Exploring trends in brain fog and quality of life outcomes in Veterans with pain symptoms: A cross-sectional study

Abstract

Introduction:

Brain fog may decrease quality of life (QOL) in Veterans with pain by reducing cognitive capacity and functional engagement. Veterans with higher pain interference (PI) experience worse QOL. Given PI’s relationship with QOL, it is important to explore brain fog within the context of PI levels. This study compared health-related QOL, functional cognition, and functional abilities between Veterans with high versus low PI and brain fog.

Method:

A cross-sectional study, using a one-way MANOVA, explored whether Veterans with brain fog and pain symptoms perceived PI-affected measures of QOL. Exploratory post hoc testing compared gender differences and correlations between perceived confidence with abilities and QOL.

Results:

Thirty-four Veterans participated. The results of the MANOVA showed a significant main effect of PI between constructs. Univariate tests revealed differences in physical health, symptoms of mental health issues, and perceived confidence with abilities. No differences in outcomes based on gender were found. The exploratory correlation analysis demonstrates that in Veterans with brain fog and painful symptoms, there are high correlations between physical health and perceived confidence with abilities and moderate correlations between mental health and perceived confidence with abilities, and between functional cognition and perceived confidence with abilities.

Discussion:

Veterans with pain symptoms and brain fog with high PI demonstrated more mental health symptoms, poorer physical functioning, and reduced perceived abilities. Results from the correlation analysis demonstrate that perceived confidence plays a role in QOL. This study contributes to the overall understanding of this experience, identifying evidence-based suggestions for future exploration.

Lay Summary

Brain fog is a symptom of pain that can affect how Veterans do their daily activities. Veterans describe brain fog as variable changes in their thinking and feeling (e.g., anger). Not a lot of information is known about how brain fog impacts the quality of life of Veterans with pain symptoms. To learn about the impacts of brain fog on quality of life, we compared three outcomes of quality of life in two groups of Veterans. The outcomes we looked at were health-related quality of life, functional cognition, and perceived confidence with abilities. The first group was Veterans with brain fog and low pain interference. The second group was Veterans with brain fog and high pain interference. A total of 34 Veterans were involved in this study. We found that Veterans with brain fog and a high level of self-reported pain interference had more self-reported mental health symptoms, less physical abilities, and less confidence with their abilities. This is the first study exploring brain fog experiences in Veterans with pain symptoms and brain fog. It shows how the experience of high pain interference and brain fog might impact the quality of life of Veterans.

Introduction

Veterans with pain symptoms who experience brain fog have described that the brain fog diminishes their quality of life by hindering the completion of goals and management of their health.¹ The quality of life of Veterans is largely dependent on engaging in meaningful activities and goal attainment.^2,3 In Veterans with pain symptoms and brain fog, their experience of brain fog has been described as “a phenomenon of cloudiness that may produce episodic instances of cognitive and emotional challenges leading to difficulties in completing daily tasks and goals. The impacts of brain fog could act reciprocally to reinforce symptoms of brain fog and defer from engagement in evidenced-based pain management strategies.”^{1(p. 41)} Despite the increased likelihood of experiencing brain fog and the need to maintain meaningful engagement for Veterans, the relationship between the impacts of brain fog and quality of life outcomes has not been explored.

The importance of exploring and measuring quality of life outcomes with Veterans is that their capacity for meaningful engagement can be directly affected by their perceptions of health conditions and their related comorbidities, including their unique collective mindset, which taken together can be related to many of the challenges they face. Essentially, Veterans are likely to live with comorbid health conditions, creating potentially overlapping impacts on cognitive and functional performance,^4–6 which then affects their capacity for engagement. For example, mental health and pain may have overlapping effects as Veterans with chronic pain and posttraumatic stress disorder (PTSD) display greater pain-related disability than Veterans with chronic pain and without PTSD, which leads to greater functional disability.⁷ This is especially likely in female Veterans, who experience health comorbidities twice as often as their male counterparts.^8,9 Further, Veterans perceive health conditions differently because of their military identity.¹⁰ As an example, Veterans tend to under-report their symptoms as they are conditioned to continue their activities and pursuit of mission objectives by pushing through any painful stimuli.¹⁰ Additionally, the quality of life of Veterans with chronic pain is impacted by pain interference with daily activities and goal attainment, rather than pain intensity.^3,11–13 In response to differences in perceptions of health conditions (e.g., pain), Veterans Affairs Canada proposed a framework for Veteran well-being that includes meaningful engagement, health, and social factors.³ This framework was used to define quality of life throughout this study.

Since Veterans perceive health conditions differently, their perception of brain fog may differ from that of civilians. Therefore, it is important to explore factors related to brain fog in Veterans with pain symptoms and brain fog to understand how to measure and interpret outcomes. Currently, the literature demonstrates a negative association between brain fog and quality of life. For example, the cognitive (e.g., attention and memory¹³) and emotional challenges (e.g., depression¹⁴) of brain fog have been reported to affect quality of life in persons with long COVID,^14–16 traumatic brain injury,¹⁴ and fibromyalgia.^17,18 Overall, brain fog impacts quality of life by affecting cognitive, physical, and emotional processes.

Present study

The purpose of this study was to explore the impacts of brain fog on the quality of life of Veterans with pain symptoms and self-identified brain fog. The primary objective was to compare health-related quality of life, perceived level of confidence with abilities, and functional cognition in Veterans with brain fog and low pain interference with Veterans with brain fog and high pain interference. Specifically, Veterans with high pain interference and brain fog would show worse health-related quality of life, functional cognition, and perceived level of confidence with abilities than Veterans with brain fog and low pain interference.

Methods

Study design

A cross-sectional study was the most appropriate design to answer the primary research objective and explore the association between variables at one point in time.¹⁹ This research received approval from the Hamilton Integrated Research Ethics Board.

Participants

Participants were recruited through email, social media, and webpage postings by Veteran community and health organizations, from May 2023 to January 2024. All participants were self-selected and were permitted to participate if they met the inclusion criteria. Veterans who were 18 years or older and who experienced brain fog were invited to participate. Veterans were defined as former members of the Canadian Armed Forces who either completed training or obtained an honourable discharge.²⁰ Brain fog was captured using a dichotomous outcome (yes or no).^21,22 Participants were asked whether they experienced moments of cloudiness accompanied by one or more of the following symptoms: fatigue, memory difficulties, word-finding difficulties, and attention difficulties.^21,22 Participants were excluded if they were unable to complete the assigned questionnaires independently or with the assistance of someone else.

Questionnaire components and administration

After obtaining informed consent, participants completed an online questionnaire administered in a McMaster University LimeSurvey portal,²³ from May 2023 to January 2024. No time limits were given for the questionnaire and participants were permitted to answer the questions with the assistance of someone else, if needed. The questionnaire included a set of demographic questions and three standardized questionnaires, the Patient Reported Outcome Measure Information System Version 29 (PROMIS-29), Multiple Abilities Self-Report Questionnaire (MASQ), and the Pain Self-Efficacy Questionnaire (PSEQ).

Demographics

Demographic information, including self-reported gender, sex, age, mental health symptoms, and concussion history, was collected.

PROMIS-29

Health-related quality of life was measured through the PROMIS-29, a 29-item self-report questionnaire examining physical, mental, and social health.²⁴ The PROMIS-29 was selected because of its 1) strong internal consistency and reliability,²⁴ 2) frequent use in pain research,²⁵ 3) few ceiling or floor effects,²⁶ and 4) alignment with our selected framework for quality of life.²⁶

MASQ

Functional cognition was assessed through the MASQ, a self-report questionnaire asking participants to report their perceived level of functioning in the domains of language, visuo-perceptual, verbal memory, visual memory, and attention.²⁷ The MASQ was selected to provide an independent measure of perceived cognitive challenges; it shows excellent internal validity in persons with fibromyalgia.²⁸

PSEQ

Perceived confidence with abilities was measured using the PSEQ, a 10-item self-report questionnaire assessing participants’ perceived confidence with their ability to perform their daily activities while experiencing pain.²⁹ The key elements assessed in the PSEQ are 1) self-perception, as it is a self-report tool assessing how Veterans perceive their abilities to manage their pain condition, and 2) comfort with completing tasks based on perception of pain.²⁹ The PSEQ was selected because of its strong psychometric properties and applicability to the target population.

Bias

Potential selection bias may occur as this study is not randomized and participants self-selected.³⁰ There is potential information bias since there is no validated measurement of brain fog. Instead, participants were selected based on a self-reported agreement with our definition.

Study size

Since brain fog has not been investigated in Veterans with pain symptoms and brain fog, this study was exploratory. Correspondingly, the sample size calculation was based on a study comparing quality of life in persons with long-COVID-related brain fog, in comparison to persons without.³¹ Using an online sample size calculator,³² a required sample size of 32 participants, with 16 participants per group, was calculated as sufficient to detect an effect size of a 5-point difference in quality of life, measured by the PROMIS-29, with a two-sided alpha level of 0.05, and a power of 80%.

Data organization and analysis

Data organization

Participants were grouped into two categories, low or high pain interference, that were treated as a dichotomous group. Level of pain interference was determined based on the median score (median = 16) on the PROMIS-29 pain interference sub-score. Participants with scores lower than the median were categorized as low pain interference, and participants with scores higher than or equal to the median were categorized as high pain interference. Pain interference was chosen as the grouping variable as chronic pain is the most common health condition in Veterans³³ and brain fog has been previously studied in persons with painful symptoms.^22,34 However, we could not identify a cut-off score in the literature signifying a meaningful level of pain interference across any pain population and therefore opted to use the median PROMIS-29 pain interference sub-scale score to categorize.¹¹

Based on an adapted model of the PROMIS-29 two-factor theory, the PROMIS-29 was categorized into three groupings to illustrate relationships between health-related quality of life domains.²⁴ The domain grouping was 1) mental health symptoms consisting of the depression and anxiety sub-scales, 2) physical health, relating to physical functioning (e.g., walking for more than 15 minutes) and ability to participate in social roles and activities sub-scales, and 3) sleep issues, containing the sleep disturbance and fatigue sub-scale.

Across all questionnaires, missing values were managed using mean value substitution. If participants were missing more than one entry, they were omitted from the analysis.

Data analysis

The data were inspected using box plots, histograms, and Q-Q plots. Descriptive statistics using mean and standard deviation were conducted for all variables. Diagnostic tests for the assumptions of a one-way MANOVA were checked using histograms and the Shapiro-Wilk test to assess normality, and the Levene’s test of equal variances for homogeneity of variance. To compare the difference in pain interference on health-related quality of life, functional cognition, and perceived confidence with abilities between groups, a one-way MANOVA was conducted with a two-tailed alpha level of 0.05. Following univariate testing, a two-tailed alpha level of 0.05 and a manual Bonferroni correction of 3 was used to identify which dependant variables differed between groups.

Next, because women Veterans are under-represented in the literature, we conducted a sub-group one-way MANOVA analysis exploring differences in gender on health-related quality of life, functional cognition, and perceived level of confidence with abilities, using a two-tailed alpha level of 0.05.

Last, an exploratory Pearson’s correlation analysis for all questionnaires was conducted to explore any relationships between constructs. Based on the Veterans Affairs Well-Being Framework³ and the results of the MANOVA analysis, we anticipated strong relationships between perceived level of confidence with abilities and the other constructs (health-related quality of life and functional cognition). To account for the error variance, we applied a manual Bonferroni correction of 3. The strength of relationships is reported using recommendations from Hinkle et al.^35,36 Diagnostic tests for normality and linearity were performed before the correlation analysis. All tests for all analyses were performed using JASP, version 0.17 (University of Amsterdam, Amsterdam, The Netherlands).

Results

Participants’ characteristics

A total of 34 (15 low pain interference, 19 high pain interference) Veterans participated in this study. Participants were all cisgender, most were male (F = 8, M = 26), and in the age group of 50-65 years. All participants had brain fog and at least one other mental health symptom. Additionally, 12% of participants experienced acute, rather than chronic, pain, and their scores on the pain interference sub-scale revealed low pain interference. Full results of participant demographics are presented in Table 1.

Table 1.

Demographic characteristics of participants by gender

Participants	Women (n = 8)	Men (n = 26)	Total (n = 34)
Age (y)	30-39 (n = 1) 40-49 (n = 4) 50-65 (n = 3)	30-39 (n = 3) 40-49 (n = 4) 50-65 (n = 12) 66+ (n = 7)	30-39 (n = 4) 40-49 (n = 6) 50-65 (n = 17) 66+ (n = 7)
Previous concussion	n = 3	n = 13	n = 15
Anxious symptoms	n = 7	n = 16	n = 23
Depressive symptoms	n = 7	n = 19	n = 26
Posttraumatic stress disorder symptoms	n = 3	n = 18	n = 21
Chronic pain	n = 6	n = 24	n = 30
Frequency of brain fog	Every day (n = 4); 2-3x/week (n = 4)	Every day (n = 15); 2-3x/week (n = 7); Once in a while (n = 4) Unsure (n = 1)	Every day (n = 19); 2-3x/week (n = 11); Once in a while (n = 3) Unsure (n = 1)

One-way MANOVA exploring differences across high or low pain interference

The scores on three structured questionnaires of 34 Veterans with brain fog and pain symptoms, with either low or high pain interference, were analyzed. The overall means of PROMIS-29 domain groupings, PSEQ, and MASQ, as well as descriptive statistics by gender are in Table 1. Descriptive statistics by group are in Table 2.

Table 2.

Mean and standard deviation per questionnaire

Questionnaire	Low pain interference, mean (SD)	High pain interference, mean (SD)	Total sample, mean (SD)
PROMIS mental health symptoms	0.46 (0.14)	0.68 (0.18)	0.58 (0.20)
PROMIS physical health	0.56 (0.09)	0.34 (0.08)	0.44 (0.14)
PROMIS sleep disturbances	0.58 (0.09)	0.52 (0.09)	0.55 (0.09)
PSEQ	0.59 (0.20)	0.40 (0.20)	0.49 (0.22)
MASQ	0.51 (0.09)	0.58 (0.14)	0.55 (0.12)

PROMIS = Patient Reported Outcome Measure Information System; PSEQ = Pain Self-Efficacy Questionnaire; MASQ = Multiple Abilities Self-Report Questionnaire.

Diagnostic assumptions for homogeneity of variance and normality were met. There was a statistically significant main effect of factors based on pain interference, F_1,32 = 10.95, p < 0.001; Wilks lambda = 0.34. As shown in Table 3, univariate tests revealed that the mean scores were statistically different between low and high pain interference in the PROMIS mental health symptoms domain, PROMIS physical health domain, and the PSEQ but not PROMIS sleep disturbances domain or the MASQ. The MANOVA results are represented in Table 3 and visual representations of the data, using boxplots, are provided in Table 4.

Table 3.

MANOVA results on mean questionnaire scores between Veterans with brain fog’s pain interference groups

Questionnaire	Sum of squares	F	P	Bonferroni p	95% CI lower	95% CI upper
PROMIS mental health symptom*	0.392	14.50	<0.001	0.003*	−0.332	−0.101
PROMIS physical health*	0.382	49.07	<0.001	0.003*	0.031	0.276
PROMIS sleep disturbances	0.038	4.87	0.035	0.105	0.005	0.130
PSEQ	0.282	7.062	0.012	0.036	0.043	0.324
MASQ	0.034	2.458	0.127	0.381	0.147	0.019

PROMIS = Patient Reported Outcome Measure Information System; PSEQ = Pain Self-Efficacy Questionnaire; MASQ = Multiple Abilities Self-Report Questionnaire.

^*Statistically significant differences were seen between groups.

Table 4.

Descriptive plots of questionnaires between veterans with brain fog and high and low pain interference

Questionnaire	Box plots
PROMIS mental health symptoms
PROMIS physical health
PROMIS sleep disturbance
PSEQ
MASQ

PROMIS = Patient Reported Outcome Measure Information System; PSEQ = Pain Self-Efficacy Questionnaire; MASQ = Multiple Abilities Self-Report Questionnaire.

Sub-group analysis considering gender

The scores on three structured questionnaires of 34 Veterans with brain fog and pain symptoms, depending on pain interference, and gender were analyzed. All diagnostic assumptions for homogeneity of variance and normality were met. We failed to reject the null hypothesis, as there is not a statistically significant difference in constructs based on pain interference, F_1,31 = 0.35, p = 0.88; Wilks lambda = 0.94.

Pearson correlation analysis of relationships between perceived confidence with functional cognition and health-related quality of life

We compared the relationship between the PSEQ and the PROMIS-29 sub-scales and MASQ mean scores to explore how quality of life outcomes were related. All diagnostic tests for linearity and homogeneity of variance were met. There is a statistically significant correlation between the scores of several questionnaires. A high correlation existed between the physical health and perceived confidence with abilities r (32) = 0.69, p = 0.003. Moderate correlations were seen between perceived confidence with abilities and 1) mental health, r (32) = -0.48, p = 0.012, and 2) functional cognition r (32) = -0.44, p = 0.003. No correlations were seen between perceived confidence with abilities and sleep disturbance. The full results of the Pearson correlation, including confidence intervals, are shown in Table 5. Visual representations are provided in Table 6.

Table 5.

Pearson’s r correlation between perceived confidence with abilities, health-related quality of life, and functional cognition

	PROMIS physical health	PROMI Smental health	PROMIS sleep disturbance	MASQ
PSEQ	r (32) = 0.69, p < 0.001 (95% CI, 0.46-0.84)	r (32) = -0.48, p = 0.004 (95% CI, −0.70 to −0.17)	r (32) = 0.14, p = 0.44 (95% CI, −0.21 to 0.4)	r (32) = -0.44, p = 0.01 (95% CI, −0.67 to −0.11)

PROMIS = Patient Reported Outcome Measure Information System; PSEQ = Pain Self-Efficacy Questionnaire; MASQ = Multiple Abilities Self-Report Questionnaire.

Table 6.

Correlation between perceived confidence with abilities, health-related quality of life, and functional cognition

Correlation	Scatterplot
PSEQ-MASQ*
PSEQ-PROMIS mental health symptoms*
PSEQ-PROMIS physical health*
PSEQ-PROMIS sleep disturbances

PROMIS = Patient Reported Outcome Measure Information System; PSEQ = Pain Self-Efficacy Questionnaire; MASQ = Multiple Abilities Self-Report Questionnaire.

^*Statistically significant differences were seen between groups.

Discussion

Overview

This study explored the relationship between pain interference and health-related quality of life, functional cognition, and perceived level of confidence with abilities in Veterans with brain fog and pain symptoms. The results demonstrated that Veterans with pain symptoms and brain fog who have high pain interference demonstrated more mental health symptoms and lower levels of physical functioning and perceived confidence in their abilities. Interestingly, there was no notable differences related to sleep disturbances or functional cognition related to the experience of high or low pain interference. Increasing sample size or power may help to further elucidate any potential impact on sleep. Surprisingly, there was no effect from gender, which is different from what has been discussed in the literature.⁸ Last, the results from the exploratory post hoc correlation analysis show that in Veterans with pain symptoms and brain fog, there is a positive relationship between low perceived confidence with abilities and low physical functioning, and low perceived confidence with abilities and more mental health symptoms. On the other hand, a positive relationship was found between higher perceived confidence with abilities and better functional cognition. However, given that we do not have a validated measure of brain fog and were under-powered for a regression analysis, we are unsure whether the differences in questionnaire scores were due to brain fog or pain interference. Despite limitations in our methods, this is the first study to explore brain fog in Veterans with pain symptoms, contributing to the overall understanding of this experience and providing evidence-based suggestions for future exploration.

Managing pain in Veterans is complex as there are many factors that health care professionals need to address for effective care.² The complex relationship between pain and mental health may negatively impact quality of life by affecting physical functioning and meaningful participation.^7,11,37 Correspondingly, mental health symptoms need to be addressed in programs for Veteran pain management.^7,11,37 This study supports this relationship as participants with high pain interference had more mental health symptoms. The surprising lack of relationship between sleep disturbance and pain interference may be due to low power in the study and because the quality of sleep can be impacted by comorbid factors in Veterans,³⁸ such as PTSD³⁹ or traumatic brain injury.⁴⁰ Although we were unable to interpret the impacts of brain fog on mental health symptoms and sleep disturbances, these conditions are common in Veterans, and all participants identified having both brain fog and a mental health issue. Thus, it is warranted to examine this relationship in future studies.

Veterans’ perceived that confidence with their ability to meaningfully engage with their everyday activities and goals is a key feature of their well-being.³ In this study, participants with higher pain interference had less confidence in their abilities to manage pain and engage in activities. Lower confidence in their abilities, represented by lower scores on the PSEQ, was correlated with more challenges with functional cognition and more mental health symptoms, and less physical functioning. This finding is consistent with the findings of a network analysis of pain-related measures in military members with chronic pain, which concluded that high pain interference 1) is correlated with less social functioning and 2) should be explicitly addressed in clinical settings to restore quality of life.¹¹ Given that brain fog is associated with challenges with daily activities like socializing and work performance,^14,41,42 it is possible that brain fog could impact perceived confidence with the ability to manage pain and activity in Veterans. It is also plausible that the PSEQ asks questions in the context of pain, and participants may have only considered pain,⁴³ instead of brain fog, when answering questions. We were unable to quantify the direct impacts of brain fog in this study and recommend exploration of this hypothesis in future research.

Finally, the findings of this study provide considerations for the assessment of brain fog. As discussed, the MASQ was intended to be a surrogate measure of brain fog, but we did not find any significant differences across groups. In both groups, participants’ raw scores fell near the mid-range of the MASQ, suggesting moderate cognitive function. This insignificant finding may be because functional cognition is complex and is not dependent on pain interference alone.^34,44 On the other hand, the MASQ might also be unsuitable to capture the cognitive impacts of brain fog. In particular, the lack of temporal or frequency references for cognitive symptoms in the questions (e.g., “I can follow telephone conversations”)⁴⁵ may be discordant with participants’ reported experience of brain fog as an episodic cognitive symptom. Therefore, a future assessment of brain fog should include frequency metrics that can account for episodic states of cognition. It is also plausible that the symptoms of the MASQ do not accurately represent the experience of pain-related brain fog. Overall, the results of this study align with the existing literature and highlight unique areas for exploration.

Limitations

This is an exploratory study and should be considered in the context of its limitations. The use of the PROMIS-29 pain interference measure to categorize participants introduces bias into this study. This was used because of a limitation with recruitment; however, the PROMIS-29 was developed using item response theory, and the pain interference or pain intensity sub-scales were omitted from the analysis. Next, the results of the correlation analysis were exploratory and should be interpreted as a suggestion for future work, rather than as a definitive relationship. Next, the small sample size is a significant limitation affecting the generalizability and true estimates of the results. The smaller sample size was due to challenges with recruitment. Potential factors affecting the recruitment may have included stigma associated with cognitive challenges in the military or lack of awareness of brain fog. Additionally, given that Veterans self-selected to participate in this study from emailed invitations and social media, the results may be impacted by response bias as Veterans who were more profoundly impacted by brain fog may have opted to participate in this study. We addressed these biases by remaining conservative in our analysis and applying a Bonferroni correction.

Conclusions and future directions

Although exploratory, this study provides important insights for clinicians and future research. The relationships between brain fog, pain interference, and mental health suggest that mental health professionals should consider possible impacts of brain fog during treatment. Additionally, this study has shown that perceived confidence with abilities is related to multiple factors in Veterans’ quality of life (mental health, physical health, and functional cognition), lending importance to the explicit targeting of health and rehabilitation strategies for improving perceptions and functional abilities in Veterans. Next, this study has informed possible mediating factors related to the experience of brain fog, including the consideration of mental health, pain interference, perceived confidence with abilities, and episodic time constraints. Last, this study has identified key areas for research that might include exploring 1) the utility of a modified MASQ to capture variability of brain fog and 2) trends in mental health and perceived confidence with abilities on quality-of-life outcomes using regression analysis. Future research might explore this phenomenon and should include larger samples and recruitment may be facilitated by including clear definitions of brain fog and emphasizing participant anonymity.

Biographies

Ronessa Dass, MSc, is a joint PhD in rehabilitation sciences and occupational therapy student at McMaster University. Her research is funded by a Capacity Building Initiative from the Chronic Pain Centre of Excellence for Canadian Veterans.

Jocelyn Harris is an occupational therapist and associate professor at McMaster University.

Diana Velikonja is a clinical neuropsychologist and associate professor at McMaster University.

Tara Packham, is an occupational therapist and associate professor at McMaster University.

Funding Statement

This study was funded by the Government of Canada and the Chronic Pain Centre of Excellence for Canadian Veterans.