Building Cognitive Resilience Against Alzheimer's Disease Through Multilingualism

273 Pages·2017·2.57 MB·English

by  Sanduni Costa

Building Cognitive Resilience Against
Alzheimer’s Disease Through Multilingualism

by

Sanduni Costa

A thesis
presented to the University of Waterloo
in fulfillment of the
thesis requirements for the degree of
Master of Science
in
Public Health and Health Systems

Waterloo, Ontario, Canada, 2017
©Sanduni Costa 2017
Author’s Declaration
I hereby declare that I am the sole author of this thesis. This is a true copy of the thesis,
including any required final revisions, as accepted by my examiners.
I understand that my thesis may be made electronically available to the public.

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Abstract
Background: Globally, there are 9.9 million new cases of dementia each year, meaning one
new case is diagnosed every 3.2 seconds (Prince et al., 2015). The risk of Alzheimer’s
disease (AD) increases with increasing age, and so with the rising aging population, the
prevalence of AD is projected to increase in the years to come. Cognitive resilience has been
a focus of preventative strategies against AD/dementia as cognitive resilience is hypothesized
to delay or prevent the onset of clinical symptoms of dementia despite the presence of
Alzheimer neuropathology (see review by Stern, 2002). Cognitive resilience has two
components: cognitive reserve refers to an ‘active’ process of using neural networks
efficiently to compensate for brain damage, and brain reserve relies on structural advantages
within the brain that increase the capacity to tolerate brain damage. Multilingualism (i.e.,
speaking more than one language) may contribute to cognitive resilience against
dementia/AD, as it can improve cognitive flexibility and executive function through constant
switching between languages and the use of inhibition and attention control.
Objectives: The first two objectives of this study were to investigate whether there was an
association of cognitive resilience with (1) multilingualism or (2) type of language. The
second two objectives of this study were to explore whether (3) cortical atrophy (an indicator
of brain reserve) or (4) education (an indicator of cognitive reserve) modified the association
of cognitive resilience with multilingualism or type of language.
Methods: Data were used from the Nun Study, a longitudinal study on aging with religious
sisters, aged 75+ at baseline. Multilingualism was determined through convent archival
records. Neuropathological diagnosis of AD was based on both Consortium to Establish a
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Registry for Alzheimer’s Disease (CERAD) and the National Institute of Neurological
Disorders and Stroke-Alzheimer’s Disease and Related Disorders Association (NIA-RI)
criteria. Dementia status was assessed by the Diagnostic and Statistical Manual of Mental
Disorders (Fourth Edition) criteria at the last cognitive assessment before death. Analyses
included logistic regression models adjusted for the presence of apolipoprotein E-ε4 allele,
age at death, education, primary language, and immigration status. Firth regression was used
to test for interactions between the exposure variables and cognitive resilience and for any
subsequent stratified models.
Results: Speaking four or more languages (versus speaking fewer languages) was
significantly associated with cognitive resilience based on NIA-RI criteria only, and
remained so after adjusting for all of the covariates (OR=5.00, 95% CI=1.08-27.56).
Speaking German significantly reduced the likelihood of cognitive resilience based on
CERAD criteria only, even after adjusting for all covariates (OR=0.50, 95% CI=0.27-0.94).
With respect to ceiling and floor effects, adjusting for education or atrophy in multivariable
models did not cause any substantial changes to the association between multilingualism and
cognitive resilience. When using type of language as an exposure variable, adjusting for
education did not substantially change the association between type of language and
cognitive resilience; however, when adjusted for atrophy the statistically significant
association observed between speaking German and cognitive resilience became
nonsignificant (OR=0.55, 95% CI=0.27-1.09). Lastly, no statistically significant associations
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were observed between multilingualism or type of language and cognitive resilience when
stratified by education or the presence of atrophy.
Discussion: Overall, speaking four or more languages significantly increased the likelihood
of cognitive resilience. However, no evidence of a benefit of bilingualism on cognitive
resilience was observed in this study. Previous research indicates that only the studies that
were cross-sectional and had used a clinic-based sample observed a bilingual benefit, while
studies that were longitudinal and had used a population-based sample found a protective
effect against dementia, only when higher number of languages were spoken. Since this
current study was longitudinal and had used a population-based sample, the findings were
consistent with the previous studies that did not observe a bilingual benefit against dementia.
Other than the methodological differences, this current study perhaps did not observe a
bilingual protective effect because of the measure of multilingualism used, which was less
stringent than in some previous studies. For example, the participants in this study only had
to self-report the number and the type of languages they were proficient in and thus, this
study could not incorporate other important aspects of multilingualism, such as reading
ability, language comprehension, frequency and intensity of language use, and age at
language acquisition, in the assessment of multilingualism. However, this current study did
use a stringent measure of the outcome, cognitive resilience, based on both the dementia
status at the last cognitive assessment and the presence of Alzheimer neuropathology.
Moreover, after controlling for various confounders, such as the presence of apolipoprotein
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E-ε4 allele, age at death, education, primary language, and occupation, a significant benefit
from speaking four or more languages on cognitive resilience was still observed.
Secondly, previous research has shown mixed findings on the cognitive benefits of
linguistically similar or linguistically dissimilar languages, where there have been studies that
observed cognitive benefits from speaking either similar or dissimilar languages or no
significant cognitive benefits at all. Because the outcomes of most previous studies were on
cognitive benefits rather than on dementia/AD/cognitive resilience, the findings from
previous studies cannot be extrapolated fully to the findings from the current study. Although
speaking similar languages has been found to benefit cognition presumably because of
greater levels of cross-linguistic interference experienced while speaking, in this current
study, speaking similar languages such as German and English did not significantly
contribute to cognitive resilience. While speaking German and English was initially shown to
significantly reduce the likelihood of cognitive resilience, since German speakers in this
study had higher levels of atrophy present than those who spoke other type of languages, it is
likely that the presence of atrophy instead of speaking the German language itself was
responsible for reducing the likelihood of cognitive resilience.
Finally, when the models were adjusted for atrophy or education to explore the floor
and ceiling effects, respectively, no substantial changes were observed between
multilingualism and cognitive resilience. Between the type of language spoken and cognitive
resilience, only the significant association between speaking German and cognitive resilience
became nonsignificant, as a higher number of German speakers had atrophy present. As there
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were no significant interactions between the exposure variables and atrophy or education and
no significant trends supporting a ceiling or floor effect were observed in the stratified
analyses, this current study did not provide supportive evidence for the presence of a ceiling
or floor effect for cognitive resilience.
Overall, speaking four or more languages was shown to increase the likelihood of
cognitive resilience, whereas there was no evidence of benefit of speaking two or three
languages on cognitive resilience. Since those who spoke four or more languages were likely
to have experienced higher levels of intellectual stimulation than those who spoke fewer
languages, the results may indicate that a higher degree of intellectual stimulation is the
underlying factor that is required to significantly build up cognitive resilience. It is also
possible that those who spoke four or more languages were different in the sense that they
had higher levels of intelligence or had a greater tendency to engage in intellectually
stimulating activities than those who spoke fewer languages. Moreover, the context within
which the languages were spoken might have influenced the results. In addition, this research
project did not find any evidence on type of language being important for contributing to
cognitive resilience; this topic has not often been studied and warrants further investigation.
Finally, multilingualism can be considered as one modifiable way to enhance cognitive
stimulation in order to build up cognitive resilience and thus reduce the impact of AD,
thereby improving the quality of life of aging populations.

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Acknowledgements
First and foremost, I praise and offer thanksgiving to the God the Father Almighty,
God the Son Jesus Christ, and God the Holy Spirit, without whose abundant graces and
blessings poured out upon me, I would not have completed this thesis. I thank my heavenly
Mother, the Blessed Virgin Mary, for her powerful intercession before God on my behalf. I
also thank all the Saints and Angels, particularly St. Jude Thaddeus, St. Anthony of Padua,
and St. Joseph for obtaining my special requests. Blessed be God forever and ever!
I thank my loving mother and father who brought me into this world and have always
been by my side with their loving care, guidance, support, countless sacrifices and prayers at
every moment of my life. I also want to thank my brother who has always been there for me
and have supported me by his advice, encouragement, and prayers. I am so thankful for
having you all in my life!
I thank my supervisor, Dr. Suzanne Tyas who has been an outstanding mentor to me
throughout my graduate studies and have provided tremendous support and guidance by her
dedication, patience, and commitment to help me complete this thesis. This thesis would not
have been possible without her. I consider myself blessed to have had such an exceptional
supervisor for my graduate studies. I also thank my committee members, Dr. Myra Fernandes
and Dr. Philip St. John who committed their time to provide valuable suggestions and advice
to help me develop this thesis.
Last but not least, I thank all my fellow graduate students in the research group for
their support and friendship throughout my graduate studies.
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Dedication
To my loving mom, dad, and brother.

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Table of Contents
Author’s Declaration ................................................................................................................. ii
Abstract .................................................................................................................................... iii
Acknowledgements ................................................................................................................ viii
Dedication ................................................................................................................................ ix
List of Figures ........................................................................................................................ xiv
List of Tables ......................................................................................................................... xiv
List of Abbreviations .............................................................................................................. xx
1.0 Introduction ......................................................................................................................... 1
2.0 Literature Review................................................................................................................ 4
2.1 Dementia ......................................................................................................................... 4
2.2 Alzheimer’s Disease ........................................................................................................ 5
2.2.1 Etiology .................................................................................................................... 5
2.2.2 Diagnosis and Treatment .......................................................................................... 6
2.2.2.1 Clinical Diagnostic Criteria for Alzheimer’s Disease ....................................... 7
2.2.2.2 Neuropathologic Diagnostic Criteria for Alzheimer’s Disease ......................... 8
2.2.2.3 Treatment ......................................................................................................... 10
2.2.3 Risk Factors ............................................................................................................ 11
2.2.3.1 Non-modifiable Risk Factors ........................................................................... 11
2.2.3.2 Modifiable Risk Factors ................................................................................... 13
2.3 Multilingualism ............................................................................................................. 22
2.3.1 Cognitive Advantages of Multilingualism ............................................................. 22
2.3.2 Cognitive Disadvantages of Multilingualism ......................................................... 26
2.3.3 Challenges Associated with Multilingualism Research ......................................... 27
2.3.3.1 Using Subjective Versus Objective Measures ................................................. 27
2.3.3.2 Frequency and Intensity of Language Use ...................................................... 28
2.3.3.3 Age of Second Language Acquisition ............................................................. 29
2.3.3.4 Typological Similarity Between Languages .................................................... 30
2.3.3.5 Measuring Outcome ......................................................................................... 32
2.3.3.6 Study Population and Study Design ................................................................ 33
2.3.3.7 External and Environmental Influences ........................................................... 34
2.4 Cognitive Resilience ..................................................................................................... 36
2.4.1 Brain Reserve ......................................................................................................... 36
2.4.2 Cognitive Reserve .................................................................................................. 37
2.4.3 Ceiling and Floor Effects of Cognitive Resilience ................................................. 38
2.4.4 Plausible Mechanisms of Cognitive Resilience...................................................... 40
2.4.5 Multilingualism and Cognitive Resilience ............................................................. 41
2.4.5.1 Neural Reserve ................................................................................................. 41
2.4.5.2 Neural Compensation ...................................................................................... 43
2.4.5.3 General Cognitive Reserve Network ............................................................... 44
2.5 Association of Multilingualism with Alzheimer’s Disease/Dementia .......................... 45
2.5.1 Sample .................................................................................................................... 45
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