Diagnostic and inclusion criteria in Alzheimer's disease clinical trials: A systematic review of the past decade.

BACKGROUND

Dementia, mainly caused by Alzheimer's disease (AD), is a leading cause of mortality and disability in the elderly. However, inconsistencies in diagnostic and inclusion criteria challenge the design and comparability of AD clinical trials.

OBJECTIVE

To review recent AD clinical trials, focusing on diagnostic methods and inclusion criteria, and identify trends and gaps to inform future research.

METHODS

We systematically searched Web of Science, PubMed, and Google Scholar for AD clinical trials, extracting data on diagnostic criteria, disease stage, cognitive assessments, biomarker use, and participant age.

RESULTS

Of the 27,471 articles screened, 71 studies were included in the final review. Most were conducted in North America (52%) and Europe (34%). NINCDS-ADRDA (56%) and NIA-AA 2011 (30%) were the most used diagnostic criterion, with the latter increasingly adopted in recent years. Over half focused on mild-to-moderate AD (56%), 16% on mild AD, and 13% included mild cognitive impairment/mild AD populations, with growing interest in early-stage interventions. However, only a minority reported notable cognitive improvements. The Mini-Mental State Examination was the most frequently used assessment tool (86%), though 36 different cutoff schemes were identified. Biomarkers were used in 38% of studies, mainly in the past three years, while others relied on symptom-based or imaging approaches. Participants ranged from 45 to 95 years old, with 50 as the most common lower age limit.

CONCLUSIONS

Symptom-based criteria still dominate AD trials. Given the limited efficacy of single interventions, future studies should consider multimodal, non-invasive approaches and prioritize objective biomarkers to enhance consistency and diagnostic precision.