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The effect of white matter hyperintensities on neurodegeneration in mild cognitive impairment
Giuseppe Tosto1, Molly E Zimmerman2, Jamie L Hamilton3
1Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Introduction:
It is unclear whether white matter hyperintensities (WMHs), magnetic resonance imaging markers of small-vessel cerebrovascular disease, promote neurodegeneration and associated clinical decline in Alzheimer's disease (AD), or simply co-occur with recognized pathogenic processes.
Methods:
In 169 patients with mild cognitive impairment, followed for 3 years, we examined the association of (1) baseline regional WMH and cerebral spinal fluid-derived t-tau (total tau) with entorhinal cortex atrophy rates, as a marker of AD-related neurodegeneration, and conversion to AD; and (2) baseline regional WMH with change in t-tau level.
Results:
In participants with low baseline t-tau, higher regional WMH volumes were associated with faster entorhinal cortex atrophy. Higher parietal WMH volume predicted conversion to AD in those with high t-tau. Higher parietal and occipital WMH volumes predicted increasing t-tau.
Discussion:
WMHs affect AD clinical and pathologic processes both directly and interacting with tau.
Insights
White matter hyperintensities (WMHs) impact Alzheimer's disease (AD) progression. These small-vessel disease markers interact with tau pathology, influencing neurodegeneration and clinical decline in AD patients.
Area of Science:
- Neurology
- Neuroimaging
- Alzheimer's Disease Research
Background:
- White matter hyperintensities (WMHs) are MRI markers of small-vessel cerebrovascular disease.
- Their role in promoting neurodegeneration and clinical decline in Alzheimer's disease (AD) remains unclear.
Purpose of the Study:
- To investigate the association between WMHs and neurodegeneration markers in mild cognitive impairment (MCI).
- To examine if WMHs predict conversion to AD and changes in tau pathology.
Main Methods:
- Longitudinal study of 169 patients with MCI over 3 years.
- Assessed baseline regional WMH volumes and cerebrospinal fluid-derived total tau (t-tau).
- Examined entorhinal cortex atrophy rates and conversion to AD.
Main Results:
- In participants with low baseline t-tau, higher WMH volumes correlated with faster entorhinal cortex atrophy.
- Higher parietal WMH predicted conversion to AD in those with high t-tau.
- Parietal and occipital WMH volumes predicted increases in t-tau levels.
Conclusions:
- WMHs influence both direct and interacting pathways in AD clinical and pathological processes.
- WMHs are implicated in AD progression, particularly in conjunction with tau pathology.
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