Age-disproportionate atrophy in Alzheimer's disease and Parkinson's disease spectra

INTRODUCTION: Brain age gap (BAG), defined as the difference between MRI-predicted ‘brain age’ and chronological age, can capture information underlying various neurological disorders. We investigated the pathophysiological significance of the BAG across neurodegenerative disorders. METHODS: We developed a brain age estimator using structural MRIs of healthy-aged individuals from one cohort study. Subsequently, we applied this estimator to people with Alzheimer's disease spectra (AD) and Parkinson's disease (PD) from another cohort study. We investigated brain sources responsible for BAGs among these groups. RESULTS: Both AD and PD exhibited a positive BAG. Brain sources showed overlapping, yet partially segregated, neuromorphological differences between these groups. Furthermore, employing with t-distributed stochastic neighbor embedding on the brain sources, we subclassified PD into two groups with and without cognitive impairment. DISCUSSION: Our findings suggest that brain age estimation becomes a clinically relevant method for finely stratifying neurodegenerative disorders. Highlights: Brain age estimated from structure MRI data was greater than chronological age in patients with Alzheimer's disease/mild cognitive impairment or Parkinson's disease. Brain regions attributed to brain age estimation were located mainly in the fronto-temporo-parietal cortices but not in the motor cortex or subcortical regions. Brain sources responsible for the brain age gaps revealed roughly overlapping, yet partially segregated, neuromorphological differences between participants with Alzheimer's disease/mild cognitive impairment and Parkinson's disease. Participants with Parkinson's disease were subclassified into two groups (with and without cognitive impairment) based on brain sources responsible for the brain age gaps.