, a cross sectional study has found.
Reporting in the journal Neurology, researchers from the Mayo Clinic in Rochester, Minn., and the University of Chicago found that only a small percentage of patients in the Mayo Clinic Study of Aging (MCSA) with mild cognitive impairment (MCI) or mild dementia due to Alzheimer’s disease would meet the clinical trial eligibility requirements of either agent.
Mayo Clinic
Dr. Maria Vassilaki
“Our study results show only a small percentage of people with early Alzheimer’s disease may be eligible to receive treatment, mostly due to chronic health conditions and brain scan abnormalities common in older adults,” said lead researcher Maria Vassilaki, MD, PhD, an epidemiologist at Mayo Clinic in Rochester, Minn.
Applying clinical trial exclusion criteria to a broader population
The study included 237 people aged 50-90, 222 who had MCI and 15 with mild dementia, and whose brain scans showed increased amounts of amyloid-beta plaques. Average age of the participants was 80.9 years and 97.5% were White (99.6% not Hispanic or Latino).
The researchers then looked at the eligibility criteria for the pivotal clinical trials for lecanemab, which the U.S. Food and Drug Administration approved in January this year, and aducanumab, which the FDA cleared in 2021. Both drugs received FDA accelerated approval.
For lecanemab, clinical trial inclusion required specific scores for the Clinical Dementia Rating (CDR) (other than 0.5 or 1.0), Wechsler Memory Scale (WMS-R) Logical Memory II (which varied with age group), or Mini-Mental State Examination (MMSE) (22 to 30). A body mass index between 17 and 35 kg/m2 was also an inclusion criteria. Only 112 people, or 47%, met the inclusion criteria. Exclusion criteria included a history of cardiovascular disease or cancer, Parkinson’s disease, or brain injury, or a positive brain scan. When the exclusion criteria were applied, only 19 people, or 8%, qualified for the lecanemab trial.
When the researchers modified the exclusion criteria to include all study participants with MCI but not applying results from additional cognitive tests, 17.4% of MCSA patients would have been eligible for the lecanemab trial.
Aducanumab clinical trial inclusion criteria were a CDR global score other than 0.5 and an MMSE below 24, with an age cutoff of 85 years. Only 104 of the MCSA population, or 44%, met the clinical trial criteria. When the researchers applied the exclusion criteria for cardiovascular disease, central nervous system-related exclusions (such as brain cancer or epilepsy), a history of cancer, or brain scan abnormalities, they found that only 12 people, or 5%, would have been eligible for an aducanumab trial.
“Clinical trials often have strict eligibility criteria and could exclude those with other conditions that could be common in older adults,” Dr. Vassilaki said in emailed comments. “Thus, we wanted to examine if we apply these criteria to a study that recruits participants from the community, how many of the individuals in the early symptomatic stages, mild cognitive impairment or mild dementia due to Alzheimer’s disease, would be eligible for the treatment.”
Dr. Vassilaki said these drugs need to be studied in larger, more diverse populations, as well as in less healthy populations, before they’re more widely available to people with Alzheimer’s disease. “In addition,” she said, “we can learn more from the postmarketing surveillance of side effects and also from registries of patients receiving these treatments.”
One limitation of the study Dr. Vassilaki pointed out is the overwhelmingly White population. Evaluating the clinical trial eligibility criteria in more diverse populations is crucial, she said.