Divergent neurodegenerative patterns: Comparison of [18F] fluorodeoxyglucose-PET- and MRI-based Alzheimer’s disease subtypes
Bibliographic record
Abstract
F] fluorodeoxyglucose (FDG)-PET and MRI are key imaging markers for neurodegeneration in Alzheimer's disease. It has been well established that parieto-temporal hypometabolism on FDG-PET is closely associated with medial temporal atrophy on MRI in Alzheimer's disease. Substantial biological heterogeneity, expressed as distinct subtypes of hypometabolism or atrophy patterns, has been previously described in Alzheimer's disease using data-driven and hypothesis-driven methods. However, the link between these two imaging modalities has not yet been explored in the context of Alzheimer's disease subtypes. To investigate this link, the current study utilized FDG-PET and MRI scans from 180 amyloid-beta positive Alzheimer's disease dementia patients, 339 amyloid-beta positive mild cognitive impairment and 176 amyloid-beta negative cognitively normal controls from the Alzheimer's Disease Neuroimaging Initiative. Random forest hierarchical clustering, a data-driven model for identifying subtypes, was implemented in the two modalities: one with standard uptake value ratios and the other with grey matter volumes. Five hypometabolism- and atrophy-based subtypes were identified, exhibiting both cortical-predominant and limbic-predominant patterns although with differing percentages and clinical presentations. Three cortical-predominant hypometabolism subtypes found were Cortical Predominant (32%), Cortical Predominant+ (11%) and Cortical Predominant posterior (8%), and two limbic-predominant hypometabolism subtypes found were Limbic Predominant (36%) and Limbic Predominant frontal (13%). In addition, little atrophy (minimal) and widespread (diffuse) neurodegeneration subtypes were observed from the MRI data. The five atrophy subtypes found were Cortical Predominant (19%), Limbic Predominant (27%), Diffuse (29%), Diffuse+ (6%) and Minimal (19%). Inter-modality comparisons showed that all FDG-PET subtypes displayed medial temporal atrophy, whereas the distinct MRI subtypes showed topographically similar hypometabolic patterns. Further, allocations of FDG-PET and MRI subtypes were not consistent when compared at an individual level. Additional analysis comparing the data-driven clustering model with prior hypothesis-driven methods showed only partial agreement between these subtyping methods. FDG-PET subtypes had greater differences between limbic-predominant and cortical-predominant patterns, and MRI subtypes had greater differences in severity of atrophy. In conclusion, this study highlighted that Alzheimer's disease subtypes identified using both FDG-PET and MRI capture distinct pathways showing cortical versus limbic predominance of neurodegeneration. However, the subtypes do not share a bidirectional relationship between modalities and are thus not interchangeable.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".