Determining Clinical Disease Progression in Symptomatic Patients With CADASIL.

Area of Science:

• Neurology
• Genetics
• Medical Research

Background:

• Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a common small artery brain disease linked to NOTCH3 gene variants.
• The progression and interrelation of deficits in CADASIL at different disease stages remain poorly understood.

Purpose of the Study:

• To model the disease progression in CADASIL.
• To identify distinct patient subgroups based on progression patterns.
• To investigate the influence of various covariates on clinical worsening.

Main Methods:

• Utilized data from 395 patients at a French CADASIL referral center, with a mean follow-up of 7.5 years.
• Employed a disease course model (Leaspy) to assess progression and variability.
• Applied Gaussian mixture models to identify progression subgroups and logistic regressions to compare group characteristics.

Main Results:

• Clinical manifestations in CADASIL patients are heterogeneous and vary significantly with disease stage.
• Identified two distinct progression subgroups: an early-onset, rapid progression group with motor symptoms and a late-onset, slow progression group with cognitive symptoms.
• Male sex, lower education, hypertension, and NOTCH3 variant location (EGFr 1-6) were associated with differences between groups.

Conclusions:

• CADASIL patients experience a gradual and heterogeneous decline in clinical and cognitive functions.
• Two primary progression profiles exist: rapid and early, or delayed and slower.
• Male sex, low education, specific NOTCH3 variant locations, smoking, and hypertension may impact clinical progression.