Whole-brain analysis reveals increased neuroanatomical asymmetries in dementia for hippocampus and amygdala

Abstract

Structural magnetic resonance imaging data are frequently analysed to reveal morphological changes of the human brain in dementia. Most contemporary imaging biomarkers are scalar values, such as the volume of a structure, and may miss the localized morphological variation of early presymptomatic disease progression. Neuroanatomical shape descriptors, however, can represent complex geometric information of individual anatomical regions and may demonstrate increased sensitivity in association studies. Yet, they remain largely unexplored. In this article, we introduce a novel technique to study shape asymmetries of neuroanatomical structures across subcortical and cortical brain regions. We demonstrate that neurodegeneration of subcortical structures in Alzheimer's disease is not symmetric. The hippocampus shows a significant increase in asymmetry longitudinally and both hippocampus and amygdala show a significantly higher asymmetry cross-sectionally concurrent with disease severity above and beyond an ageing effect. Our results further suggest that the asymmetry in these structures is undirectional and that primarily the anterior hippocampus becomes asymmetric. Based on longitudinal asymmetry measures we subsequently study the progression from mild cognitive impairment to dementia, demonstrating that shape asymmetry in hippocampus, amygdala, caudate and cortex is predictive of disease onset. The same analyses on scalar volume measurements did not produce any significant results, indicating that shape asymmetries, potentially induced by morphometric changes in subnuclei, rather than size asymmetries are associated with disease progression and can yield a powerful imaging biomarker for the early presymptomatic classification and prediction of Alzheimer's disease. Because literature has focused on contralateral volume differences, subcortical disease lateralization may have been overlooked thus far.

Asymmetrical atrophy of thalamic subnuclei in Alzheimer's disease and amyloid‐positive mild cognitive impairment is associated with key clinical features

“…Our findings were consistent with previous investigations [5,24,25] in that patients with AD did not differ from nondemented participants on global thalamic asymmetries. A breakdown by subnuclei, however, revealed lateralization of atrophy.…”

“…The cerebral atrophy characteristic of AD is bilateral but may not be symmetrical across hemispheres. With the advent of high‐resolution magnetic resonance imaging (MRI), detailed brain atlases, probabilistic models of neuroanatomy, and advanced neuroimaging segmentation tools, there is a growing body of evidence that AD is asymmetrical [2–5]. This has been supported by studies which have found that AD is associated with asymmetrical cortical thinning [2], cortical surface area [3], and global cerebral atrophy [4] across hemispheres.…”

The Role of MRI Biomarkers and Their Interactions with Cognitive Status and APOE ε4 in Nondemented Elderly Subjects

“…This interaction effect is not significant for right CA2_3 and CA4_DG, although they also showed significant atrophy and correlation with MoCA. This result may suggest asymmetry of AD pathology, as previously reported [43, 44]. …”

Disruption of Neurosynaptic Physiology and Neuron Network Dysfunction in Brain Disorders: An Environmental and Occupational Health Perspective

“…White matter association tracts and frontopolar cortex are critically included in the network [123]. White matter integrity of the target regions is key for a correlation to performance on the Wechsler Intelligence Scales, both in young and adults [138,139]. The study in Mexico city, children exposed to pollution projects possibility of differential regional effects of inflammatory cytokines in brain.…”