A new visual rating scale to assess strategic white matter hyperintensities within cholinergic pathways in dementia

Area of Science:

• Neuroimaging
• Neurology
• Vascular Dementia

Background:

• Subcortical vascular disease can cause cognitive decline by disrupting cholinergic fibers via ischemic lesions like white matter hyperintensities (WMH).
• Alzheimer Disease (AD) and subcortical ischemic microvascular disease share mechanisms potentially involving WMH within critical brain pathways.

Purpose of the Study:

• To develop and validate a novel MRI visual rating scale assessing WMH specifically within human cholinergic pathways.
• To evaluate the association between WMH in cholinergic pathways and cognitive performance in AD patients.

Main Methods:

• A new visual rating scale, the Cholinergic Pathways HyperIntensities Scale, was developed based on human cholinergic pathway tracings.
• Sixty AD patients and 15 controls underwent MRI assessment of WMH in ten cholinergic pathway regions and standardized neuropsychological testing.
• The new scale's reliability was assessed, and its correlation with cognitive measures was compared to a general WMH scale.

Main Results:

• The Cholinergic Pathways HyperIntensities Scale demonstrated reliability and correlated with volumetric WMH measures.
• Ratings from the new scale were significantly associated with impaired performance on the Mattis Dementia Rating Scale in AD patients (r=0.40; P=0.02), explaining 12% of the variance.
• General WMH scores did not show a significant association with cognitive performance in the same model.

Conclusions:

• The novel MRI rating scale for WMH in cholinergic pathways is reliable and shows superior correlation with cognitive performance compared to general WMH scales in AD.
• These findings suggest that the precise localization of WMH within specific neurotransmitter systems, like the cholinergic pathways, is crucial for understanding cognitive decline in AD and related disorders.