Clinical Scorecard: Intersecting Pathways to Hippocampal Sclerosis in the Elderly: Perspectives from LATE-NC and Vascular Conditions

At a Glance

Key Highlights

• HS-A is strongly associated with LATE-NC, showing a dose-dependent increase with LATE-NC stage, especially stage 3.
• Cerebrovascular disease independently contributes to HS-A, highlighting vascular pathology as a separate pathogenic pathway.
• Associations of HS-A with Alzheimer’s disease neuropathologic changes and Lewy body disease are largely mediated through LATE-NC co-pathology.

Guideline-Based Recommendations

Diagnosis

• Consider LATE-NC in differential diagnosis of dementia with prominent memory impairment in the oldest-old.
• Use clinical criteria emphasizing hippocampal atrophy disproportionate to global brain atrophy to support LATE diagnosis.
• Recognize the current lack of in vivo biomarkers for LATE-NC but monitor emerging radiologic and fluid-based candidates.

Management

• No specific treatments currently exist for LATE-NC or HS-A; management remains supportive and symptomatic.
• Address cerebrovascular health as a potential therapeutic target to mitigate HS-A progression.

Monitoring & Follow-up

• Monitor cognitive decline with attention to episodic memory impairment characteristic of LATE-NC.
• Follow developments in biomarker research for early and accurate in vivo diagnosis.

Risks

• Advanced age increases risk primarily via accumulation of LATE-NC pathology.
• Co-existing cerebrovascular disease elevates risk independently.
• Microinfarctions may have complex, not fully understood associations with HS-A.

Patient & Prescribing Data

Elderly patients with dementia exhibiting hippocampal atrophy and memory impairment

Currently no disease-modifying treatments; focus on managing vascular risk factors and symptomatic care

Clinical Best Practices

• Incorporate comprehensive neuropathologic assessment including LATE-NC staging when evaluating hippocampal sclerosis.
• Consider cerebrovascular disease burden in clinical evaluation and management of HS-A.
• Use updated clinical criteria for LATE diagnosis to improve diagnostic accuracy in the oldest-old.
• Support research and clinical trials aimed at developing in vivo biomarkers and targeted therapies for LATE-NC and HS-A.

References

• Woodworth et al., Common neuropathologic change drivers of hippocampal sclerosis of ageing
• LATE-NC staging and diagnostic criteria update