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.

Highlights

  • Progressive episodic memory impairment is a central, defining feature of Alzheimer’s disease (AD) (Dubois et al 2007; McKhann et al 1984)

  • Symptomatic carriers were older and on average three years after expected onset, had lower mini-mental state examination (MMSE) and higher global Clinical Dementia Rating (CDR) and had significantly worse scores on neuropsychology tasks including arithmetic, RMT for words, digit span, Stroop and verbal IQ scores compared to controls (Table 1)

  • Localisation performance was the only Visual short-term memory (VSTM) metric to show a significant association with expected years to onset (EYO), predicting cognitive decline up to 6 years prior to estimated symptom onset

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Summary

Introduction

Progressive episodic memory impairment is a central, defining feature of Alzheimer’s disease (AD) (Dubois et al 2007; McKhann et al 1984). STM has been tested using ‘span’ measures where participants are asked to remember a string of stimuli (Groeger et al, 1999). Such quantal (discrete) measures have been fundamental to developing our understanding of memory function, they are not as sensitive to detect changes in memory resolution due to the binary nature of responses measured (correct vs incorrect recall). In recent studies, delayed-reproduction tasks have been reported to be more sensitive than conventional span measures of STM, especially in clinical populations (Zokaei et al 2015)

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