Tracking Alzheimer’s Disease

A novel investigative technique has for the first time revealed asymmetrical alterations in specific anatomical structures in the human brain during the progression of dementia.

A computational model of the brain that forms the basis of the BrainPrint, a system for representing the whole brain based on the shape, rather than the size of structures. The hippocampus is labeled in dark blue, the amygdala in light blue, and anterior to the latter is the putamen (white). Source: Christian Wachinger

Alzheimer’s disease is characterized by pathological changes in the structure of the brain. As the disease progresses, brain tissue is irrevocably lost, in particular in the hippocampus, which plays crucial roles in memory and the processing of emotions. A team around LMU neuroscientist Christian Wachinger has now, for the first time, shown that morphological asymmetry increases as dementia progresses. Moreover, the asymmetry of a number of cortical and subcortical structures is predictive for disease onset.

The study demonstrates that abnormal asymmetries in the morphology of certain brain areas (without concomitant alterations in overall volume) are already detectable at early stages in the development of Alzheimer’s. “Our study shows for the first time that, in Alzheimer’s patients, the asymmetries in the hippocampus and the amygdala become more pronounced over time and are therefore correlated with disease progression,” says Christian Wachinger, the first author of the new report and Professor for Neurobiological Research at LMU’s Hospital for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy. The findings have just been published in the journal Brain.

Together with Dr. Martin Reuter of the Martinos Center at Massachusetts General Hospital in Boston – with whom he worked prior to 2015 – Wachinger examined Magnetic Resonance Imaging (MRI) data obtained in the course of a multicenter study in which patients with Alzheimer’s disease, mild cognitive impairment and healthy controls took part. The primary aim was to search for evidence of shape changes in neuroanatomical structures. For this purpose, the researchers made use of a novel computer program called BrainPrint, which they have previously developed and described in an article published in the journal Neuroimage in 2015. Based on the BrainPrint, they developed a new measure of asymmetry that captures shape changes, which is more sensitive than previously used size measurements. Their analysis revealed that asymmetries were most marked in persons suffering from advanced dementia and least prominent in healthy participants. “The degree of asymmetry of brain structures could serve as a useful marker for predicting the future disease trajectory of the disorder,” says Wachinger. “However, we must first obtain a better understanding of the underlying mechanisms that are responsible for the development of the asymmetries themselves.” (Brain 2016)