Lecture 2: longitudinal studies of aging, Nun Study Lecture Notes 10/10/17, Nun/ alzheimers disease, Nun Study, Nun/ alzheimers disease

The Nun Study "Healthy Aging and Dementia": What is passive reserve?

Degree of normal development of brain function and performance -likely formed early in life, maintained by lifestyle and health behaviors

Method of the nun study

**assessments: -during life: cognitive functioning social functioning chronological age physical health -after death: brain studies

brain donation and the church

-1950s catholic church approved voluntary organ donation -taught that the body is the temple of the Holy Spirit -others felt they must return to God the way they came

brain donation

-678 of 1027 sisters enrolled in brain donation program, 66% -pathologist makes elliptical incision around top of skull, removes brain, weighs it and places it in one gallon plastic matter of formallin to fix the tissue

The Nun Study "Healthy Aging and Dementia": What are some other findings from the Nun study?

-Analyzed of autobiographies (assessed for idea density and positive/negative emotions) -Both factors linked to later risk for Alzheimer's

The Nun Study "Healthy Aging and Dementia": what were the three sources of data for this study?

-Convent archives (early risk for Alzheimer's) -Annual examinations (cog. function) -Brain donations at deaths

What are the take home messages of this lecture?

-Psychological factors can be protective against morbidity and mortality -Examples of protective facts are cog complexity, positive affect, and purpose in life

the nun study results cont...

-a one page writing sample could predict who would have cognitive problems about 60 years later -brain pathology was confirmed based on category of autobiographical writing ---high idea density sisters had healthy brains 58 years later -90% of alzheimers sisters had low idea density in their auto biogs ---their brains were already compromised

autobiographies

-categories of writing: -multisyllabic words, "particulary", "quarantined" -frequency of rarely used words "grandeur" -idea density -grammatical complexity (associated with working memory capacity)

implications of the nun study

-control your environment as much as you can -have physical and mental excercise -reduce stress: meditation, relaxation -resolve any traumatic experiences from earlier in your life; therapy -actively improve your mood: be positive -read to your children -become like nuns (care for others, life of meaning, faith, moderation in diet, not smoking, drugs, drinking, excercise, quiet, and meditative life)

the take away

-depressions and pessimism increase risk of disease -although you cannot prevent the alzheimer's plaques and tangles, you can do things to prevent stroke, so alzheimer's symptoms have less chance of affecting functioning. -excercise, diet, keep mind active, good social relationships, loving family connections -the older you get, the healthier you have been

preventing strokes

-have a diet high in veggies, fruits, low in fats and keep weight down, dont smoke -folic acid from dark green leafy veggies is good

The Nun Study

-longitudinal study of the teaching sisters of Norte Dame -678 enrolled since 1991 aged 75-102 -written autobiographies within 2 years of study -annual cognitive testing -brain autopsies -400 deceased by 2003

the nun study results

-low linguistic ability in early life was a strong prediction of poor cognitive function and Alzheimers disease in later life -autobiographies predicted who would show the symptoms of Alzheimers --those who has the richest vocabulary, most complex sentences, most ideas in sentences (idea density) 60 years later had lower probability of having Alzheimers -

strokes and alzheimers symptoms

-mini strokes or TIAs transient ischemic (low blood flow or oxygen to brain) attacks -associated with high blood pressure or hypertension; connections between Alz and vascular diseases -astherosclerosis: fatty deposits from plaques on interior walls of blood vessels, reducing supply of oxygen to tissues and organs, heart pumps more blood, stressing the heart and not giving the brain enough oxygen ( brain = 2% of bodys weight but consumes 25% of the available oxygen)

hypothesis of the nun study

-more verbally adept sisters have more resistance to the alzheimers disease -adept means more verbally skilled

study population

-nuns are in a pure environment from age 16, no smoking, access to health care. vows of poverty, chastity, and obedience -chastity=means to engage in sexual activities -David Snowdon got nuns to donate their brains after death ----donations were mandatory for all participants in the study

brain tissue study

-post modern pathology examination of nun's brains by pathologist "blind" to patients' scores on tests -other researchers compared the pathology results with the nuns' cognitive test results and daily functioning scores, and their autobiographies written almost 60 years earlier

physical test

-put on a sweater -read instructions on a pill bottle -how long to walk 6', 50' -hand cordination -grip strength -put on shoes and tie them -other simple tasks of daily living

Results of sisters and stroke/Alz symptoms

-sisters with evidence of a stroke (shown by pits [lacunae] of dead tissue [infracts] required fewer tangles in the neocortex to show symptoms of dementia than the stroke-free sisters -stroke free sisters had brain damage from Alzheimer's but did not have dementia (were asymptomatic) -there is an interaction effect between strokes and Alzheimer's : preventing strokes can help prevent symptoms of Alzheimers. ---Dementia is not a specific disease. It's an overall term that describes a wide range of symptoms associated with a decline in memory or other thinking skills severe enough to reduce a person's ability to perform everyday activities. Alzheimer's disease accounts for 60 to 80 percent of cases.

3 Sources of Data in the Nun Study

1. Convent archives (family history, educational history, SES) 2. Annual Examinations (mental capacities) 3. Brain donations at death

Protective Resources of Alzheimer's

1. High education 2. continued mental activities 3. social networks 4. diet, exercise, limited alcohol intake 5. purposeful life engagement

4 Key themes from Nun Study:

1. degree of pathology in the brain 2. location of lesions 3. stroke free participants 4. some could tolerate plaque buildup in the brain

results cont on strokes/alz symptoms

1.) a college education and an active intellectual life may have stave off Alzheimers disease and other forms of dementia 2.) stokes and brain trauma might worsen the symptoms of Alzheimers disease 3.) among the nuns with phsyical evidence of Alzheimer's in the brain, it was more likely the more severe and debilitating symptoms of Alz disease 4.) thus folic acid ( found in breads, cereals, and leafy green veggies) seems to protect the brains central language and reasoning regions in the neocortex from shrinkage. however, this association did not extend to other nutrients such as antioxidants ( vitamin C or E)

questions not answered

1.) did temperament or environment or both cause differences in writing ability and optimism/ pessimism? -what were the effects of the pre nun period of their lives (early attachment history) 2.) could alzheimer's have caused those in their twenties to be more pessimistic and less complex writers?

Results

1.) for every 1% in the number of positive sentences in their writings, there was a 1.4% decrease in mortality rate 2.) the happiest nuns lived 10 years longer than the least happy nuns 3.) by age 80, the most cheerful group had only 25% of its population while the least cheerful group has lost 60% 4.) cheerful nuns had an 80% chance of getting to age 85 while the least cheerful nuns only had a 54% chance of reaching 85 5.) by age 90 the cheerful sisters survived 65% of the time while the least cheerful sisters survived 30% 6.) 54% of the happy nuns reached 94 while only 15% of the least happy nuns reached that age

limitation of the nun study

1.) the results are correlational a. correlation doesnt prove causation b. the positive correlation between life style and longevity could be caused by other factors like genetic differences -i. genes could cause longer life and more positive attitudes 2.) the results may not apply to the general population

the research questions of the nun study?

1.)does mental activity ward off memory loss? 2.) is linguistic ability in early life correlated with cognitive function and alzheimers disease in late life? 3.) what is the impact of the positive emotions and thoughts on the health of the body?

Brain donation rate

678 of 1,027 eligible sisters enrolled. 66% rate of participation

Education

95% had bachelors degrees 45% had masters degrees

The Nun Study "Healthy Aging and Dementia": What is active reserve?

Activation of new brain regions and networks to compensate AD pathology

Brain Donations

Made brain donation mandatory so that they could study sick and healthy brains

The Nun Study "Healthy Aging and Dementia": What is cognitive reserve?

Capacity of brain to resist expression of symptoms in face of neuropathology

What was tested (mental)

orientation to time and place, basic memory, simple arithmetic

example #1

I was born in Eau Claire, Wis., on May 24, 1913 and was baptized in St. James Church. ---- Sister Helen -this has low idea density, simple sentence construction, simple vocabulary

example #2

It was about a half hour before midnight between February twenty-eighth and twenty- ninth of the leap year nineteen-hundred-twelve when I began to live and to die as the third chjild of my mother, whose maiden name is Hild Hoffman and my father, OMo SchmiM. O ---Sister Emma this has high idea density, complex linguistic construction, rich vocabulary

The Nun Study "Healthy Aging and Dementia": What are the two types of reserve?

Passive and active

The Nun Study "Healthy Aging and Dementia": How do strokes relate to lesions and dementia?

Stroke-free patients tolerate more lesions before showing symptoms of dementia (co-morbid conditions matter)

Better educated

Sisters with more education had extra brain reserve and hence more resistance to the symptoms of Alzheimer's

The Nun Study "Healthy Aging and Dementia": what is the importance of resistance to clinical expression of neuropathology?

Some are able to tolerate abundance of plaques and NF tangles -Possibly linked to nutrition

Nun Process

years of training, aspirant, postulant, and then a novice, took vows of poverty, chasity, and obedience

T/F Nun Study has limited generalizability

True

T/F Study 2 found that purpose in life modifies association between AD pathology and cognitive function

True

T/F people with higher purpose in life have lower depression, disability, neuroticism, # of medical conditions, and income

True

T/F positive/negative emotions are linked to AD

True

T/F psychological factors (cognitive complexity, positive affect, purpose in life) can be protective against morbidity and mortality

True

T/F there was notable variability among the nuns

True

T/F, in Study 2 they looked at brains and how they were functioning before and after death

True

The Nun Study "Healthy Aging and Dementia": are the location of lesions important?

Yes, locations of lesions may be critical

Biological changes due to alzheimer's.....

accumulation of plaque destruction of neurons neurofibrillary tangles

Active Reserve

activation of new brain regions and networks to compensate AD pathology

background to the nun study

active longetivity: -successful aging= maintaining independence -age alone does not equal mental frality-disease does (age related does not equal to age caused) -link between the level of education and longevity; college degree----> better chance of living to old age. -nuns are well educated: most become teachers

Study Agreements

agree to open their historical records, participate in physical and mental evaluations, and donate their brains for autopsies

David Snowdon

assistant professor of epidemiology at the University of Minnesota

Cognitive Reserve

capacity of brain to resist expression of symptoms in face of neuropathology

Passive Reserve

degree of normal development of brain function and performance; maintained by lifestyle and healthy behaviors

Idea Density

depends on two important learned skills vocabulary and reading comprehension

Other factors

family upbringing and environment, depression

Probable cause of alzheimer's

genetic abnormalities

Key Finding of Rush Memory and Aging Project (MAP)

greater purpose in life is associated with reduced risk of AD

Risk factors for Alzheimer's

head trauma, genetic influences, being female

What was the key finding of Study 2 in MAP

high purpose in life helped maintain high cognitive function even in the face of brain based pathology

cheerfulness quartiles

look at graph from lecture slides

Alzheimer's development

may be developing even in adolescence may take 50 years or more for the Alzheimer's pathology to progress from stage 1 to stage 5 or 6

the nun study results cont.....

mood and longetivity -sisters with positive emotional content at age 22 lived 7 years longer than those with negative emotional content

What was tested (physical)

near and distant vision, grip strength, timed opening and closing cabinets, could they rise from a char, how long it took them to walk 6 feet

cognitive assessment

pathologist compared post mortem brain tissue with cognitive test results -name objects -state date -identify location -spell words backwards -do simple tasks -verbal fluency (how many fruits and vegetables can you name in one minute?) -delayed word recall test

Exercise

preserves cardiovascular health, improves blood flow, reduces stress, increases chemicals that nourish the brain, helps ward off depression

Braak Staging

stages 1 or 2 22% had evidence of dementia, stage 3 and 4 43% and stage 5 and 6 70%

Pathological Features

tangles and plaques, hardening of the arteries

Findings in Brain

tangles first surface in the entorhinal cortex, near the base of the skull that is important for memory, the tangles move higher and deeper into the brain invading the hippocampus and neighboring tissues, finally, reaching the neocortex

Brain Reserve

the amount of disability seen in people with Alzheimer's does not simply reflect how much damage their brains have suffered from the disease rather, the way a brain develops in the womb during and during adolescence may lead to a stronger or weaker structure

Hormones and Aging

the later the age at natural menopause, the older the age at death

The Study

the links between a sister's level of education and her mental and physical abilities later in life

why study nuns?

the nuns living conditions, histories and environmental factors were "controlled" by their life choice -nuns live similar lifestyles, dont smoke or drink alcohol, dont have sex, dont get married or have children and they eat the same simple diet -could collect 180 nun autobiograhies (good sample size) -could be evaluated over a 60 or 70 year period -could find out what happened to all the subjects in the study -these conditions were very rare for a non-laboratory longitudinal study

Why Nuns

they have similar life styles, similar histories, do not smoke, similar jobs and income, celibate, and receive similar health care

Epidemiology

understanding the causes of a disease in a population can lead to prevention strategies

Healthy Brain

weighs between 1,100 and 1,400 grams. brains of Alzheimer's patients are noticeably smaller as the disease destroys brain tissue