 Offspring cohort

19482010

1971 2007

Gen 3 cohort

2002 2010

Page 5: Framingham Study

OvervieOvervieww

Core Exam

Anthropometry (ht, wt, girth)

Blood Pressure (resting)

Urinalysis

Lifestyle/Habits (drinking, smoking, work,

sociodemographic)

Medical History (dr.visits, hopitalization, illness, health

status, medication)

MD Physical Exam

Chemistries (lipids, cholesterol, triglycerides,

glucose, TSH, apoprotein)

Echocardiography

Electrocardiogram

Holter Monitor

Pulmonary Function

Twins

Sleep

Cardiac MRI

Hearing

Hypergen

Stroke (PSIP)

MRI, Cognition & Genetics

Bone StudyAncillary Studies

Carotid Doppler

Cognition (MMSE) Psychosocial (self-report, CES-D, Type A)

Physical Activity/Fitness (ADL, walk/jog, falls)

Alcohol Use and Abuse Epidemiology of Dementia

Page 6: Framingham Study

Framingham Heart StudyFramingham Heart Study Dementia Study – Prevalence: Gen 1 Original Dementia Study – Prevalence: Gen 1 Original cohortcohort

1948 2010

1976-78Baseline NP

1984NINDS-ADRDA AD Diagnostic Criteria

Dementia/AD Diagnosis: Moderate/Severe

1981MMSE

Page 7: Framingham Study

Baseline NP BatteryBaseline NP Battery

WMS Logical MemoryWMS Logical Memory– Immediate Recall (IR)Immediate Recall (IR)– Delayed Recall (DR)Delayed Recall (DR)– Retained (LM-IR/LM-DR)Retained (LM-IR/LM-DR)

WMS Visual Reproductions – IRWMS Visual Reproductions – IR WMS Paired Associates -IRWMS Paired Associates -IR Controlled Word Association Test (COWAT)Controlled Word Association Test (COWAT) WAIS SimilaritiesWAIS Similarities WAIS Digit SpanWAIS Digit Span

Page 8: Framingham Study

Linn et al., 1995Linn et al., 1995

13 years follow-up13 years follow-up– 65+ years old65+ years old

AD cases, n=55AD cases, n=55 Results (age & education adjusted)Results (age & education adjusted)

– LM- IR/RetainedLM- IR/Retained– VR-IRVR-IR– PA-IRPA-IR– SimilaritiesSimilarities– Digit Span (DS-B)Digit Span (DS-B)

Page 9: Framingham Study

Elias et al., 2000Elias et al., 2000

22 years follow-up22 years follow-up– 65+ yrs. old65+ yrs. old

AD cases, n=109AD cases, n=109 Results (age, edu, occupation & Results (age, edu, occupation &

gender adjusted)gender adjusted)– LM- RetainedLM- Retained– PA-IRPA-IR– SimilaritiesSimilarities

Page 10: Framingham Study

Elias et al., 2000Elias et al., 2000

Censored - 5 yrs follow-up dementia-Censored - 5 yrs follow-up dementia-freefree– LM-retainedLM-retained– PA-IRPA-IR– SimilaritiesSimilarities

Censored – 10 yrs follow-up dementia Censored – 10 yrs follow-up dementia freefree– LM-retainedLM-retained– SimilaritiesSimilarities

Page 11: Framingham Study

Current Findings - 2010Current Findings - 2010

32 years of follow-up32 years of follow-up– >>65 years old65 years old

AD Cases, n=215AD Cases, n=215 Results (age, edu, gender, FSRP Results (age, edu, gender, FSRP

adjusted)adjusted)– LM-IR, DR, retainedLM-IR, DR, retained– VR-IRVR-IR– PA-IRPA-IR– COWATCOWAT– SimilaritiesSimilarities

Page 12: Framingham Study

Addit ional Findings - 65+Addit ional Findings - 65+

Censored – 10 yrs follow-up dementia Censored – 10 yrs follow-up dementia freefree

AD Cases, n=76AD Cases, n=76 ResultsResults

– LM-IR, DR, retainedLM-IR, DR, retained– COWATCOWAT– SimilaritiesSimilarities

Page 13: Framingham Study

Addit ional Findings – Addit ional Findings – 65+65+ Adjusted for age, educ, gender, Adjusted for age, educ, gender,

ApoE4ApoE4 AD Cases, n=76AD Cases, n=76 ResultsResults

– LM-IR, DR, retainedLM-IR, DR, retained– COWATCOWAT– SimilaritiesSimilarities

Page 14: Framingham Study

Framingham Heart StudyFramingham Heart Study Incident Incident Dementia + Pre-ClinicalDementia + Pre-Clinical

Gen 11948

2010

1976-78Baseline NP

1984NINDS-ADRDA AD Diagnostic Criteria

1981MMSE

1999Brain MRI/NP

Gen 21971

2010

1991MMSE

1999Brain MRI/NP

2014Gen 3 2002

Brain MRI w/ DTI +NP (n= 3000)

Page 15: Framingham Study

What is Pre-clinical?What is Pre-clinical?

65+ years old65+ years old– Measures differentiate cognitively intact Measures differentiate cognitively intact

vs. clinically dementedvs. clinically demented 45-65 years old45-65 years old

– Measures differentiate cognitively intact Measures differentiate cognitively intact vs. pre-clinicalvs. pre-clinical

>45 years old>45 years old– Measures differentiate cognitively intact Measures differentiate cognitively intact

vs. cognitively intactvs. cognitively intact

Page 16: Framingham Study

Other Team MembersInvestigators Clinical Team

FHS Neurological Research TeamFHS Neurological Research Team

Philip A. Wolf, M.D.PI/Professor of Neurology,

Sudha Seshadri, M.D.Asst. Professor of Neurology

Margaret Kelly-Hayes, Ed.D.Investigator/Clinical Professor ofNeurology

Emelia Benjamin, M.D.investigator/Professor of Medicine

Carole Palumbo, Ph.D.Investigator/Assitant Professor ofNeurology

Neil Kowall, M.D., Ph.D.Investigator/Professor of Neurology & Pathology

Monica KimResearch Assistant/Neuropsy

Catherine AmbleResearch Assistant/Neuropsy

Joseph Massaro, Ph.D.Assistant Professor ofEpdemiology & Biostatics

Qiong Yang, Ph.D. Investigator/Associate Professor of Biostatistics

Karen MutalikSenior Data Manager/Analyst

Betty LiuData Manager

Yulin LiuData Manager

Charlie DeCarli, Ph.D.Investigator/Professor of Neurology, UCDavis

Carlos Case, M.D.Professor of Neurology

Paulina DrummondResearch Assistant/Neuropsy

Zaldy Tan, M.D.Gerontologist

Sanford Auerbach, M.D. Investigator/Professor of Neurology

Sherral Devine, Ph.D.Clinical Neuropsychologist

Ann McKee, M.D.Investigator/Associate Professor of Neurology & Pathology

Linda Farese, Deborah Foulkes, Patient Coordinators/Recruiters

Lindsay Farrer, Ph.D.Investigator/Professor of Genetics

Anita DeStefano, Ph.D.Investigator/AssociateProfessor of Biostatistics

Larry Atwood, Ph.D.Investigator/Associate Professor ofNeurology

Rafael Romero, M.D.Assistant Professor of Neurology

Richard AhlResearch Assistant/Neuropsy

Alexa Beiser, Ph.D.Investigator/ Professor of Neurology& Biostatistics

Coreyann Poly, Ph.D.Research Assistant/Neuropsy

Kristen KnoxResearch Assistant/Neuropsy

Rhoda Au, Ph.D.Investigator/ Associate Professor of Neurology

Jayandra HimaliResearch Assistant /Biostatistics

Jessica SaurmanResearch Assistant /Neuropsy

Vasan Ramachandran M.D.Investigator/Professor of Medicine

Elizabeth WilsonFinancial Manager/Administrator