Early- vs late-onset subcortical vascular cognitive impairment

Area of Science:

• Neurology
• Neuroimaging
• Cognitive Neuroscience

Background:

• Subcortical vascular cognitive impairment (SVCI) is a significant cause of dementia.
• Understanding the distinct features of early-onset SVCI (EO-SVCI) versus late-onset SVCI (LO-SVCI) is crucial for targeted interventions.
• Age at onset may influence the underlying pathology and clinical presentation of SVCI.

Purpose of the Study:

• To compare pathological burden, structural brain changes, and cognitive function between EO-SVCI and LO-SVCI.
• To elucidate the role of age at onset in shaping the phenotype of SVCI.

Main Methods:

• Prospective recruitment of 142 SVCI patients, categorized into EO-SVCI (<65 years) and LO-SVCI (≥65 years).
• Comprehensive assessment including neuropsychological tests, 3T brain MRI, and amyloid PET imaging using [11C] Pittsburgh compound B (PiB).
• Comparison of small vessel disease markers (lacunes), amyloid burden (PiB SUVR), structural network integrity, cortical thickness, hippocampal volume, and cognitive performance.

Main Results:

• EO-SVCI patients demonstrated a higher burden of lacunes and more severe frontal network disruptions, leading to greater frontal-executive dysfunction.
• LO-SVCI patients exhibited higher amyloid burden (PiB SUVR) and more pronounced cortical and hippocampal atrophy.
• Despite similar overall disease severity, distinct pathological profiles correlated with age at onset.

Conclusions:

• EO-SVCI is characterized by vascular pathology and frontal network involvement, while LO-SVCI shows features suggestive of co-existing Alzheimer's disease pathology.
• Age at onset is a critical determinant of the distinct pathological burdens and clinical manifestations in SVCI.
• These findings highlight the need for age-stratified approaches in diagnosing and managing SVCI.