CADASIL has a recognizable life-course. Understanding the typical age and order of symptoms is the single most important step in catching this disease earlier — for yourself, your family, or your patients.
Five overlapping symptom domains define the CADASIL phenotype. Most patients experience several over the course of decades.
Often the earliest symptom — appearing in the 20s or 30s. About 30–40% of CADASIL patients experience migraine with aura. Auras may be visual, sensory, or aphasic, and are sometimes prolonged (hours rather than minutes), atypical, or hemiplegic.
Onset: 20s–30s · Frequency: 30–40% of patients
Recurrent lacunar (small, deep) ischemic strokes and TIAs are the clinical hallmark — most often beginning in the 40s–50s. They typically occur in patients without classical vascular risk factors, which is part of why diagnosis is delayed.
Onset: 40s–60s · Frequency: 60–85% over a lifetime
Subcortical vascular cognitive impairment — typically affecting attention, processing speed, and executive function first. Memory tends to be relatively spared early on. Decline is often stepwise rather than smooth.
Onset: 50s–70s · Frequency: Eventually in most patients
Depression and apathy affect ~30% of patients and may precede other symptoms. Apathy in CADASIL is a distinct clinical feature, not just "low mood" — it reflects disconnection of frontal–subcortical circuits and often goes unrecognized.
Onset: Any age · Frequency: ~30%
Later in the disease course, many patients develop small-stepped, magnetic gait with imbalance, falls, and pseudobulbar features (emotional incontinence, dysphagia). These reflect cumulative deep white-matter and basal-ganglia injury.
Onset: 60s+ · Frequency: Common in advanced disease
The pattern is autosomal dominant — strokes, "early dementia," migraines, or psychiatric illness across multiple generations. Some families have already been told their relatives had MS, a "weak vessel," or unexplained early decline.
Inheritance: 50% per child · Penetrance: Near-complete, variable expressivity
The first symptom in roughly a third of patients. Often dismissed or misclassified for years.
Apathy, low motivation, depression, mild executive dysfunction. Frequently attributed to life stress or burnout.
Often the diagnostic moment — but only if CADASIL is on the differential. White matter changes are usually well-established on MRI by this stage.
Vascular cognitive impairment dominates. Function may decline rapidly during clusters of events, then plateau.
Many patients require assistance with daily activities. Pseudobulbar features and dementia are common in advanced disease.
Some carriers remain mildly affected into their 70s. Vascular risk factor control, smoking history, and likely other genetic and lifestyle factors all modify the course.
Any one of these alone raises suspicion. Two or more — and CADASIL belongs explicitly on the workup list.
Knowing what doesn't fit is just as important as knowing what does. The following features should prompt consideration of alternative diagnoses.
If you recognize this pattern in your own life, talk to your physician about NOTCH3 testing — and bring our printable physician handout with you.
Resources →One diagnosis often unlocks understanding for an entire family tree. We can help you think through who to involve, and how.
Family support →Pattern recognition matters. Our quick-reference card distills the signs, MRI findings, and testing pathway onto a single page.
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