Jack and colleagues [ 44] showed that in cognitively normal persons the change of brain atrophy over time is associated with a change in cognitive scores.
A striking example of the effect of changes in tHcy concentrations on brain atrophy over two years is shown in Fig. 4, which illustrates subtraction cranial MRI scans from a participant in the placebo group whose tHcy concentration increased (Fig. 4A), and from a member of the active treatment group whose tHcy concentration decreased (Fig. 4B).
Several SNPs in the BDNF gene were associated with more rapid brain atrophy over two years [ 111].
Moreover N-acetylaspartate, another biomarker for neuronal loss, was found to decrease by ∼12% in a traumatic brain injury cohort who suffered ∼1.09% of total brain atrophy over one year (Cohen et al., 2007).
15 16 Thus, if TCS is to be considered useful for observing brain atrophy over the disease course, it should also consistently demonstrate clinical correlations in patients with less severe disease.
Carriers of the Met allele also showed faster cognitive decline and greater brain atrophy over 36 months compared to Val/Val carriers; however, this only occurred in elderly adults with high basal A β at the start of the study, suggesting that neurotrophin dysregulation accelerates rather than initiates neurodegeneration in AD [ 114].
Of note, Khan and colleagues [ 14] described two patients with bvFTD-SP who demonstrated no significant brain atrophy over the course of 3 years and 8 years, respectively; the seeming lack of progressive atrophy contributed some uncertainty to the patients' initial bvFTD diagnosis.
In support, while the reduction in mean annualized relapse rate by laquinimod in the two Phase III trials was on the order of ∼20% compared to placebo, its reduction in the progression of disability or brain atrophy over 2 years ranged between 25%and35%5%.
This has shown associations with other disease markers, particularly brain atrophy in a few, but not all, studies [35 37].
Research also shows that supplementing with B vitamins, including B12, helps to slow brain atrophy in elderly people with mild cognitive impairment (brain atrophy is a well-established characteristic of Alzheimer's disease).
