Summary: UCL researchers have developed a new cognitive test able to detect subtle memory problems years before Alzheimer’s symptoms develop.
A UCL-led team has developed a cognitive test to detect subtle memory deficits years before Alzheimer’s disease symptoms develop, set out in a new paper published in The Lancet Neurology.
The study involved 21 people who carry the mutation for early onset Alzheimer’s disease who have not shown any symptoms based on standard cognitive tests, alongside 14 controls. On average the study participants were seven years away from predicted onset of symptomatic disease.
The participants underwent a memory test with 30-minute recall, and were then checked seven days later to see if they still remembered. The authors found that people who were closest to the expected onset of symptoms could remember things after 30 minutes but then had forgotten things after seven days.
The researchers say their findings demonstrate that memory formation wasn’t the issue, so typical tests wouldn’t identify any problems.
“It’s really a case of accelerated forgetting. Many people have a feeling that something is going wrong with their memory, but when they take the current test, it doesn’t show anything – 30 minutes isn’t really enough time. The people who carried the mutation and are at an early stage of the disease did no worse at 30 minutes but at seven days they were quite a lot worse. The difference was really quite remarkable,” senior author Professor Nick Fox (UCL Dementia Research Centre, UCL Institute of Neurology), told The Telegraph.
The researchers found a correlation between long-term forgetting and subjective memory complaints. They say this could be the earliest test to detect changes in someone’s cognition that lead to Alzheimer’s disease.
The study’s first author, Dr Philip Weston (UCL Dementia Research Centre), said: “The study would appear to significantly advance our knowledge of the earliest cognitive changes in Alzheimer’s, and offers a new useful approach to testing people both in drug trials and in the clinic.”
They say their study advances the scientific understanding of how exactly memory losses begin, as the researchers say this kind of long-term forgetting seems to start quite early.
While the study was only done in people who carry the mutation for autosomal dominant Alzheimer’s disease, alongside healthy controls, the researchers are hopeful that their findings would also be relevant to later-onset (sporadic) Alzheimer’s disease, as the disease progression is understood to be very similar. The early test could help identify people for early clinical trials, in addition to helping monitor whether a treatment is working.
Funding: The study involved researchers at UCL, the London School of Hygiene & Tropical Medicine, the University of Oxford and the University of Exeter, and was funded by the Medical Research Council, the National Institute for Health Research, Alzheimer’s Research UK, Dementias Platform UK, Dunhill Medical Trust, Epilepsy Research UK, Great Western Research, Health Foundation and the Patrick Berthoud Trust.
Source: Chris Lane – UCL
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is adapted from the UCL news release.
Original Research: Open access research in Lancet Neurology.
Accelerated long-term forgetting in presymptomatic autosomal dominant Alzheimer’s disease: a cross-sectional study
Tests sensitive to presymptomatic changes in Alzheimer’s disease could be valuable for clinical trials. Accelerated long-term forgetting—during which memory impairment becomes apparent over longer periods than usually assessed, despite normal performance on standard cognitive testing—has been identified in other temporal lobe disorders. We assessed whether accelerated long-term forgetting is a feature of presymptomatic autosomal dominant (familial) Alzheimer’s disease, and whether there is an association between accelerated long-term forgetting and early subjective memory changes.
This was a cross-sectional study at the Dementia Research Centre, University College London (London, UK). Participants were recruited from a cohort of autosomal dominant Alzheimer’s disease families already involved in research at University College London, and had to have a parent known to be affected by an autosomal dominant Alzheimer’s disease mutation, and not report any current symptoms of cognitive decline. Accelerated long-term forgetting of three tasks (list, story, and figure recall) was assessed by comparing 7-day recall with initial learning and 30-min recall. 7-day recognition was also assessed. Subjective memory was assessed using the Everyday Memory Questionnaire. The primary outcome measure for each task was the proportion of material retained at 30 min that was recalled 7 days later (ie, 7-day recall divided by 30-min recall). We used linear regression to compare accelerated long-term forgetting scores between mutation carriers and non-carriers (adjusting for age, IQ, and test set) and, for mutation carriers, to assess whether there was an association between accelerated long-term forgetting and estimated years to symptom onset (EYO). Spearman’s correlation was used to examine the association between accelerated long-term forgetting and subjective memory scores.
Between Feb 17, 2015 and March 30, 2016, we recruited 35 people. 21 participants were mutation carriers (mean EYO 7·2 years, SD 4·5). Across the three tasks, we detected no differences between carriers and non-carriers for initial learning or 30-min recall. The proportion of material recalled at 7 days was lower in carriers than non-carriers for list (estimated difference in mean for list recall −30·94 percentage points, 95% CI −45·16 to −16·73; p=0·0002), story (–20·10, −33·28 to −6·91; p=0·0048), and figure (–15·41, −26·88 to −3·93; p=0·012) recall. Accelerated long-term forgetting was greater in carriers nearer to their estimated age at onset (p≤0·01 for all three tests). Mutation carriers’ 7-day recognition memory was also lower across all tasks (list [mean difference −5·80, 95% CI −9·96 to −2·47; p<0·01], story [–6·84, −10·94 to −3·37; p<0·01], and figure [–17·61, −27·68 to −7·72; p<0·01] recognition). Subjective memory scores were poorer in asymptomatic carriers compared with non-carriers (adjusted difference in means 7·88, 95% CI 1·36 to 14·41; p=0·016), and we found a correlation between accelerated long-term forgetting and subjective memory in mutation carriers.
Accelerated long-term forgetting is an early presymptomatic feature of autosomal dominant Alzheimer’s disease, which appears to pre-date other amnestic deficits and might underpin subjective memory complaints in Alzheimer’s disease. Accelerated long-term forgetting testing might be useful in presymptomatic Alzheimer’s disease trials.