Progression from mild to pronounced MCI is not associated with cerebrospinal fluid biomarker deviations

Area of Science:

• Neuroscience
• Biomarker Research
• Cognitive Impairment Studies

Background:

• Cerebrospinal fluid (CSF) biomarkers are crucial for predicting the progression of mild cognitive impairment (MCI) to dementia.
• Early detection of neurodegenerative processes is vital, yet patterns in very early MCI stages remain unclear.

Purpose of the Study:

• To investigate if CSF biomarker deviations (total tau, β-amyloid 1-42, neurofilament light protein) predict progression within MCI stages.
• To determine if these biomarkers are indicative of early neurodegeneration in MCI.

Main Methods:

• A cohort of 246 memory clinic patients (non-progressive MCI, progressive MCI, converting MCI, stable dementia) and 80 controls were followed for 24 months.
• Baseline CSF levels of total tau (T-tau), β-amyloid 1-42 (Aβ42), and neurofilament light protein (NFL) were measured.

Main Results:

• Patients with converting MCI and stable dementia showed lower Aβ42 and higher T-tau and NFL compared to controls and non-progressive/progressive MCI groups (p < 0.0005).
• No significant biomarker differences were observed between progressive and non-progressive MCI groups.
• Biomarker deviations successfully predicted MCI to dementia conversion.

Conclusions:

• CSF biomarker deviations predict progression from MCI to dementia, aligning with expectations.
• Contrary to the hypothesis, biomarker changes did not reflect progression from very mild to more pronounced MCI.
• The findings suggest that Aβ42, T-tau, and NFL may not serve as early indicators of MCI progression, or that other pathologies are involved.