Hypometabolic subtypes of AD are linked to comorbid hippocampal sclerosis and Lewy body pathology.

Background: Neuroimaging studies have identified distinct 'typical/neocortical' and 'limbic-predominant' hypometabolic subtypes of AD with different clinical and biomarker characteristics. We investigated associations of these subtypes with postmortem neuropathological measures in an observational study.

Methods: Antemortem FDG-PET scans of 74 participants from the ADNI autopsy cohort were classified into previously described typical/neocortical and limbic-predominant subtype patterns. We used Bayesian regression and ANCOVA to test associations between the subtypes and neuropathological features.

Results: Results were inconclusive for Thal phases, Braak stages, CERAD neuritic plaque scores, hippocampal tangle density, and TDP-43 pathology (BF₁₀ between 0.447 and 1.146). However, the limbic-predominant subtype was associated with hippocampal sclerosis (BF₁₀ = 3.842, moderate level of evidence), whereas the typical/neocortical subtype was associated with Lewy body pathology (BF₁₀ = 10.093, strong level of evidence).

Conclusions: These findings highlight the influence of AD and non-AD-specific pathologies on neurodegeneration patterns and may provide directions for research into hypometabolic pattern analysis as an indirect marker of comorbid pathology.