Homocysteine, neural atrophy, and the effect of caloric restriction in rhesus monkeys

Abstract

Higher serum homocysteine (Hcy) levels in humans are associated with vascular pathology and greater risk for dementia, as well as lower global and regional volumes in frontal lobe and hippocampus. Calorie restriction (CR) in rhesus monkeys (Macaca mulatta) may confer neural protection against age- or Hcy-related vascular pathology. Hcy was collected proximal to an MRI acquisition in aged rhesus monkeys and regressed against volumetric and diffusion tensor imaging indices using voxel-wise analyses. Higher Hcy was associated with lower white matter volume in pons and corpus callosum. Hcy was correlated with lower gray matter volume and density in prefrontal cortices and striatum. CR did not influence Hcy levels. However, control monkeys exhibited a strong negative correlation between Hcy and global gray matter, whereas no relationship was evident for the CR monkeys. Similar group differences were also seen across modalities in the splenium of the corpus callosum, prefrontal cortices, hippocampus, and somatosensory areas. The data suggest that CR may ameliorate the influence of Hcy on several important age-related parameters of parenchymal health.

Interleukin-8 and interleukin-10, brain volume and microstructure, and the influence of calorie restriction in old rhesus macaques

“…The interaction between age and CR in prior reports implicated gray matter in the mid-cingulate cortex and small clusters in the thalamic bundle and superior longitudinal fasciculus for FA and MD. For other age-related biomarkers of interest, such as homocysteine (Willette et al 2012a), the interaction with dietary condition revealed a shallower slope of association with gray matter in the right hippocampus. A similar association with hippocampal gray matter was found in the current analyses of IL-8.…”

Does the brain shrink as the waist expands?

“…In addition CR monkeys showed less WM atrophy and more microstructural density per point higher homocysteine levels primarily in brainstem and cerebellum, as well as less GM atrophy in occipital, hippocampal, caudoputamen, and anterior cingulate areas (Willette et al, 2012b). CR also considerably reduced stress reactivity (Willette et al, 2012c), where aged monkeys on CR showed less corresponding atrophy per point increase in a z-scored stress factor in many WM tracts, as well as similar amelioration in GM volume or microstructural density for orbital PFC and hippocampus.…”

Higher homocysteine associated with thinner cortical gray matter in 803 participants from the Alzheimer's Disease Neuroimaging Initiative

“…This new cortical mapping study complements prior studies associating high levels of homocysteine with overall brain volume reduction, WM atrophy rate, baseline volume and atrophy rate of the hippocampus and medial temporal lobe (Clarke et al, 1998a, den Heijer et al, 2003, Douaud et al, 2013, Firbank et al, 2010, Williams et al, 2002), lower tissue volumes in frontal and parietal WM (Rajagopalan et al, 2011), greater cortical atrophy (den Heijer et al, 2003), longitudinal ventricular volume enlargement in elderly individuals with arteriosclerotic disease (Jochemsen et al, 2012), lower whole brain GM volume in non-demented elderly (Whalley et al, 2003) in humans and with lower GM volume and density in prefrontal cortices and striatum in rhesus monkeys (Willette et al, 2012). Our prior study in an almost entirely overlapping subject population – but with a different method, TBM – found WM tissue contraction (Rajagopalan et al, 2011) in areas that structurally connect the GM regions we see here in the cortex.…”