Ralph Green

The objective of the present study was to provide normative data for Trail Making Test (TMT) time to completion and performance errors among cognitively normal older adults, and to examine TMT error rates in conjunction with time scores for pre-clinical and clinical Alzheimer's disease (AD) diagnostic decision-making. A sample of 526 individuals was classified into three diagnostic groups (normal controls, N=269; mild cognitive impairment, MCI, N=200; AD, N=57) by a multidisciplinary consensus conference. Results indicated that performance differed among the three groups for TMT A and B time scores as well as TMT B error rate. Diagnostic classification accuracy (i.e., sensitivity, specificity, and positive and negative predictive powers) is described for various combinations of the diagnostic groups. The findings show that TMT B time and errors are independently meaningful scores, and both therefore have clinical utility in assessing individuals referred for dementia evaluations.

Abstract B12 deficiency is the leading cause of megaloblastic anemia, and although more common in the elderly, can occur at any age. Clinical disease caused by B12 deficiency usually connotes severe deficiency, resulting from a failure of the gastric or ileal phase of physiological B12 absorption, best exemplified by the autoimmune disease pernicious anemia. There are many other causes of B12 deficiency, which range from severe to mild. Mild deficiency usually results from failure to render food B12 bioavailable or from dietary inadequacy. Although rarely resulting in megaloblastic anemia, mild deficiency may be associated with neurocognitive and other consequences. B12 deficiency is best diagnosed using a combination of tests because none alone is completely reliable. The features of B12 deficiency are variable and may be atypical. Timely diagnosis is important, and treatment is gratifying. Failure to diagnose B12 deficiency can have dire consequences, usually neurological. This review is written from the perspective of a practicing hematologist.

BACKGROUND: High plasma homocysteine is associated with premature coronary artery disease in men, but the threshold concentration defining this risk and its importance in women and the elderly are unknown. Furthermore, although low B vitamin status increases homocysteine, the link between these vitamins and coronary disease is unclear. METHODS AND RESULTS: We compared 304 patients with coronary disease with 231 control subjects. Risk factors and concentrations of plasma homocysteine, folate, vitamin B12, and pyridoxal 5'-phosphate were documented. A homocysteine concentration of 14 mumol/L conferred an odds ratio of coronary disease of 4.8 (P < .001), and 5-mumol/L increments across the range of homocysteine conferred an odds ratio of 2.4 (P < .001). Odds ratios of 3.5 in women and of 2.9 in those 65 years or older were seen (P < .05). Homocysteine correlated negatively with all vitamins. Low pyridoxal 5'-phosphate (< 20 nmol/L) was seen in 10% of patients but in only 2% of control subjects (P < .01), yielding an odds ratio of coronary disease adjusted for all risk factors, including high homocysteine, of 4.3 (P < .05). CONCLUSIONS: Within the range currently considered to be normal, the risk for coronary disease rises with increasing plasma homocysteine regardless of age and sex, with no threshold effect. In addition to a link with homocysteine, low pyridoxal-5'-phosphate confers an independent risk for coronary artery disease.