the nun study: past, present and future kelvin o. lim, m.d. director, nun study drs. t.j. and ella...
TRANSCRIPT
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The Nun Study: Past, Present and Future
Kelvin O. Lim, M.D.
Director, Nun StudyDrs. T.J. and Ella M. Arneson Land-Grant Chair in Human Behavior
Professor and Vice ChairDepartment of PsychiatryUniversity of Minnesota
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Outline
• A Brief History of the Nun Study
• Key Findings of the Nun Study
• Present
• Future
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School Sisters of Notre Dame(SSND)
• International congregation of Roman Catholic sisters
• Founded in 1833 in Germany to teach poor girls
• Began in North America in 1847
• Seven provinces in the United States
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School Sisters of Notre Dame(SSND)
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Sister Carmen to DavidSnowdon
“No matter what you do, I want you to remember who these women are … I don’t want you to treat them as research subjects. Get to know them. …we treat them with the care and respect they deserve. We will expect nothing less from you.”
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Nun Study Timeline• 1986 – Study begun by David Snowdon in Mankato while
at the University of Minnesota• 1990 – Snowdon moves the Study to the Sanders-Brown
Center for Aging at the University of Kentucky (1R01AG009862)
• 2008 October – Agreement signed by UKY, UMN and SSND to move study back to Minnesota
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Unique Features of Nun Study
• Multiple evaluations over many years• Extensive data from early life• Homogeneity in living conditions, working
conditions, lifestyle• Brain donation is a requirement• Follow-up easy – live in congregation• Single cohort – 75 years old or older
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SSND population strengths
• Dedicated research participants• Sisters see the Study as their job• Minimal attrition (98% for autopsy)• Complete collection of data• Study is done in partnership with the SSND
Ideal for longitudinal study with multiple and demanding measures
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Findings
• Idea Density
• Positive Emotions
• Infarcts
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Autobiographical Essays at Entry to Convent
• Written on entry into the convent• Instructed to write a short sketch of [her] life.
“This account should not contain more than two to three hundred words and should be written on a single sheet of paper . . . include place of birth, parentage, interesting and edifying events of childhood, schools attended, influences that led to the convent, religious life, and outstanding events.”
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Low and High Idea Density
• I was born in Eau Claire, Wis., on May 24, 1913 and was baptized in St. James Church. (ID 3.9)
• The happiest day of my life so far was my First Communion Day which was in June nineteen hundred and twenty when I was but eight years of age, and four years later in the same month I was confirmed by Bishop D.D. McGavick. (ID 8.6)
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Idea Density and % with Alzheimer’s Disease pathology
Snowdon et al., JAMA, 1996
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Idea Density and number of neocortex lesions
Snowdon et al., JAMA, 1996
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Positive Emotions
• Coding system was developed for rating positive emotions
• Autobiographies were rated without knowledge of the status of the participant
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Low Positive Emotion Example
I was born on September 26, 1909, the eldest of seven children, five girls and two boys . . . . My candidate year was spent in the Motherhouse, teaching Chemistry and Second Year Latin at Notre Dame Institute. With God's grace, I intend to do my best for our Order, for the spread of religion and for my personal sanctification.
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High Positive Emotion Example
God started my life off well by bestowing upon me a grace of inestimable value... . The past year which I have spent as a candidate studying at Notre Dame College hasbeen a very happy one. Now I look forward with eager joy to receiving the Holy Habit of Our Lady and to a life of union with Love Divine.
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Survival and Positive Emotions
Danner et al., J. Personality and Social Psychology, 2001
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Influence of Infarcts on dementia
• Quantify size and location of infarcts throughout the brain
• Examined in those who met Neuropathologic Criteria for Alzheimer Disease
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Influence of infarcts on dementia in subjects with AD pathology
Snowdon et al., JAMA, 1997
0 1 or 2
Infarcts in basal ganglia,thalamus,deep white matter
% w
ith d
em
entia
020
4060
8010
0
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Present• Completed Waves 13 and 14• Complete the study – 21 of 678 Sisters
remain• Make the materials from the Nun Study an
international scientific and teaching resource• Perform analyses that take advantage of the
longitudinal data • Design the next generation of studies
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Cognitive Reserve
• What characteristics are related to…– Lower risk of diagnosis & age of symptom onset– Slower progression of disease– Greater clinical resistance to pathology– Lower risk of death
• Genetic risk: APOE e4 / e2• Demographic factors: Age, Education, IQ• Linguistic abilities
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• Nun Study Wave 13 sample (n=48)– Sisters aged 75+ years followed since 1991– Sisters who completed 13 evaluations (approx 17 yrs)
• Semantic space: verbal fluency measures– How many animals can you think of without
“switching” subcategory (pets, zoo, farm, safari, etc.)
• Semantic space at baseline was related to– Significantly lower risk of dementia at follow-up– Significantly slower rate of decline over time
* All analyses included age as a covariate
Semantic Space - Risk of Dementia & Rate of Cognitive Decline (Hemmy)
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Study Design Goal
“A study that any Sister can be a participant”
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• Goals:– Characterize a younger cohort of SSNDs
– Open to any Sister
– Provide pilot data (time 1) for future work
– Longitudinal follow-up
• Data collection– Demographics & genetics
– Medical history & health risk factors
– Cognition
– Mood, personality, & psychological resiliency
– Activity level, physical function, & quality of life
UMN-SSND Foundation Study
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Future
• Shift in focus to pre-disease state
• Identify early predictors that could serve as intervention targets
• Earlier age: 50-80 years old
• Longitudinal
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Center for Magnetic Resonance Research
• Human• 3 Tesla (2)• 4 Tesla• 7 Tesla (2)• 10.5 Tesla• PET/CT
• Animal• 9.4 Tesla• 16.4 Tesla
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Studying the “Vascular” Effect
• Infarcts are a binary determination • Scales of vascular risk (diabetes, smoking,
HTN) have limitations• Need for a continuous, quantitative measure
of tissue vulnerability• Combine this with other measures of brain
pathology (amyloid,tau)
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Midlife Risk Factors for Dementia
• Hypertension
• Diabetes
• Obesity
• Smoking
• Dyslipidemia
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Artery-Arterioles-Capillaries-Venules-Veins
http://www.merck.com/mmhe/sec03/ch020/ch020c.html
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CO2 is a potent vasodilator
• Acetazolamide– Carbonic anhydrase inhibitor– CO2 + H2O >> CA >> H2CO3 >> H+ + HCO3
• Non invasive CO2 manipulation– Breathhold– Increased CO2 in air mixture– Control of end tidal CO2
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Control End Tidal CO2
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BOLD Signal Change in Response to PCO2 change
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Cerebrovascular Reactivity
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PET Amyloid imaging (AV45)
Clark et al., JAMA, 2011
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Acknowledgements
• School Sisters of Notre Dame
• David Snowdon and team
• Funding– National Institutes of Aging– UMN – Academic Health Center– UMN – Institute for Translational
Neuroscience– Mohl Estate Gift
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That you may have life to the full
www.nunstudy.org