Abstract

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.