Dementia medications do not yield uniform results for every patient; instead, their clinical efficacy depends heavily on a distinct "optimal therapeutic window." While the terms "Alzheimer’s disease" and "dementia" are frequently used interchangeably in everyday conversation, they represent biologically distinct concepts. Dementia is a broad clinical umbrella term describing a decline in cognitive function resulting from brain damage. Alzheimer’s disease, conversely, is a specific neurodegenerative illness characterized by the progressive accumulation of toxic proteins in the brain. As these abnormal proteins accumulate and damage vital nerve cells over time, the pathology ultimately manifests as dementia.
In essence, Alzheimer’s disease is merely one underlying cause of dementia. While there are more than 100 known causes—including vascular dementia, which typically occurs as a secondary complication of cerebrovascular disease, and Lewy body dementia, which is characterized by visual hallucinations—Alzheimer’s remains the primary driver, accounting for approximately 70% of all dementia cases. In recent years, the regulatory approval of several disease-modifying Alzheimer’s treatments has raised global expectations that dementia can finally be effectively managed.
Missing the Optimal Window Diminishes Treatment Efficacy
Two breakthrough anti-amyloid therapies currently utilized in clinical practice operate on a shared mechanism: targeting the underlying pathology that drives cognitive decline. Leqembi (generic name lecanemab), jointly developed by the American biotechnology firm Biogen and Japan’s Eisai, is engineered to clear the amyloid plaques that trigger Alzheimer's pathology. Eli Lilly’s Kisunla (generic name donanemab), a subsequent market entry, functions on a parallel principle, clearing toxic protein aggregates to slow the rate of cognitive decline.
Because of their targeted mechanism of action, both drugs require highly specific clinical conditions to be effective. The patient's cognitive decline must still be in its earliest stages, toxic proteins must be actively accumulating in the brain, and the patient must maintain a rigorous dosing schedule while being closely monitored for side effects. Consequently, these multi-thousand-dollar treatments offer virtually no clinical benefit to patients who have already transitioned into moderate or advanced stages of the disease, where permanent neuronal damage is already widespread..
Replacing Costly PET Scans with a Simple Blood Test
The primary challenge for clinicians has been the lack of scalable, accessible methods to determine exactly where a patient falls on the Alzheimer’s progression spectrum. Currently, the standard diagnostic method relies on a positron emission tomography (PET) scan. This advanced imaging technique allows physicians to visually map the accumulation of toxic proteins and track the localized decline of brain-cell function. However, PET imaging carries significant drawbacks. A single scan costs between 1 million and 1.6 million won on average, an expense that remains entirely uncovered by national health insurance. Furthermore, because the procedure requires the injection of radioactive isotopes, it introduces legitimate concerns regarding diagnostic radiation exposure.
To address these limitations, a joint research team from Gangnam Severance Hospital, Wonju Severance Christian Hospital, and the U.S.-based diagnostics company C2N Diagnostics recently developed a breakthrough approach capable of replacing expensive PET imaging with a standardized blood test. The researchers recruited 237 patients from specialized dementia clinics who had undergone both blood testing and multi-modal PET scans. The cohort spanned the entire diagnostic spectrum, including cognitively normal individuals, patients with mild cognitive impairment, and those with advanced dementia.
By evaluating the overlapping data, the research team successfully constructed a predictive model capable of mapping the pathological progression of Alzheimer’s disease directly from blood biomarkers. Most notably, the model distinguished the exact volume of toxic protein accumulation with an accuracy rate exceeding 90%. This high degree of precision could allow clinicians to effortlessly screen and identify the precise subset of early-stage patients who are genuinely positioned to benefit from the new targeted therapies.
Cho Han-na, a professor of neurology at Gangnam Severance Hospital who spearheaded the international study, expressed strong optimism regarding its real-world implementation. "If we can first confirm a patient's pathological stage using an accessible blood test, we can reserve costly PET scans as a secondary confirmatory step exclusively for those individuals highly likely to respond to treatment," Cho Han-na stated. "This tiered diagnostic strategy will dramatically maximize clinical efficiency, optimize healthcare utilization, and significantly alleviate the financial and physical burdens placed on patients and their families."
