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Cognitive dysfunction and occupations with likely significant magnetic field exposure: A cross-sectional study of elderly Mexican Americans
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Cognitive dysfunction and occupations with likely significant magnetic field exposure: A cross-sectional study of elderly Mexican Americans
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Content
Cognitive Dysfunction and Occupations with Likely
Significant Magnetic Field Exposure:
A Cross-Sectional Study of Elderly Mexican Americans
Copyright 2001
by
Chiu-Chen Tseng
A Thesis Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(APPLIED BIOMETRY&EPIDEMIOLOGY)
May 2001
Chiu-Chen Tseng
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UMI Number: 1 4 06470
UMI
UMI Microform 1406470
Copyright 2001 by Bell & Howell Information and Learning Company.
All rights reserved. This microform edition is protected against
unauthorized copying under Title 17, United States Code.
Bell & Howell Information and Learning Company
300 North Zeeb Road
P.O. Box 1346
Ann Arbor, Ml 48106-1346
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UNIVERSITY O F SO U T H E R N C ALIFO RNIA
THE GRADUATE SCHOOL.
UNIVERSITY PARK
LOS ANGELES. CALIFORNIA 9 0 0 0 7
T his thesis, written by
under the direction of h£.a*....Thesis Committee,
and approved by all its members, has been pre
sented to and accepted by the Dean of The
Graduate School, in partial fulfillm ent of the
requirements for the degree of
Date...Ms..lX.u.ZQQl„
THESIS COMM!
/
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TABLE OF CONTENTS
List of Tables
Abstract
1. Introduction
1.1 Background and Risk factors
1.2 Cognition Dysfunction Assessment
1.3 Present study
2. Methods
2.1 Study population
2.2 Differences in cognitive functions between AD and VaD
2.3 MMSE Questionnaire
2.4 Cut-point for the MMSE
2.5 Occupational EMF exposure data
2.6 Procedure for Statistical Analyses
3. Results
4. Discussion
Master Reference List
Appendix
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LIST OF TABLES
Page
Table 1: Descriptive statistics for entire sample and 2058 subjects with 14
occupational information and MMSE score in Phase 1 o f the
HEPESE study.
Table 2: Respondent status for subjects while completed questionnaire 15
data by MMSE score in Phase 1 of the HEPESE study, 1993-1994.
Table 3: List job title for total 3050 subjects and 2058 participant subjects 16
with M/H EMF in Phase 1 o f the HEPESE study, 1993-1994.
Table 4: Crude odds ratio between risk factor and total MMSE in Phase 1 17
of the HEPESE study, 1993-1994.
Table 5: MMSE scores by gender within age group in Phase 1 of the 19
HEPESE study, 1993-1994.
Table 6: Odds ratio of severe cognitive dysfunction associated with MF 20
exposure by gender in Phase 1 o f HEPESE study, 1993-1994.
Table 7: Odds ratio of severe cognitive dysfunction associated with MF 21
exposure by age groups in Phase 1 of HEPESE study, 1993-1994.
Table 8: Odds ratio (OR) of severe cognitive dysfunction associated with 22
MF exposure, age, medical history of stroke and having ever smoked
in the initial phase (Phase 1) of the Hispanic Established Populations
for Epidemiologic studies o f the Elderly (HEPESE), 1993-1994 .
in
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Chiu-Chen Tseng Eugene Sobel
ABSTRACT
COGNITIVE DYSFUNCTION AND OCCUPATIONS
WITH LIKELY SIGNIFICANT MAGNETIC FIELD
EXPOSURE: A CROSS-SECTIONAL STUDY OF
ELDERLY MEXICAN AMERICANS
There was a clear trend o f increased severe cognitive dysfunction with MF
exposure (P for trend = 0.012) and increasing age (P for trend = 0.001), but no
difference between men and women (P = 0.6570). Among subjects with age 75+ or
65+, an increase of MF exposure was statistically significantly associated with
severe cognitive dysfunction after adjustment for age at examination, having ever
smoked, and medical history of stroke for men, women and both, respectively
(P<0.05). Among subjects with 65+, the risk for high MF exposure compared with
low MF exposure was 12.08 (95% Cl = 1.27-115.1) for men. For women the OR was
4.98 (95% Cl - 1.46-17.01). For both sexes, the OR was 5.36 (95% Cl = 1.82-
15.76). Results are consistent with previous findings.
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INTRODUCTION:
I. Background and Risk factors
Epidemiological studies report that the expected prevalence of dementia in
individuals over the age of 60 years is 2 percent or higher. Age-specific prevalence
rises up to perhaps 40 percent in those over age 85 (13, 25). The AD brain is
characterized by two types of lesions: senile plaques and neurofibrillary tangles (23).
Formation of these lesions is likely to result in severe impairment of
neurotransmission, decline in cognitive abilities and eventual neuronal death. The
neuropathologic characteristics of AD include senile plaques, neurofibrillary tangles,
amyloid angiopathy, neuronal loss, and decreased activity o f the enzyme
acetyltransferase leading to decreased presence of acetylcholine (52). The clinical
symptoms of the disease include memory loss, confusion, personality changes,
impaired coordination, and speech problems. AD is characterized by progressive
dementia with death occurring an average of 8-10 years after apparent onset. Age,
previous severe head injury, depression, low educational level, atherosclerosis, and
exposure to aluminum have been found, although not consistently, to be risk or
antecedent factors in previous studies of AD (30, 53, 80). Early onset AD is defined
as having an onset age before 60-65 years of age. Early onset AD is often inherited
in an apparently autosomal dominant fashion. Mutations in three genes have been
identified to date that result in early onset familial AD. The genes are the amyloid
precursor protein (APP), presenilin (PS-1 and PS-2) genes (8, 22). These mutations
1
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result in significantly increased production of amyloid beta (AP), the putative
neurotoxic element in AD. However, most AD cases are late onset (onset age after
60-65) apparently due to a combination of environmental and genetic susceptibility
factors. For example, the apolipoprotein E (ApoE) epsilon 4 (s4) allele is a well-
established risk factor for late onset AD (3, 11, 61, 64, 74). The ApoE s4 allele is
neither sufficient nor necessary for development o f the disease, which certainly
involves other factors (31). For example, a previous case-control study suggested
that the association between ApoE genotype and AD was stronger when cholesterol
levels were higher (32). In a community-based study of white, African American,
and Caribbean Hispanic elderly in New York City, decreased total cholesterol level
had a weak but significant inverse association with incident AD, independent of
ApoE genotype (60). ApoE s4 carriers without a previous head trauma may have a 2-
fold increase in risk of AD, while ApoE e4 carriers with previous head trauma may
have a 10-fold increase in risk (49). After age 75-80 or 80, the risk associated with
the ApoE s4 allele appears to decrease with age, until it apparently ceases around age
100 (68). The evidence that a high level of education is protective for AD and
dementia in general continues to accumulate. Jorm reported that the risk of AD
decreased by 17 % for each year o f education among persons who do not carry an
ApoE e4 allele and hence those with more formal education generally have a slower
rate of memory decline (35).
The use of anti-inflammatory drugs or estrogens may be protective against the risk
2
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of AD (75, 80). Previous studies have reported evidence that estrogen replacement
therapy is protective in women (26, 75). The Baltimore Longitudinal Study of Aging
reported that use o f estrogens at any time can apparently reduce the risk of
developing AD (38). However, because randomized clinical trials have not been
completed, Kristine et al do not recommend estrogen for the prevention or treatment
o f AD or other dementias until adequate trials have been completed (83). Besides,
long-term recent use of HRT may increase the risk of breast and endometrial cancers
(56).
Organic solvents are widely used in industry. Chronic exposure to solvents at lower
concentration can lead to various forms of neuropsychiatric disease. Previous
epidemiological studies of the association between occupational exposure to solvents
and AD are inconsistent. Some studies found positive results (4, 42) but some studies
did not (9, 43, 78). Small sample size in the older age groups may have been the
main reason for the inconsistent results in these studies. In the study of Kukull et al,
which used proxies to assess exposure for cases and controls, the adjusted OR for
exposure to solvents among men was 6.0 (95 % Cl = 2.1-17.3) and among women
was 0.7 (95 % Cl = 0.2-2.1) (42). Because the use of industrial hygienists to assess
exposure is generally better than that o f proxies, the use of proxies to assess solvent
exposure may have caused bias in this study (73).
Sobel et al. (69) provided evidence that electromagnetic field exposure in the
“primary” occupation (usually the last occupation) is statistically significantly
3
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associated with the occurrence of AD in case-control analyses in 4 case-control
series. The predominant occupation among medium (2-10mG or >10 mG
intermittently) to high (> 10 mG or > 100 mG intermittently) exposed cases was
seamstress, dressmaker and tailor. In a case-control study, Sobel found that
electromagnetic field exposure was associated with the occurrence of AD (70).
Feychting et al (19) indicated that magnetic field exposure during the last occupation
was a risk factor for dementia (not caused by a single stroke). The last occupation
was held an average of over 20 years. Consequently exposure was over a significant
period of time. For the last occupation, the odds ratios for all types o f dementia
combined in the highest exposure category was increased about 3 to 4 -fold in using
different reference groups (P < 0.05), and for AD was increased about 2 to 3 -fold
(P > 0.05). A age -specific analyses indicated that workers exposed to magnetic
fields during their last occupation before disease onset (age < 75 years) had a high
risk (OR-5.9, P < 0.05) of dementia including AD and 5.0 (95% Cl = 1.1-21.8) for
Alzheimer’s disease compared to workers in low-exposure occupations (19). Using
U.S. death certificates with occupational coding, Savitz et al (65) found that being a
power plant operator may increase the risk AD.
II. Cognition Dysfunction Assessment:
Factors thought to be associated with cognitive capacity include genetic makeup,
nutritional status during embryogenesis and childhood, health status, formal
education, and age-related developmental processes. This capacity generally reaches
4
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its maximum in early adulthood and then declines later in life (84). Cognitive decline
is an important public health problem that is associated with impaired physical
functioning and increased mortality and dementia (84). There are two primary
classes of screening tests for dementia: short cognitive tests and informant
questionnaires. Short cognitive tests include the Mini-Mental State Examination
(MMSE) (20), the Mental Status Questionnaire (36), the Blessed Orientation-
Memory-Concentration Test (5), the Information/Orientation Test (55), the Short
Portable Mental Status Questionnaire (57), and the Abbreviated Mental Test Score
(28). Informant questionnaires include Informant Questionnaire on Cognitive
Decline in the Elderly (33), the Short-Memory Questionnaire (39), and the
Deterioration Cognitive Observe’e (34). Assessing inter-correlation, linear equations
for converting test scores between different dementia screening/rating instruments
(e.g., the Mini-Mental State Examination, the Blessed Information-Memory-
Concentration Test, the Alzheimer’s Disease Assessment Scale, Global Deterioration
Scale, Activities of Daily Living Scale) have been developed (72). However, poor
performance on a cognitive test does not imply progressive cognitive decline. To
provide evidence of cognitive decline, the most common methods are to interpret the
cognitive test performance after considering an individual’s medical history,
education, social class and previous occupation (44) or to conduct follow-up
examinations.
5
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III. Present study:
Until now, no study with published results has investigated the relationship between
cognitive decline and electromagnetic field exposure in a large population-based
epidemiological sample. Sobel et al provided a plausible hypothesis that
electromagnetic field exposure may cause increased production o f amyloid beta and
subsequent AD onset (71). Sobel et al found that AD is statistically significantly
associated with MF exposure for primary or usual occupation (69-70). To determine
whether previous findings could be replicated among Mexican-Americans, this study
used data from the initial phase (Phase 1) of Hispanic Established Populations for the
Epidemiologic Study o f the Elderly (HEPESE) to examine the association between
very low Mini-Mental State Examination (MMSE) scores and magnetic field
exposure. Factors such as smoking, stroke, and alcohol consumption which may be
positively or negatively associated with dementia or cognitive dysfunction were
included in the analyses.
METHOD:
Study population: The subjects in this study came from the initial phase (Phase 1)
of the Hispanic Established Populations for Epidemiologic Studies of the Elderly
(HEPESE). This longitudinal study of Mexican Americans age 65 and older was
conducted in the five southwestern states o f Arizona, California, Colorado, New
Mexico and Texas during 1993 and 1994. The HEPESE was modeled after the
EPESEs conducted in East Boston, rural Iowa, North Carolina and New Haven (12).
6
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An area probability sample design was developed by listing counties in the
southwestern states by the number of Mexican Americans, in descending order, so as
to cover 90% of all Mexican Americans in that region. Moreover, counties not
chosen through this method that were at least 30% Mexican American were added to
assure inclusion of small counties with a significant percentage of Mexican
Americans. The number of Mexican Americans in the census tracts and enumeration
districts in the above counties were estimated. Three hundred census tracts were
selected as primary sampling units, providing clusters for door-to-door screening.
Systematic procedures were used to list households for screening. Interviews were
conducted with up to four Mexican Americans age 65 and older in each household.
Trained bilingual interviewers conducted in-home personal interviews. After
weighting, the 3050 male and female Mexican Americans aged 65 and older in the
sample represent the estimated 500,000 Mexican Americans aged 65 and older in the
5 states in 1993.
Differences in cognitive functions between AD and VaD: AD and vascular
dementia (VaD) are the first and the second most common types of dementia in
Western countries. O f the current clinical criteria for AD (1, 50, 62), the NINCDS-
ADRDA (National Institute of Neurological and Communicative Disorders and
Stroke and the Alzheimer’s Disease and Related Disorders Association) criteria (50)
has a better inter-rater reliability and validity among clinicians compared with other
criteria (15, 17, 40-41, 47). VaD is used most commonly to describe dementias
7
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caused by thromboembolic cerebrovascular disease and is a treatable or preventable
form of dementia o f late life (46, 63, 82). Because of its multifactorial etiology and
variable symptoms, it has been difficult to diagnosis and classify VaD. Diagnostic
protocols from the Diagnostic and Statistical Manual of Mental Disorders, 4th
edition, and the International classification of Diseases, 10th edition, are used for the
diagnosis(2, 10). The protocols have been operationalized as research criteria
(Alzheimer’s Disease Diagnostic and Treatment Centers (ADDTC), National
Institute of Neurological Disorders and Stroke-Association (NINDS) pour la
Recherch et l’Ensignement en Neurosciences (59, 81). The criteria of the first group
describe the decline in cognitive function as permanent memory loss, dysfunction in
at least one other cognitive domain (i.e., language, praxis, gnosis, constructional
ability, frontal executive function) and a significant impairment of social or
occupational function. NINDS divides VaD into six distinct entities: multi-infarct
dementia; strategic single-infarct; small-vessel disease with dementia;
hypoperfusion; hemorrhagic dementia; and other dementias. The ADDTC criteria
modify the NINDS criteria to include neuroimaging and possible, probable and
mixed categories in the diagnosis to improve compatibility with Alzheimer’s
diagnostic criteria. Neuropathologic findings suggest that mixed AD-VaD is
relatively common (16). AD and VaD can be difficult to distinguish clinically.
Different researchers may utilize different diagnostic criteria for VaD and AD. For
example, Erkinjuntti et al found low agreement o f classification o f dementia when
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different diagnostic criteria for VaD were compared on the same population (14). It
is difficult to demonstrate differences in cognitive functions between AD and VaD.
Data: Questionnaire data include sociodemographic characteristics (e.g., gender,
age at examination, years of education, family yearly income), medical histories
(e.g., has a doctor told that you had stroke or a heart attack?), lifestyle habits (e.g.,
have you ever smoked cigarettes in your life? have you ever consumed alcohol?),
Mini-Mental State Examination score and usual occupation information.
M M SE Questionaire: The test is not timed and has a maximum score of 30 (20).
See the appendix for the actual MMSE questionnaire. The MMSE has 20 short
questions:
1. “Orientation” -1 0 points:
5 points - time: what is the (year) (season) (month) (day) (date) ?
5 points - place: where are we (state) (county) (town) (building) (address) ?
2. “Registration” - 3 points:
Repeat naming of three objects
3. “Attention and Calculation” - 5 points:
Spell a five-letter word backwards
4. “Recall” - 5 points:
Recalling the 5 objects
5. “Language Skill and Construction Ability” - 7 points:
1 point - Repeat “No ifs, ands, or buts”
9
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3 points - Follow a three-stage command
1 point - Read and close eyes
1 point - Write a sentence
1 point - Copy the design
Cut-Point for the MMSE: Crum et al reported that education effects MMSE
scores and suggested cut-points for cognitive dysfunction: 19 for those with below 4
years of education, 23 for those with 5-8 years of education, 27 for those with 9-12
years of education and 29 for those with college education (76). Other studies
reported or used different MMSE cut-points to screen dementia in older populations
(7,18). Among the Mexican-American elderly, MMSE scores are generally lower
than white non-Hispanic MMSE scores perhaps due to lower literacy levels. To be
sure of actual severe cognitive dysfunction, a score below 10 on the MMSE was used
to define cognitive dysfunction. Cut-points up to 15 were later used in analyses
related to the stability o f the initial findings. Subjects who were physically ill,
recovering from illnesses in a hospital, deaf, or visually impaired and who could not
complete the MMSE were excluded if (1) they were not available for the MMSE (2)
their partial score was below 10 but the total score could have been above 10 if they
were given full credit for all unanswered questions.
Occupational EMF exposure data: Occupational data included information
regarding the usual-type of work, the primary tasks, and the job titles. The
quantitative criteria for classifying occupations with high or medium MF exposure
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were: a high MF exposure occupation is one with an average exposure above 10 mG
or regular intermittent exposure above 100 mG; a medium exposure occupation is
one with an average exposure between 2 and 10 mG or regular intermittent above 10
mG (69). Each occupation was blindly classified, i.e., the Mini-Mental State
Examination scores of the subjects were unknown by the classifier (E. Sobel).
Implementation of the classification definitions followed on previous exposure
assessment studies and duplicated the implementation in Sobel et al (69-70) and
Davanipour et al (71).
Procedure for Statistical Analyses: SAS statistical software and Epilog Plus were
used to estimate ORs, P-value and 95% confidence intervals (CIs). Variables were
checked for consistency and missing data. Initial descriptive statistical analyses
were conducted using all subjects and then subjects with both MMSE and MF
exposure data. For examination o f the association between likely MF exposure and
MMSE, as well as possible confounding factors (e.g., gender, age, years of
education, family yearly income, histories of heart attack and stroke, alcohol
consumption and smoke cigarettes), the following numerical values for each ordinal
or categorical variable were used: gender (e.g., male = 0, female = 1); MMSE (e.g.,
1 for <10, 0 for >= 10); EMF (e.g., low = 0, medium = 1, high = 2); family yearly
income (e.g., 1 for < $10000, 0 for > - $10000); years of education (e.g., 0 for >= 12,
1 for < 12); ever regularly smoked cigarettes, alcohol consumption and heart attack
and stroke (e.g., no = 0, yes =1). Dichotomized versions of both MMSE score and
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MF occupational classification were used to calculate crude odds ratio for other
variables to identify possible confounders. All P-values for the association between
dichotomious variables were calculated using Fisher’s two-sided exact test with
P < 0.05 for significance. To determine whether the association between MF exposed
occupations and MMSE scores was modified by gender or age, the odds ratios of low
MMSE score for MF exposed occupations within age (such as 65-74, 75-84, 85+,
75+, 65+) and gender categories (such as men, women, men and women) were
determined. In multivariate modeling, stepwise, forward logistic regression was used
to examine odds ratios of low MMSE score (<10 vs. >= 10). The risk factors
(subject’s age at examination, sex, income, education, previous stroke, ever having
smoked? ever having drunk any type of alcohol? previous heart attack? MF
exposure) were considered in model. Further analyses were also limited to subjects
75 and older. Model parameters were estimated by the maximum likelihood method.
Risk factors/confounders were incorporated into the multivariate models if their
significance was 0.05 or below. Two-sided significance tests and confidence
intervals were used. The Maentel-Haenszel chi-square test was used to examine
whether there was an-increasing trend o f severe cognitive dysfunction with
increasing MF exposure. Using Epilog Plus software, odds ratio, 95% confidence
intervals and, for the Mantel-extension test for trend, two-sided P-values in
multivariate models were calculated.
12
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RESULTS:
Table 1 provides the descriptive statistics for the 3050 Mexican-American elderly
subjects. Of the subjects, 57.6% were women. 65.6% were 65-74 years old, 1.7%
had a MMSE score below 10. The distributions of MMSE score of 10 or higher were
1.9% (10-14); 8.9% (15-19); 32.2% (20-24); 55.3% (25-30). 177 (5.8%) of the
subjects had a missing MMSE score. 2179 (71.4%) subjects had occupational
information; 89% were classified as low MF exposure, 6.3% as medium MF
exposure and 4.7% as high MF exposure. 820 (26.9%) women and 51 (1.7%) men
did not have an occupation listed. The plurality (41.5%) of subjects had a yearly
family income between $5001-$9999. This study population had a relatively low
education: 61.7% did not complete the 6th grade Approximately 11% of the subjects
had a history of myocardial infarction, while 6.7% had a history of stroke. 45.8% of
the subjects had consumed alcohol and 41.4% had smoked regularly (likely to be
mostly men) in their life. The distributions of age, total MMSE score, occupational
MF exposure, family yearly income, histories o f heart attack and stroke for 2058
subjects with occupational data were not statistically significantly different from the
distributions for all 3050 subjects (P>0.05). There were statistically significant
differences between men and women within 2058 subjects (P<0.05) for occupational
MF exposure, family yearly income, education, having ever drunk any type of
alcohol and having ever-smoked regularly.
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Table 1: Descriptive statistics for entire sample and 2058 subjects with occupational information and
MMSE score in Phase 1 of the HEPESE study._____________ _ _ _ _ _ _ _ _ _ _ ________
Attribute GroupAa Group Bb P-
value0
P-
valued N(%) N(%)
Gender Men 1292 (42.4) 1149 (55.8)
0.0001 Women 1758(57.6) 909(44.2)
Age at
examination
(years)
65-74 2002 (65.6) 1373 (66.7)
0.1622 0.7215
75-84 834 (27.3) 568 (27.6)
85+ 214(7.0) 117(5.7)
Total MMSE
score
<10 49(1.7) 29(1.4)
0.4036 0.6570
>=10 2824 (98.3) 2029 (98.6)
Missing 177 (— ) 0(0)
Occupational
EMF exposure
Low 1940(89.0) 1829 (88.9)
0.8700 0.0003
Medium 137(6.3) 131 (6.4)
High 102(4.7) 98 (4.8)
Missing 871 (— ) 0 (0)
Family yearly
income
$0-$5000 432 (15.9) 256 (13.6)
0.0793 0.0001
$5001-$9999 1129(41.5) 795(42.3)
$10000-
$14999
649 (23.9) 451 (24.0)
$15000-
$19999
299(11.0) 224(11.9)
$20000+ 211 (7.7) 153 (8.1)
Missing 330 ( — ) 179 ( — )
Education 0-5m grade 1853 (61.7) 1187 (58.3)
0.0082 0.0003
6-9th grade 754(25.1) 540 (26.5)
>=10* grade 395 (13.2) 310(15.2)
Missing 48 ( - - ) 21 ( ~ )
Ever drunk any
type of alcohol
Yes 1393 (45.8) 1130(54.9)
0.0001 0.0001
No 1648 (54.2) 927 (45.1)
Missing 9 ( —)
l ( - )
Ever had heart Yes 333 (11.0) 225(11.0)
attack No 2703 (89.0) 1824(89.0)
Missing 14 ( — ) 9 ( - )
0.9888 0.0559
Ever had stroke Yes 204 (6.7) 120 (5.8)
No 2839 (93.3) 1937(94.2)
Missing 7 ( — ) l ( - )
0.2057 0.0840
Ever smoked Yes 1258 (41.4) 999 (48.6)
regularly No 1783 (58.6) 1057(51.4)
Missing 9 ( — ) 2 ( — )
0.0001 0.0001
a: Entire sample
b: 2058 subjects with occupational information and MMSE score
c: Test o f difference between group A and group B
d: Test of difference between men and women for 2058 subjects with occupational information
and MMSE score
Table 2 describes the respondent status for subjects with completed questionnaire
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data by MMSE score. 94.81% o f the entire sample completed the questionnaire by
themselves. 49 (1.6%) subjects with a MMSE score of 9 or lower could not provide
answers by themselves and had proxy assistance. 156 (5.1%) subjects with missing
MMSE scores needed a proxy, but not necessarily because of their cognitive status.
A total o f 316 (10.4%) subjects had proxy assistance. The reasons for a proxy were
as follows: physical illness or recovering from hospitalization (97, 3.2%); deafness
(20, 0.7%); away indefinitely (46, 1.5%); mental incapacitation or more than 13
errors on the MMSE (73, 2.4%); no accessibility (80, 2.6%) (data not shown). In
addition, 815 had MMSE scores but were without occupational data, 121 subjects
had occupational data but were without MMSE scores and 56 subjects were without
both.
Table 2: Respondent status for subjects while completed questionnaire data by MMSE score in Phase
1 of the HEPESE study, 1993-1994. ___________ __________________________________________
Status All of 3050 subjects
Respondent only Proxy only Self and Proxy
N % N % N %
Total MMSE >=10 2724 94.9 0 0 100 3.48
Total MMSE < 10 0 0 0.73 28 0.97
Missing 10
—
156
—
11
—
Status 2058 subjects with occupationa data
Respondent only Proxy only Self and Proxy
N % N % N %
Total MMSE >=10 1966 95.53 0 0 63 3.06
Total MMSE < 10 0 0 ................f ............ 0.34 22 1.07
Missing 0 0 0 0 0 0
* These subjects could not comprehend any part o f the MMSE or missed at least 13 questions
on the MMSE and missed enough of the MMSE questions to MMSE score below 10.
Table 3 lists the job titles for the entire sample and for the 2058 subjects with
MMSE scores associated with medium or high MF exposure. The major occupations
o f subjects with medium MF exposure were carpenter and machine operator. The
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major occupations of subjects with high MF exposure were seamstress and welder.
For the subjects in the analyses (i.e., with MMSE score) with medium or high MF
exposure, the distribution of job title was similar to the distribution for the entire
sample.
Table 3: List job title for total 3050 subjects and 2058 participant subjects with M/H EMF in Phase 1
of the HEPESE study, 1993-1994. ___________ ____________________________________
EMF Job 3050 subjects 2058 subjects
N (239) N (229)
Medium Beautician 2 2
Carpenter 34 32
Clothes inspector in manufacturing company 4 4
Electric Lineman 1 1
Electrician 7 7
Electronic Technician 1 1
Electronic Assembler 2 2
Equipment Repair 7 7
Fabric Cutter 1 1
Foam Cutter 1 1
Forklift Operator 6 6
Furniture Maker 4 4
Machine Operator 27 27
Machinery Repair 3 3
Machinist 8 5
Newspaper Pressman 1 1
Presser in clothing manufacturing company 2 2
Seamstress-part time 3 3
Sheet mental machine operator 4 4
Shoemaker 5 5
Typist 2 2
Upholstery; Re-upholstery 4 4
Welder-part time 5 4
Wood cutter; machinery repair-forestry 1 1
Wood Sander-fumiture 2 2
High Cutter (cloth) 2 1
Power plant operator (power man) 1 1
Repair sewing machine 1 1
Seamstress 84 83
Welder 14 12
The unadjusted crude odds ratios (ORs) for MF exposure, age, gender, household
yearly income, history o f stroke or heart attack, alcohol consumption and ever
R eproduced with perm ission of the copyright owner. Further reproduction prohibited without perm ission.
smoked regularly in life are provided in Table 4. The unadjusted OR of high MF
exposure vs low MF exposure was 4.22 (95 %CI = 1.57-11.35; P = 0.012). The
increasing MF exposure was associated with statistically significant higher risk (P
for trend = 0.012). The unadjusted OR for age 75+ vs. age 65-74 was 5.70 (95% Cl
3.23-10.70; P = < 0.001); the unadjusted OR for ever having had a stroke vs never
having had a stroke was 5.04 (95% Cl = 2.70-9.42; P = <0.001).
Table 4: Crude odds ratio between risk factor and total MMSE in Phase 1 o f the HEPESE study,
1993-1994.
Univariable status Total MMSE score
OR 95% Cl P-valuea
# of >=10 # o f <10
MF exposure Low 1806 23
Medium 130 1 0.60 0.08-4.51 1.000
High 93 5 4.22 1.51-11.35 0.012
P for trend b = 0.012
Sex Male 1181 16
Female 1643 33 1.48 0.81-2.71 0.242
Age 65-74 1903 13
75+ 923 36 5.70 3.23-10.70 <0.001
Education >= 12 274 5
< 12 2550 44 0.95 0.37-2.41 0.809
Household yearly >=$10000 1068 25
income < $10000 1484 16 0.46 0.25-0.87 0.014
Ever had heart No 2521 41
attack Yes 292 8 1.69 0.79-3.60 0.233
Ever had stroke No 2663 37
Yes 157 11 5.04 2.70-9.42 <0.001
Ever smoked No 1658 26
regularly Yes 1162 23 1.26 0.72-2.22 0.465
Ever drunk any No 1543 29
type of alcohol Yes 1277 20 0.83 0.47-1.48 0.565
a: 2-sided Fisher’s exact test b: Maentel-Haenszel Chi-Square test for trend
17
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Table 5 describes the dichotomized MMSE scores by gender within age group.
Among female subjects aged 65-74, 0.8% of those with likely low MF exposure had
an MMSE score below 10. None of the 64 subjects with either likely medium or
high MF exposure had an MMSE score below 10. The distributions of MMSE score
by MF exposure classification for males were similar to those for females. Among
female subjects aged 75-84, 1.7% of those with a likely low MF exposed occupation
had an MMSE score below 10. None of the 11 with a likely medium MF exposed
occupation had MMSE scores below 10, while 3 (11.1%) of those with a likely high
exposed occupation had an MMSE score below 10. Among male subjects’ aged
75-84, 2.2% of those with likely low MF exposure had an MMSE score below 10; 2
(7.1%) of the 28 subjects with likely medium or high MF exposure had MMSE
below 10. For females aged 85 or above, 4.9% of the 69 subjects with likely low MF
exposure had MMSE scores below 10; 1 (33.3%) of 3 with likely medium or high
MF exposure had an MMSE score below 10. For males aged 85 or above, 5.9% of
those with likely low MF exposure had an MMSE score below 10, and none of the 4
subjects with likely medium or high MF exposure had an MMSE score below 10.
18
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T able 5: MMSE scores by gender within age group in Phase 1 o f the HEPESE study. 1993-1994.
Characteristic MF
classification
MMSE score (%) Total
Age group =65-74
Women
<10 >=10
Low
Medium
High
4 (0.8)
0 (0 )
0 (0 )
526 (99.2)
13 (100)
51 (100)
530
13
51
Men Low 3 (0.4) 684 (99.6) 687
Medium 0 (0 ) 77 (100) 77
High 0 (0 ) 15(100) 15
AgejrouE = 75- Low 4(1.7) 229 (98.3) 233
84 Medium 0 (0 ) 11 (100) 11
Women High 3(11.1) 24 (88.9) 27
Men Low 6 (2.2) 263 (97.8) 269
Medium 1(4.0) 24 (96.0) 25
High 1 (33.3) 2 (66.7) 3
Age group = 85+ Low 2 (4.9) 39(95.1) 41
Women Medium 0(0 ) 1 (100) 1
High 1 (50.0) 1 (50.0) 2
Men Low 4 (5.8) 65(94.2) 69
Medium 0 (0 ) 4(100) 4
High 0(0 ) 0(0 ) 0
All Age grouns Low 10(1.2) 39 (98.8) 804
Women Medium 0(0 ) 25 (100) 25
High 4 (5.0) 76 (95.0) 80
Men Low 13 (1.3) 1012 (98.7) 1025
Medium 1 (0.9) 105 (99.1) 106
High 1(5.6) 17(94.4) 18
Table 6 provides odds ratio (OR) estimates by gender. For female subjects, the OR
for high MF exposure was 4.18 (95 %CI = 1.28-13.64, P = 0.031). Among male
subjects, only 1 subject with likely medium MF exposure and 1 subject likely high
MF exposure had an MMSE score below 10. Thus, the ORs were not statistically
significant.
19
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Table 6: Odds ratio of severe cognitive dysfunction associated with MF exposure by gender in
Phase 1 o f HEPESE study, 1993-1994. ___________ __
Exposure Totmmse >=10 Totmmse < 10 OR 95 % Cl P-valuea
Women
L 794 10
M 25 0 0 1.000
H 76 4 4.18 1.28-13.64 0.031
M/H 101 4 3.15 0.97-10.21 0.067
Men
L 1012 13
M 105 1 0.74 0.10-5.72 1.000
H 17 1 4.58 0.57-37.01 0.218
P for trend b = 0.426
M/H 122 2
1.28 0.29-5.72 0.672
Men and
Women
L 1806 23
M 130 1 0.60 0.08-4.51 1.000
H 93 5 4.22 1.57-11.35 0.012
P fo r trend b = 0.C 12
M/H 223 6
2.11 0.85-5.24 0.127
a: 2-sided Fisher’s exact test
b: Mantel-Haenszel Chi-Square test for trend
Table 7 provides odds ratios by age groups. Among subjects’ aged 65-74, none of
subjects with medium or high MF exposure had MMSE score below 10. Thus, the
odds ratios were 0. Among those aged 75-84 (OR = 7.57 for high MF exposure, 95%
Cl = 2.22-25.76) or age of 75+ (OR = 6.90 for high MF exposure, 95% Cl = 2.35-
20.23) or age 65+ (OR = 4.22 for high MF exposure, 95% Cl = 1.57-11.35),
increasing MF exposure was associated with significantly higher risk.
2 0
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Table 7: Odds ratio of severe cognitive dysfunction associated with MF exposure by age groups in
Phase 1 of HEPESE study, 1993-1994.______________________________________
Ages Exposure Totmmse
>= 10
Totmmse
< 1 0
OR 95% Cl P-
value
65- L 1210 7
74 M 90 0 0 1.0
H 66 0 0 1.0
M/H 156 0 0 1.0
75- L 492 10
84 M 35 1 1.41 0.18-11.30 0.537
H 26 4 7.57 2.22-25.76 0.006
P for trendb = 0.001
M/H 61 5 4.00 1.33-12.19 0.022
85+ L 104 6
M 5 0 0 1.0
H 1 1 17.33 0.96-312.32 0.122
M/H 6 1 2.89 0.30-28.0 0.358
75+ L 596 16
M 40 1 0.93 0.12-7.20 0.946
H 27 5 6.90 2.35-20.23 0.003
P for trendb = 0.001
M/H 67 6 3.34 1.36-8.81 0.022
65+ L 1806 23
M 130 1 0.60 0.08-4.51 1.0
H 93 5 4.22 1.57-11.35 0.012
P for trendb = 0.012
M/H 223 6 2.11 0.85-5.24 0.127
A: 2-sided Fisher’s exact test B: Mantel-Haenszel Chi-Square test for trend
Table 8 describes the odds ratio estimates, 95% confidence interval and P-value of
risk factors in multivariate analyses for both sexes and for men and women
separately. Among subjects with age 75+ or 65+, the risk associated with MF
exposure was statistically significantly associated with severe cognitive dysfunction
for men, women or both, respectively (P<0.05) after adjustment for age, history of
stroke and history of smoking as appropriate.
21
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Table 8: Odds ratio (OR) o f severe cognitive dysfunction associated with MF exposure, age,
medical history of stroke and having ever smoked in the initial phase (Phase 1) of the Hispanic
Established Populations for Epidemiologic studies of the Elderly (HEPESE), 1993-1994 .
Subjects’ age at examination 75+ 65+
Sub Main effect ORa 95% Cl P- ORa 95% Cl P-
group value value
MF Low 1 1
exposure Medium 1.04 0.13-8.42 0.9728 0.61 0.08-4.63 0.6305
High 13.25 3.56-49.29 0.0001 5.36 1.82-15.76 0.0023
Men
and P for trend = 0.0000 P for trend = 0.0000
Women
(*) Age Per year 1.19 1.08-1.30 0.0003 1.15 1.09-1.21 0.0000
Have ever No 1 1
stroke? Yes 4.61 1.63-13.04 0.0039 3.66 1.45-9.21 0.0059
Have ever No 1 1
smoked? Yes 5.63 1.85-17.10 0.0023 2.32 1.04-5.18 0.0395
MF Low 1 1
exposure Medium 1.86 0.21-16.66 0.5793 0.99 0.12-7.97 0.9923
Men High 70.58 4.55-1093.9 0.0023 12.08 1.27-115.1 0.0303
(*)
P for trend = 0.00096 P for trend = 0.0042
Age Per year 1.20 1.06-1.36 0.0046 1.17 1.09-1.26 0.0000
Have ever No 1 1
stroke? Yes 16.30 4.10-64.86 0.0001 8.33 2.63-26.39 0.0003
MF Low 1 1
exposure Medium
— . . .
NSb
— —
NSb
High 12.87 2.71-61.20 0.0013 4.98 1.46-17.01 0.0105
Women
P for trend < 0.05 P for trend <0.001
Age Per year 1.20 1.04-1.39 0.0135 1.14 1.05-1.23 0.0007
Have ever No 1 1
smoked? Yes 7.39 1.70-32.16 0.0077 3.11 1.04-9.27 0.0418
*: Using Epilog Plus software calculated odds ratio, 95% confidence intervals and, for the
Mantel- extension test for trend, two-sided P-values.
**: Using SAS software calculated odds ratio, 95% confidence intervals and, two-sided P-values
because of convergent problem in Epilog Plus software.
a Adjusted for the other factors included in the table for men, women, men and women,
respectively.
bNS: not significant
22
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DISCUSSION:
The 3050 Mexican-American elderly subjects in this study are representative of 90
% o f the Mexican-Americans elderly group in the United States. 61.7% of this
population did not complete the 6th grade.
The MMSE is a quick cognitive function screening tool. Repeated use is helpful in
establishing declining cognitive function. The MMSE has limitations including its
dependence on verbal skills to communicate the test instructions and the different
degrees o f sensitivity o f its various items (21). Grigoletto et al showed that elderly
Italian women with a low educational level have significant problems with taking the
MMSE. It is thus important to account for age, gender and education (48). Lopez et
al used an MMSE score of 9 or lower as the cut-off points in their study because this
point could represent o f moderate to severe AD (58). This study uses the same
MMSE cut-point to determine severe cognitive dysfunction for the following
reasons. There are three demonstrable normative influences on MMSE scores - age,
education and ethnicity. Between ages 50 and 70, the 'average' MMSE score declines
roughly 1.25 points for each successive decade of life. After age 70, the 'average'
MMSE score decline is above 3 points per decade (66, 76-77). Persons with low
education are less able to earn an income sufficient for maintaining good nutrition
and health. To minimize the number o f false positive findings of severe cognitive
dysfunction, a cut-point of 10 on the MMSE is conservative even for this low
education, low income, elderly population.
23
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Stroke may also cause cognitive impairment and the domains most likely to be
affected are memory, orientation, language and attention (79). In the HEPESE
population, 7 (5.8 %) of the 120 subjects with a stroke, who also had an MMSE
score and occupational information, had MMSE scores below 10. For all ages 65+,
the risk factors identified in the multivariate analyses were age, MF exposure, stroke
history, and ever smoked regularly. This was not the situation for age 75+: for
women, a history of stroke was not significant; for men, a history of smoking was
not significant.
Some epidemiological studies reported that there was a negative association
between smoking and AD, possibly because nicotine might be protective against AD
(6, 27, 29). However, other studies reported that daily smokers had a significantly
higher risk than never smokers (24, 67). For persons with low education and no
history o f hypertension, an increasing number of pack-years was associated with an
increased risk of AD (29). In the Hebert et al study, there was a non-significant
association between AD and smoking after adjusting for age, sex and education (37).
The Rotterdam Longitudinal Study indicated that smokers had an increased risk of
dementia (RR = 2.2; 95 % Cl = 1.3-3.6) and AD (RR - 2.3; 95 % Cl = 1.3-4.1)
compared to never smokers (54). Merchant et al also found a similar positive result
(51). In this longitudinal study, Leibovici et al did not find evidence that wine and
tobacco consumption were protective factors in AD (45). Thus, the association
between smoking and cognitive impairment has been inconsistent among previous
24
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studies.
Feychting et al found occupational MF exposure to be related to dementia (not
caused by a single stroke) (19). Sobel and Davanipour mentioned that MF exposure
might act independently or synergistically with the ApoE s4 isoform to cause
sporadic AD (71). Kalmijn et al found that cerebrovascular disease and ApoE s4
might be synergistically related to cognitive impairment. Carriers of the ApoE s4
gene have an increased risk of heart disease, stroke and cognitive impairment in
certain age groups. The present study found that smoking, high MF exposure, and
having had a stroke are joint risk factors for severe cognitive impairment. However,
this study could not examine the possible association between MF exposure and
cognitive impairment after considering the possible modifier effect(s) of ApoE e4.
Thus, a future study should examine the association between sporadic AD and MF
exposure among those with the ApoE s4 or s3 alleles.
25
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APPENDIX:
Questionnaire (Cognition-MMSE):
The questions are about memory. The questions may seem unusual, but they are
routine questions we ask of everyone. Some of the questions are very easy and some
are difficult, so don’t be surprised if you have trouble with some of them. (If refuse
to answer record as error).
1. What is the year? (probe if don’t know; It is ok to guess.)
_______ Year Correct—(67(____-1 Error— _ _ _ _ _ _ - 0
(65-66)
2. What is the season? ( Do not read list)
Spring--------------------------(68( -1 Correct— (69( -1
Sum m er---------- -— —------- _ _ _ _ _ -2 , E rror - 0
F all--------------------------------- -3
W inter------------- -4
Don’t know ; — _ _ _ _ _ -8
Refused---------------------------- -9
3. What is the month?
January ------- -— (70( -1 Correct— (72(____ -1
February----------------------- -2 . E rror------------------- --0
M arch-------------------------------- -3
A pril--------------------------— -4
M ay ---------------------------- -5
June---------------------------- -6
Ju ly ----------------------------- -7
A ugust------------------ -8
September------------------- -9
October --------------- -0
November--------------- (71(______ -1
Decem ber--------------------- -2
Don’t know ------------------- -8
R efused — -9
4. What is the date?
Date: (day) Correct— (14(_____-1 Error— ______-0
5. What is the day of the week?
M onday------------------------------- (15( _ _ _ _ _ -1
3 4
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Tuesday ----------- --------------------- ------------ -2 Correct — (16( _ _ -1
W ednesday------------------------------------------ -3 E rror------------ -0
Thursday —-----------------------------_ _ _ _ _ -4
F riday------------------------------------ ------------ -5
Saturday------------ ------------------- - ------------- -6
Sunday— . — ------------------------ ------------ -7
Don’t know —--------------------------_ _ _ _ _ _ -8
R efused----------------— -------------------------------9
6. Can you tell me where we are right now? For instance, what state are we in?
A rizona_________________ (17(___ -1
California----------------------------------2 Correct------(18(____ - 1
Colorado----------------------------- _ ---- - -3 E rror______ —____ - 0
New M exico---------------------- ------- - 4
T exas------------------------------- ----------5
Other (specify)------------ ------- ----------6
Don’t know ----------------------- --- ----- -8
Refused---------------------------------------9
7. What county are we in?
County:_____ ____________ Correct — (64( _ _ _ -1 Error — - 0
8. What (city/town) are we in?
C ity:_____________________ Correct — (54( -1 Error — - 0
9. What floor of the building are we in?
_ _ _ _ _ _ _ (55-57) floor
Basem ent------------------------- (58(___-1 Correct---------(59(_____-1
Ground level----------------------------- -2----- E rror----------------------- - 0
Don’t know ------------------------------ -8
Refused----------------------------------- -9
10. What is this address? (You only need street address - If they refuse to answer
record as error)
Address:
Correct — (54( -1 Error— ______ -0
11. I’m going to name three objects. After I have said them, I want you to repeat
them. Remember what they are because I am going to ask you to name them
again in a few minutes.
35
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“ Apple” “Table” “Penny”
(Clearly and slowly, about one second for each. After you have said all three, ask
respondent to repeat the words. The first repetition determines their score, but
continue saying them (up to 6 repetitions) until respondent can repeat all three. If
refuses to answer record as error. )
Record answers Correct Error
From 1st trial
a. A pple---------------------- (55( -1 -0
b. T able----------------------
(56( -1 -0
c. Penny---------------------
.................... (57(
-1 -0
Record number o f trials:
12. Now I’d like you to spell a word for me. The word is “world”. (If respondent is
unable to spell the word “world”, spell it for him/her.) Now please spell the word
“world” backwards.
D L R O W
(59 - 63)
Letters in correct order: 1 ----- (64(____ -1
None — ___ - 0
Refused —___ -9
13. Now what were the objects I asked you to remember? (If refuses to answer
record as error.)
Record answers Correct Error
a. A pple------------------------------ _ ---------------------- (65( _ _ - 1 -0
b. Table____________ (66(______-1 -0
c. Penny------------------------------------- _-- (67(___ -1 -0
36
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14. What is this called? (If respondent says “wristwatch” or “watch”, count as
correct. If refuses to answer record as error.) If “clock” probe: Is there another
word for it? Then if only response is clock, code as error.
Correct Error
W atch-------------------------------(68(____ -1 -0
If unable to do record reason:
B lind-------------- (69( ____ -1
Other (specify)
-2
Show respondent a pencil and ask:
15. What is this called? (If refuses to answer record as error.)
Correct Error
Pencil — -------------------------- (70(_____ -1 _ _ _ _ _ -0
If unable to do record reason:
B lind--------------- (71(_____ -1
Other (specify)
-2
16. I’d like you to repeat a phrase after me. The phrase is (read them). (Allow only I
trial. Code “correct” requires an accurately articulated repetition., Code correct if
“s” are dropped.)
Correct Error
No i f s, and’s, or but’s -----------------(72(______ -1 -0
Show respondent the card that has printed on it “close your eves”.
17. Please read the words on this card and then do what it says, (code “correct” if
participant closes eyes.)
Correct Error
Close your ey es---------------------- -----( 7 3 (______-1 _ _ _ _ _ -0
If unable to do record reason:
Blind — ------------------------ (74(_____ -1
Other (specify)
2
37
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Read the following statement and then hand the respondent a blank piece of
paper with both hands.
18. Please listen carefully to the following instructions. I’m going to give you a piece
o f paper. When I do, take the paper in your right hand, fold it in half with both
hands, and put it on the floor. (Do not repeat instruction or coach.)
Interviewer observation Correct Error
a. Takes paper in right hand----------------- ( 0 8 (_____ -1
b. Folds paper in h alf.------------------------ (0 9 (_____ -1
c. Puts paper down on the floor-------------(10 ( _____ -1
If unable to do record reason:
Paralyzed------
Am putee-------
Other (specify)
Give respondent a piece of paper and a pen or pencil and ask the following:
19. Please write a complete sentence on the piece of paper. ( must have a verb and a
subject and make sense. Spelling and grammatical errors are ok.)
Correct Error
Full sentence correctly written —-------—— (12 (____ -1 _____-0
If unable to do record reason:
B lind--------------------—- (13( -1
Illiterate------------------------- ----------2
. Paralyzed------------------------- _____ -3
Other (specify)
_4
Hand respondent drawing holding it with left pentagon pointing up
20. Here is a drawing. Please copy it exactly on this sheet of paper. (Must have all 10
angles and two pentagons must intersect. Tremor and rotation are ignored.)
Correct Error
Diagram correctly copied -------(14 (_____-1 -0
38
(H (_ -1
-2
-3
-0
-0
-0
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If unable to do record reason:
Paralyzed-------------- ; -------- (15 (_____-1
Am putee----------------------- ----------------2
Other (specify)
----------------- ----- ----------3
Interviewer: Scoring MMSE - Award 1 point for each item correct in Q.l
Q.20. On Q. 12, award 1 point for each letter that is correct.
MMSE SCORE_______________
IF 18+, proceed with respondent.
If 17 or less, follow procedures for proxy interview.
R eproduced with perm ission of the copyright owner. Further reproduction prohibited without perm ission.
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Tseng, Chiu-Chen
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Cognitive dysfunction and occupations with likely significant magnetic field exposure: A cross-sectional study of elderly Mexican Americans
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Applied Biometry
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