Hippocampal/medial temporal sclerosis is associated with clinical severity, regional TDP-43, and hippocampal atrophy in Alzheimer disease

Alzheimer disease neuropathologic change does not fully explain clinical severity in patients, indicating the presence of other coexisting pathologies. Researchers analyzed data from a large autopsy cohort to study the role of hippocampal/medial temporal sclerosis (HS/MTL sclerosis) in clinical severity, regional TDP43 involvement, and hippocampal atrophy.

The study identified that HS/MTL sclerosis was present in 13% of cases and was linked to higher dementia staging instrument severity scores, both in non-AD and AD populations. In particular, HS/MTL sclerosis was associated with a greater regional TDP43 topography in later versions of the study and greater hippocampal atrophy, suggesting that it co-occurs with both AD pathology and TDP43 involvement.

Notably, among AD cases assessed near the end of life, participants without HS/MTL sclerosis were more likely to have non-dementia status compared to those with HS/MTL sclerosis. The presence of HS/MTL sclerosis was linked to greater clinical severity in both AD and non-AD cases, highlighting its importance in understanding clinical outcomes in Alzheimer's disease.