DTI Correlates of Cognition in Conventional MRI of Normal-Appearing Brain in Patients with Clinical Features of Subacute Combined Degeneration and Biochemically Proven Vitamin B12 Deficiency

BACKGROUND AND PURPOSE:Vitamin B₁₂ deficiency may cause neural injury that results in cognitive deficits. The main purpose of our study was to evaluate morphometric and microstructural changes in the brain and relate them to cognition in subacute combined degeneration of the spinal cord and patients with biochemically deficient vitamin B₁₂.MATERIALS AND METHODS:Fifty-one patients were recruited and underwent nerve-conduction velocity tests and routine hematologic examinations. Serum vitamin B₁₂ and homocystine levels were also measured. All patients and 46 age- and sex-matched controls underwent cervical spine and brain MR imaging along with cognition tests. MR imaging included conventional scans and DTI. Voxel-based morphometry was performed for determining the WM and GM volumes, based on T1-weighted images. DTI measures that included fractional anisotropy, ADC, radial diffusivity, and axial diffusivity were determined by using tract-based statistics.RESULTS:None of the patients showed any abnormality on conventional MR imaging. No significant changes in GM and WM volumes were observed in patients compared with controls. Significant reductions in the fractional anisotropy and an increase in ADC and radial diffusivity values were observed in multiple brain regions in patients compared with controls. These changes were confirmed on the region-of-interest analysis. Neuropsychological scores were significantly different in patients compared with controls and showed significant correlation with fractional anisotropy and radial diffusivity in a few brain regions.CONCLUSIONS:Microstructural changes are seen in WM regions on DTI in patients with vitamin B₁₂ deficiency and correlate with cognition scores. DTI can be used for objective assessment of microstructural changes in the brain in vitamin B₁₂ deficiency.

Bvitamins contribute to CNS development and proper functioning by acting as a cofactor in numerous catalytic reactions in the human body that are required for the synthesis and functioning of neurotransmitters and myelination. A deficiency of vitamin B₁₂ may result in injury to the neural tissue. A limited number of clinical studies in children demonstrated a correlation between vitamin B₁₂ deficiency and cognition.^1,2 Studies in elderly subjects suggest that vitamin B₁₂ deficiency is associated with cognitive decline and may contribute to Alzheimer dementia,^3,4 whereas others have failed to demonstrated an increased risk.^5,6Subjects with B₁₂ deficiency may also show changes in the posterolateral column of the spinal cord on MR imaging. Clinical symptoms relating to neuropathy and spinal cord involvement, referred to as subacute combined degeneration (SACD) of the spinal cord, are common in adult subjects with B₁₂ deficiency. Changes in the brain parenchyma on MR imaging have been sporadically reported, with poor sensitivity.^7,8 In a cross-sectional study on an elderly population, a reduction in brain volume was observed with B₁₂ deficiency.⁹ There are isolated reports of brain demyelination in patients with SACD, which may or may not show resolution following vitamin B₁₂ replacement.^10,11Elderly populations with vitamin B₁₂ deficiency are reported to show whole-brain atrophy and white matter damage.^12,13 On the basis of a number of case reports, brain atrophy is also a pathologic feature in infants with vitamin B₁₂ deficiency.^14–16 Advanced MR imaging–based modalities such as DTI and MR spectroscopy showed abnormalities in a variety of diffuse neurologic disorders, whereas conventional MR imaging findings appeared normal. We hypothesized that patients with clinical symptoms of SACD and biochemical evidence of vitamin B₁₂ deficiency will have an associated cognitive decline and microstructural alterations in brain WM on DTI, even when conventional MR imaging findings appear normal. To verify this hypothesis, we performed whole-brain DTI and cognitive assessment in patients who presented with clinical signs of SACD and a biochemical deficiency of vitamin B₁₂. The DTI measures were correlated with neuropsychological test scores. We also performed voxel-based morphometry analysis for volumetric changes in GM and WM. To the best of our knowledge, this is the first study to quantify the microstructural changes in normal-appearing brain on MR imaging in patients with SACD and biochemically confirmed vitamin B₁₂ deficiency.