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The Leiden 85-Plus Study

Wendy P. J. den Elzen, MSc; Rudi G. J. Westendorp, MD, PhD; Marijke Frölich, PhD; Wouter de Ruijter, MD; Willem J. J. Assendelft, MD, PhD; Jacobijn Gussekloo, MD, PhD

Arch Intern Med. 2008;168(20):2238-2244.

Background  Screening for deficiencies in vitamin B₁₂ and folate is advocated to prevent anemia in very elderly individuals. However, the effects of vitamin B₁₂ and folate deficiency on the development of anemia in old age have not yet been established.

Methods  The current study is embedded in the Leiden 85-Plus Study, a population-based prospective study of subjects aged 85 years. Levels of vitamin B₁₂, folate, and homocysteine were determined at baseline. Hemoglobin levels and mean corpuscular volume (MCV) were determined annually during 5 years of follow-up.

Results  We analyzed data from 423 subjects who did not use any form of cyanocobalamin, hydroxocobalamin, or folic acid supplementation, neither at baseline nor during follow-up. Folate deficiency (<7 nmol/L; n = 34) and elevated homocysteine levels (>13.5 µmol/L; n = 194) were associated with anemia at baseline (adjusted odds ratio [OR], 2.44; 95% confidence interval [CI], 1.06-5.61; and adjusted OR, 1.82; 95% CI, 1.08-3.06, respectively), but vitamin B₁₂ deficiency (<150 pmol/L; n = 68) was not (adjusted OR, 1.51; 95% CI, 0.79-2.87). Furthermore, vitamin B₁₂ deficiency was not associated with the development of anemia during follow-up (adjusted HR, 0.92; 95% CI, 0.46-1.82) or with changes in MCV (adjusted linear mixed model; P = .77). Both folate deficiency and elevated homocysteine levels were associated with the development of anemia from age 85 years onward (adjusted HR, 3.33; 95% CI, 1.55-7.14; and adjusted HR, 1.70; 95% CI, 1.01-2.88, respectively), but not with an increase in MCV over time (P > .30).

Conclusion  In the general population of very elderly individuals, anemia in 85-year-old subjects is associated with folate deficiency and elevated homocysteine levels but not with vitamin B₁₂ deficiency.

Author Affiliations: Departments of Public Health and Primary Care (Ms den Elzen and Drs de Ruijter, Assendelft, and Gussekloo), Gerontology and Geriatrics (Dr Westendorp), and Clinical Chemistry (Dr Frölich), Leiden University Medical Center, Leiden, the Netherlands.

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