Genetic Testing for Stroke and Alzheimer’s Risk: When to Get Tested

Genetic testing is becoming an increasingly central component in the clinical management of adults with various neurologic conditions. According to a manuscript published in the Journal of Neurology on May 15, 2024, clinicians in adult neurogenetics programs are frequently tasked with determining which patients require testing, which specific tests to order and how the resulting data will practically benefit the patient.

For those concerned with cognitive decline, genetic testing offers a way to identify specific markers associated with Alzheimer’s disease and other forms of dementia. However, the utility of these tests varies significantly depending on the type of genetic mutation being sought.

Deterministic Genes versus Risk Variants

Researchers have categorized the genetic drivers of Alzheimer’s into two primary groups: deterministic genes and risk variants. Deterministic genes are rare mutations that directly cause the disease to develop.

In contrast, risk variants are more common genetic changes that increase the likelihood of developing the condition but do not guarantee its onset. A primary example of a risk variant is APOE4.

The Alzheimer’s Society notes that testing for risk variants like APOE4 does not provide certainty regarding a person’s chances of developing dementia. Because these variants only indicate a higher probability rather than a certainty, genetic testing for risk variants is not always considered appropriate for every patient.

Determining the Appropriateness of Genetic Testing

Genetic testing for dementia is most appropriate in specific clinical scenarios. It is typically offered when there is a strong family history of dementia, suggesting the presence of a single-gene change that causes the condition.

In most families, dementia is not caused by a single-gene change, making genetic testing less useful for the general population. When testing is conducted, it generally falls into two categories:

• Diagnostic testing: Used to confirm a diagnosis in an individual already experiencing symptoms.
• Predictive testing: Used to identify the risk of developing a condition in individuals who are currently asymptomatic.

Beyond diagnosis and risk assessment, individuals affected by dementia may also use genetic testing to assist with family planning.

The Comprehensive Diagnostic Process

While genetic markers provide valuable data, there is no single test that can definitively determine if a person is living with Alzheimer’s or another form of dementia. Physicians must use a combination of diagnostic tools and patient history to reach an accurate diagnosis.

The diagnostic workup typically includes several layers of evaluation:

• Medical and Family History: Providers review psychiatric history and a history of cognitive or behavioral changes, as well as medical conditions affecting other family members.
• Physical and Neurological Exams: These include assessments of overall health, blood pressure, pulse, and heart and lung function, alongside specialized neurological examinations.
• Cognitive Assessments: Physicians use functional and behavioral tests, including computerized cognitive tests and depression screenings.
• Brain Imaging: Tools such as Magnetic Resonance Imaging (MRI), Computed Tomography (CT), and Positron Emission Tomography (PET) scans are used to visualize brain structure and function.
• Biological Testing: Cerebrospinal fluid (CSF) tests and blood tests are employed to identify specific biomarkers.

This multifactorial approach ensures that the diagnosis is based on a holistic view of the patient’s health rather than relying on a single genetic or imaging result.

Clinical Impact and Future Directions

The integration of genetic testing into adult neurology allows for a more personalized approach to care. Non-invasive tests now exist to assess the risk of cognitive decline, providing a starting point for clinical intervention and monitoring.

The National Institute on Aging released a 2025 Research Progress Report on Alzheimer’s Disease and Related Dementias, highlighting continued advances and achievements in the field. As the understanding of neurogenetics evolves, the focus remains on refining the indications for testing to ensure that the results provide actionable clinical value for patients and their families.