Beyond proof of concept: Alzheimer’s and the next chapter of early-stage neurodegenerative trials

Over the past decade, neurodegenerative research and development has responsibly answered a foundational question: can we identify and intervene earlier in diseases that unfold over years, not months?

In Alzheimer’s disease, the answer is now “yes.” Research has demonstrated that some individuals at elevated risk can be identified before symptoms emerge, biological changes can be measured ahead of formal diagnosis, and earlier intervention is scientifically possible.

Importantly, these advances are no longer confined to academic prototypes. A growing ecosystem of digital, imaging-based, and AI-driven tools, some validated in clinical studies or currently advancing through regulatory pathways, now supports efforts in risk identification years before diagnosis. Research shows that Alzheimer’s-related biomarker changes can emerge more than a decade prior to clinical onset.

Alzheimer’s has moved the field further than any other neurodegenerative disease towards a reality of early intervention. What was once scientific aspiration is increasingly feasible in practice, providing a reference point for sponsors exploring earlier-stage approaches in other neurodegenerative conditions. At the same time, this progress introduces a more complex phase of therapy development. In Alzheimer’s, the discussion has shifted from whether early intervention can work to how sponsors can operationalise early identification at scale and how trials should be designed to demonstrate meaningful long-term benefit. Public readiness is not the limiting factor in this transition. In a 2025 Alzheimer’s Association survey of more than 1,700 adults, nearly four in five respondents said they would want to know if they had Alzheimer’s disease before symptoms emerged, and more than 90% indicated they would opt for a simple blood-based test if available.

Below, we examine what this shift means in practice: specifically how early identification is changing trial design, what operational challenges sponsors may face, and what additional evolution is needed across screening, endpoints, and engagement to support earlier-stage neurodegenerative research.

The early intervention foundation is in place

Much of the progress in Alzheimer’s over the last several years has effectively focused on building the infrastructure for earlier action.

Biologically, the disease is now better understood to begin long before clinical symptoms appear. That recognition has been matched by advances in detection, including:

Fluid biomarkers that signal amyloid and tau pathology earlier in the disease course
(e.g., plasma Aβ42/40 ratio; phosphorylated tau, such as p-tau181 or p-tau217; and neurofilament light chain (NfL)).
Neuroimaging that visualises pathological change years before diagnosis
(e.g., amyloid PET imaging, tau PET imaging, and volumetric MRI showing hippocampal atrophy). Also, emerging retinal imaging techniques, including optical coherence tomography [OCT] and OCT-angiography, which capture neurodegenerative and microvascular changes associated with preclinical and early Alzheimer’s disease – also in use as a complementary biomarker within multimodal early-detection strategies.
Digital and cognitive tools capable of detecting subtle longitudinal decline
(e.g., computerised cognitive assessments, smartphone-based cognitive tasks, passive digital biomarkers from wearables, or speech analysis).
Artificial intelligence-enabled methods that integrate imaging, laboratory, demographic, and clinical data to estimate progression risk (e.g., multimodal machine-learning models combining PET/MRI, blood biomarkers, cognitive scores, and demographics to predict disease trajectory).

Importantly, these tools don’t replace established regulatory endpoints in neurodegenerative disease clinical trials, but are rather ways to triage risk earlier and more efficiently. The emergence of these detection tools reflects a shared industry understanding that late-stage screening alone is not feasible to support early-intervention trials at scale.

Beyond identifying risk earlier, biomarker-based screening also enables more precise trial population enrichment. By narrowing eligibility earlier, sponsors can focus resources on individuals most likely to progress and improve signal detection in early-stage studies while reducing unnecessary downstream screening.

In this sense, the field has already crossed a critical threshold. Early intervention in Alzheimer’s is no longer theoretical. The science exists, pilot programmes are underway, and multiple approaches to risk enrichment and prescreening have demonstrated promise.

Entering the ‘What now?’ phase

With early-detection tools maturing, the Alzheimer’s landscape is now defined by a different set of questions, ones that extend beyond biomarkers and algorithms. Today’s challenge is less about finding signals and more about integrating them into R&D workflows that are operationally viable, aligned with evolving regulatory expectations and sustainable over the long term.

This ‘What now?’ phase has run up against several realities:

Screening can identify higher-risk individuals earlier, but confirming diagnosis remains resource intensive.
Trials can move upstream, but endpoints take longer to reach.
Participants can enrol earlier, but retention must be maintained over many years and account for changes in life and interest in ongoing participation.
Technology can narrow populations, but healthcare systems are not yet optimised for widespread early screening.

Essentially, the industry is shifting from scientific validation of early intervention to the need to scale for implementation complexity.

When decline is delayed: Rethinking trial design

Moving earlier in Alzheimer’s fundamentally changes how trials must be designed and executed. Traditional Alzheimer’s studies were built around measurable decline over relatively short periods. By contrast, early intervention studies must account for:

Slower disease trajectories.
Fewer significant events, such as conversion to symptomatic disease.
Greater reliance on longitudinal measures vs short-term change.

In this context, meaningful benefit is increasingly defined not by short-term improvement, but by evidence of slowed progression or delayed onset of clinical symptoms. These goals require longer observation, sensitive longitudinal measures, and clear alignment on what constitutes success.

As a result, sponsors are increasingly combining time-to-event outcomes, biomarker trajectories. and sensitive cognitive or digital measures to establish efficacy signals. However, regulatory frameworks remain anchored to endpoints developed for later disease stages.

As interventions move earlier in the disease course, stakeholders are increasingly encountering the practical reality that clear measures of benefit may take longer to emerge. Alzheimer’s has highlighted the need to carefully reconsider what meaningful R&D success looks like when the objective is to slow or prevent decline.

Screening at scale: Ambition meets reality

The most consequential ‘What now?’ question may be operational.

Early-intervention trials require access to large populations, many of whom are asymptomatic and unaware of their risk. Without scalable prescreening approaches, screen-failure rates can rapidly strain trial feasibility and efficiency.

In response, Alzheimer’s trials are increasingly adopting multi-step screening strategies, often starting outside traditional specialty clinics. These approaches may include:

Remote cognitive or digital assessments to identify early signals.
Use of routine clinical or lab data to stratify risk.
Selective referral to advanced imaging or biomarker testing.

These advances also have practical implications for how early-stage neurodegenerative trials are conducted. Earlier risk stratification reduces reliance on late-stage specialty‑centre recruitment and supports more decentralised or hybrid trial models, expanding reach across geographies and care settings while helping sites manage the resource demands of high screen-failure rates.

Efforts to broaden patient screening have expanded the stakeholder ecosystem of early intervention. Primary care providers, patient advocacy organisations, diagnostic networks, and digital health platforms are playing increasingly important roles in identifying at-risk individuals earlier in the disease course.

Earlier, less invasive screening modalities also open the door to engaging younger, still-asymptomatic individuals who may be more receptive to risk awareness, lifestyle modification, and long-term participation in prevention-focused research.

Though the neurodegenerative community has made substantial progress in identifying individuals earlier in the disease course, a remaining challenge is how to thoughtfully integrate these approaches into healthcare pathways not originally designed to address preclinical or early-stage neurodegenerative disease. How these stakeholders are coordinated and supported will need to be addressed in the next steps of ‘What now?’

Participant engagement over longer journeys

Earlier intervention also changes the participant experience and, by extension, trial operations.

Individuals may enter studies without measurable cognitive impairment and be asked to commit to years of follow-up while remaining uncertain about personal benefit. This reality elevates the importance of:

Ongoing, adaptive consent models, recognising consent as a dynamic process, rather than a one-time event.
Long-term engagement strategies, including regular communication, support, and reduced burden.
Clear and consistent communication about evolving risk, study goals, and expectations for participation.

Alzheimer’s trials are effectively redefining participation as a longitudinal partnership, rather than a singular clinical episode.

Implications for the broader neurodegenerative landscape

While Alzheimer’s is furthest along, its experience is increasingly influential across CNS R&D.

Parkinson’s disease, ALS, multiple sclerosis, and other neurodegenerative conditions are all being explored for earlier biological markers and risk-based identification approaches. Cross-cutting measures, such as neurofilament light chain, are gaining traction as indicators of neurodegeneration beyond a single disease.

The shift from managing late-stage Alzheimer’s symptoms to earlier disease understanding and proactive management introduces longer development timelines and greater operational demands, but promises more durable long-term outcomes.

From early promise to sustained progress

For Alzheimer’s, the early steps of biomarker discovery, preclinical detection, and risk stratification have been taken. The industry now stands firmly in the ‘What else is needed?’ phase.

Answering that question requires progress on multiple fronts:

Alignment on endpoints that reflect early benefit.
Regulatory openness to evidence that unfolds over longer horizons.
Operational models for large-scale early screening.
Sustained engagement with participants well before symptoms appear.

Earlier-intervention strategies pioneered in Alzheimer’s disease have fundamentally reshaped how neurodegenerative disorders are studied and treated, establishing a biomarker-driven, preclinical framework that is now being adopted across multiple neurodegenerative diseases.

What is unfolding in Alzheimer’s is increasingly informing how sponsors think about other neurodegenerative conditions where pathology precedes symptoms by years. The next chapter will be defined not by whether early action is possible, but by how effectively the ecosystem can support it across diseases, timelines, and care settings.

About the authors

Marek Bieniek, MD, is senior director, medical strategy, CNS Center of Excellence, at IQVIA. Bioeniek is a board-certified neurologist with more than 25 years of experience in neurology, more than a decade of medical affairs experience in the pharmaceutical industry primarily related to multiple sclerosis and Alzheimer’s disease, and over six years of experience in clinical research. His clinical and industry roles were primarily related to multiple sclerosis, dementia, and rare diseases. In his current role with IQVIA’s CNS Center of Excellence, Bieniek applies his extensive practical knowledge of all stages of medicines’ lifecycles to support development of innovative therapies for neurological disorders.

Anu Chaudhary, PhD, is global technical lead, immunology, at IQVIA Laboratories. Chaudhary is the technical lead for global immunology testing at IQVIA Laboratories and oversees assay development and execution to support clinical testing needs. Trained in chemistry, cell biology, microbiology, and immunology, she has more than 28 years of experience in basic and clinical research, assay development, and drug discovery. Chaudhary earned her PhD from SUNY-Stony Brook and performed postdoctoral studies at Harvard Medical School and the Fred Hutchinson Cancer Center.

Elizabeth Marriott, MD, is medical director, medical strategy, CNS Center of Excellence, at IQVIA. With nearly two decades of clinical experience, Marriott is a board-certified neurologist in neurology and vascular neurology. In her role with IQVIA’s CNS Center of Excellence, she supports the development of therapies across a broad range of neurological disorders, with a focus on vascular and acute neurology indications. Marriott brings deep expertise in clinical trial design and execution, supported by leadership experience at The Joint Commission-certified Comprehensive and Primary Stroke Centers. Her clinical research background includes stroke treatment and prevention, vaccine trials, and other general indication studies.