AUTHOR=Requena-Komuro Maï-Carmen , Marshall Charles R. , Bond Rebecca L. , Russell Lucy L. , Greaves Caroline , Moore Katrina M. , Agustus Jennifer L. , Benhamou Elia , Sivasathiaseelan Harri , Hardy Chris J. D. , Rohrer Jonathan D. , Warren Jason D. TITLE=Altered Time Awareness in Dementia JOURNAL=Frontiers in Neurology VOLUME=11 YEAR=2020 URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2020.00291 DOI=10.3389/fneur.2020.00291 ISSN=1664-2295 ABSTRACT=

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.