Imagine exploring a new neighborhood, where each house represents a different brain structure. By deconstructing the brain into its composite parts, scientists have gained a deeper understanding of the aging process. Using a combination of deep learning and surface analysis, they studied the changes that occur in individual structures during healthy and pathologic aging. The results were fascinating! The analysis revealed that while both mild cognitive impairment (MCI) and Alzheimer’s disease dementia (ADD) impact the aging process, they do so in different ways. It’s like comparing two neighboring houses: one might have slight wear and tear, while the other is in complete disrepair. Similarly, some subcortical structures were mildly affected by MCI, whereas others showed severe deterioration in ADD patients. These findings emphasize the need to study brain aging at a micro level to truly understand its nuances and develop targeted interventions.

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BackgroundBrain age has historically been investigated primarily at the whole brain level. The ability to deconstruct the brain into its composite parts and explore brain age at the sub-structure level offers unique advantages. These include the exploration of dynamic and interconnected relationships between different brain structures in healthy and pathologic aging. To achieve this, individual brain structures can be rendered as surface representations on which morphologic analysis is carried out. Combining the advantages of deep learning with the strengths of surface analysis, we investigate the aging process at the individual structure level with the hypothesis being that pathologic aging does not uniformly affect the aging process of individual structures.MethodsMRI data, age at scan time and diagnosis of dementia were collected from seven publicly available data repositories. The data from 17,440 unique subjects were collected, representing a total of 26,276 T1-weighted MRI accounting for longitudinal acquisitions. Surfaces were extracted for the cortex and seven subcortical structures. Deep learning networks were trained to estimate a subject’s age either using several structures together or a single structure. We conducted a cross-sectional analysis to assess the difference between the predicted and actual ages for all structures between healthy subjects, individuals with mild cognitive impairment (MCI) or Alzheimer’s disease dementia (ADD). We then performed a longitudinal analysis to assess the difference in the aging pace for each structure between stable healthy controls and healthy controls converting to either MCI or ADD.FindingsUsing an independent cohort of healthy subjects, age was well estimated for all structures. Cross-sectional analysis identified significantly larger predicted age for all structures in patients with either MCI and ADD compared to healthy subjects. Longitudinal analysis revealed varying degrees of involvement of individual subcortical structures for both age difference across groups and aging pace across time. These findings were most notable in the whole brain, cortex, hippocampus and amygdala.ConclusionAlthough similar patterns of abnormal aging were found related to MCI and ADD, the involvement of individual subcortical structures varied greatly and was consistently more pronounced in ADD patients compared to MCI patients.

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