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Running head: NTRS 417B GROUP ASSIGNMENT PROJECT 1
GROUP ASSIGNMENT PROJECT
Cheuk Chung (Article research, Part I, III, VI, VII)
Tin Hlaine (Article research, revised aims, part III, IV, VI, VII)
Janet Chow (Article research, revised aims, part III, search criteria, part VI, VII)
Eric Pau (Article research, part II, part III, V, VI, VII)
NTRS 417B, Sec 02
Winter Quarter 2015
California State University, Los Angeles
NTRS 417B GROUP ASSIGNMENT PROJECT 2
Table of Contents
Title Page
1. Abstract………………………………………………………………..3
2. Introduction……………………………………………………………4
3. Literature Review……………………………………………………...7
4. Description of Population of Interest………………………....……….10
5. Summary and Overview of Proposed Work…………………………..12
6. Reference List………………………………………………………… 13
7. Appendices…………………………………………………………….16
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Abstract
Numerous research studies have found strong linkages between vitamin D deficiency and
cognitive impairment. Being the most prevalent group to dementia and Alzheimer’s disease
(AD), it is necessary to inform the elderly population as to how vitamin D deficiency may
potentially affect their quality of life mentally. 10 research studies with distinctive assessment
screening tools were carefully selected from Europe and the United States to evaluate the
legitimate association between vitamin D and cognitive impairment. These screening tools
include: Cantab neuropsych test, Cognitive Telephone Screening Instrument (COGTEL),
Mini-Mental Status Exam (MMSE), Spatial working memory test (SWM), Trail-Making Tests
(visuospatial scanning, sequential processing, motor speed, attention, and executive function). In
cooperation with cohort and cross-sectional studies, these findings provide valuable evidence for
consideration. The established goal of this project is to promote public awareness of the issue
and ultimately educate the community to maintain optimal vitamin D status by making better
food selections and extending their sunlight exposure. By doing so, incidence of vitamin D
deficiency and its possible association with cognitive impairments would be reduced, and the
older adult population could live an improved quality of life and experience healthful aging.
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Introduction
Vitamin D deficiency has always been one of the major conditions that hugely affect the
older adult population. In general, adequate intakes of vitamin D is achieved via direct sunlight
exposure and absorption from the diet. Among the older adult population, however, their ability
to obtain adequate amounts of vitamin D diminishes with age, as their cells could not efficiently
convert and metabolize vitamin D. Without adequate amounts of vitamin D, older adults’
chances of having deficiency implications increase.
When speaking consequences associated with vitamin D deficiency, researches have
begun establishing possible connections between vitamin D deficiency and dementia. According
to the Vitamin D Council (n.d.), people who are age 65 years or older with vitamin D deficiency
are four times more likely of having cognitive impairments than people with adequate intake.
Also, those with Alzheimer’s disease (AD), the sixth leading cause of death in the United States,
have fewer vitamin D receptors in the brain (Alzheimer’s Association, 2015). These vitamin D
receptors that are in the brain, according to scientists, possess neuro-protective effects by
possibly inhibiting the formation of tangles and plaques that characterizes AD (Vitamin D
Council, n.d.). With that being said, providing proper nutritional knowledge about vitamin D’s
benefits and the possible consequences of vitamin D deficiency in relation to dementia is critical
in maintaining the older adult population’s nutritional status, improving their quality of life, and
preserve their brain function.
Specific Aims
Goals:
To alleviate knowledge-deficits related to vitamin D deficiency, our goals are: 1) to
educate the older adult population on the importance of adequate vitamin d intake and the
NTRS 417B GROUP ASSIGNMENT PROJECT 5
consequences of vitamin D deficiency, and 2) to promote awareness about the prevalence of
vitamin D deficiency in elderly population and its effects on cognitive function.
Expected Outcome(s):
The expected outcomes, in correspondence to the goals, would be: 1) increased intake of
vitamin D and reduced incidence of vitamin D deficiency, as well as possible consequences with
impaired cognitive function, and 2) increased public awareness of vitamin D deficiency and its
impact on mental health.
Impact(s) on the area of interest:
In terms of impacts, public awareness of vitamin D’s benefits, as well as consequences of
its deficiency, would increase. In fact, several research studies have shown that vitamin D has the
potential to protect against cognitive decline. In addition, people with adequate vitamin D intake
have lower risks of cardiovascular disease and hypertension, all of which affect the brain. Hence,
incorporating vitamin D into one’s lifestyle helps improve the diet and physical activity of older
adults, as eating good sources of vitamin D is a step towards a better diet and performing outdoor
physical activity certainly extends the time of sunlight exposure. Therefore, understanding the
importance of vitamin D intake and its link to cognitive function can help the general public age
healthfully, as well as reduce the rate of vitamin D deficiency.
Specific Objectives:
1. Providing educational resources about the importance of vitamin D and prevention of
vitamin D deficiency such as handouts and videos at community centers and senior
centers.
2. Incorporating food sources of vitamin D into the senior meals and snacks at the
community centers/senior centers as a way to promote vitamin D intake.
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3. Community health fairs are held every other month in senior centers, community
hospitals, and parks to increase public awareness of vitamin D deficiency and its
possible consequences.
4. Health education classes about vitamin D deficiency and its complication, vitamin D
rich foods, and also about potential danger of excessive intake vitamin D (toxicity).
5. Create community events with posters and talks regarding vitamin D deficiency and
its possible relation to dementia and other cognitive dysfunctions.
6. Encourage older adults to engage in outdoor exercises, such as tai chi or walking as a
way to increase vitamin D intake through sun exposure
Search Criteria
Criteria for selecting articles were:
o Choosing articles that are related to vitamin D deficiency and cognitive impairment in
the older adult population.
o Using keywords such as: “dementia and vitamin D in older adults”, “vitamin D and
brain health”, “vitamin D and cognition”, “vitamin D and dementia”, “vitamin D and
older adults”, “vitamin D and brain health in older adults” “vitamin D deficiency in
older adults”, and “vitamin D and cognitive dysfunction”.
o Used health and science based database for the article research that included
“ScienceDirect”, “Google Scholar”, “Medline”, “Pubmed”
o Defined the older adult population as aged 65 and older.
o Chose articles that had both men and women.
o The articles had to be within 5 years.
o The articles had to be original research articles
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Exclusion criteria were as follows:
o Non-English language
o Children and teens
o Small sample size of < 100 people
o Animal studies
o Review articles
Critical appraisal plan:
The first step of selecting the articles was to assess the abstracts of each article and
then examine the articles as a whole. Afterwards, the inclusion criteria was followed, where
only the articles that related to the vitamin D deficiency and the risk of cognitive
impairments in the older adult population was chosen. Articles that did not follow the
inclusion criteria were discarded. Results and discussions of each article were used for the
literature review. Further analysis and comparisons of the research articles are also reported
in the literature review.
Literature Review
All of the original research articles support vitamin D deficiency’s associations in
increasing the risk of cognitive impairment disorders such as dementia and AD. The majority of
the original research articles used the same methods to reach their conclusion, where they used
neurological instruments to measure cognitive function and blood samples to measure serum
levels of vitamin D. There were some differences between European studies and U.S. studies in
assessing vitamin D deficiency. European studies defined vitamin D deficiency as < 50 nmol/L,
50-75 nmol/L as insufficient, and ≥ 50 as sufficient; while U.S. studies defined vitamin D
NTRS 417B GROUP ASSIGNMENT PROJECT 8
deficiency as < 25 nmol/L as severely deficient, ≥ 25 nmol/L as deficient, and ≥ 50 as sufficient.
There are strengths and weaknesses to each study.
In the European studies, Lang et al. (2010), Annweiler et al. (2012), Afzal et al. (2014),
Toffanello et al. (2014), Seamans et al. (2010), and Breitling et al. (2011) researched on the
association between plasma vitamin D status and changes in cognitive level in Caucasians of
European origin ages 65 years and older, with conclusions about tight bondages between low
serum vitamin D levels and cognitive impairment at some level. In addition, one interesting finding
was revealed by Seamans et al. (2010) that although low serum 25-hydroxy vitamin D level was
associated with reduction in capacity for spatial working memory. The study, however, failed to
prove vitamin D deficiency’s causation to cognitive decline. Seamans concluded the study with
suggestion that extensive randomized controlled intervention studies are needed.
Among these researches, cognitive function was measured by COGTEL (Cognitive
Telephone Screening Instrument), MMSE (Mini-Mental Status Exam), Trail-Making Tests
(visuospatial scanning, sequential processing, motor speed, attention, and executive function), and
clinical diagnosis. Lang et al. (2010) and Afzal et al. (2014) used prospective cohort study,
Annweiler et al. (2012) used cross-sectional study while Toffanello et al. (2014) and Breitling et
al. (2011) used observational cohort study. Subjects with previous history of stroke, initial MMSE
score less than 10, abnormal gait, recent mental illness, delirium, or severe depression were filtered
out. Potential confounders such as obesity, age, gender, education, alcohol intake, and smoking
habits were identified and adjusted.
There were strengths as well as limitations to the European studies. The common strengths
between these studies included using a large sample size and using multiple cognitive functioning
instruments to cover multiple cognitive domains, as indicated in studies of Lang et al. (2010),
NTRS 417B GROUP ASSIGNMENT PROJECT 9
Annweiler et al. (2012), Afzal et al. (2014), and Breitling et al. (2011). As for limitations, Lang et
al. (2010), Annweiler et al. (2012), and Afzal et al. (2014) used clinician’s diagnosis without the
utilization of imaging studies, Toffanello et al. (2014), used only one cognitive tool to measure
cognitive function, and Breitling et al. (2011) lacked baseline assessment of cognitive functioning,
which does not allow for adjustments in reverse causality. Finally, all of the subjects that were
selected were Caucasians from a confined geographic area.
In the U.S. studies, Littlejohns et al. (2014), Littlejohns et. al. (2013), and Llewellyn et al.
(2010) reached on the same conclusion that low vitamin D levels are associated with the increased
risk of cognitive impairments. All of these studies are using the prospective cohort study method.
According to these studies, there is a strong connection between vitamin D and the brain. For
instance, vitamin D receptors are expressed in areas throughout the brain. These areas include
those involved with memory, such as the hippocampus and dentate gyrus (Littlejohns et al., 2014).
There are also vitamin D receptors in brain-related cells, such as neurons and glial cells (Llewellyn
et al., 2010). Additionally, there are enzymes that synthesize the active form of vitamin D that is
produced in several cerebral regions and the active form regulates neurotrophin expression
involved in nerve growth and function of neural cells. The genes encoding the enzymes that are
involved in the metabolism of vitamin D are also expressed in the brain (Llewellyn et al., 2010).
Vitamin D also stimulates macrophages to help increase the clearance of amyloid plagues
associated with AD (Littlejohns et al., 2014).
As for another U.S. cohort study conducted by Wang et. al. (2012), data suggested that risk
alleles in association with late-onset AD have a relationship with lower vitamin D receptor (VDR)
activity, which could be a possible genetic link between VDR and late-onset AD risk. Like the
other U.S. studies that are previously mentioned, this study also suggests that vitamin D
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insufficiency increases the risk of developing AD. Though this study suggests a possible link
between vitamin D and late-onset AD risk, people with other conditions such as multiple sclerosis
(MS) and Type I diabetes mellitus (T1DM) could influence gene activity. As a result, direct
relationships between VDR and late-onset AD risk are unclear.
Strengths of the U.S. studies consisted of using large sample sizes, using an ethnically
diverse older adult population, using multiple cognitive tools, and as well as biological assays to
measure cognitive function and compare gene activity. The limitations of the US studies consisted
of excluding the Hispanic and Asian population, biased results, possible missing data, and
excluding those with cardiovascular disease, stroke, and cases of vascular dementia. The findings
of the U.S. studies were consistent with the European studies.
Nutritional insufficiency is a threat to the well-being of any given population, and it is
usually a preventable cause of multiple diseases, illnesses, or complications of dietary deficiency.
Since being too young or too old is a risk factor of nutritional deficiency, the elderly population is
especially susceptible to deficiencies such as vitamin D deficiency. Lifestyle (inadequate diet, not
enough sunlight/UVB exposure) or physiologic effects of aging can influence the needs of vitamin
D in elderlies. Thus, through the research articles and public awareness of adequate vitamin D, the
aging population will know how to maintain good health with good nutrition in order to age
healthfully.
Description of Population of Interest
In this research project, population of interest is elderly people of both genders with a mean
age of 65 years and above. This group of population is chosen for the project, because first of all,
elderly population is growing in western countries, especially in the U.S. Secondly, like any other
nutrients, vitamins, and minerals, vitamin D deficiency is more prone in elderly people. This may
NTRS 417B GROUP ASSIGNMENT PROJECT 11
be due to either inadequate dietary intake or insufficient sunlight exposure. However, aging itself
can contribute to increase needs of vitamin D in older people. Factors of aging that effect vitamin
D synthesis are reduced synthesis of 7-dehydrocholesterol in the skin and decreases activity of
renal 1-hydroxylase enzyme. Lang et al. (2010) states that about 40 to 100 percent of older people
in European countries and the United States are vitamin D deficient. Thirdly, elderly population
have higher incidence of cognitive dysfunctions such as Alzheimer’s disease, vascular dementia,
and other types of dementia.
Moreover, cognitive impairments are common in aging population, and sometimes older
people dismiss their memory loss, which is one of the common symptoms of cognitive disorders,
as something trivial or something usual for their age. There are a number on studies done to learn
if there is association between vitamin D deficiency and occurrence of cognitive decline. Vitamin
D is believed to play an important role in calcium homeostasis, neurotrophic factor expression,
neurogenesis, and beta amyloid clearance. Thus, vitamin D may have neuro-protective effect or
have some role in preventing neurodegeneration.
In addition, if a strong association does exist between vitamin D and cognitive dysfunction
as suggested by the studies and researches done this particular aspect, there will be promising
options for prevention and treatment neurodegenerative diseases like Alzheimer’s disease. Not
only the elderly population but also the society as a whole will benefit if debilitating
neurodegenerative disorders can be prevented and treated. With more studies, researches, and
randomized control trials, vitamin D’s role in possible prevention or treatment of cognitive
impairment should be establish, and the minimum level of vitamin D in plasma which is required
to have neuro-protective effect. This is also important as vitamin D, like other fat-soluble vitamin,
have potential to have toxic effect when overdosed. Recommended daily allowances are 600 IU
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(15 μg) of vitamin D for ages 1 to 70, and 800 IU (20 μg) of vitamin D for those older than 70
years of age. Higher dosage of vitamin D supplementations need to be avoided to prevent
complications of vitamin D toxicity such as hypercalcemia, calcinosis, hyperphosphatemia,
hypertension, and renal dysfunction.
Summary/Overview of Proposed Work
Vitamin D deficiency is a condition that affects the majority of the older adult
population. As the aforementioned reports suggest, adequate amounts of vitamin D are obtained
through the body’s synthesis of the vitamin from sufficient sunlight exposure and adequate
dietary intake. As people age, their ability of obtaining the vitamin decreases. Hence, with the
diminished ability to obtain the vitamin, older adults have higher chances of developing
cognitive dysfunction as suggested by the studies. Since the majority of the population are
unaware of vitamin D’s benefits and the negative consequences of its deficiency, it is imperative
to provide proper nutritional education and promote nutritional well-being in an attempt to
reduce the incidence of deficiency. With proper nutritional knowledge and improved well-being,
older adults could improve their quality of life and age healthfully.
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References
Afzal, S., Bojesen, S., & Nordestgaard, B. (2014). Reduced 25-hydroxyvitamin D and risk of
Alzheimer’s disease and vascular dementia. The Journal of the Alzheimer's Association,
10(3), 296-302. Retrieved January 18, 2015, from PubMed.
Annweiler, C., Gall, D. L., Sarre, M., Remondiere, S., & Beauchet, O. (2010). Vitamin D
deficiency and moderate-to-severe dementia: Cross-sectional association in geriatric
inpatients. Alzheimers & Dementia, 59(1), 169-171. doi:10.1016/j.jalz.2010.05.1556
Annweiler, C., Gall, D. L., Sarre, M., Remondiere, S., & Beauchet, O. (2010). Vitamin D
deficiency and moderate-to-severe dementia: Cross-sectional association in geriatric
inpatients. Alzheimers & Dementia, 59(1), 169-171. doi:10.1016/j.jalz.2010.05.1556
Annweiler, C., Fantino, B., Schott, A., Krolak-Salmon, P., Allali, G., & Beauchet, O. (2012).
Vitamin D insufficiency and mild cognitive impairment: Cross-sectional association.
European Journal of Neurology, 19, 1023-1029. Retrieved January 18, 2015, from
PubMed.
Breitling, L. P., Perna, L., Müller, H., Raum, E., Kliegel, M., & Brenner, H. (2012). Vitamin D
and cognitive functioning in the elderly population in Germany. Experimental
Gerontology, 47, 122-127.
CA de Jager (2014) Vitamin D and Cognition: Are There Any Cautions against Intervention
Trials for Older Adults?. Vitamin Miner 3:e128. Doi: 10.4172/vms.1000e128
Elsevier. (2013). Vitamin D and incident Alzheimer's disease in the Cardiovascular Health
Cognition Study. Alzheimer's and Dementia, 9(4), 880. doi:10.1016/j.jalz.2013.08.227
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Gropper, S., & Smith, J. (2013). Fat Soluble Vitamin. In Advanced nutrition and human
metabolism (Sixth ed., p. 398,399). Belmont, California: Wadsworth.
LittleJohns, T., Soni, M., Annweiler, C., Chaves, P., Fried, L., Kesternbaum, B., . . . Lang, I.
(2013). Vitamin d and incident Alzheimer’s disease in the cardiovascular health cognition
study. doi:10.1016/j.jalz.2013.08.227
Littlejohns, T. J., Henley, W. E., Lang, I. A., Annweiler, C., Beaucher, O., Chaves, P., . . .
Llewellyn, D. J. (2014). Vitamin D and the risk of dementia and Alzheimer disease.
American Academy of Neurology, 83, 920-928.
Llewellyn, D., Lang, I., Langa, K., Muniz-Terrera, G., Phillips, C., Cherubini, A., ... Melzer,
D. (2010). Vitamin D and Risk of Cognitive Decline in Elderly Persons. ARCH
INTERN MED, 170(13), 1135-1141. Retrieved January 18, 2015, from PubMed.
Llewellyn, D. J., Lang, I. A., Langa, K. M., & Melzer, D. (2010). Vitamin D and cognitive
impairment in the elderly US population. Journal of Gerontology: Medical Sciences, 1-7.
National Center on Elder Abuse/ Administration of Aging. (2015). America's growing elderly
population. Retrieved from http://www.ncea.aoa.gov/Library/Data/
Seamans, K. M., Hill, T. R., Scully, L., Meunier, N., Andrillo-Sanchez, M., Polito, A., . . .
Cashman, K. D. (2010). Vitamin D status and measures of cognitive function in healthy
older European adults. European Journal of Clinical Nutrition.
doi:10.1038/ejcn.2010.117
Toffanello, E. D., Coin, A., Perissinotto, E., Zambon, S., Sarti, S., Veronese, N., . . . Sergi, G.
(2014). Vitamin D deficiency predicts cognitive decline in older men and women.
American Academy of Neurology, 83, 2292-2298.
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Vitamin D and cognitive impairment | Vitamin D Council. (n.d.). Retrieved from
https://www.vitamindcouncil.org/health-conditions/cognitive-impairment/
Vitamin D receptor and Alzheimer's disease: a genetic and functional study. (2012).
Neurobiology of Aging, 33(8), 1844e1-1844e9. doi:10.1016/j.neurobiolaging.2011.12.038
Wang, L., Hara, K., Van Baaren, J. M., Price, J. C., Beecham, G. W., Gallins, P. J., . . .
Whitehead, P. L. (2012). Vitamin D receptor and Alzheimer's disease: a genetic and
functional study. Neurobiology of Aging, 33, 1844.e1-1844.e9.
doi:10.1016/j.neurobiolaging.2011.12.038
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VII. Appendices
National Center on Elder Abuse/ Administration of Aging (2015) shows America’s growing
older adult population
US study data by Llewellyn et al. (2010), p. 5 illustrating odds of cognitive impairment by low
vitamin D levels. There is 95% confidence level.
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Table 1. Lang et al. (2010), p.1135
Baseline Characteristics of 858 InCHIANTI27 Participants by Serum 25(OH) D
Concentration
Table 4. Lang et al. (2010) p.1135
Random-Effects Models Illustrating Change in MMSE-Measured Cognitive Function by
Serum 25(OH) D Level
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Table 1. Breitling et al. (2012) p.124
Major characteristics and analysis variables in the elderly German study population
Table 2. Seamans et al. (2010) p.1175
SWM test scores in the entire group of 55- to 87-year-old ZENITH subjects stratified by
tertile of serum 25(OH) D concentration
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Fig. 2. Wang et al. (2012). p.1844.e5.
Expression analysis of Cdx-2 and VDR in brain regions and analysis of VDR promoter
activity in Neuro2A cells.
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Fig. 3. Wang et al. (2012). P.1844.e6.
Analysis of APP promoter activity regulated by VDR and 1, 25-(OH) 2 D3