Alzheimer’s disease and other dementias represent a significant medical and societal challenge. These disorders typically progress to cause disability, significantly impacting a person's ability to function and their quality of life, which also negatively affects their family and causes financial burden.
As populations age worldwide, the burden of dementia will continue to rise, underscoring the importance of innovation in diagnosis, prevention, and treatment. The overarching goal of modern dementia drug development is not merely to extend life but to preserve functional independence and quality of life for as long as possible, minimizing the period of significant disability before death.
Fundamental shift in dementia research and care
Over the past 35 years, researchers have made substantial progress in understanding the neurochemistry, structural changes, and pathological cascades underlying dementia. For example, amyloid beta accumulation and tau pathology are now recognized as central drivers of Alzheimer’s disease, with amyloid deposition often beginning almost two decades before cognitive symptoms emerge.
As a result, clinical research in dementia is undergoing a fundamental shift. Historically, diagnosis relied on late-stage clinical symptoms, and treatments largely addressed just symptoms. Today, advances in diagnostics, therapeutics, and drug delivery are enabling earlier intervention, greater precision, and more convenient, less burdensome care for participants and caregivers, such as shifting from infusions toward oral medications.
Rethinking diagnosis: From late detection to early identification
The most transformative progress in diagnostics and precision treatment has occurred in the last five to seven years with the development of blood-based biomarkers and the first approval of a blood test used to diagnose Alzheimer’s disease by the Food and Drug Administration (FDA) in May 2025. The approved test measures two proteins, phosphorylated tau 217 (ptau217) and β-amyloid 1-42. p-tau217, in particular, has emerged as one of the most promising indicators of Alzheimer’s pathology. It serves as a proxy for amyloid plaque build-up in the brain, a hallmark of Alzheimer’s disease, and blood levels closely correlate with amyloid and tau burden measured by positron emission tomography (PET) imaging or cerebrospinal fluid (CSF) analysis, making it a powerful and far less invasive diagnostic tool.
Traditionally, confirmation of Alzheimer’s disease required PET scans or lumbar punctures, procedures that are expensive, invasive, and impractical for routine screening, contributing to missed or misdiagnoses. Blood-based tests change this equation entirely: they are inexpensive, scalable, repeatable, and feasible in a standard clinical setting. These biomarkers also open the door to identifying individuals at risk before symptoms appear and could play an important role for individuals with subjective cognitive decline — those who report memory problems despite normal performance on standard cognitive tests.
Tracking risk over time: The promise of longitudinal biomarkers
Repeated blood-based measurements of biomarkers such as p-tau217, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) could also help track disease trajectory over time. In a prospective cohort followed for nearly five years, individuals with increasing biomarker levels were significantly more likely to progress to mild cognitive impairment or dementia.
For clinicians, this supports the potential use of serial blood testing as a practical tool for early risk stratification, monitoring, and clinical decision-making. For researchers, it enables better trial design by identifying participants at the earliest, most treatable stages of disease, and trials are increasingly using biomarkers to determine eligibility and measure outcomes. In addition, this allows the early identification of individuals who may be at the highest risk of cognitive decline, including those who have emerging risk factors like the potential link between chronic emotional distress, trauma, and cognitive impairment.
Early intervention: Targeting disease before symptoms arise
In Alzheimer’s disease, amyloid pathology may begin 18-20 years before symptoms, indicating a time ripe for interventions that could slow amyloid accumulation and therefore its negative effects. Both FDA-approved Alzheimer’s drugs, Leqembi (lecanemab) and Kisunla (donanemab), work on the premise of slowing the progression of early Alzheimer's disease by targeting amyloid plaques in the brain. Although currently approved for those with an Alzheimer’s disease diagnosis, they are also being investigated for people with biological markers such as amyloid or tau but are asymptomatic. Delivered via infusion, they require close monitoring for adverse events such as amyloid-related imaging abnormalities (ARIA) and infusion-related reactions.
Parallel to these efforts, novel therapeutic strategies are emerging. Experimental compounds are targeting previously unidentified toxic subtypes of amyloid beta oligomers that appear to drive early neuronal dysfunction, inflammation, and immune activation. Results from these studies suggest that intervening at the earliest stages of pathology could dramatically alter disease trajectory. An N3pH-Aß monoclonal antibody is also being investigated for its ability to slow amyloid accumulation in early symptomatic Alzheimer’s disease as well as in individuals with a genetic mutation that puts them at an increased risk of early-onset Alzheimer’s disease, even before they become symptomatic.
Together, these advances underscore a shift toward earlier, biologically driven intervention in dementia, but they also highlight the practical limitations of current infusion-based therapies. As treatment moves earlier and potentially into asymptomatic populations, developing safer, more convenient administration routes will be critical to scaling prevention, improving adherence, and integrating dementia care into routine clinical practice.
Safer and more accessible treatments: The shift in drug delivery
The next steps in treatment include finding ways to get more compound past the blood-brain barrier using transfer molecules to reduce side effects like the microhemorrhages and swelling associated with global amyloid lowering using the approved drugs.
For example, a Phase I clinical trial is evaluating the safety, feasibility, and biological activity of an AAV-based gene therapy that delivers brain-derived neurotrophic factor (BDNF) across the blood-brain barrier in individuals with early Alzheimer’s disease or mild cognitive impairment. The goal is to determine whether sustained BDNF expression can support neuronal survival and function, potentially slowing neurodegeneration and cognitive decline. In addition, intranasal delivery systems are being investigated, with the aim of reducing the invasiveness of therapies, enhancing stability, accelerating absorption, and bypassing the blood-brain barrier.
An investigational, oral Alzheimer’s medication designed to block toxic amyloid beta aggregates could provide a safe treatment option for individuals with two copies of the APOE4 gene, who are at the highest genetic risk for the disease. In clinical testing, it slowed brain degeneration and cognitive decline in early disease without causing the brain swelling or microbleeds sometimes seen with infusion-based antibody treatments. Building on the promise of oral amyloid-targeting therapies, researchers are also exploring an oral medication that addresses tau protein abnormalities, offering another potential avenue to slow disease progression. It demonstrated the ability to reduce clinical decline and progression of brain atrophy in early clinical trials, with sustained effects over time.
Together, these developments highlight a broader trend toward administration routes that could be used earlier, more safely, and more conveniently, making dementia care increasingly accessible outside specialized infusion centers.
Future outlook: Toward proactive, everyday dementia care
Looking ahead, I’m hopeful that dementia care will become more practical, earlier, and easier to manage. Routine blood-based testing for dementia risk could become part of standard care, allowing clinicians to identify risk well before symptoms appear. As diagnostics and therapies continue to improve, Alzheimer’s disease and other dementias may increasingly be managed like other chronic conditions, such as high cholesterol or type 2 diabetes, with primary care physicians handling much of the diagnosis, treatment, and ongoing monitoring. If this progress continues, the conversation around Alzheimer’s may shift away from fear and toward earlier action, better planning, and more realistic hope for participants and families.
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About the author
Dr. Scott Losk is Principal Investigator (PI) at Summit Research, part of the Headlands Research network.
Dr. Losk has served as PI for 90 clinical trials focused on Alzheimer’s disease and other dementias, contributing to research on every FDA-approved Alzheimer’s therapy currently available. He has also been a sub-investigator in more than 125 trials across a wide range of central nervous system conditions, including depression, anxiety disorders, ADHD, bipolar disorder, schizophrenia, migraine, and fibromyalgia.
Deeply involved in the Alzheimer’s community, Dr. Losk regularly provides education and presentations to caregivers, clinicians, and community groups. His extensive expertise and long-standing industry relationships give him unique access to the latest research opportunities in cognitive disorders.