Preprint Identifies Two MRI Subtypes of Alzheimer's Disease with Different Patterns of Decline
Preprint Identifies Two MRI Subtypes of Alzheimer's Disease with Different Patterns of Decline
On September 11, the authors of a preprint pooled baseline MRI scans from 1 396 participants across four North American research cohorts. The model identified two statistical orderings of change: one beginning with shrinkage of memory-related brain regions, the other with white-matter lesions in tracts that connect brain areas.
Changes of equal severity on a scan can belong to different stages of the disease. Conventional MRI grouping often conflates the type of trajectory with its stage. The authors used the SuStaIn algorithm, proposed in 2018: it assigns each participant a probable trajectory type and stage from a single baseline scan, while deriving the overall ordering of changes from the full cohort.
When the model was validated across ten data splits, two subtypes best described the sample. In the first, the parahippocampal and temporal regions involved in memory shrank earliest; white-matter lesion volume increased later. In the second, MRI-visible white-matter lesion volume increased first, particularly in the occipital lobe; the internal brain cavities then enlarged and memory-related regions shrank.
In the available analyses, both groups showed abnormal levels of amyloid and tau, proteins linked to Alzheimer's disease. The lesion-first subtype had higher blood pressure. In one of the research cohorts, this same subtype also had a larger volume of enlarged perivascular spaces.
In the atrophy-first subtype, tests of memory, attention, language, and global cognitive ability declined faster. Among 1 145 participants with clinical follow-up, a model adjusted for age and sex associated the atrophy-first trajectory with higher odds of progressing to an Alzheimer's disease diagnosis than the lesion-first trajectory. Future studies may account for these two trajectories when enrolling participants and assessing prognosis, because each is associated with a different pace of cognitive decline.