Abstract
Background: Cross-sectional studies in presymptomatic familial Alzheimer’s disease (FAD), have associated binding deficits with preclinical AD. How impairments in visual-short term memory (VSTM) relate to longitudinal change and proximity to expected symptom onset (EYO) is less characterized.Methods: Thirty-two FAD mutation carriers (23 presymptomatic; 9 symptomatic) carrying a mutation in either presenilin 1 or amyloid precursor protein genes and 67 healthy controls were included in an extension VSTM cross-sectional study. Forty-eight participants (23 presymptomatic carriers, 6 symptomatic and 19 healthy controls) who had at least two annual visits (median= 3), were 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. Results: While cross-sectionally only symptomatic carriers (N=9) showed significant impairments in VSTM performance, longitudinally, presymptomatic carriers within 8.5 years of estimated symptom onset (mean=5.8 years ±SD [1.8], N=11) showed a faster rate of decline in localisation performance in long-delay conditions (4s) compared to controls: increase/year in localisation error was 6.9% greater in the high-memory load condition (p=0.008) and 7.0% greater for the low-memory load condition (p=0.043). Change in this metric preceded presymptomatic changes in traditional measures of verbal episodic memory. Symptomatic carriers had 15% faster reduction in identification performance per year compared to controls (p=0.036) and some evidence of faster increase in localisation error (6.5% increase/year; p=0.066). The earliest significant difference in VSTM performance between FAD mutation carriers (presymptomatic and symptomatic) and controls was in localisation performance, six years prior to estimated symptom onset (p=0.024). Conclusions: This longitudinal study of FAD, suggests changes in VSTM resolution, which measure precision and thus quality of recall of the memory presentation, may be sensitive markers for tracking and predicting cognitive decline in preclinical AD.
Visual short-term memory for 3D shapes reveals similar properties to simple 2D features
