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The role of dyadic cognitive report and subjective cognitive decline in early ADRD clinical research and trials: Current knowledge, gaps, and recommendations

Nosheny RL, Amariglio R, Sikkes SAM, Van Hulle C, Bicalho MAC, Dowling NM, Brucki SMD, Ismail Z, Kasuga K, Kuhn E, Numbers K, Aaronson A, Moretti DV, Pereiro AX, Sánchez-Benavides G, Sellek Rodríguez AF, Urwyler P, Zawaly K

Abstract

Efficient identification of cognitive decline and Alzheimer's disease (AD) risk in early stages of the AD disease continuum is a critical unmet need. Subjective cognitive decline is increasingly recognized as an early symptomatic stage of AD. Dyadic cognitive report, including subjective cognitive complaints (SCC) from a participant and an informant/study partner who knows the participant well, represents an accurate, reliable, and efficient source of data for assessing risk. However, the separate and combined contributions of self- and study partner report, and the dynamic relationship between the two, remains unclear. The Subjective Cognitive Decline Professional Interest Area within the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment convened a working group focused on dyadic patterns of subjective report. Group members identified aspects of dyadic-report information important to the AD research field, gaps in knowledge, and recommendations. By reviewing existing data on this topic, we found evidence that dyadic measures are associated with objective measures of cognition and provide unique information in preclinical and prodromal AD about disease stage and progression and AD biomarker status. External factors including dyad (participant-study partner pair) relationship and sociocultural factors contribute to these associations. We recommend greater dyad report use in research settings to identify AD risk. Priority areas for future research include (1) elucidation of the contributions of demographic and sociocultural factors, dyad type, and dyad relationship to dyad report; (2) exploration of agreement and discordance between self- and study partner report across the AD syndromic and disease continuum; (3) identification of domains (e.g., memory, executive function, neuropsychiatric) that predict AD risk outcomes and differentiate cognitive impairment due to AD from other impairment; (4) development of best practices for study partner engagement; (5) exploration of study partner report as AD clinical trial endpoints; (6) continued development, validation, and optimization, of study partner report instruments tailored to the goals of the research and population.

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Reference

Nosheny RL, Amariglio R, Sikkes SAM, Van Hulle C, Bicalho MAC, Dowling NM, Brucki SMD, Ismail Z, Kasuga K, Kuhn E, Numbers K, Aaronson A, Moretti DV, Pereiro AX, Sánchez-Benavides G, Sellek Rodríguez AF, Urwyler P, Zawaly K; Dyadic Patterns of Subjective Report working group within the Subjective Cognitive Decline Professional Interest Area, Alzheimer's Association ISTAART. The role of dyadic cognitive report and subjective cognitive decline in early ADRD clinical research and trials: Current knowledge, gaps, and recommendations. Alzheimers Dement (N Y). 2022 Oct 4;8(1):e12357. doi: 10.1002/trc2.12357. PMID: 36226046; PMCID: PMC9530696.