framingham study
TRANSCRIPT
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
Disclosures
NoneNone
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
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
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
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
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
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)
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
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
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
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
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
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)
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
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