Clinically meaningful changes in cognitive and functional outcomes in a population-based study of cognitive aging

Research is limited regarding meaningful change thresholds for individual patients on clinical outcome assessments (COAs) frequently used in clinical trials for Alzheimer's disease and related dementias (ADRD), particularly in population-based studies early in the disease course.

There were 646 study participants in the population-based Mayo Clinic Study of Aging (MCSA), 54-99 years old (47% females), who developed the clinical syndromes of mild cognitive impairment (MCI) with complete data to establish clinically meaningful within-patient change thresholds in cognitive and functional COAs.

Using the diagnosis of incident MCI as the anchor, mean (95% confidence interval [CI]) annualized estimates of change were: Clinical Dementia Rating (CDR) scale Sum of Boxes (SB) 0.49 (0.43, 0.55), Mini-Mental State Examination (MMSE) -1.01 (-1.12, -0.91), and Functional Activities Questionnaire (FAQ) score 1.04 (0.82, 1.26).

This study provides within-patient estimates of clinically meaningful change early in disease progression in a community-based sample.

We studied incident mild cognitive impairment (MCI) participants from a population-based study.Within-patient change thresholds were estimated for clinical outcome assessments (COAs) used in clinical trials for Alzheimer's disease and related dementia (ADRD).These estimates may be used to plan and evaluate clinical trials involving disease-modifying therapies (DMTs).