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  1. Philip Weston1,
  2. Yuying Liang1,
  3. Susie Henley1,
  4. Jennifer Nicholas2,
  5. Natalie Ryan1,
  6. Jonathan Schott1,
  7. Martin Rossor1,
  8. Christopher Butler3,
  9. Adam Zeman4,
  10. Nick Fox1
  1. 1University College London
  2. 2London School of Hygiene and Tropical Medicine
  3. 3University of Oxford
  4. 4Peninsula Medical School


In Alzheimer's disease (AD), detecting presymptomatic cognitive change has proven difficult. Accelerated long-term forgetting has been identified in other diseases involving the temporal lobe, in individuals who perform normally on standard cognitive testing. We assessed whether accelerated long-term forgetting is a feature of presymptomatic familial AD (FAD).

We recruited 21 asymptomatic carriers of autosomal dominant FAD mutations (mean years to predicted onset=7.2) and 11 non-carrier controls. Participants were assessed on three memory tasks: list recall, story recall and figure recall. Participants had to first learn the material, to recall it 30 minutes later, and then again after 7 days. Subjective memory was assessed using the Everyday Memory Questionnaire.

For each test, mutation carriers and non-carriers were very similar for initial learning and 30-minute recall. However, recall at 7 days was significantly reduced in mutation carriers compared to non-carriers, for list recall (p=0.0011), story recall (p=0.012) and figure recall (p=0.021). Subjective memory scores were significantly poorer in mutation carriers than non-carriers (p=0.0163).

Accelerated long-term forgetting of both verbal and non-verbal material is an early, preclinical, feature of FAD; and may be the earliest feature of AD-related cognitive decline. Accelerated long-term forgetting may underpin early, subtle, subjective cognitive changes.

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