Hippocampus, Amygdala Asymmetries May Track Alzheimer’s Progression

A unique approach to analyzing brain structure that focuses on the shape instead of the size of features may allow identification of individuals in early pre-symptomatic stages of Alzheimer’s disease.

A team of Massachusetts General Hospital (MGH) investigators using advanced computational tools to analyze data from standard MRI scans report that individuals with Alzheimer’s disease, including those diagnosed partway through a multi-year study, had greater levels of asymmetry, differences in shape between the left and right sides of the brain, of key brain structures.

Lead author Christian Wachinger, PhD, formerly with the Martinos Center for Biomedical Imaging at MGH, said:

“Our results show for the first time that asymmetry of the hippocampus and amygdala increases with disease severity, above and beyond age-associated effects. By studying the progression of asymmetry from mild cognitive impairment to dementia, we demonstrated that greater asymmetry in those and a few other structures can predict disease progression and could be a biomarker allowing early detection of dementia.”

BrainPrint

Wachinger is part of a team led by Martin Reuter, PhD, of the Martinos Center, that developed BrainPrint, a computer-aided system for representing the whole brain based on the shapes rather than the size or volume of structures.

Originally described in a 2015 article, BrainPrint appears to be as accurate as a fingerprint in distinguishing among individuals. In a recent paper, Wachinger and Reuter demonstrated the use of BrainPrint for automated diagnosis of Alzheimer’s disease.

The current study used BrainPrint to analyze structural asymmetries in a series of MR images of almost 700 participants in the National Institute of Health-sponsored Alzheimer’s Disease Neuroimaging Initiative (ADNI).

Participation in that study involves MR brain imaging taken upon enrollment and repeated every 6 to 12 months, along with cognitive and genetic testing; and the MGH study analyzed data from ADNI participants with at least three MRI scans.

Participants were divided into four groups: those diagnosed with probable Alzheimer’s when entering the study, healthy controls with no sign of dementia, individuals with mild cognitive impairment that remained stable over the two to three years for which scans were available, and those with mild cognitive impairment that progressed to Alzheimer’s disease during the study.

Increased Asymmetry

BrainPrint analysis of the data revealed that initial, between-hemisphere differences in the shapes of the hippocampus and amygdala (structures known to be sites of neurodegeneration in Alzheimer’s disease) were highest in individuals with dementia and lowest in healthy controls.

Among those originally classified with mild cognitive impairment, baseline asymmetry was higher in those that progressed to Alzheimer’s dementia and became even greater as symptoms developed. Increased asymmetry was also associated with poorer cognitive test scores and with increased cortical atrophy.

The senior author of the Brain paper, Reuter explains,

“Several studies have indicated that Alzheimer’s has different effects in different sub-structures of the hippocampus and amygdala. Since the shape descriptors of BrainPrint are more sensitive to subtle changes within a structure than are standard volume-based measures, they are better suited to quantify early disease effects and predict future progression, which opens up new research directions into the mechanisms that cause these asymmetries.

For example, in addition to asymmetric distribution of amyloid beta, which has been reported, the differences could reflect disease subtypes that affect hemispheres differently.”

Christian Wachinger et al
Whole-brain analysis reveals increased neuroanatomical asymmetries in dementia for hippocampus and amygdala
Brain (2016). DOI: 10.1093/brain/aww243

Image: Martin Reuter, Ph.D., and Christian Wachinger, Ph.D., Martinos Center for Biomedical Imaging, Massachusetts General Hospital