The role of choline in cognitive performance and cerebrovascular health of older adults.
Roe, Annie.
2015
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Abstract: Choline is
an essential nutrient with multiple links to brain health. As a component of
phospholipids, choline is involved in cell signaling, lipid transport, and cell membrane
structure. In addition, choline is a precursor to the neurotransmitter acetylcholine and
the methyl donor betaine. There is evidence that changes in DNA methylation play a role
in early neuronal development ... read moreas well as in the pathogenesis of neurodegenerative
diseases by altering gene expression. In addition, dietary choline and betaine intakes
have been differentially associated with risk of cardiovascular disease and may also be
related to cognitive performance via cerebrovascular health. Better understanding the
role of choline in cognition and cerebrovascular health will be important factors in
improving dietary intake recommendations for this nutrient in adults. To date, no human
study has evaluated both dietary intake and plasma concentration of choline and choline
metabolites in relation to cognitive function, cardiometabolic risk and cerebrovascular
pathology. In this dissertation, the role of choline in cognitive performance,
cerebrovascular health, and cardiometabolic risk in the older adult was explored through
four separate studies. In the first study, data and stored plasma samples from the
Nutrition, Aging and Memory in Elders cohort were used to conduct a cross-sectional
analysis evaluating relationships between dietary and plasma choline and related
compounds, and cognitive performance, cerebrovascular pathology, and cardiometabolic
risk. We found differences in associations between choline related compounds and outcome
measures depending on whether dietary intake or plasma concentrations were used in the
statistical model. There was no relationship between dietary intake and radiological
evidence of cerebrovascular disease by magnetic resonance imaging (MRI) or self-reported
cardiovascular disease; however, those individuals with lower plasma concentrations of
choline had higher odds of small vessel infarct on brain MRI, and those with higher
plasma concentrations had higher odds of large vessel infarcts and self-reported
cardiovascular disease, indicating that the relationship between choline and vascular
disease is different when considering the location of blood vessels, cerebrovascular or
cardiovascular, as well as the size of the blood vessel, small vessel versus large
vessel disease. Dietary betaine intake was positively associated with executive
function, while dietary choline intake was inversely related to memory; in contrast,
plasma concentrations of choline were positively related to executive function and
plasma betaine concentrations were positively associated with memory. These
discrepancies may be due to variations in choline metabolism due to single nucleotide
polymorphisms (SNPs), variations in intestinal microflora that utilize
phosphatidylcholine, or other unknown factors that influence the use of dietary choline
and the production of endogenous choline. In the second study, we evaluated the
relationship between dietary choline and cognitive outcomes, and whether SNPs in choline
and folate metabolism modify this relationship, using data from the longitudinal Boston
Puerto Rican Health study. Significant associations were found between 25 SNPs in
choline and folate metabolism and cognitive outcomes, as well as interactions between
dietary choline intake and 22 SNPs on cognitive outcomes. These relationships should be
assessed in similar populations in order to draw significant conclusions regarding
dietary choline recommendations based on genotype. In the third study, stored brain
tissue, serum, and associated cognitive data from the Georgian Centenarian study were
analyzed to assess relationships between measures of methylation capacity from choline
in serum and gene expression of genes related to memory in the frontal cortex, as well
as global cognitive performance. We found that higher methylation capacity from choline,
as assessed by the ratio of serum choline plus betaine to dimethylglycine, was
associated with less cognitive impairment and better memory. The expression of EGR-1, a
gene shown to be necessary for long-term memory in rodent models, was greater in those
with methylation capacity in the upper 50% compared to those with methylation capacity
in the lower 50%. This was the first study to look at gene expression related to
methylation capacity in humans. While these relationships are correlational, they do
provide some support of the hypothesis that choline is related to cognitive function via
its role in methylation. Future studies should look at gene specific DNA methylation and
determine whether differences in methylation are related to differences in gene
expression. The final study was a randomized controlled trial to assess the effects of a
6-month dietary intervention to increase dietary choline intake in adults on
concentration of plasma choline-related compounds, cardiometabolic risk factors, and
cognitive outcomes. Preliminary data have yielded significant associations between
changes in concentration of plasma choline-related compounds and changes in scores on
cognitive tests. In these preliminary results, we have not yet analyzed blood samples
for high density lipoprotein cholesterol, low density lipoprotein cholesterol, or
triglycerides in order to assess how the dietary intervention affects these
cardiometabolic risk factors. In summary, the role of choline in cognition and
cerebrovascular health in the older adult was explored through four specific aims. From
the first two aims, we were able to identify the best biomarker of dietary choline
intake in blood and directly relate this parameter to measures of cognitive function and
cerebrovascular pathology as well as identify single nucleotide polymorphisms that may
modify these relationships. Aim 3 provided insight into the possible mechanism by which
choline affects cognitive function by assessing methylation capacity and gene
expression, and helped to generate hypotheses for further studies. From the fourth aim,
we were able to test our hypothesis that increasing daily dietary choline intake will
improve cognitive function. This intervention study is on-going and a progress report
was presented in this dissertation.
Thesis (Ph.D.)--Tufts University, 2015.
Submitted to the Dept. of Biochemical and Molecular Nutrition.
Advisor: Tammy Scott.
Committee: Irwin Rosenberg, Natalia Crivello, Elizabeth Johnson, Caren Smith, and Alice Lichtenstein.
Keywords: Nutrition, Cognitive psychology, and Aging.read less - ID:
- 3f462j49b
- Component ID:
- tufts:20527
- To Cite:
- TARC Citation Guide EndNote
