Pain, Fatigue, and Cognitive Symptoms Are Temporally Associated Within but Not Across Days in Multiple Sclerosis
Open accessAbstract
Objective To examine the temporal associations, within-day and day-to-day, between pain, fatigue, depressed mood, and cognitive function in multiple sclerosis (MS). Design Repeated-measures study involving seven days of ecological momentary assessment (EMA) of symptoms five times a day. Multilevel mixed models were used to analyze data. Setting Community. Participants Ambulatory adults (N=107) with MS. Interventions Not applicable. Main Outcome Measure(s) EMA of pain, fatigue, depressed mood, and cognitive function rated on a 0–10 scale. Results Fatigue and pain were linked within-day such that higher pain was associated with higher subsequent fatigue (B=0.09, p=0.04; likewise, higher fatigue was associated with higher pain in the following time frame (B=0.05, p=0.04). Poorer perceived cognitive function preceded increased subsequent pain (B=0.08, p=0.007) and fatigue (B=0.10, p=0.01) within-day. Depressed mood was not temporally linked with other symptoms. In terms of day-to-day effects, a day of higher fatigue related to decreased next day fatigue (B=−0.16, p=0.01), and a day of higher depressed mood related to increased depressed mood the next day (B=0.17, p=0.01). There were no cross-symptom associations from one day to the next. Conclusions Findings provide new insights on how common symptoms in MS relate to each other and vary within and over days. Pain and fatigue show evidence of a dynamic bidirectional relation over the course of a day, and worsening of perceived cognitive function preceded worsening of both pain and fatigue. Most temporal associations between symptoms occur within the course of a day, with relatively little carry-over from one day to the next.
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Methodological studies of EMA of symptoms demonstrate that surveys relying on respondent recall, such as the baseline measures in this study, are biased toward peak (worst) and recent symptoms.
“Methodological studies of EMA of symptoms demonstrate surveys that rely on respondent recall, such as the baseline measures in this study, are biased toward peak (worst) and recent symptoms76–78; EMA ratings may provide a more valid estimate of true symptom intensity compared to standardized surveys.”
From Ecological momentary assessment of pain, fatigue, depressive, and cognitive symptoms reveals significant daily variability in multiple sclerosis (2017) · cites this paper as [78]
The Study Limitations section (page not available in our copy) reports higher symptom ratings on surveys than on EMA, but says the reason is unclear. It does not establish that recall surveys are biased toward peak or recent symptoms. (LLM, conf=0.86)
Experimental — accuracy not yet measured
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“Overall fluctuations (general, between-day, or within-day, respectively) were defined as the average of the respective fluctuations over all individual symptoms.”
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“are strongly associated with each other among people with MS, even at diagnosis,(33) and bi-directional, dynamic relationships exist among them.(34) Collectively, this symptom cluster is also associated with work impairment.”
BackgroundSharma, S., Braley, T. J., Alschuler, K. N., Ehde, D. M., & Kratz, A. L. (2025) · Quality of Life Research · doi:10.1007/s11136-025-03948-5 · Cited by 2 · see citing works
“…often associated with greater activity restrictions, pain severity, sleep disturbances, depressive symptoms, cognitive problems, physical, and functional disability [17, 18], indirectly accounts for over 80% of the variance in health-related quality of life (HRQoL) in people with MS (pwMS) [19].”
Self-citationMeza, C., Bennett, A., & Feinstein, A. (2026) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2026.107979 · Cited by 1 · see citing works
VanNostrand, M., Ehde, D. M., Murphy, S. L., Alschuler, K. N., Kratz, A. L., & Fritz, N. E. (2026) · Archives of Physical Medicine and Rehabilitation · doi:10.1016/j.apmr.2026.04.019
Self-citationCognitive Failures, Emotion Regulation Difficulties and Fatigue in Patients with Multiple Sclerosis
Modaresi, Z. S., Rezapour-Mirsaleh, Y., & Choobforoushzadeh, A. (2026) · Journal of Rational-Emotive & Cognitive-Behavior Therapy · doi:10.1007/s10942-026-00672-y
“This inability to regulate emo - tions may increase psychological distress and exacerbate fatigue symptoms (Kratz et al., 2017).”
Influential
- Authors
- Kratz, A. L., Murphy, S. L., & Braley, T. J.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Kratz, Anna L.
- Venue
- Archives of Physical Medicine and Rehabilitation
- Publisher
- Elsevier BV
- Published
- 2017-11
- Volume
- 98
- Issue
- 11
- Pages
- 2151-2159
- ISSN
- 0003-9993 (ISSN-L)
- PMC
- PMC5660935
- OpenAlex
- W2735763993
- Semantic Scholar
- 2ecf772de97ccdc3f7593522185c26d283a2576f
- Cited by
- 36
- References
- 58
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 3 · 2023: 6 · 2022: 6 · 2021: 4 · 2020: 4 · 2019: 1 · 2018: 3 · 2017: 2
- FWCI
- 2.15
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Archives of Physical Medicine and Rehabilitation (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Nursing Research (R03NR014515)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (K01AR064275)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Mental Health Research Topics
- Health Sciences › Medicine › Oncology › Cancer survivorship and care
- Keywords
- multiple sclerosis, pain, fatigue, cognitive symptoms, depressive mood, perceived cognitive function
- MeSH terms
- Ecological Momentary Assessment, Adult, Age Factors, Aged, Cognition, Fatigue, Female, Humans, Male, Middle Aged, Multiple Sclerosis, Pain, Pain Measurement, Sex Factors, Socioeconomic Factors, Time Factors
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