Long-Term Forgetting May Identify Alzheimer Disease Symptoms Before Onset

The investigators assessed the amount of material retained at 30 minutes and compared this with material recalled at 7 days.

Episodic memory is often compromised prior to the onset of autosomal-dominant Alzheimer disease (AD) symptoms, and testing for long-term memory retention may help in the early identification of verbal and visual memory deficits in affected patients, according to a cross-sectional study published in Lancet Neurology.

A total of 35 people from families with autosomal-dominant AD participating in research at the Dementia Research Centre of the University College London were enrolled in this study. None of the patients had reported any symptoms of cognitive decline, despite having a parent with an autosomal-dominant AD mutation. Investigators evaluated accelerated long-term forgetting of a 15-item word list, a short story, and a complex visual figure. The Everyday Memory Questionnaire was used to evaluate subjective memory. Investigators assessed the amount of material retained at 30 minutes and compared this with material recalled at 7 days.

In this cohort, a total of 21 participants were known carriers of the autosomal-dominant AD mutation (mean estimated years to symptom onset 7.2 years, standard deviation 4.5). No differences were observed between carriers of the mutation and those who were not carriers with regard to information retained at 30 minutes for the list, story, or figure (80.0% vs 80.0% [95% CI, -6.52 to 7.84]; P =.85; 83.3% vs 87.9% [95% CI, -5.77 to 4.29]; P =.76; 83.3% vs 87.9% [95% CI, -6.55 to 17.98]; P =.76, respectively).

At 7 days, carriers recalled a lower proportion of material compared with non-carriers for the list (estimated difference in mean for list recall -30.94 percentage points; 95% CI, -45.16 to -16.73; P =.0002), story (-20.10; 95% CI, -33.28 to -6.91; P =.0048), and figure (-15.41; 95% CI, -26.88 to -3.93; P =.012). For all 3 tests, carriers demonstrated greater accelerated long-term forgetting when they were nearest to their estimated age at symptom onset (P ≤.01).

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In addition, the 7-day recognition memory was significantly lower among mutation carriers vs non-carriers across all 3 recall tasks (list [mean difference -5.80; 95% CI, -9.96 to -2.47; P <.01], story [-6.84; 95% CI, -10.94 to -3.37; P <.01], and figure [-17.61; 95% CI, -27.68 to -7.72; P <.01]). Asymptomatic carriers also demonstrated worse subjective memory scores than non-carriers (adjusted difference in means 7.88; 95% CI, 1.36-14.41; P =.016).

Because of the rarity of autosomal-dominant AD, this study was comprised of a fairly small sample, thereby limiting the generalizability of the findings. Additionally, the investigators suggest some patients could have rehearsed the list, story, and figure material between initial learning and 7-day follow-up, which could have had an impact on recall statuses.

The findings from this study indicate that the clinical evaluation “of accelerated long-term forgetting appears to provide a means of discriminating healthy ageing from asymptomatic individuals in the presymptomatic phase of AD.”


Weston PSJ, Nicholas JM, Henley SMD, et al. Accelerated long-term forgetting in presymptomatic autosomal dominant Alzheimer’s disease: a cross-sectional study. Lancet Neurol. 2018;17(2):123-132.