Evidence supports an independent association between plasma total homocysteine concentrations and the risk of vascular disease. Recent epidemiologic studies reappraised the possibility that vascular risk factors might play a role in the pathogenesis not only of vascular dementia (VaD) but also of Alzheimer disease (AD). The objective was to investigate the relations of mild cognitive impairment, AD, and VaD with blood homocysteine, folate, and vitamin B-12. The study population consisted of 314 consecutive subjects, 228 of whom were eligible for analyses. Plasma total homocysteine, serum folate, and serum vitamin B-12 concentrations were measured in 55 nondemented elderly control subjects, 81 mildly cognitively impaired subjects (Clinical Dementia Rating: 0.5), and 92 demented patients prevalently in a mild disease stage and with a clinical diagnosis of AD (n = 74) or VaD (n = 18). Subjects in the lowest folate tertile had significantly higher adjusted odds ratios (ORs) for mild cognitive impairment (OR: 3.1; 95% CI: 1.2, 8.1) and dementia (3.8; 1.3, 11.2). Hyperhomocysteinemia was significantly associated with dementia (adjusted OR: 4.3; 1.3, 14.7) and AD (adjusted OR: 3.7; 1.1, 13.1). In subjects with a Clinical Dementia Rating of 0.5, the mean (+/- SE) Mini-Mental State Examination score was significantly lower (P < 0.05) in the highest homocysteine tertile (24.5 +/- 0.5) than in the lowest tertile (26.6 +/- 0.5). No significant associations were found between minimum medial temporal lobe thickness or leukoaraiosis and any biochemical measure in the dementia and AD groups. These findings suggest that relative folate deficiency may precede AD and VaD onset. Hyperhomocysteinemia might also be an early risk factor for cognitive decline in the elderly, but its role in dementia development must be addressed in future longitudinal studies.

Hemoglobin concentrations slightly below the lower limit of normal are a common laboratory finding in the elderly, but scant evidence is available on the actual occurrence of mild anemia despite its potential effect on health. The objectives of this study were to estimate the prevalence and incidence of mild grade anemia and to assess the frequency of anemia types in the elderly. This was a prospective, population-based study in all residents 65 years or older in Biella, Italy. Blood test results were available for analysis from 8,744 elderly. Hemoglobin concentration decreased and mild anemia increased steadily with increasing age. Mild anemia (defined as a hemoglobin concentration of 10.0-11.9 g/dL in women and 10.0-12.9 g/dL in men) affected 11.8% of the elderly included in the analysis, while the estimated prevalence in the entire population was 11.1%. Before hemoglobin determination, most mildly anemic individuals perceived themselves as non-anemic. Chronic disease anemia, thalassemia trait, and renal insufficiency were the most frequent types of mild anemia. The underlying cause of mild anemia remained unexplained in 26.4% of the cases, almost one third of which might be accounted for by myelodysplastic syndromes. In a random sample of non-anemic elderly at baseline (n=529), after about 2 years, the annual incidence rate of mild anemia was 22.5 per 1000 person-years and increased with increasing age. The prevalence and incidence of mild anemia increase with age and mild anemia affects more than one out of ten elderly individuals. Unexplained anemia is common and may be due to myelodysplastic syndromes in some cases.