Medicine Care Team

Administrative Assistant: Richelle Bercasio
Phone: 416-480-6100 ext. 2461
Email: richelle.bercasio@sunnybrook.ca

Education:

• B.Sc., 1999, microbiology and immunology, University of British Columbia, Canada
• MD, 2003, University of Toronto, Canada
• FRCPC, 2008, adult neurology, Royal College of Physicians and Surgeons of Canada
• Diploma in electroencephalography, 2008, Canadian Society of Clinical Neurophysiologists
• Clinical fellowship, 2009, sleep medicine, Harvard University, U.S.
• MMSc, 2011, clinical investigation, Harvard University, U.S.

Appointments and Affiliations:

• Scientist, Evaluative Clinical Sciences, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute
• Staff neurologist, department of medicine, Sunnybrook Health Sciences Centre
• Associate professor, department of medicine, U of T

Research Foci:

• Sleep and circadian biology
• Noninvasive ambulatory monitoring of sleep and circadian rhythms
• Genetic epidemiology of sleep and circadian traits
• Impact of sleep and circadian function on cognitive decline, dementia and neurodegenerative diseases

Research Summary:

Dr. Lim’s research is focused on answering three broad questions:

1. What is the impact of sleep and circadian rhythm disruption on human brain health, particularly Alzheimer's disease and other dementias, from neurobiological mechanisms to health outcomes?
2. What are the genetic mechanisms contributing to human sleep and circadian function, and how can we modify their impact on brain health?
3. What are the molecular substrates of circadian and seasonal rhythms of human brain biology in health and disease?

To answer these questions, and in collaboration with laboratories in Toronto and elsewhere, he uses a number of complementary techniques. These include the following:

• ambulatory at-home measurement of sleep and circadian biology using a battery of novel wearable movement, cardiopulmonary, and neurophysiological sensors; Development of analytical tools for data from these devices is an important focus of the laboratory;
• genome-wide association analyses, mendelian randomization, and other population genetic approaches;
• time-series analysis of genome-scale RNA sequencing, single-nucleus RNA sequencing, DNA methylation, and ChIP-seq (chromatin immunoprecipitation sequencing) data;
• MR brain imaging;
• linkage to administrative health databases;

He is applying these techniques in several large studies including:

1. The Ontario Sleep Health Study, which has prospectively obtained objective sleep and circadian measurements and blood samples from more than 3,200 Ontarians, of whom more than 100 have had brain MR imaging and psychometric testing. The team also has consent for linkage to administrative health databases at the Institute for Clinical Evaluative Sciences.
2. The Sunnybrook Brain Changes in Sleep Apnea study, in collaboration with Dr. Sandra Black and Dr. Brad Macintosh. We are obtaining detailed ambulatory measures of sleep physiology and cardiovascular physiology, detailed brain MR imaging, and psychometric testing on patients with severe sleep apnea before and after treatment with a continuous positive airway pressure device.
3. The Memory and Aging project, in collaboration with Dr. David Bennett and Dr. Aron Buchman. We have obtained ambulatory measurements of sleep physiology from more than 1,500 older adults. and are linking these sleep and circadian data to cognitive outcomes, MR imaging, genotype, genome-scale transcriptome and epigenome data, and postmortem histopathology.
4. The Canadian Consortium on Neurodegeneration in Aging, whose sleep team he co-leads, which includes the n=1,200 COMPASS-ND clinical cohort, and the n=350 CTU Alzheimer's disease prevention cohort. We are obtaining ambulatory sleep EEG and cardiorespiratory measurements and relating these to dementia biomarkers and outcomes.

Work in the laboratory is funded by grants from the Canadian Institutes of Health Research, the National Institute on Aging, and the Ontario Ministry of Research, Innovation and Science.

The laboratory is looking to take on one or more graduate students at the master’s level through the Institute of Medical Science at U of T, 1 or more postdoctoral fellows, as well as residents or medical students interested in undertaking sleep and circadian rhythm-related research projects, in the 2021-2022 academic year. In particular, Dr. Lim is looking for candidates with programming (especially R and MATLAB) and statistics experience, coupled with undergraduate-level knowledge of mathematics, genetics and neurobiology. If you are interested in applying, please contact Dr. Lim at andrew.lim@utoronto.ca.

Selected Publications:

View full bibliography »

Representative recent publications include: 

1. Kaneshwaran K, Olah M, Tasaki S, Yu L, Bradshaw EM, Schneider JA, Buchman AS, Bennett DA, De Jager PL, Lim ASP. Sleep fragmentation, microglial aging, and cognitive impairment in adults with and without Alzheimer's dementia. Sci Adv. 2019 Dec;5(12):eaax7331. doi: 10.1126/sciadv.aax7331. eCollection 2019 Dec. PubMed PMID: 31844665; PubMed Central PMCID: PMC6905859.
2. Wilcox ME, Rubenfeld GD, Walczak KD, Black SE, McAndrews MP, Lim AS. Actigraphic measures of sleep on the wards after ICU discharge. J Crit Care. 2019 Dec;54:163-169. doi: 10.1016/j.jcrc.2019.08.006. Epub 2019 Aug 16. PubMed PMID: 31472397.
3. Lim ASP, Gaiteri C, Yu L, Sohail S, Swardfager W, Tasaki S, Schneider JA, Paquet C, Stuss DT, Masellis M, Black SE, Hugon J, Buchman AS, Barnes LL, Bennett DA, De Jager PL. Seasonal plasticity of cognition and related biological measures in adults with and without Alzheimer disease: Analysis of multiple cohorts. PLoS Med. 2018 Sep;15(9):e1002647. doi: 10.1371/journal.pmed.1002647. eCollection 2018 Sep. PubMed PMID: 30180184; PubMed Central PMCID: PMC6122787.
4. Sohail S, Yu L, Schneider JA, Bennett DA, Buchman AS, Lim ASP. Sleep fragmentation and Parkinson's disease pathology in older adults without Parkinson's disease. Mov Disord. 2017 Dec;32(12):1729-1737. doi: 10.1002/mds.27200. Epub 2017 Oct 30. PubMed PMID: 29082554; PubMed Central PMCID: PMC5778902.
5. Lim AS, Klein HU, Yu L, Chibnik LB, Ali S, Xu J, Bennett DA, De Jager PL. Diurnal and seasonal molecular rhythms in human neocortex and their relation to Alzheimer's disease. Nat Commun. 2017 Apr 3;8:14931. doi: 10.1038/ncomms14931. PubMed PMID: 28368004; PubMed Central PMCID: PMC5382268.

Related News and Stories:

• How is poor sleep affecting Ontarians? Preliminary data show good quality slumber eludes many (Jan. 10, 2020)
• Portrait of a sleepy city: The numbers behind Toronto's sleep problems (CBC News, Jan. 8, 2020)
• Sleep disruptions related to changes in immune cells in brain and worse cognition: study: new research may help explain link between poor slumber and dementia (Dec. 17, 2019)
• Study finds link between dementia and lack of sleep (The Globe and Mail, Dec. 11, 2019)
• To sleep perchance to think: Scientist studies link between poor slumber and mental decline in later life (Oct. 31, 2017)
• That syncing feeling: Seasonal rhythms affect gene expression in the brain; they also are linked with daily rhythms—and both are disrupted in Alzheimer's disease: study (SRI Magazine, 2017)
• Poor sleep linked to hardened blood vessels, small strokes in seniors: Elderly people who sleep poorly and awaken frequently are more likely to have hardened blood vessels or small strokes in the brain (Jan. 14, 2016)
• Study helps explain sleep problems in the elderly: a group of neurons are found to function as a "sleep switch" in the brain (Aug. 20, 2014)
• Rhythm of the night: Want a healthy brain? Get a good night's sleep (SRI Magazine, 2013)
• Sound sleep can reduce Alzheimer's risk: Genetic risk factor for Alzheimer's disease may be offset by better sleep (Oct. 21, 2013)
• Making the cut: Amid fiscal challenges, SRI researchers get funded (Feb. 7, 2013)
• Are you an early riser or a night owl? Check your DNA, Radio Canada International (Dec. 20, 2012)
• Genes may predict when you'll die: researchers, CTV News (Nov. 26, 2012)
• University of Toronto professor discovers gene that predicts time of death (The Toronto Star, Nov. 19, 2012)
• Scientists stimulate dreaming sleep for the first time PDF, Sunnybrook News (Sep. 30, 2009)
• Sleep research wakes up to clinical relevance PDF, Neurology Today (Nov. 6, 2007)
• Brain waves of dreaming sleep found for first time PDF, Sunnybrook News (July 13, 2007)

Related Links:

• The Ontario Sleep Health Study