Alzheimer’s: Doctor explains how disease-modifying therapies offer fresh hope

For decades, medical interventions for Alzheimer’s disease were strictly limited to managing symptoms temporarily. Today, however, we are witnessing a historic paradigm shift as medicine enters the era of disease-modifying therapies (DMTs). The advent of monoclonal antibodies such as Lecanemab and Donanemab has fundamentally altered the treatment landscape.

While it is important to clarify that these treatments do not cure the disease, clinical studies spanning roughly 18 months show they can slow cognitive decline by 25 to 35 per cent. Ultimately, this buys precious time, allowing patients to retain their independence and quality of life for significantly longer. Dr Sona S, Associate Consultant in Neurology, Aster Mims, Kannur, explains.

Targeting the root cause: how new therapies work
One of the hallmark characteristics of Alzheimer’s disease is the abnormal accumulation of amyloid-beta protein in the brain. Over time, these proteins cluster together to form sticky plaques that disrupt communication between nerve cells and eventually trigger cell death. While traditional medications focused purely on mitigating cognitive symptoms like memory loss, newer drugs like Lecanemab and Donanemab enlist the power of the patient's own immune system. As synthetic antibodies, they are engineered to locate and attach to amyloid plaques. This binding serves as a homing signal for microglia—the brain's specialised immune cells—prompting them to engulf and clear away the toxic plaques.

Are these treatments right for everyone?
Despite the excitement surrounding these therapies, they are not a universal cure-all. Strict criteria govern their use to ensure safety and efficacy:
• Early-stage intervention: These drugs are specifically designed for individuals experiencing mild cognitive impairment (MCI) or the very early stages of Alzheimer’s disease.
• Confirming amyloid presence: Before treatment can begin, the presence of amyloid plaques must be verified using a PET scan or cerebrospinal fluid (CSF) analysis.
• Genetic screening: Patients carrying the APOE4 gene, particularly those with two copies of the gene, face a substantially higher risk of side effects. Genetic testing is therefore essential to help families weigh the risks and benefits alongside their physician.
• Monitoring side effects (ARIA): These advanced therapies can cause amyloid-related imaging abnormalities (ARIA), which present as localised brain swelling or microbleeds. Consequently, patients require regular MRI scans throughout their treatment cycle to monitor safety.

The crucial link between cardiovascular health and brain health
The emergence of these new treatments brings renewed focus to a long-standing medical maxim: what is bad for the heart is bad for the brain. For patients undergoing monoclonal antibody therapies, maintaining optimal cardiovascular health is of paramount importance. There are several vital connections to keep in mind:
• Blood pressure control: High blood pressure weakens and damages delicate blood vessels in the brain, elevating the risk of microbleeds—one of the main potential side effects of drugs like Lecanemab. Therefore, these treatments may not be safe for those with uncontrolled hypertension.
• The risk of blood thinners: Patients taking anticoagulants to prevent stroke or manage heart conditions face an elevated risk of cerebral bleeding. It is absolutely crucial to disclose any such medications to your specialist.
• Cholesterol and circulation: Arterial plaques caused by high cholesterol restrict blood flow to the brain. Proper blood circulation is vital because it helps clear waste products, including amyloid proteins, out of brain tissue.
• Managing diabetes: Diabetes negatively impacts vascular health. Managing blood sugar levels protects the brain's microvasculature, allowing disease-modifying therapies to work safely and more effectively.

The importance of early diagnostic screenings
Catching Alzheimer's at the mild cognitive impairment or early stage is vital to slow down brain degeneration. Modern medicine relies on four main diagnostic pathways to achieve this:

1. Cognitive and mental evaluations
• Montreal Cognitive Assessment (MoCA): A rapid screening tool that evaluates memory, attention, language skills, and problem-solving abilities.
• Mini-Mental State Examination (MMSE): Widely used to test orientation, registration, attention, and basic language skills to help doctors gauge the extent of cognitive impairment.

2. Advanced neuroimaging
• Amyloid PET scan: This advanced imaging scan confirms the accumulation of amyloid plaques in the brain, which is a mandatory prerequisite for starting therapies like Lecanemab.
• MRI scan: Used to assess structural brain shrinkage and rule out other causes of memory loss, such as strokes or brain tumours.

3. Biomarker and spinal fluid testing
• Cerebrospinal fluid (CSF) analysis: Performed via a lumbar puncture, this test measures levels of amyloid-beta and tau proteins in the spinal fluid.
• Blood-based biomarkers: Next-generation blood tests, such as those detecting p-tau217, are now emerging, offering a minimally invasive way to screen for amyloid pathology.

4. Excluding alternative causes
Cognitive decline can sometimes be triggered by reversible conditions, such as Vitamin B12 deficiency, thyroid imbalances, or clinical depression. Comprehensive blood tests and psychological assessments help ensure an accurate diagnosis of Alzheimer's disease. If you or a loved one notices persistent memory issues, consulting a neurologist at the earliest is key to protecting long-term brain health.