Visual short-term memory impairments in presymptomatic familial Alzheimer's disease: A longitudinal observational study

Abstract

Visual short-term memory (VSTM) deficits including VSTM binding have been associated with Alzheimer's disease (AD) from preclinical to dementia stages, cross-sectionally. Yet, longitudinal investigations are lacking. The objective of this study was to evaluate VSTM function longitudinally and in relation to expected symptom onset in a cohort of familial Alzheimer's disease. Ninety-nine individuals (23 presymptomatic; 9 symptomatic and 67 controls) were included in an extension cross-sectional study and a sub-sample of 48 (23 presymptomatic carriers, 6 symptomatic and 19 controls), attending two to five visits with a median interval of 1.3 years, included in the longitudinal study. Participants completed the "What was where?" relational binding task (which measures memory for object identification, localisation and object-location binding under different conditions of memory load and delay), neuropsychology assessments and genetic testing. Compared to controls, presymptomatic carriers within 8.5 years of estimated symptom onset showed a faster rate of decline in localisation performance in long-delay conditions (4s) and in traditional neuropsychology measures of verbal episodic memory. This study represents the first longitudinal VSTM investigation and shows that changes in memory resolution may be sensitive to tracking cognitive decline in preclinical AD at least as early as changes in the more traditional verbal episodic memory tasks.

Keywords: Alzheimer's disease; Estimated symptom onset; Familial Alzheimer's disease; Preclinical Alzheimer's disease; Visual short-term memory.

Fig. 1

Schematic of “What was there?” (adapted from (Liang et al., 2016) under the terms of the Creative Commons Attribution License (CC BY)).

Fig. 2

Cross-sectional adjusted mean performance by group (from model adjusted for age, sex and NART). A. Identification performance (across all conditions); B. Localisation error (across all conditions); C. Swap error proportion across all conditions and by delay in block 1. Error bars show ± standard error of the mean. PMC = presymptomatic mutation carrier. * = significant at p < 0.05; ** = significant at p < 0.01.

Fig. 3

Longitudinal adjusted estimated mean performance by group (from model adjusted for age at baseline, sex and NART). A. Identification performance (across all conditions). B. Localisation error performance for the 3-item, 4s delay condition. C. Swap error performance (across all conditions). PMC = presymptomatic mutation carrier. Error bars indicate ± standard error by time from baseline visit. * = the rate of change between groups was statistically significant at p < 0.05 (control as reference); ** = the rate of change between groups was statistically significant at p < 0.01 (control as reference).

Fig. 4

Relationship between VSTM performance and proximity to symptom onset. Identification performance is presented across all task conditions; localisation error specifically for the 3-items, 4s delay condition (where the association was strongest) and swap error proportion across delays (by definition only assessed in the 3-items condition). Panels A., B., D., E., G. and H. show the predicted mean of each VSTM metric (from model adjusted for age, sex and NART) against EYO or AYO. Shaded area indicates 95% confidence intervals. Panels C., F. and I. shows the unadjusted raw data plotted against EYO for each VSTM metric with visits marked as dots and connected for each participant; note there is no scale on the x-axes to preserve participant anonymity. Converters are PMCs who transitioned into a symptomatic stage at their last visit. PMC = presymptomatic mutation carrier. EYO = estimated years to/from symptom onset; AYO = actual years to/from symptom onset.

Fig. 5

Longitudinal estimated mean performance for RMT for words by group (from model adjusted for age at baseline, sex and NART). PMC = presymptomatic mutation carrier; RMT = recognition memory test. Error bars indicate ± standard error by time from baseline visit. * = the rate of change between groups was statistically significant at p < 0.05 (control as reference).