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

Ivanna M. Pavisic*, Jennifer M. Nicholas, Yoni Pertzov, Antoinette O'Connor, Yuying Liang, Jessica D. Collins, Kirsty Lu, Philip S.J. Weston, Natalie S. Ryan, Masud Husain, Nick C. Fox, Sebastian J. Crutch

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


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.

Original languageAmerican English
Article number108028
StatePublished - 12 Nov 2021

Bibliographical note

Funding Information:
We thank participants and their families for their generous support throughout the course of the study. Y. Pertzov was supported by the Israel Science Foundation (ISF) grant ( 1747/14 ); A. O'Connor is supported by an Alzheimer's Society Clinical Research Training Fellowship; P.S.J Weston was supported by an MRC Clinical Research Training Fellowship; N.S. Ryan is supported by a University of London Chadburn Academic Clinical Lectureship (548951), and held a Clinical Research Training Fellowship (G0 900421) from the Medical Research Council; M. Husain is supported by the Wellcome Trust Principal Research Fellowship ( 206330/Z/17/Z ). This work was supported by the NIHR UCLH Biomedical Research Centre ( 540602 ) and UK Dementia Research Institute which receives its funding from DRI Ltd, funded by the UK Medical Research Council , Alzheimer's Society and Alzheimer's Research UK . The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

Publisher Copyright:
© 2021 The Author(s)


  • Alzheimer's disease
  • Estimated symptom onset
  • Familial Alzheimer's disease
  • Preclinical Alzheimer's disease
  • Visual short-term memory


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