journal articles
CLINICAL AND BIOLOGICAL RELEVANCE OF OBJECTIVELY-DEFINED SUBTLE COGNITIVE DECLINE IN ALZHEIMER’S DISEASE: A NARRATIVE REVIEW OF NEUROIMAGING, BIOMARKER, AND CLINICAL PROGRESSION STUDIES
Amanda I. Gonzalez, Jairo E. Martinez, Averi Giudicessi, Meredith Rowe, Vivian Ku, Catarina Tristão-Pereira, Bing He, Vincent Malotaux, Yakeel T. Quiroz
Preclinical Alzheimer’s Disease stages represent possible targets for disease-modifying intervention as well as opportunity for early identification of risk for future decline. Recent research has explored the use of objectively-defined subtle cognitive decline (Obj-SCD), an emerging classification that may identify individuals at risk for neurodegeneration before the onset of mild cognitive impairment (MCI). The Edmonds/Thomas actuarial Obj‐SCD criteria (> 1 SD below expectations, single cognitive test impaired per domain) aims to capture those who exhibit minimal cognitive difficulties that do not meet a MCI or dementia diagnosis. Given the novelty of the Obj-SCD classification, this narrative review provides an overview of neuroimaging, biomarker, and clinical progression studies to evaluate its biological and clinical significance. Using fluid-based biomarkers, neuroimaging, and longitudinal designs, studies have indicated that the Obj-SCD classification has the potential to capture AD-related pathological changes detectable before the clinical onset of MCI. In particular, recent studies indicate a unique pathological profile of Obj-SCD, differentiating it from the cognitively unimpaired and MCI stages. Studies comparing Obj-SCD and subjective cognitive complaints show that the Obj-SCD criteria may be more closely associated to early AD pathology. While the existing literature is limited, findings uphold Obj-SCD as a sensitive classification able to identify individuals at risk for future cognitive impairment. Studies on Obj-SCD indicate utility in research settings, although it faces challenges regarding its clinical implementation and effectiveness.
CITATION:
Amanda I. Gonzalez ; Jairo E. Martinez ; Averi Giudicessi ; Meredith Rowe ; Vivian Ku ; Catarina Tristão-Pereira ; Bing He ; Vincent Malotaux ; Yakeel T. Quiroz (2025): Clinical and biological relevance of objectively-defined subtle cognitive decline in Alzheimer’s disease: a narrative review of neuroimaging, biomarker, and clinical progression studies. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100604