Summary: Researchers say there is a link between improved cognitive functioning in Alzheimer’s disease and different seasons. The study reports those with Alzheimer’s have better cognitive skills during late summer and early fall. Additionally, there was an association with seasonality and levels of Alzheimer’s related proteins in the brain.
Adults both with and without Alzheimer’s disease have better cognition skills in the late summer and early fall than in the winter and spring, according to a new study published this week in PLOS Medicine by Andrew Lim of Sunnybrook Health Sciences Centre and the University of Toronto, Canada, and colleagues.
There have been few previous studies concerning the association between season and cognition in older adults. In the new work, researchers analyzed data on 3,353 people enrolled in three different cohort studies in the U.S., Canada, and France. Participants had undergone neuropsychological testing and, for some participants, levels of proteins and genes associated with Alzheimer’s disease were available.
The authors found that average cognitive functioning was higher in the summer and fall than the winter and spring, equivalent in cognitive effect to 4.8 years difference in age-related decline. In addition, the odds of meeting the diagnostic criteria for mild cognitive impairment or dementia were higher in the winter and spring (odds ratio 1.31, 95% CI: 1.10-1.57) than summer or fall. The association between season and cognitive function remained significant even when the data was controlled for potential confounders, including depression, sleep, physical activity, and thyroid status. Finally, an association with seasonality was also seen in levels of Alzheimer’s-related proteins and genes in cerebrospinal fluid and the brain. However, the study was limited by the fact that each participant was only assessed once per annual cycle, and only included data on individuals from temperate northern-hemisphere regions, not from southern-hemisphere or equatorial regions.
“There may be value in increasing dementia-related clinical resources in the winter and early spring when symptoms are likely to be most pronounced,” the authors say. “By shedding light on the mechanisms underlying the seasonal improvement in cognition in the summer and early fall, these findings also open the door to new avenues of treatment for Alzheimer’s disease.”
Funding: This study was funded by National Institutes of Health (http://www.nih.gov; P30AG10161, R01AG052488, R01AG043379, R01AG15819, R01AG17917, R01AG36042, R01AG36836, U01AG046152, RF1AG022018, R01AG042210, and R01NS078009); Canadian Institutes of Health Research (http://www.cihr-irsc.gc.ca/; MOP125934, and MSH136642); Alzheimer’s Association (http://www.alz.org) and Brain Canada (http://www.braincanada.ca; AARG501466); National Sciences and Engineering Research Council of Canada (http://www.nserc-crsng.gc.ca; RGPIN-2017-0692); Agence Nationale de la Recherche (http://www.agence-nationale-recherche.fr; MALZ grant 2013); Agence Publique Hopitaux de Paris (http://fondationrechercheaphp.fr/); Institut National de la Sante et de la Recherche Medicale (http://www.inserm.fr/en); the Illinois Department of Public Health (http://www.dph.illinois.gov/); the Alzheimer Society of Canada (alzheimer.ca/); the Heart and Stroke Foundation of Canada (http://www.heartandstroke.ca/); and the Robert C. Borwell Endowment Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: SEB has ad-hoc consultancies with the following: GE Healthcare, Boehringer Ingelheim, Novartis, Merck, Eli Lilly, Pfizer. Continuing medical education from: Novartis, Eisai, Medscape/Biogen, Eli Lilly. SEB receives grants to her institution from: Elan, Roche, GE Healthcare, Eli Lilly, Pfizer, Lundbeck, Transition Therapeutics, Biogen Idec, Novartis, Genentech, and Optina. CP is a consultant for FUJIRIBIO laboratory.
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Original Research: Open access research for “Seasonal plasticity of cognition and related biological measures in adults with and without Alzheimer disease: Analysis of multiple cohorts” by Andrew S. P. Lim, Chris Gaiteri, Lei Yu, Shahmir Sohail, Walter Swardfager, Shinya Tasaki, Julie A. Schneider, Claire Paquet, Donald T. Stuss, Mario Masellis, Sandra E. Black, Jacques Hugon, Aron S. Buchman, Lisa L. Barnes, David A. Bennett, and Philip L. De Jager in PLOS Medicine. Published September 4 2018.
Seasonal plasticity of cognition and related biological measures in adults with and without Alzheimer disease: Analysis of multiple cohorts
There are few data concerning the association between season and cognition and its neurobiological correlates in older persons—effects with important translational and therapeutic implications for the diagnosis and treatment of Alzheimer disease (AD). We aimed to measure these effects.
Methods and findings
We analyzed data from 3,353 participants from 3 observational community-based cohort studies of older persons (the Rush Memory and Aging Project [MAP], the Religious Orders Study [ROS], and the Minority Aging Research Study [MARS]) and 2 observational memory-clinic-based cohort studies (Centre de Neurologie Cognitive [CNC] study at Lariboisière Hospital and the Sunnybrook Dementia Study [SDS]). We performed neuropsychological testing and, in subsets of participants, evaluated cerebrospinal fluid AD biomarkers, standardized structured autopsy measures, and/or prefrontal cortex gene expression by RNA sequencing. We examined the association between season and these variables using nested multiple linear and logistic regression models. There was a robust association between season and cognition that was replicated in multiple cohorts (amplitude = 0.14 SD [a measure of the magnitude of seasonal variation relative to overall variability; 95% CI 0.07–0.23], p = 0.007, in the combined MAP, ROS, and MARS cohorts; amplitude = 0.50 SD [95% CI 0.07–0.66], p = 0.017, in the SDS cohort). Average composite global cognitive function was higher in the summer and fall compared to winter and spring, with the difference equivalent in cognitive effect to 4.8 years’ difference in age (95% CI 2.1–8.4, p = 0.002). Further, the odds of meeting criteria for mild cognitive impairment or dementia were higher in the winter and spring (odds ratio 1.31 [95% CI 1.10–1.57], p = 0.003). These results were robust against multiple potential confounders including depressive symptoms, sleep, physical activity, and thyroid status and persisted in cases with AD pathology. Moreover, season had a marked effect on cerebrospinal fluid Aβ 42 level (amplitude 0.30 SD [95% CI 0.10–0.64], p = 0.003), which peaked in the summer, and on the brain expression of 4 cognition-associated modules of co-expressed genes (m6: amplitude = 0.44 SD [95% CI 0.21–0.65], p = 0.0021; m13: amplitude = 0.46 SD [95% CI 0.27–0.76], p = 0.0009; m109: amplitude = 0.43 SD [95% CI 0.24–0.67], p = 0.0021; and m122: amplitude 0.46 SD [95% CI 0.20–0.71], p = 0.0012), which were in phase or anti-phase to the rhythms of cognition and which were in turn associated with binding sites for several seasonally rhythmic transcription factors including BCL11A, CTCF, EGR1, MEF2C, and THAP1. Limitations include the evaluation of each participant or sample once per annual cycle, reliance on self-report for measurement of environmental and behavioral factors, and potentially limited generalizability to individuals in equatorial regions or in the southern hemisphere.
Season has a clinically significant association with cognition and its neurobiological correlates in older adults with and without AD pathology. There may be value in increasing dementia-related clinical resources in the winter and early spring, when symptoms are likely to be most pronounced. Moreover, the persistence of robust seasonal plasticity in cognition and its neurobiological correlates, even in the context of concomitant AD pathology, suggests that targeting environmental or behavioral drivers of seasonal cognitive plasticity, or the key transcription factors and genes identified in this study as potentially mediating these effects, may allow us to substantially improve cognition in adults with and without AD.