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Accelerated long-term forgetting in presymptomatic autosomal dominant Alzheimer's disease: a cross-sectional study

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Title: Accelerated long-term forgetting in presymptomatic autosomal dominant Alzheimer's disease: a cross-sectional study
Authors: Weston, PSJ
Nicholas, JM
Henley, SMD
Liang, Y
Macpherson, K
Donnachie, E
Schott, JM
Rossor, MN
Crutch, SJ
Butler, CR
Zeman, AZ
Fox, NC
Item Type: Journal Article
Abstract: Background 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. Methods 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. Findings 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. Interpretation 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. Funding MRC, NIHR, Alzheimer's Research UK, Dementias Platform UK, Dunhill Medical Trust, ERUK, Great Western Research, Health Foundation, Patrick Berthoud Trust.
Issue Date: 1-Feb-2018
Date of Acceptance: 1-Jan-2018
URI: http://hdl.handle.net/10044/1/91231
DOI: 10.1016/S1474-4422(17)30434-9
ISSN: 1474-4422
Publisher: Elsevier
Start Page: 123
End Page: 132
Journal / Book Title: Lancet Neurology
Volume: 17
Issue: 2
Copyright Statement: © The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/)
Keywords: Science & Technology
Life Sciences & Biomedicine
Clinical Neurology
Neurosciences & Neurology
SUBJECTIVE COGNITIVE DECLINE
TRANSIENT EPILEPTIC AMNESIA
MEMORY COMPLAINTS
PRECLINICAL PHASE
CONSOLIDATION
DEFICITS
PROGRESSION
IMPAIRMENT
DEMENTIA
ATROPHY
Science & Technology
Life Sciences & Biomedicine
Clinical Neurology
Neurosciences & Neurology
SUBJECTIVE COGNITIVE DECLINE
TRANSIENT EPILEPTIC AMNESIA
MEMORY COMPLAINTS
PRECLINICAL PHASE
CONSOLIDATION
DEFICITS
PROGRESSION
IMPAIRMENT
DEMENTIA
ATROPHY
Adult
Age of Onset
Alzheimer Disease
Chromosome Aberrations
Cohort Studies
Correlation of Data
Cross-Sectional Studies
DNA Mutational Analysis
Early Diagnosis
Female
Genes, Dominant
Genetic Carrier Screening
Genetic Testing
Humans
Male
Memory, Long-Term
Middle Aged
Neuropsychological Tests
Humans
Alzheimer Disease
Chromosome Aberrations
Early Diagnosis
Cohort Studies
Cross-Sectional Studies
DNA Mutational Analysis
Neuropsychological Tests
Age of Onset
Genes, Dominant
Adult
Middle Aged
Female
Male
Genetic Testing
Memory, Long-Term
Genetic Carrier Screening
Correlation of Data
1103 Clinical Sciences
1109 Neurosciences
Neurology & Neurosurgery
Publication Status: Published
Open Access location: https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(17)30434-9/fulltext
Online Publication Date: 2018-01-17
Appears in Collections:Department of Brain Sciences



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