Background: Alzheimer's Disease (AD) has a lengthy asymptomatic preclinical phase during which individuals may show pathological signs like β-amyloid (Aβ) pathology and tau tangles without noticeable objective cognitive impairments. Subjective cognitive impairment reports may offer valuable and early insights into individuals' cognitive functioning and serve as indicators of early stages of cognitive decline. Objective: To investigate the associations of the item-level response to Cognitive Function Index (CFI) by participant and study partner with tau pathology and adjusted hippocampal volume (HVa). Method: Participants were 339 cognitively unimpaired, Aβ positive, individuals enrolled in the Anti-Amyloid Asymptomatic Alzheimer's (A4) Study who underwent tau-PET imaging. Participants and their study partners assessed subjective changes in cognition and function over the past year using the 15-item CFI questionnaire. For each CFI item, the relationship among tau, HVa, and CFI reports was investigated. Result: Participants were on average 72.38 (SD = 4.87) years old, 58.1% were female, and 23.6% were tau positive. Higher tauMTL was significantly associated with participant report of decline on three CFI items including depending on written notes, seeing a doctor for memory concern, and feeling lost while navigating. Higher tauMTL was associated with study partner report of decline on two different items: needing help from others to remember appointments/occasions and asking same questions. Additionally, HVa was linked to challenges with driving for participants and noticeable memory decline for study partners. Conclusion: We showed that early changes reported on specific items of the CFI are associated with higher tauMTL and lower HVa in Aβ+ participants. Different CFI items were associated with tau and hippocampal volume for participants and study partners, highlighting the importance of both perspective.

The authors have declared no competing interest.

This study was supported in part by grants from the National Institute of Health (NIA K23 AG063993; AG080635); the Alzheimer's Association (SG-24-988292 ISAVRAD); Cure Alzheimer's Fund, the Leonard and Sylvia Marx Foundation.

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