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Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease.

Abstract

BACKGROUND

Recent studies suggest that vascular disease may contribute to the cause of Alzheimer disease (AD). Since elevated plasma total homocysteine (tHcy) level is a risk factor for vascular disease, it may also be relevant to AD.

OBJECTIVE

To examine the association of AD with blood levels of tHcy, and its biological determinants folate and vitamin B12.

DESIGN

Case-control study of 164 patients, aged 55 years or older, with a clinical diagnosis of dementia of Alzheimer type (DAT), including 76 patients with histologically confirmed AD and 108 control subjects.

SETTING

Referral population to a hospital clinic between July 1988 and April 1996.

MAIN OUTCOME MEASURES

Serum tHcy, folate, and vitamin B12 levels in patients and controls at entry; the odds ratio of DAT or confirmed AD with elevated tHcy or low vitamin levels; and the rate of disease progression in relation to tHcy levels at entry.

RESULTS

Serum tHcy levels were significantly higher and serum folate and vitamin B12 levels were lower in patients with DAT and patients with histologically confirmed AD than in controls. The odds ratio of confirmed AD associated with a tHcy level in the top third (> or = 14 micromol/L) compared with the bottom third (< or = 11 micromol/L) of the control distribution was 4.5 (95% confidence interval, 2.2-9.2), after adjustment for age, sex, social class, cigarette smoking, and apolipoprotein E epsilon4. The corresponding odds ratio for the lower third compared with the upper third of serum folate distribution was 3.3 (95% confidence interval, 1.8-6.3) and of vitamin B12 distribution was 4.3 (95% confidence interval, 2.1-8.8). The mean tHcy levels were unaltered by duration of symptoms before enrollment and were stable for several years afterward. In a 3-year follow-up of patients with DAT, radiological evidence of disease progression was greater among those with higher tHcy levels at entry.

CONCLUSIONS

Low blood levels of folate and vitamin B12, and elevated tHcy levels were associated with AD. The stability of tHcy levels over time and lack of relationship with duration of symptoms argue against these findings being a consequence of disease and warrant further studies to assess the clinical relevance of these associations for AD.

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  • Authors+Show Affiliations

    ,

    Clinical Trial Service Unit, Nuffield Department of Clinical Medicine, Oxford, England.

    , , , ,

    Source

    Archives of neurology 55:11 1998 Nov pg 1449-55

    MeSH

    Aged
    Aged, 80 and over
    Aging
    Alzheimer Disease
    Case-Control Studies
    Disease Progression
    Female
    Folic Acid
    Homocysteine
    Humans
    Male
    Memory Disorders
    Middle Aged
    Polymorphism, Genetic
    Predictive Value of Tests
    Risk Factors
    Vascular Diseases
    Vitamin B 12

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    9823829

    Citation

    Clarke, R, et al. "Folate, Vitamin B12, and Serum Total Homocysteine Levels in Confirmed Alzheimer Disease." Archives of Neurology, vol. 55, no. 11, 1998, pp. 1449-55.
    Clarke R, Smith AD, Jobst KA, et al. Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. Arch Neurol. 1998;55(11):1449-55.
    Clarke, R., Smith, A. D., Jobst, K. A., Refsum, H., Sutton, L., & Ueland, P. M. (1998). Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. Archives of Neurology, 55(11), pp. 1449-55.
    Clarke R, et al. Folate, Vitamin B12, and Serum Total Homocysteine Levels in Confirmed Alzheimer Disease. Arch Neurol. 1998;55(11):1449-55. PubMed PMID: 9823829.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. AU - Clarke,R, AU - Smith,A D, AU - Jobst,K A, AU - Refsum,H, AU - Sutton,L, AU - Ueland,P M, PY - 1998/11/21/pubmed PY - 2000/2/19/medline PY - 1998/11/21/entrez SP - 1449 EP - 55 JF - Archives of neurology JO - Arch. Neurol. VL - 55 IS - 11 N2 - BACKGROUND: Recent studies suggest that vascular disease may contribute to the cause of Alzheimer disease (AD). Since elevated plasma total homocysteine (tHcy) level is a risk factor for vascular disease, it may also be relevant to AD. OBJECTIVE: To examine the association of AD with blood levels of tHcy, and its biological determinants folate and vitamin B12. DESIGN: Case-control study of 164 patients, aged 55 years or older, with a clinical diagnosis of dementia of Alzheimer type (DAT), including 76 patients with histologically confirmed AD and 108 control subjects. SETTING: Referral population to a hospital clinic between July 1988 and April 1996. MAIN OUTCOME MEASURES: Serum tHcy, folate, and vitamin B12 levels in patients and controls at entry; the odds ratio of DAT or confirmed AD with elevated tHcy or low vitamin levels; and the rate of disease progression in relation to tHcy levels at entry. RESULTS: Serum tHcy levels were significantly higher and serum folate and vitamin B12 levels were lower in patients with DAT and patients with histologically confirmed AD than in controls. The odds ratio of confirmed AD associated with a tHcy level in the top third (> or = 14 micromol/L) compared with the bottom third (< or = 11 micromol/L) of the control distribution was 4.5 (95% confidence interval, 2.2-9.2), after adjustment for age, sex, social class, cigarette smoking, and apolipoprotein E epsilon4. The corresponding odds ratio for the lower third compared with the upper third of serum folate distribution was 3.3 (95% confidence interval, 1.8-6.3) and of vitamin B12 distribution was 4.3 (95% confidence interval, 2.1-8.8). The mean tHcy levels were unaltered by duration of symptoms before enrollment and were stable for several years afterward. In a 3-year follow-up of patients with DAT, radiological evidence of disease progression was greater among those with higher tHcy levels at entry. CONCLUSIONS: Low blood levels of folate and vitamin B12, and elevated tHcy levels were associated with AD. The stability of tHcy levels over time and lack of relationship with duration of symptoms argue against these findings being a consequence of disease and warrant further studies to assess the clinical relevance of these associations for AD. SN - 0003-9942 UR - https://www.unboundmedicine.com/medline/citation/9823829/Folate_vitamin_B12_and_serum_total_homocysteine_levels_in_confirmed_Alzheimer_disease_ L2 - https://jamanetwork.com/journals/jamaneurology/fullarticle/vol/55/pg/1449 DB - PRIME DP - Unbound Medicine ER -