Patient- and Caregiver-Reported Impact of Symptoms in Alzheimer Disease, Mild Cognitive Impairment, and Dementia

Background and objectives: In preparation for future clinical trials involving individuals with Alzheimer disease (AD), mild cognitive impairment (MCI), and dementia, it is important to ascertain the widespread impact of symptoms from the direct perspectives of patients and caregivers. In this study, we performed cross-sectional surveys using large-scale patient and caregiver data to identify the prevalence and average impact of symptoms and symptomatic themes experienced by adults with AD, MCI, and dementia. Subsequent analyses were used to determine which demographic and disease-specific factors are associated with more severe disease.

Methods: Fifteen adults with AD (6), MCI (8), and dementia (1) and 15 caregivers of adults with AD (7), MCI (6), and dementia (2) participated in qualitative interviews providing 1,166 and 1,097 unique quotes pertaining to symptom burden. Using open-ended questions from a comprehensive interview guide, participants were asked to identify the symptoms of AD that have the greatest effect on their lives or the lives of the individual for whom they provide care. A cross-sectional survey was then implemented inquiring about the potential symptoms of importance identified during preliminary qualitative interviews. Four-hundred thirty-three individuals (patients and caregivers) participated in the cross-sectional survey, providing more than 35,000 symptom rating responses. Subsequent analyses were conducted to determine how demographic and disease-specific characteristics correlate with symptomatic theme prevalence.

Results: The most frequent symptomatic themes reported by individuals with AD, MCI, and dementia in the cross-sectional survey were memory problems (99.0%), problems thinking (90.3%), and communication difficulties (80.4%). Patients identified decreased satisfaction in social situations (1.45), fatigue (1.45), and memory problems (1.41) as the most impactful symptomatic themes (range 0-4). Patient-reported symptomatic theme prevalence was strongly associated with the Modified Rankin Scale (mRS) for neurologic disability.

Discussion: Individuals with AD, MCI, and dementia experience a variety of symptoms that significantly affect their daily lives. These symptoms, many underrecognized, are of variable importance to individuals with these diseases and may inform potential targets for future therapeutic intervention as well as facilitate the development and validation of disease-specific outcome measures.