TY - JOUR
T1 - Altered Time Awareness in Dementia
AU - Requena-Komuro, Maï Carmen
AU - Marshall, Charles R.
AU - Bond, Rebecca L.
AU - Russell, Lucy L.
AU - Greaves, Caroline
AU - Moore, Katrina M.
AU - Agustus, Jennifer L.
AU - Benhamou, Elia
AU - Sivasathiaseelan, Harri
AU - Hardy, Chris J.D.
AU - Rohrer, Jonathan D.
AU - Warren, Jason D.
N1 - Funding Information:
The Dementia Research Center was supported by Alzheimer’s Research UK, Brain Research UK and the Wolfson Foundation. This work was funded by the Alzheimer’s Society, Alzheimer’s Research UK, the National Institute for Health Research University College London Hospitals Biomedical Research Center, and the UCL Leonard Wolfson Center for Experimental Neurology. Individual authors were supported by the Wellcome Trust (4-year Ph.D. Studentship in Neuroscience 102129/B/13/Z to M-CR-K; 091673/Z/10/Z to JW), the Wolfson Foundation (Clinical Research Fellowship previously to CM), Bart’s Charity (MGU0366 to CM), the Medical Research Council (Ph.D. studentship to RB and previously to CH; MRC Clinician Scientist Fellowship MR/M008525/1 to JR), Alzheimer’s Society (Ph.D. studentship AS-PhD-2015-005 to KM), Brain Research UK (4-year Ph.D. Studentship to EB), and Action on Hearing Loss (Dunhill Medical Trust Pauline Ashley Fellowship to CH).
Publisher Copyright:
© Copyright © 2020 Requena-Komuro, Marshall, Bond, Russell, Greaves, Moore, Agustus, Benhamou, Sivasathiaseelan, Hardy, Rohrer and Warren.
PY - 2020/4/21
Y1 - 2020/4/21
N2 - Our awareness of time, specifically of longer intervals spanning hours, days, months, and years, is critical for ensuring our sense of self-continuity. Disrupted time awareness over such intervals is a clinical feature in a number of frontotemporal dementia syndromes and Alzheimer's disease, but has not been studied and compared systematically in these diseases. We used a semi-structured caregiver survey to capture time-related behavioral alterations in 71 patients representing all major sporadic and genetic syndromes of frontotemporal dementia, in comparison to 28 patients with typical Alzheimer's disease and nine with logopenic aphasia, and 32 healthy older individuals. Survey items pertained to apparent difficulties ordering past personal events or estimating time intervals between events, temporal rigidity and clockwatching, and propensity to relive past events. We used a logistic regression model including diagnosis, age, gender, and disease severity as regressors to compare the proportions of individuals exhibiting each temporal awareness symptom between diagnostic groups. Gray matter associations of altered time awareness were assessed using voxel-based morphometry. All patient groups were significantly more prone to exhibit temporal awareness symptoms than healthy older individuals. Clinical syndromic signatures were identified. While patients with typical and logopenic Alzheimer's disease most frequently exhibited disturbed event ordering or interval estimation, patients with semantic dementia were most prone to temporal rigidity and clockwatching and those with behavioral variant frontotemporal dementia commonly exhibited all these temporal symptoms as well as a propensity to relive past events. On voxel-based morphometry, the tendency to relive past events was associated with relative preservation of a distributed left-sided temporo-parietal gray matter network including hippocampus. These findings reveal a rich and complex picture of disturbed temporal awareness in major dementia syndromes, with stratification of frontotemporal dementia syndromes from Alzheimer's disease. This is the first study to assess symptoms of altered temporal awareness across frontotemporal dementia syndromes and provides a motivation for future work directed to the development of validated clinical questionnaires, analysis of underlying neurobiological mechanisms and design of interventions.
AB - Our awareness of time, specifically of longer intervals spanning hours, days, months, and years, is critical for ensuring our sense of self-continuity. Disrupted time awareness over such intervals is a clinical feature in a number of frontotemporal dementia syndromes and Alzheimer's disease, but has not been studied and compared systematically in these diseases. We used a semi-structured caregiver survey to capture time-related behavioral alterations in 71 patients representing all major sporadic and genetic syndromes of frontotemporal dementia, in comparison to 28 patients with typical Alzheimer's disease and nine with logopenic aphasia, and 32 healthy older individuals. Survey items pertained to apparent difficulties ordering past personal events or estimating time intervals between events, temporal rigidity and clockwatching, and propensity to relive past events. We used a logistic regression model including diagnosis, age, gender, and disease severity as regressors to compare the proportions of individuals exhibiting each temporal awareness symptom between diagnostic groups. Gray matter associations of altered time awareness were assessed using voxel-based morphometry. All patient groups were significantly more prone to exhibit temporal awareness symptoms than healthy older individuals. Clinical syndromic signatures were identified. While patients with typical and logopenic Alzheimer's disease most frequently exhibited disturbed event ordering or interval estimation, patients with semantic dementia were most prone to temporal rigidity and clockwatching and those with behavioral variant frontotemporal dementia commonly exhibited all these temporal symptoms as well as a propensity to relive past events. On voxel-based morphometry, the tendency to relive past events was associated with relative preservation of a distributed left-sided temporo-parietal gray matter network including hippocampus. These findings reveal a rich and complex picture of disturbed temporal awareness in major dementia syndromes, with stratification of frontotemporal dementia syndromes from Alzheimer's disease. This is the first study to assess symptoms of altered temporal awareness across frontotemporal dementia syndromes and provides a motivation for future work directed to the development of validated clinical questionnaires, analysis of underlying neurobiological mechanisms and design of interventions.
KW - Alzheimer's disease
KW - clockwatching
KW - frontotemporal dementia
KW - primary progressive aphasia
KW - semantic dementia
KW - time perception
KW - voxel-based morphometry
UR - http://www.scopus.com/inward/record.url?scp=85084258971&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85084258971&partnerID=8YFLogxK
U2 - 10.3389/fneur.2020.00291
DO - 10.3389/fneur.2020.00291
M3 - Article
C2 - 32373055
AN - SCOPUS:85084258971
SN - 1664-2295
VL - 11
JO - Frontiers in Neurology
JF - Frontiers in Neurology
M1 - 291
ER -