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VITAMIN D AND COGNITION IN ELDERLY1

The Effects of Vitamin D on Cognition in the Elderly

Alyssa Gormaly

California Polytechnic State University

November 25, 2014

Alzheimer’s Disease


Alzheimer’s disease is a neurodegenerative disease that plagues a portion of the elderly.

This paper will review clinical trials that have examined the effects of sufficient serum vitamin D

levels on the risk for Alzheimer’s disease.

Disease Background

Alzheimer’s disease is a progressive brain disease that affects the memory and thinking

skills of as many as 5.1 million Americans. It is irreversible and most symptoms appear after age

sixty. It was named after Dr. Alois Alzheimer, who studied the brain tissue of a woman with an

“unusual mental illness”. He discovered what are now known as amyloid plaques and neurofibril-

lary tangles as well as a depletion of neuron connections, which are the main features of the dis-

ease. Those plaques and tangles are formed by an excess deposit of protein in the brain, causing

neurons to function less efficiently [1]. Over time, this spreads throughout the brain. The true

cause of Alzheimer’s disease has not yet been pinpointed.

Stages of Alzheimer ’ s Disease

In the preclinical stage of Alzheimer’s disease, the brain begins to make changes without

showing symptoms. The earliest symptoms can include abnormal memory loss, difficulty with

movement, trouble with word-finding, vision and spatial issues, and impaired reasoning or

judgement.

The patient then progresses into mild Alzheimer’s disease, whose symptoms include

worsening memory and cognitive abilities; this is a common time for the disease to be noticed

and diagnosed.

In moderate Alzheimer’s, memory loss and cognitive abilities grow even worse. The pa-

tient’s activities of daily living become impaired and he or she may find it difficult to recognize

friends and loved ones.


In the final stage of Alzheimer’s, the patient is entirely dependent on others for care. The

plaques and tangles have spanned the shrunken brain tissue. The body often shuts down at this

stage [1].

Risk Factors

The main risk factors associated with Alzheimer’s disease are age, genetics, environment,

and lifestyle. The most outstanding risk factor of the four is age. The risk for developing

Alzheimer’s disease will double every five years after the age of 65.

Scientists have also found a genetic linkages to Alzheimer’s. This can enable a person to

get early-onset Alzheimer’s as early as 30 years old. It is related to a mutation in one of three

genes. Researchers have found a multitude of gene mutations that can induce late-onset

Alzheimer’s. Currently, genetic screening is being used to make predictions about the likelihood

of a person getting early-onset Alzheimer’s if he or she has a significant enough family history

[29].

Researchers speculate the role of environmental factors in cognitive decline, such as

other conditions like stroke, obesity, vascular disease, high blood pressure, and diabetes. Studies

have found a positive correlation between these conditions and cognitive decline related to

Alzheimer’s disease.

Two major lifestyle factors that affect Alzheimer’s disease are diet and exercise. Moder-

ate exercise has been shown to promote blood circulation, reducing risk for cognitive decline and

dementia. Some clinical studies have even shown a short-term improvement in skills like plan-

ning, organizing, and decision-making in the elderly. Socialization and brain stimulation have

also been shown to affect cognition. In a study, researchers found that those elderly people who


engaged in social or stimulating activities like games, puzzles, and reading showed a forty-seven

percent lower risk of developing Alzheimer’s disease. [2]

Diet has also been shown to make a difference in cognition of the elderly. Some research

suggests that eating a Mediterranean diet is associated with a reduced risk of Alzheimer’s. An-

other study also showed that a Mediterranean diet in those who already had Alzheimer’s pro-

longed survival [2]. The foods which seemed to be most beneficial were nutrient-dense, crucifer-

ous vegetables for increased antioxidants, and those foods with omega-3 fatty acids to reduce

plaques. Additionally, diets high in vitamin E and C were linked to lower risk of developing

Alzheimer’s [3,4,5].

Prevalence in American Elderly

In 2005, 24.2 million people in the world had dementia, with a growing annual rate of 4.6

million of new cases. Approximately 70% of those cases were caused by Alzheimer’s disease.

Pictured above is a graph displaying the past and current data relevant to Alzheimer’s disease as

Projections of Alzheimer’s Disease Prevalence in the United States. [6]


well as projected estimates of where Alzheimer’s is headed in terms of prevalence. Though the

affected population increases through the years, it is important to keep in mind that these esti-

mates were also adjusted for the growing overall population. These estimates also included state-

ments about the status of these individuals, namely, that the majority of them would continue to

be female and no longer have a spouse to care for them due to females’ statistically longer life-

spans [7].

Vitamin D

Sources of Vitamin D

A study shows that adequate vitamin D levels are associated with the intake of whole

milk dairy products, red meat, and eggs [8]. The flesh of fatty fish, their oils, and vitamin-D-for-

tified foods also provide food bound sources. Supplementation can also increase levels of serum

vitamin D [9]. Another shows that increased sun exposure, lower BMI, and use of indoor tanning

all have a positive correlation with increased levels of vitamin D [10].

Vitamin D Inadequacy Risk in the Elderly

Elderly persons are more at risk for a vitamin D deficiency because, as they age, vitamin

D becomes harder to synthesize from sun exposure through the skin. This is only amplified by

the fact that many elderly people tend to spend much more time indoors than younger persons

due to lack of mobility with age. Their food intake of vitamin D is also likely to decrease be-

cause many older people tend to have trouble getting themselves to eat; their overall food intake

decreases, and therefore, their oral vitamin D intake tends to decrease [9].

Safety: Deficiency and UI Levels of Vitamin D


Safe intake levels are important in assessing the effects of vitamin D on the elderly so

that the individual is not prescribed too much to make up for deficiency or too little to promote

deficiency. Below is a table indicating the upper intake (UI) levels for vitamin D.

[28]

Vitamin D deficiency in the elderly is a common concern and is defined as a serum level

of <25-50 nmol/L [9]. The rates of deficiency in the elderly could be affected by a number of

things including the increased DRI for the elderly (200 additional IU by age 70), decreased ab-


sorption with age, inadequate dietary intake, or increased excretion. Vitamin D deficiencies are

especially common in those who omit the common sources of vitamin D listed previously from

their diets. With vitamin deficiency comes the risk for developing rickets and osteomalacia [11].

Vitamin D and Alzheimer’s Disease

Role of Vitamin D in Cognition

Upon being ingested, vitamin D remains essentially dormant until it is metabolized in the

liver, then the kidneys. It then takes the psychologically active form of vitamin D labeled

1,25(OH)2D3. This activated form promotes the regulation of gene transcription through vitamin

D receptors present in the brain [12,13]. 1,25(OH)2D3 produces biological effects 50+ different

tissues throughout the body [14]. Vitamin D receptors and the enzyme responsible for formation

of the active form of the vitamin in the brain [13] span neurons and glial cells in the parts of the

brain which are crucial for cognition [15, 16].

Amyloid beta is a known brain lesion seen in victims of Alzheimer’s disease. A study has

shown that the activated form of vitamin D will induce phagocytosis and clear the brain of amy-

loid beta [17]. In a study, introduction of the activated form to areas with amyloid beta protected

the neurons. It was seen to prevent cytotoxicity and cell death, while upregulating vitamin D re-

ceptors. 1,25(OH)2D3 treatment works against specific types of cell death in the hippocampal

cells, acting a neuroprotective mechanism [18].

Correlation Between Cognitive Dysfunction and Vitamin D Deficiency

Several studies across the globe have lent to the conclusion that vitamin D deficiency can

lead to cognitive decline. The results of a study done in the United States concluded that vitamin

D deficiency (serum level of <25 nmol/L) had a significant correlation with cognitive impair-


ment [19]. Another community sample in the United States found that those with vitamin D defi-

ciency were four times as likely to be cognitively impaired compared to those who had serum

levels of 75 nmol/L or greater [21].

A study done in France showed that women 75 or over participating in a trial who were

deficient in vitamin D were twice as likely to develop cognitive impairment in comparison to

those women who were not deficient [20]. A similar study done in England yielded the same re-

sults [22]. A six-year trial done in a population of 858 elderly Italians, deficient persons (<25

nmol/L) had an increased risk of cognitive decline in comparison to non-deficient persons [23].

A conducted trial assigning treatment of vitamin D to prevent cognitive decline resulted in the

finding that an improvement of cognitive function occurred in a small group of lean individuals

[24].

Clinical Trials of Alzheimer ’ s and Vitamin D Deficiency

A recent trial in the US was conducted using 1658 elderly persons. 102 of those partici-

pants developed Alzheimer’s disease. When tested, the serum levels of vitamin D of those who

developed Alzheimer’s was significantly lower. The study concluded that vitamin D deficiency is

associated with a substantial increase in risk for all-cause Alzheimer disease [25].

Another trial followed 498 women aged 75 or older for seven years. The results showed

that the women who developed Alzheimer’s were the ones with the lowest baseline vitamin D

levels. The study concluded that higher vitamin D intake is associated with a lower risk of devel-

oping Alzheimer’s disease among older women [30].

Another, less conclusive trial tested the serum vitamin D levels in 75 older persons in

Sweden. Some factors associated with Alzheimer’s disease, like amyloid-beta presence, were as-


sociated with the lowest serum vitamin D values. Other factors, like tau proteins (contributing to

tangles in the brain), were not significantly associated with the low vitamin D levels [32].

A longer longitudinal study followed 418 participants over thirty years. The study

grouped participants into 3 sections: those with severe deficiency (<25 nmol/L), moderate defi-

ciency (> 50 nmol/L), and sufficiency (> 75nmol/L). The study concluded that the more deficient

the individual was, the greater risk he or she had of developing Alzheimer’s disease [31].

Research Limitations

The variety of genetic makeup in trial participants plays a role in the standards of what is

considered “low” or “sufficient” serum vitamin D levels when using those numbers to suggest

risk for cognitive decline. Because one of the risk factors for Alzheimer’s is a specific genetic

mutation, one might not be deficient in vitamin D according to the standards, but that person’s

specific genetic sequence might put them at higher risk for Alzheimer’s. This type of occurrence

could have swayed the results of trials.

Assessments of the correlation between serum vitamin D levels and cognitive dysfunc-

tion have used different methods to measure serum vitamin D levels, such as competitive protein

binding assay, ELISA and liquid chromatography-tandem mass spectrometry. These different

methods have the potential to yield different results for the same set of data. Liquid chromatogra-

phy-tandem mass is currently seen as the most reliable method [26].

Another study speculates the idea of reverse causation, in which cognitive decline is the

cause of a vitamin D deficiency [27]. It is said that the severity of the disease could cause de-

creased mobility, lack of exposure to sunlight, and restricted intake of food and therefore vitamin

D.

Future Research


At this point, there is an ample amount of research, but more studies should be done over

long periods of time. Studies should also include a broad variety of people and a great amount of

people in order to draw conclusive data. Researchers should use the same, reliable standardized

methods to determine amounts of vitamin D. There is very little research on the affects of vita-

min D supplementation on the prevention of improvement of Alzheimer’s disease. More work

needs to be done to determine if supplementation has the same effects and ease of absorption as

food-bound sources and sunlight. Supplementation is a more convenient alternative for some el-

derly people and could make a positive difference if proven to be beneficial.

Conclusion

Much of recent research has determined a positive correlation between vitamin D defi-

ciency and increased risk for Alzheimer’s disease. There are still limitations in the research and

methods that could decrease the strength of the evidence shown, though the evidence is fairly

unanimous. Vitamin D deficiency is common in older adults and solidification in methods for

testing vitamin D sufficiency should be improved because recent research associates deficiency

with cognitive decline and Alzheimer’s disease.

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