To explore the relationship between hippocampal sclerosis of aging (HS-A) and various neuropathological conditions, particularly LATE-NC and cerebrovascular disease, highlighting the significance of these associations for clinical practice.
Key Findings:
HS-A is significantly associated with LATE-NC, with a dose-dependent increase observed, indicating a critical relationship.
Chronological age's effect on HS-A is secondary to the burden of LATE-NC, suggesting age-related neurodegenerative processes.
ADNC and limbic LBD associations with HS-A diminish when accounting for LATE-NC, indicating mediation rather than independent effects.
Global cerebrovascular disease shows an independent association with HS-A, emphasizing the need for cerebrovascular health considerations.
Interpretation:
LATE-NC is likely a primary driver of HS-A, suggesting a need for revised diagnostic criteria and potential therapeutic targets focusing on cerebrovascular health, which could significantly impact patient management.
Limitations:
Neuropathologic assessment in the NACC dataset is limited to a single hemisphere, which could impact analyses for a condition that not infrequently occurs unilaterally.
Lateral presence or absence of pathology is not recorded, limiting detailed analyses and potentially introducing biases.
Conclusion:
The study reinforces the complex relationship between HS-A and various neuropathological conditions, highlighting LATE-NC as a key factor and the importance of cerebrovascular health, which could inform future research and clinical practices.
