RELATING IRON STATUS AND AEROBIC FITNESS TO COGNITIVE PERFORMANCE IN YOUNG ...

266 Pages·2015·3.77 MB·English

The Pennsylvania State University
The Graduate School

College of Health and Human Development
RELATING IRON STATUS AND AEROBIC FITNESS TO COGNITIVE
PERFORMANCE IN YOUNG ADULT FEMALES
A Dissertation in
Nutritional Sciences

by
Samuel P. Scott
 2015 Samuel P. Scott

Submitted in Partial Fulfillment
of the Requirements
for the Degree of
DOCTOR OF PHILOSOPHY

August 2015
The dissertation of Samuel P. Scott was reviewed and approved* by the following:

Laura E. Murray-Kolb
Assistant Professor of Nutritional Sciences, The Pennsylvania State University
Dissertation Advisor
Chair of Committee

Jere D. Haas
The Nancy Schlegel Meinig Professor Emeritus of Maternal and Child Nutrition,
Cornell University
Special Member

A. Catharine Ross
Professor and Occupant of Dorothy Foehr Huck Chair in Nutritional Sciences,
The Pennsylvania State University

Rick O. Gilmore
Associate Professor of Psychology, The Pennsylvania State University

Shannon L. Kelleher
Associate Professor, Departments of Cell and Molecular Physiology,
Pharmacology, and Surgery, Penn State Hershey College of Medicine;
Department of Nutritional Sciences, The Pennsylvania State University

Gordon L. Jensen
Professor and Head of Nutritional Sciences, The Pennsylvania State University

*Signatures are on file in the Graduate School
iii
ABSTRACT
Iron deficiency (ID) is the most prevalent single micronutrient deficiency worldwide,
with women of reproductive age (WRA) being disproportionately affected due to menstrual iron
losses. Previous research has demonstrated a critical role of iron in early-life brain development
and function but few studies have examined this relation in WRA, despite continued reliance on
neural processes shown to be impacted by iron supply such as dopaminergic signaling. Even less
evidence exists regarding whether cognitive alterations manifest during mild ID without anemia.
Similarly, though a strong link between exercise and brain health has been shown, little work has
documented how physical fitness in WRA relates to cognition, a troubling fact given that 40-50%
of WRA in the United States are physically inactive. We sought to explore interrelations between
iron status, physical fitness, cognition, and academic performance in WRA within a university
setting, where optimal cognitive functioning has direct implications for current livelihood and
future wellbeing.
This observational study involved 127 generally healthy, non-anemic females aged 18-35
years (average 22 years). Each woman underwent a blood draw to assess iron status, a maximal
exercise test to assess cardiorespiratory fitness, and five computerized cognitive tests of executive
function—Attentional Network Task, Berg’s Card Sorting Task, Go/No-Go, Sternberg Memory
Search, and Tower of London—using the Psychology Experiment Building Language platform.
The sample was selected for low ferritin levels, with 40% having Ft ≤ 12 µg/L. Fitness was
generally high, with an average peak VO of 44.5 ml/min/kg, corresponding to the American
2
College of Sports Medicine’s 80th-85th percentile for females aged 20-29 years in the United
States.
After controlling for a set of potential covariates, results suggested that executive
function remains largely intact in mild ID, with one exception being planning ability as measured
iv
using the Tower of London task. Positive associations were found between fitness and
performance measures on four of the five cognitive tasks, suggesting that fitness widely benefits
executive ability. No added cognitive benefit of concurrent high iron status and high physical
fitness was found. However, grade point average (GPA) was positively associated with both iron
status and fitness such that a group with concurrent ID and lower fitness had the lowest GPA,
whereas a group with concurrent iron sufficiency and higher fitness had the highest GPA.
Furthermore, better academic performance was found in women with higher scores on a latent
factor representing high-level executive processes.
In conclusion, this study has expanded the knowledge base in two underexplored areas
with public health relevance: how both mild ID and physical fitness impact cognition in healthy
young adult females. Our findings support earlier work showing that most cognitive components
remain intact during early ID, but that certain aspects may be negatively impacted. Additionally,
the current study extends previous research by showing that cardiorespiratory fitness in WRA is
related to multiple executive tasks known to recruit fronto-parietal circuits. We are the first to
demonstrate that iron status in WRA is related to academic performance, and this observation
alone deserves further consideration given the number of ID individuals worldwide.
v
TABLE OF CONTENTS
LIST OF FIGURES ................................................................................................................. viii
LIST OF TABLES ................................................................................................................... ix
ACKNOWLEDGEMENTS ..................................................................................................... xii
Chapter 1 Introduction ............................................................................................................ 1
Chapter 2 Literature Review ................................................................................................... 4
Iron status and the brain ................................................................................................... 4
Magnitude of the problem- iron deficiency .............................................................. 4
Iron deficiency in women of reproductive age ......................................................... 5
Brief overview of intestinal iron absorption............................................................. 6
Regulation of iron homeostasis ................................................................................ 7
Dietary constituents and the brain ............................................................................ 10
Brain iron uptake and regulation .............................................................................. 10
The functional roles of brain iron ............................................................................. 11
Iron, brain, and behavior in women of reproductive age ......................................... 15
Fitness and the brain ........................................................................................................ 26
Magnitude of the problem- overweight and lack of physical activity ...................... 26
Holistic perspective of mental and physical health .................................................. 27
Neuroplasticity and neurotrophins: mechanisms underlying exercise-induced
cognitive benefits ............................................................................................. 27
Beyond the neurotrophins: evidence of relations between exercise, fitness, brain
and behavior ..................................................................................................... 30
General considerations and implications of fitness/brain research .......................... 32
Chapter 3 Methods .................................................................................................................. 34
General Study Design ...................................................................................................... 34
Recruitment and screening ............................................................................................... 35
Blood draw and iron status assessment ............................................................................ 39
Cognitive Assessment ...................................................................................................... 41
Questionnaires .......................................................................................................... 41
Computerized cognitive tests ................................................................................... 41
Physical testing ................................................................................................................ 53
Data Processing and Statistical Methods ......................................................................... 55
Criteria for group classification ................................................................................ 55
Data processing, transformation, and outlier removal.............................................. 57
Assessment of covariates ......................................................................................... 58
Task-specific data processing notes ......................................................................... 59
Model fitting ............................................................................................................. 62
Factor Analysis ......................................................................................................... 63
vi
Chapter 4 Sample summary characteristics and covariate identification ................................ 65
Introduction .............................................................................................................. 65
Results ...................................................................................................................... 65
Chapter 5 Relations between iron status and cognitive performance ..................................... 78
Introduction ...................................................................................................................... 78
Results .............................................................................................................................. 79
Group summary characteristics ................................................................................ 79
Attentional Network Task ........................................................................................ 82
Berg’s Card Sorting Task ......................................................................................... 87
Go/No-Go Task ........................................................................................................ 92
Sternberg Memory Search Task ............................................................................... 96
Tower of London Task ............................................................................................. 107
Overall summary of findings .................................................................................... 115
Discussion ........................................................................................................................ 117
Chapter 6 Relations between fitness and cognitive performance ........................................... 126
Introduction ...................................................................................................................... 126
Results .............................................................................................................................. 126
Group summary characteristics ................................................................................ 126
Attentional Network Task ........................................................................................ 130
Berg’s Card Sorting Task ......................................................................................... 136
Go/No-Go Task ........................................................................................................ 138
Sternberg Memory Search Task ............................................................................... 140
Tower of London Task ............................................................................................. 148
Overall summary of findings .................................................................................... 151
Discussion ........................................................................................................................ 152
Chapter 7 Combined effects of iron status and aerobic fitness on cognitive performance ..... 158
Introduction ...................................................................................................................... 158
Results .............................................................................................................................. 158
Group summary characteristics ................................................................................ 158
Attentional Network Task ........................................................................................ 162
Berg’s Card Sorting Task ......................................................................................... 165
Go/No-Go Task ........................................................................................................ 165
Sternberg Memory Search Task ............................................................................... 165
Tower of London Task ............................................................................................. 166
Overall summary of findings .................................................................................... 171
Discussion ........................................................................................................................ 172
Chapter 8 Relating iron status, fitness, and cognitive performance to academic success ....... 174
Introduction ...................................................................................................................... 174
Results .............................................................................................................................. 174
vii
Relating iron status and fitness to academic success................................................ 175
Relating academic success to cognitive performance .............................................. 176
Mediation Analysis .................................................................................................. 180
Overall summary of findings .................................................................................... 183
Discussion ........................................................................................................................ 184
Chapter 9 Factor analysis ........................................................................................................ 188
Introduction ...................................................................................................................... 188
Results .............................................................................................................................. 188
Factor loadings ......................................................................................................... 188
Interpretation of factor structure............................................................................... 189
Covariate assessment................................................................................................ 190
Regression of iron and fitness variables on factor scores......................................... 190
Overall summary of findings .................................................................................... 191
Discussion ........................................................................................................................ 192
Chapter 10 Overall conclusions and future directions ............................................................ 200
Appendix A Recruitment and screening materials ................................................................. 205
Study flyer ................................................................................................................ 205
Online Screening form ............................................................................................. 206
Appendix B Questionnaires .................................................................................................... 208
Work Drive Scale for Students ................................................................................. 208
Written Study Questionnaire .................................................................................... 210
Physical activity habits and menstrual cycle questions ............................................ 211
Appendix C Cognitive Testing Forms .................................................................................... 213
Cognitive testing checklist ....................................................................................... 213
Cognitive pre-test instructions ................................................................................. 214
Appendix D Physical Testing Materials ................................................................................. 215
Maximal Exercise Testing Form .............................................................................. 215
Pre-maximal exercise testing questions ................................................................... 217
References ................................................................................................................................ 218
viii
LIST OF FIGURES
Figure 1-1: Conceptual framework relating iron status and fitness to executive function
and academic success ....................................................................................................... 3
Figure 3-1: Screening and recruitment flow diagram .............................................................. 38
Figure 3-2: VO testing protocol .............................................................................................. 53
2
Figure 3-3: Rating of Perceived Exertion Scale ....................................................................... 54
Figure 5-1: Iron status and ANT performance ........................................................................ 86
Figure 5-2: BCST accuracy by TfR groups ............................................................................. 91
Figure 5-3: Iron status and GNG performance. ...................................................................... 95
Figure 5-4: SMS performance by iron status groups. ............................................................ 103
Figure 5-5: TOL performance by iron status groups .............................................................. 112
Figure 6-1: ANT performance by fitness groups ..................................................................... 133
Figure 6-2: SMS performance by fitness groups ..................................................................... 145
Figure 6-3: Average number of TOL excess moves made by fitness group and difficulty
level; *, overall (across difficulty) group difference, p < 0.05 ......................................... 151
Figure 7-1: ANT performance by combined iron and fitness groups ..................................... 164
Figure 8-1: GPA iron and fitness group comparisons .............................................................. 177
Figure 8-2: Regression of GPA with (a) ferritin, (b) estimated body iron, (c) peak VO
2
and (d) body mass index .................................................................................................. 178
Figure 8-3: Regression of GPA on each of the cognitive outcomes ........................................ 179
Figure 8-4: General scheme of mediation analysis .................................................................. 180
Figure 9-1: Factor structure and factor loadings ...................................................................... 196
Figure 9-2: Association between grade point average and factor scores ................................. 199
ix
LIST OF TABLES
Table 2-1: Studies examining relations between iron status and cognition in women of
reproductive age; study design and characteristics .......................................................... 21
Table 2-2: Studies examining relations between iron status and cognition in women of
reproductive age; cognitive tests and findings ................................................................. 23
Table 3-1: Cognitive testing chains ......................................................................................... 44
Table 3-2: Attentional Network Task outcomes ...................................................................... 46
Table 3-3: Berg’s Card Sorting Task outcomes ....................................................................... 47
Table 3-4: Go/No-Go task outcomes ....................................................................................... 49
Table 3-5: Sternberg Memory Search task outcomes .............................................................. 50
Table 3-6: Tower of London Task outcomes ........................................................................... 51
Table 3-7: Computerized cognitive task screenshots, duration, and behavioral correlates ..... 52
Table 3-8: Iron status and fitness group classification ............................................................. 57
Table 3-9: Tower of London excess moves categories ............................................................ 60
Table 3-10: Tower of London difficulty ranking scheme ........................................................ 61
Table 4-1: Overall sample characteristics, demographics and blood measures (n = 127) ....... 67
Table 4-2: Overall sample characteristics, physical assessment measures (n = 120) .............. 68
Table 4-3: Overall sample characteristics, self-reported questionnaire measures (n = 127) ... 70
Table 4-4: Overall sample performance, cognitive measures (n = 127) .................................. 72
Table 4-5: Covariates of cognitive measures ........................................................................... 76
Table 4-6: Covariates for group comparisons .......................................................................... 77
Table 5-1: Characteristics by iron status (n = 127), demographic and physiological
measures ........................................................................................................................... 80
Table 5-2: Characteristics by iron status groups (n = 127), questionnaire measures ............... 81
Table 5-3a: Summary of findings relating iron status to ANT performance, dichotomous
predictors .......................................................................................................................... 84
x
Table 5-3b: Summary of findings relating iron status to ANT performance, continuous
predictors .......................................................................................................................... 85
Table 5-4a: Summary of findings relating iron status to BCST performance, dichotomous
predictors .......................................................................................................................... 89
Table 5-4b: Summary of findings relating iron status to BCST performance, continuous
predictors .......................................................................................................................... 90
Table 5-5a: Summary of findings relating iron status to GNG performance, dichotomous
predictors .......................................................................................................................... 93
Table 5-5b: Summary of findings relating iron status to GNG performance, continuous
predictors .......................................................................................................................... 94
Table 5-6: Summary of findings relating iron status to SMS performance, dichotomous
predictors .......................................................................................................................... 100
Table 5-7a: Summary of findings relating iron status to SMS performance (at set-size 8),
continuous predictors ....................................................................................................... 101
Table 5-7b: Summary of findings relating iron status to SMS performance (change from
set-size 3 to 8), continuous predictors .............................................................................. 102
Table 5-8: Summary of findings relating iron status to TOL performance, dichotomous
predictors .......................................................................................................................... 109
Table 5-9a: Summary of findings relating iron status to TOL performance (overall),
continuous predictors ....................................................................................................... 110
Table 5-9b: Summary of findings relating iron status to TOL performance (change from
lower to high difficulty), continuous predictors ............................................................... 111
Table 6-1: Fitness group characteristics using VO classification ........................................... 128
2
Table 6-2: Fitness group characteristics using BMI classification .......................................... 129
Table 6-3: Summary of findings relating fitness to ANT performance ................................... 132
Table 6-4: Summary of findings relating fitness to BCST performance ................................. 137
Table 6-5: Summary of findings relating fitness to GNG performance ................................... 139
Table 6-6: Fitness group comparisons for SMS performance ................................................. 143
Table 6-7: Relations between continuous fitness measures and SMS performance ................ 144
Table 6-8: Fitness group comparisons for TOL performance .................................................. 149