Folate Deficiency May Triple Dementia Risk in the Elderly

Caroline Cassels

February 08, 2008

To read this article for CME, click here.

February 8, 2008 — Folate deficiency has been associated with a tripling of dementia risk in the elderly.

New research by investigators at Chonnam National University Medical School, in 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 significantly increased dementia risk.

"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 nondeficient range," study author Robert Stewart, MD, told Medscape Neurology & Neurosurgery.

The study is published online February 5 in 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 over 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 using the Mini-Mental State Examination (MMSE), 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 neurological 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 a median follow-up of 2.4 years, 45 (8.7%) individuals developed dementia. Of these, 34 (6.6%) had Alzheimer's disease (AD), 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 compared with Western populations, possibly because of the high intake of green vegetables in the Korean diet.

Adjusted analyses revealed 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

Over the follow-up period, dementia occurred more commonly in subjects with a relative decline in folate and vitamin B12 levels. The investigators also noted 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 E4 allele.

According to Dr. Stewart, when researchers adjusted for weight loss over 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, B12, and homocysteine.

"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 UK 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.

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

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