Memory Markers in Preclinical Alzheimer’s Disease

AbstractBackgroundEpisodic memory impairment is a widely known core clinical symptom of Alzheimer’s disease (AD). However, it is still uncertain if it is possible to detect meaningful signs or changes in memory in the preclinical stage of AD due to their within‐normal‐range performance. In the current study, we investigated both verbal and visuospatial memory as markers to track the disease progression in the preclinical AD.MethodWe selected cognitively normal (CN) participants from the Gwangju Alzheimer’s Disease and Related Dementia Cohort in Korea. We included a group of CN individuals who showed a significant amyloid‐beta (aß) deposition, defined by amyloid PET, at baseline and completed at least two follow‐up evaluations. In the final analysis, we included 130 individuals in the preclinical stage of AD. Episodic memory measures were delayed recall scores from the Rey Complex Figure Test (RCFT_delayed) and Seoul Verbal Learning test (SVLT_delayed). We performed logistic regression analysis with stepwise selection to examine associations between memory tests and progression.ResultThe mean follow‐up month was 36.21. Twenty‐one (16.2%) participants were converted to MCI (n = 19) or AD dementia (n = 2), while the rest stayed as CN. When both RCFT_delayed and SVLT_delayed at baseline were entered in the logistic regression model, only the RCFT_delayed was significantly associated with the progression (OR = 0.288; 95% CI, 0.138‐0.602; p = 0.001). When change scores were added to the model, RCFT_delayed at baseline (OR = 0.223; 95% CI, 0.101‐0.496; p < 0.001), RCFT_delayed change score (OR = 0.470; 95% CI, 0.258‐0.857; p = 0.014), and SVLT_delayed change score (OR = 0.523; 95% CI, 0.290‐0.942; p = 0.031), were significant.ConclusionOur results suggest that visuospatial, not verbal, memory measures may play an important role in sensitively detecting the relevant sign of future progression in asymptomatic individuals. In terms of verbal memory, the longitudinal decline was associated with progression. Our study suggests that the inclusion of a visuospatial memory test and repeated evaluation can help to detect the earliest decline in the preclinical stages of AD.