Archief Roodbont

---

This activity is developed and funded by Medscape.

News Author: Caroline Cassels
CME Author: Désirée Lie, MD, MSEd

Complete author affiliations and disclosures, and other CME information, are available at the end of this activity.

Release Date: February 11, 2008; Valid for credit through February 11, 2009

Credits Available

Physicians - maximum of 0.25 AMA PRA Category 1 Credit(s)™ for physicians;
Family Physicians - up to 0.25 AAFP Prescribed credit(s) for physicians

All other healthcare professionals completing continuing education credit for this activity will be issued a certificate of participation.
Physicians should only claim credit commensurate with the extent of their participation in the activity.

---

February 11, 2008 — Folate deficiency has been associated with a tripling of dementia risk in elderly people.

New research by investigators at Chonnam National University Medical School, Kwangju, Republic of Korea, found that individuals who were folate deficient at study outset were 3.5 times more likely to develop dementia. However, individuals with lower folate levels, but who were not folate deficient at baseline, were also at significant increased risk for dementia.

"Folate deficiency is clearly associated with a higher risk of dementia, but there also appears to be a significant association [between dementia and folate] across the non-deficient range," study author Robert Stewart, MD, MRCPsych, told Medscape Neurology & Neurosurgery.

The study is published online in the February 5 Early Release Article issue of the Journal of Neurology, Neurosurgery, and Psychiatry.

Inconsistent Findings

According to the study, previous research investigating a possible association between serum folate, vitamin B₁₂, and homocysteine levels as predictors of dementia have been inconsistent.

To explore this relationship, the researchers conducted a prospective community-based study and looked at baseline concentrations of folate, vitamin B₁₂, and homocysteine levels and changes in these factors with time and the relationship to incident dementia.

The 2-year study included 518 subjects aged 65 years or older living in 1 of 2 geographic catchment areas (1 urban, 1 rural) in Kwangju, South Korea.

At baseline, all subjects were evaluated for dementia as defined by the Mini-Mental State Examination, the Instrumental Activities of Daily Living Scale, and the Clinical Dementia Rating scale. In addition, a complete medical history was taken and full physical and neurologic examinations conducted.

Blood samples were collected at baseline and again at study follow-up. Demographic information as well as data on depression, smoking, alcohol consumption, and daily physical activity was also gathered, and subjects were assigned a summary score.

At median follow-up of 2.4 years, 45 individuals (8.7%) developed dementia. Of these, 34 (6.6%) had Alzheimer's disease, 7 (1.4%) had vascular dementia, and 4 had "other" dementia types.

The prevalence of baseline folate deficiency was 3.5%. This, said Dr. Stewart, is relatively low vs Western populations, possibly because of the high intake of green vegetables in the Korean diet.

Adjusted analyses revealed that incident dementia increased significantly across descending quintiles of baseline folate concentrations. However, incident dementia was not associated with baseline vitamin B₁₂ or homocysteine levels.

Brain-Body Connection Sometimes Overlooked

During the follow-up period, dementia occurred more commonly in subjects with a relative decline in folate and vitamin B₁₂ levels. The investigators also noted that declining folate levels were associated with an increase in homocysteine concentrations.

In addition, incident dementia was significantly linked to older age, lower education, more severe cognitive impairment and disability, lower physical activity, and the presence of the apolipoprotein E ε4 allele.

According to Dr. Stewart, when researchers adjusted for weight loss during the study period, the strength of all associations lessened. This finding, said Dr. Stewart, is consistent with previous research that physical changes such as weight loss occur very early in dementia, before the onset of clinical symptoms, and may, at least in part, be responsible for changes in folate, vitamin B₁₂, and homocysteine levels.

"When a doctor sees a patient with suspected dementia, it is very important that their physical health and nutritional status are checked right at the outset. One of the problems that we have in the [United Kingdom] is that physicians tend to be less attentive to dementia patients' physical health, possibly because they view dementia purely as a problem of brain function. This is something that needs to be remedied," he said.

The study was supported by the Korea Health 21 R&D, Ministry of Health & Welfare, Republic of Korea. The study authors have disclosed no relevant financial relationships.

J Neurol Neurosurg Psychiatry. Published online February 5, 2008.

Learning Objectives for This Educational Activity

Upon completion of this activity, participants will be able to:

1. Describe the predictive value of baseline plasma folate, vitamin B₁₂, and homocysteine levels for predicting incident dementia in older adults.
2. Describe the predictive value of changes in levels of folate, vitamin B₁₂, and homocysteine for predicting incident dementia.

Clinical Context

Folate, vitamin B₁₂, and homocysteine are all involved in 1-carbon transfer (methylation) reactions necessary for the production of monoamine neurotransmitters, phospholipids, and nucleotides. Cross-sectional studies have found correlations between folate deficiency and hyperhomocysteinemia and dementia and cognitive impairment, but results from prospective cohort studies have been controversial.

This is a 2-year community-based prospective cohort study of elderly adults without dementia at baseline to examine the association between baseline and changing folate, vitamin B₁₂, and homocysteine levels and incident dementia.

Study Highlights

• Included were adults older than 65 years from 2 geographic catchment areas (1 rural, 1 urban) in 1 country who completed identical assessments at baseline and at follow-up.
• Participants were identified from a national registry and were seen at baseline and at 2 years.
• Examinations included the Mini-Mental Status Examination, the Clinical Dementia Rating Scale, Instrumental Activities of Daily Living Scale, history, disability (World Health Organization Disability Assessment Schedule II), and full physical and neurologic examination.
• Risk factors for dementia that were assessed and accounted for included alcohol, smoking, and physical activity.
• Apolipoprotein E ε4 allele status was determined.
• Senior investigators assigned diagnoses for dementia, Alzheimer's disease, and vascular dementia using standard criteria.
• Investigators were blinded to the blood assay status of each participant evaluated.
• Fasting morning blood samples were collected for plasma folate, vitamin B₁₂, and homocysteine levels at baseline and at follow-up.
• At baseline, 732 of 1204 residents completed all measures, and 518 subsequently completed all follow-up evaluations.
• Mean follow-up duration was 2.4 years.
• Of this cohort, 45 participants developed incident dementia for a rate of 8.7%, with 6.6% having Alzheimer's disease, 1.4% having vascular dementia, and 0.8% having "other" dementia.
• Incident dementia was significantly predicted by older age, lower educational level, more severe cognitive impairment, disability, lower physical activity, and presence of the apolipoprotein E ε4 allele.
• Mean age was 71.6 years for those without and 74.3 years for those with dementia.
• 54.9% of those without dementia were women vs 63.8% of those with dementia.
• With time, folate levels decreased whereas vitamin B₁₂ levels increased, which may have reflected vitamin B₁₂ supplementation.
• Incident dementia was significantly predicted by lower baseline folate levels, with incidence increasing across quintiles of decreasing folate levels (P = .025).
• Baseline vitamin B₁₂ and homocysteine levels did not predict incident dementia.
• Vitamin B₂ level was positively associated with folate levels (P = .001), whereas homocysteine levels were inversely associated with folate levels (P < .001).
• Decreasing folate, weakly increasing vitamin B₁₂, and increasing homocysteine levels with time were all predictive of dementia, with adjusted odds ratios (ORs) of 1.49, 1.55, and 1.21, respectively.
• Adjustment for weight loss reduced the magnitude of the associations.
• The prevalence of folate deficiency at baseline was 3.5%; vitamin B₁₂ deficiency, 17.4%; and hyperhomocysteinemia, 19.7%.
• The adjusted ORs for incident dementia associated with deficiency conditions were 3.43, 1.53, and 1.57 for reduced folate and vitamin B₁₂ and increased homocysteine levels, respectively.
• The authors suggested that changes in folate, vitamin B₁₂, and homocysteine levels with older age may reflect somatic manifestations of early dementia, such as weight loss.
• The authors suggested that interventions for preventing dementia include addressing the nutrition of frail elderly adults.

Pearls for Practice

• Baseline serum folate level predicts later incident dementia.
• With time, decreasing levels of folate, weakly increasing vitamin B₁₂ and greater increasing levels of homocysteine are associated with increased risk for incident dementia.

Instructions for Participation and Credit

There are no fees for participating in or receiving credit for this online educational activity. For information on applicability and acceptance of continuing education credit for this activity, please consult your professional licensing board.

This activity is designed to be completed within the time designated on the title page; physicians should claim only those credits that reflect the time actually spent in the activity. To successfully earn credit, participants must complete the activity online during the valid credit period that is noted on the title page.

FOLLOW THESE STEPS TO EARN CME/CE CREDIT*:

1. Read the target audience, learning objectives, and author disclosures.
2. Study the educational content online or printed out.
3. Online, choose the best answer to each test question. To receive a certificate, you must receive a passing score as designated at the top of the test. Medscape encourages you to complete the Activity Evaluation to provide feedback for future programming.

You may now view or print the certificate from your CME/CE Tracker. You may print the certificate but you cannot alter it. Credits will be tallied in your CME/CE Tracker and archived for 5 years; at any point within this time period you can print out the tally as well as the certificates by accessing "Edit Your Profile" at the top of your Medscape homepage.

*The credit that you receive is based on your user profile.

Target Audience

This article is intended for primary care clinicians, geriatricians, neurologists, psychiatrists, and other specialists who care for patients at risk for or who have dementia.

Goal

The goal of this activity is to provide medical news to primary care clinicians and other healthcare professionals in order to enhance patient care.

Accreditation Statements

---

Authors and Disclosures

As an organization accredited by the ACCME, Medscape, LLC requires everyone who is in a position to control the content of an education activity to disclose all relevant financial relationships with any commercial interest. The ACCME defines "relevant financial relationships" as financial relationships in any amount, occurring within the past 12 months, including financial relationships of a spouse or life partner, that could create a conflict of interest.

Medscape, LLC encourages Authors to identify investigational products or off-label uses of products regulated by the US Food and Drug Administration, at first mention and where appropriate in the content.

News Author

Caroline Cassels
is a journalist for Medscape. Caroline has been a journalist in the health field for 18 years, writing extensively for both physician and consumer audiences. She launched an awarding-winning consumer publication and edited several consumer health websites before joining thekidney.org, a nephrology site recently acquired by WebMD. She can be contacted at CCassels@medscape.net.

Disclosure: Caroline Cassels has disclosed no relevant financial relationships.

CME Author

Désirée Lie, MD, MSEd
Clinical Professor, Family Medicine, University of California, Orange; Director, Division of Faculty Development, UCI Medical Center, Orange, California

Disclosure: Désirée Lie, MD, MSEd, has disclosed no relevant financial relationships.

Brande Nicole Martin
is the News CME editor for Medscape Medical News.

Disclosure: Brande Nicole Martin has disclosed no relevant financial information.

Legal Disclaimer

Registration for CME credit and the post test must be completed online. To access the activity Post Test, please go to: http://www.medscape.com/viewarticle/569976