Clinical Trial Intelligence

Which Endpoints Are Measured Most Often in European Alzheimer’s and Dementia Phase II & III Trials?

9 July 2026

Across 56 unique European Alzheimer’s and dementia Phase II, Phase II/III, and Phase III CTIS-authorized trials, safety and tolerability endpoints are the dominant measurement family, appearing in 34 trials (60.7%). Blood or cerebrospinal-fluid biomarkers appear in 23 trials (41.1%), followed by Clinical Dementia Rating / CDR-SB in 17 trials (30.4%), MRI or structural neuroimaging in 15 trials (26.8%), and ADAS-Cog in 14 trials (25.0%). The endpoint pattern splits into two major designs: disease-modifying Alzheimer’s trials emphasize biomarkers, CDR, ADAS-Cog, amyloid/tau imaging, and function, while neuropsychiatric AD trials emphasize NPI-C, CGI, and CMAI.

56
Unique EU trials
280
Endpoint entries
60.7%
Use safety endpoints
112
Median CTIS days
Top endpoint families by trial presence
Safety / tolerability34/56 · 60.7%
Blood / CSF biomarkers23/56 · 41.1%
CDR / CDR-SB17/56 · 30.4%
MRI / neuroimaging structure15/56 · 26.8%
ADAS-Cog14/56 · 25.0%
Endpoint families counted once per trial if present in primary, secondary, or other/exploratory endpoints.

What endpoint families dominate the full Alzheimer’s and dementia cohort?

Safety / tolerability is the most common endpoint family, present in 34 of 56 trials (60.7%). Biomarker measurement is the second major pillar: blood or cerebrospinal-fluid (CSF) biomarkers appear in 23 trials (41.1%), tau-related pathology in 10 trials (17.9%), and amyloid PET / amyloid burden in 8 trials (14.3%).

Endpoint family frequency across 56 trials
Endpoint family Trials Share
Safety / tolerability34/5660.7%
Blood / CSF biomarkers23/5641.1%
CDR / CDR-SB17/5630.4%
MRI / structural neuroimaging15/5626.8%
ADAS-Cog14/5625.0%
NPI-C / neuropsychiatric symptoms13/5623.2%
MMSE13/5623.2%
ADCS-ADL / iADL13/5623.2%
Trial-level presence; one trial can contribute to multiple endpoint families.
Interpretation

European Alzheimer’s CTIS submissions are not built around a single dominant cognitive scale. They combine safety, fluid biomarkers, clinical staging, imaging, and function, reflecting the split between disease-modifying trials and symptom-management trials.

How do primary, secondary, and exploratory endpoints differ?

The dataset contains 280 endpoint entries: 79 primary endpoints, 198 secondary endpoints, and 3 other/exploratory endpoints. Primary endpoints are most often safety-led, with safety / tolerability appearing as a primary endpoint family in 18 of 56 trials (32.1%). Secondary endpoints carry most biomarker and functional breadth: blood / CSF biomarkers appear as secondary endpoints in 23 trials (41.1%), and ADCS-ADL / iADL appears in 13 trials (23.2%).

Primary vs secondary endpoint emphasis
Primary endpoints
Safety / tolerability18
MRI / neuroimaging8
CDR / CDR-SB7
CMAI5
Secondary endpoints
Blood / CSF biomarkers23
Safety / tolerability18
CDR / CDR-SB13
ADCS-ADL / iADL13
Percent bars use 56 trials as denominator; labels show number of trials.
Interpretation

Primary endpoints are concentrated around safety and a smaller set of pivotal clinical or imaging measures, while secondary endpoints carry the broader disease-biology package. Other/exploratory endpoint fields are rare, appearing in only 2 of 56 trials (3.6%) and accounting for 3 endpoint entries.

How do Phase II and Phase III endpoint strategies differ?

Phase II trials account for 28 of 56 trials (50.0%), Phase III for 23 trials (41.1%), and Phase II/III for 5 trials (8.9%). Phase II is more biomarker-intensive: blood / CSF biomarkers appear in 16 of 28 Phase II trials (57.1%) versus 3 of 23 Phase III trials (13.0%). Phase III places more relative emphasis on symptom and global scales, including CGI measures in 6 of 23 trials (26.1%).

Endpoint family frequency by phase
Endpoint family Phase II
n=28
Phase II/III
n=5
Phase III
n=23
Safety / tolerability20/28 · 71.4%4/5 · 80.0%10/23 · 43.5%
Blood / CSF biomarkers16/28 · 57.1%4/5 · 80.0%3/23 · 13.0%
CDR / CDR-SB9/28 · 32.1%3/5 · 60.0%5/