Alzheimer’s, Parkinson’s & Migraine
A comprehensive analysis of the neurology clinical trial landscape — from cognitive assessment certification and amyloid biomarker screening to caregiver retention strategies, digital endpoints, and the operational demands of disease-modifying therapy programs.
The CNS Trial Landscape in 2026
Central nervous system and neurology clinical trials are experiencing an unprecedented period of growth and transformation. The approval and continued development of disease-modifying therapies for Alzheimer’s disease has catalyzed a wave of investment in neuroscience research, expanding the pipeline beyond symptomatic treatments into mechanistic interventions that target the underlying pathology of neurodegenerative diseases.
Alzheimer’s disease dominates the CNS pipeline, with over 140 agents in active clinical development globally. The enrollment demand created by these programs is extraordinary — large Phase III disease-modifying therapy studies require 1,500 to 2,000 patients each, with screening ratios often exceeding 3:1 due to biomarker confirmation requirements. This demand far outstrips the current capacity of qualified investigative sites, making site readiness and enrollment infrastructure critical competitive differentiators.
The Parkinson’s disease pipeline is experiencing parallel growth, with increasing emphasis on neuroprotective and disease-modifying approaches alongside symptomatic therapies. Gene therapy programs targeting GBA and LRRK2 mutations, alpha-synuclein immunotherapy, and GLP-1 receptor agonists repurposed for neuroprotection are reshaping the Parkinson’s trial landscape. Migraine has evolved from acute treatment studies to a robust pipeline of preventive therapies including next-generation CGRP pathway modulators, glutamate receptor antagonists, and neuromodulation devices.
Key Performance Metrics
Network-wide benchmarks from our CNS and neurology portfolio reflect the unique operational dynamics of this therapeutic area.
Alzheimer's disease-modifying therapy studies experience the highest screen failure rates in our network, averaging 52%. The primary drivers are amyloid PET negativity (accounting for approximately 40% of screen failures), ARIA risk factors identified on baseline MRI, and concomitant medication exclusions. Studies requiring both amyloid and tau biomarker confirmation push screen failure rates above 60%.
The overall patient retention rate across CNS studies is 78%, lower than the network-wide average of 83% due to the long duration of neurology trials (often 18-24 months), progressive cognitive decline that impacts consent capacity, caregiver fatigue, and transportation challenges for patients with mobility or cognitive impairment. Migraine studies achieve the highest CNS retention at 86%, while long-duration AD studies average 72%.
CNS studies require longer site startup timelines than most therapeutic areas, with a median of 18.6 weeks from contract execution to first patient enrolled. This extended timeline reflects the complexity of cognitive assessment rater certification, specialized imaging protocol validation (amyloid PET, volumetric MRI), and the operational setup required for caregiver involvement in study visits and consent processes.
Alzheimer's disease studies achieve a median enrollment rate of 0.9 patients per site per month, reflecting the high screen failure rates and the complexity of the patient and caregiver recruitment process. Sites with established memory care referral networks and pre-screening registries consistently outperform this benchmark, achieving 1.4-1.8 patients per month by reducing the time from referral to screening visit.
Network Capabilities
CNS clinical trials demand highly specialized site capabilities that go far beyond standard clinical research infrastructure. Our network has invested systematically in the personnel, technology, and processes required to execute complex neurology protocols with the precision and consistency that sponsors require.
Cognitive Assessment Certified Raters
Cognitive assessment endpoints are the foundation of nearly every Alzheimer’s and dementia clinical trial, and the quality of rater administration directly determines data integrity. Our network maintains a pool of 85+ certified raters trained across ADAS-Cog (11 and 13), MMSE, MoCA, CDR-SB, and NTB composite batteries. All raters undergo initial certification through sponsor-approved training vendors and participate in quarterly recertification and inter-rater reliability exercises. Rater drift — the gradual divergence in scoring standards over long study durations — is monitored through centralized quality review of recorded assessments, with corrective training deployed within 2 weeks of any identified scoring deviation.
Sites with certified backup raters ensure continuity of assessment even in cases of staff turnover, reducing the risk of protocol deviations due to rater unavailability. Our network maintains a minimum of 2 certified raters per active CNS study at each participating site.
Amyloid PET & Advanced Imaging
Amyloid PET imaging has become a standard screening requirement for Alzheimer’s disease-modifying therapy studies, with tau PET increasingly incorporated as a stratification or secondary biomarker. Our network sites have established partnerships with 22 PET imaging centers offering FDA-approved amyloid tracers (florbetapir, florbetaben, flutemetamol) and tau tracers (flortaucipir). Sites coordinate centralized PET read workflows with sponsor-designated imaging core laboratories to ensure consistent eligibility determination.
Volumetric MRI for ARIA monitoring is a critical safety requirement in anti-amyloid immunotherapy studies. Network sites maintain MRI protocols calibrated to detect ARIA-E (edema) and ARIA-H (hemorrhage) at the earliest stages, with scan-to-read turnaround times averaging 48 hours through centralized neuroradiology review partnerships. This rapid turnaround enables timely dose modification decisions and patient safety management.
Lumbar Puncture Capabilities
CSF biomarker collection via lumbar puncture (LP) is increasingly used as an alternative or complement to PET imaging for amyloid and tau confirmation, as well as for pharmacodynamic biomarker assessment. Our network includes 28 sites with LP capabilities performed by board-certified neurologists or trained proceduralists, with standardized collection, processing, and shipping protocols aligned with Alzheimer’s Disease Neuroimaging Initiative (ADNI) standards. LP refusal rates are managed through patient education programs that have demonstrated a 35% reduction in LP-related screen failures at participating sites.
Caregiver Engagement Infrastructure
Alzheimer’s and Parkinson’s studies almost universally require a study partner (caregiver) who accompanies the patient to visits and provides informant-based outcome assessments. The caregiver is effectively a second participant who must consent, attend visits, and remain engaged throughout trials that may last 18 months or longer. Our network sites have developed caregiver support programs including flexible scheduling to accommodate caregiver work obligations, dedicated caregiver waiting areas, respite referral services, and caregiver-specific communication protocols that keep study partners informed and motivated. Sites with formalized caregiver engagement programs demonstrate 15% higher retention rates than sites without such programs.
Enrollment Dynamics
CNS enrollment dynamics are characterized by high complexity, long timelines, and multiple stakeholders whose engagement determines study success. These dynamics require fundamentally different planning assumptions than most other therapeutic areas.
The screen failure challenge in Alzheimer’s disease trials is the defining operational issue of the therapeutic area. Current disease-modifying therapy protocols typically require biomarker confirmation of amyloid pathology through either PET imaging or CSF analysis, followed by MRI screening to exclude patients with pre-existing ARIA or other structural abnormalities. The multi-step screening process means that patients may undergo 3-5 screening visits over 4-8 weeks before eligibility is confirmed or excluded. Each screening step represents a point of potential dropout — patients may decline LP, fail to complete PET imaging, or withdraw during the extended screening period.
Caregiver recruitment represents an underappreciated bottleneck. Approximately 20% of otherwise eligible patients are unable to participate because they lack a qualified study partner who can commit to the time and travel requirements of a long-duration trial. This is particularly acute in patients who live alone, have caregivers with full-time employment, or reside in rural areas where travel to study sites is burdensome. Our network addresses this through caregiver recruitment assistance programs, remote visit options for caregiver assessments where protocols allow, and transportation reimbursement that covers both patient and caregiver travel.
Key Challenges in CNS Trial Execution
The inherent complexity of neurological conditions creates operational challenges that require specialized approaches and deep therapeutic expertise.
Diagnostic Complexity
Unlike many other therapeutic areas where diagnosis is straightforward, neurodegenerative diseases present significant diagnostic uncertainty. Clinical diagnosis of Alzheimer's disease at the mild cognitive impairment (MCI) stage has a misdiagnosis rate of 20-30%, meaning that a substantial proportion of patients who present with cognitive complaints may have non-AD etiologies including vascular dementia, frontotemporal dementia, depression-related cognitive impairment, or normal aging. Biomarker confirmation has improved diagnostic accuracy but has also raised the screening cost and complexity. Our network sites employ multi-step diagnostic algorithms that combine clinical assessment, cognitive testing, and biomarker confirmation to maximize the proportion of truly eligible patients who enter the screening pipeline.
Cognitive Assessment Variability
Cognitive endpoints are inherently more variable than biomarker or imaging endpoints, making consistent, high-quality administration essential for detecting treatment effects. Sources of variability include rater experience and technique, patient factors such as fatigue, anxiety, and time of day, environmental factors including testing room conditions and interruptions, and practice effects from repeated administration. Our network implements standardized testing environments (quiet, private rooms with controlled lighting), fixed testing windows (same time of day for each patient across visits), and audio/video recording of all cognitive assessments for centralized quality review. These measures have been shown to reduce inter-rater variability by 25% compared to uncontrolled testing conditions.
Caregiver Burden as a Retention Factor
In long-duration CNS trials, caregiver burden is the single strongest predictor of patient dropout. Caregivers who report high levels of emotional exhaustion, work-life conflict, or financial strain are 3x more likely to withdraw their care recipient from a clinical trial. Our network has implemented caregiver burden screening at baseline and every 6 months during long-duration studies, with proactive intervention when burden scores exceed threshold levels. Interventions include connecting caregivers with community support resources, adjusting visit schedules to reduce time commitment, and offering remote visit options for assessments that do not require in-person administration.
Long Trial Durations and Disease Progression
Alzheimer's disease-modifying therapy trials typically run 18-24 months for the core study period, with optional open-label extensions that may add another 12-24 months. Over these timescales, meaningful disease progression occurs in many participants, potentially affecting their capacity to consent, complete cognitive assessments, and participate in study visits independently. Our network sites implement rolling capacity assessment protocols that monitor each participant's ability to provide ongoing informed consent, with clearly defined escalation procedures when capacity concerns arise. Sites also maintain established relationships with legal and ethics consultants for complex consent situations involving legally authorized representatives.
Patient Retention Strategies
Given the long duration and high burden of CNS trials, patient retention requires deliberate, multi-faceted strategies that address the unique needs of neurological patient populations and their caregivers.
Flexible Visit Scheduling
CNS study visits are often lengthy, requiring 3-5 hours for cognitive assessments, safety evaluations, and study procedures. Accommodating these visits within the schedules of both patients (many of whom are elderly) and their caregivers (many of whom work full-time) demands flexibility. Our sites offer early morning, late afternoon, and selected weekend appointment windows. Visit splitting — distributing procedures across two shorter visits within the protocol-allowed window — is implemented where protocols allow, reducing per-visit burden by approximately 40%.
Caregiver Support Programs
Recognizing that caregiver engagement is essential to patient retention, our network provides structured caregiver support including dedicated caregiver coordinators at each site who serve as the primary point of contact for scheduling, questions, and concerns. Caregiver support groups facilitated by site staff connect study partners with others in similar situations, building community and reducing isolation. Educational materials about the disease, the study, and available community resources are provided at enrollment and updated throughout the study.
Transportation Assistance
Transportation is a critical barrier to retention in CNS trials, particularly for patients with cognitive impairment who cannot drive and patients in rural areas where travel distances to study sites are significant. Our network provides coordinated transportation services including medical transport for patients who require assistance, ride-share partnerships for ambulatory patients, and mileage reimbursement for caregiver-driven transportation. Sites that implement comprehensive transportation assistance programs demonstrate 12% higher retention rates than sites without such programs.
Digital Innovation in CNS Trials
Digital technologies are creating new possibilities for endpoint measurement, patient monitoring, and trial decentralization in neurology — reshaping what is possible in CNS clinical development.
Actigraphy, gait analysis, and continuous activity monitoring through wearable devices provide objective, high-frequency measures of motor function in Parkinson’s disease and physical activity in Alzheimer’s disease. These devices capture real-world functional data between clinic visits, offering a more ecologically valid picture of disease progression than periodic in-clinic assessments alone. Our network supports 6 validated wearable platforms with standardized onboarding, compliance monitoring, and data quality review processes.
Tablet-based and smartphone-delivered cognitive assessments enable more frequent, standardized measurement of cognitive function outside the clinic setting. Digital cognitive tools reduce rater variability through automated administration and scoring, increase measurement frequency without proportional site burden, and can detect subtle cognitive changes earlier than traditional paper-based instruments. Our network sites are trained in 4 FDA-cleared digital cognitive assessment platforms and support hybrid assessment protocols combining traditional and digital endpoints.
Decentralized visit models are particularly valuable in CNS trials where patient and caregiver travel burden is a primary driver of dropout. Telehealth visits for safety assessments, caregiver questionnaires, and non-cognitive endpoints can be conducted remotely, reducing the number of in-person visits by 20-30% in many protocols. Home health nursing visits for blood draws, vital signs, and medication compliance checks further reduce site visit frequency while maintaining data quality and patient safety monitoring.
AI-powered analysis of speech patterns, word-finding difficulty, semantic fluency, and language complexity is emerging as a sensitive digital biomarker for cognitive decline. These assessments can be collected passively during structured phone calls or active assessments via smartphone apps, providing longitudinal cognitive data with minimal patient burden. Our network is piloting speech analytics integration in 3 active Alzheimer’s studies.
Disrupted sleep architecture is both a symptom and a potential biomarker in neurodegenerative diseases. Wearable sleep monitoring devices and under-mattress sensors provide continuous data on sleep stages, nighttime movement, and circadian rhythm patterns that correlate with disease progression and treatment response. This data stream complements traditional polysomnography and actigraphy endpoints while being substantially less burdensome to collect.
eCOA platforms enable real-time capture of patient-reported and caregiver-reported outcomes on validated electronic instruments, reducing transcription errors, enforcing completion windows, and enabling immediate data review by site and sponsor teams. Our network achieves 94% eCOA compliance rates across CNS studies, compared to an industry average of 82%, through dedicated eCOA training for patients and caregivers at enrollment.
Discuss Your Neurology Program
Connect with our team to explore cognitive assessment infrastructure, imaging capabilities, and enrollment strategies for your CNS clinical development program.