Lim AS, 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. Epub 2018 Sep 4 PubMed.

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  1. This is a fascinating paper showing seasonal differences in cognition and related biological measures. The authors show that cognitive performance peaks around the time of the fall equinox. The impact of seasonal variation on cognition is large, equivalent to ~four years of normal brain aging. The authors lend plausibility to their findings by reproducing the association in multiple cohorts. They also demonstrate that findings are clinically important by showing that participants had almost 30 percent higher odds of clinical cognitive impairment or dementia in winter and spring compared with summer and fall. Lastly, the authors looked at biological variables and showed that CSF A42 levels peaked during the summer and that season was also tied to the brain expression of gene modules related to cognition.

    The factors contributing to these findings are intriguing and require further investigation. In this study, the authors adjusted for age, sex, years of education, depressive symptoms, hours of sleep and physical activity, and serum TSH. However, as noted by the authors, other aspects of lifestyle (i.e., diet), sleep (circadian alignment and sleep quality) and mood may potentially drive seasonal differences in cognition. Seasonal differences in hormones and vitamin D may also contribute. 

    Not all countries experience such distinct seasons. Participants from this study were mostly from temperate regions of the northern hemisphere. It would be interesting to investigate seasonal differences in cognition and related biological variables in regions where temperature and sunlight are more stable throughout the year. For example, the opposite findings might be expected in the southern hemisphere, with cognition peaking in February. Also, perhaps people in countries close to the equator may show no seasonal differences.

    One limitation of the study is that it compared between people, rather than within people. Understanding individual trajectories of cognitive function across the year may also be informative. 

    These results may have diagnostic implications. Neuropsychologists and physicians should already be cognizant of the fact that a single neuropsychological assessment can underestimate performance; seasonality may be one contributor that needs to be considered. Whereas dementia diagnosis is not based solely on cognitive test data, mild cognitive impairment is often diagnosed based on comparing neuropsychological scores to a normative sample. Many persons diagnosed with MCI may revert back to normal. Repeated cognitive assessments across the year may provide more robust estimates of cognition and reduce the rate of false positive classifications. Pending further replication of these findings in diverse geographical areas, seasonal cognitive test norms could also be considered.

    View all comments by Matthew Pase

  2. This paper builds on work from the same lab showing seasonal variation in brain gene expression, and the data are in keeping with other studies linking seasonality to cognition (Meyer et al., 2016). These findings are very interesting and important, as they could explain some year-to-year variability in cognitive performance (and CSF Aβ levels) in patients and research participants. Much as time of day can influence these parameters, this paper would suggest that time of year does as well, and that memory clinics, research studies, and clinical trials might investigate this phenomenon further and, if needed, consider some type of adjustment.

    Certainly, longitudinal studies would be very helpful in evaluating this further. One concern I have is that the specific questionnaires used to detect depression in these studies may lack sensitivity to detect more subtle changes in mood that might impact cognitive test performance. Seasonal variation in other hormones besides TSH, such as cortisol, or in autonomic function, could contribute.

    While the molecular machinery driving circadian timing in the body is now understood, it is unknown if a seasonal clock exists, and if so, what it is or how it works. It is simplest to assume that these changes represent responses to the changing environment, but it is possible that an undiscovered seasonal clock regulates gene expression. Seasonal change in many aspects of peripheral metabolism have been demonstrated, and perhaps the brain is responding to those. The most obvious potential mechanism is that changes in the amount and timing of light exposure influence the circadian clock, which can directly regulate gene transcription. There are clear effects of photoperiod on mood (seasonal affective disorder), and it is well established that the circadian clock can influence learning and memory systems. However, many variables change seasonally, so there are many potential explanations.

    References:

    Meyer C, Muto V, Jaspar M, Kussé C, Lambot E, Chellappa SL, Degueldre C, Balteau E, Luxen A, Middleton B, Archer SN, Collette F, Dijk DJ, Phillips C, Maquet P, Vandewalle G. Seasonality in human cognitive brain responses. Proc Natl Acad Sci U S A. 2016 Mar 15;113(11):3066-71. Epub 2016 Feb 8 PubMed.

    View all comments by Erik Musiek

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  1. Does Cognition Change With the Seasons?