Association of nociplastic pain with executive function decline in a longitudinal cohort of middle-age adults: a prospective cohort study.

BACKGROUND

Patients with chronic pain, frequently report cognitive problems ('brain fog'), particulary those with nociplastic pain, which involves dysregulated pain processing. However, the association with objective executive dysfunction and decline over time is unclear. We examined whether nociplastic pain severity is associated with executive dysfunction and decline, and explored which factors, such as sex or associated non-pain symptoms, mediate this relationship.

METHODS

We conducted a prospective cohort study using UK Biobank. Baseline cognitive assessments (2017-20), a pain questionnaire (2019), and follow-up cognitive assessments (2021-2) were analysed. Nociplastic pain severity was measured using the fibromyalgia index (0-31), a continuous measure of widespread pain and symptom severity. A latent executive function measure was derived using confirmatory factor analysis. Cross-sectional associations were examined using linear regression, and longitudinal structural equation modelling assessed cognitive decline. Mediation analysis evaluated indirect effects of abnormal sleep duration, anxiety, depression, brain fog, fatigue, and pain qualities.

RESULTS

We included 35 423 participants (median age 65 yr; 52% female). Greater nociplastic pain severity was associated with worse executive function cross-sectionally (β=-0.49 centiles per 1 point increase in fibromyalgia index; 95% confidence interval -0.59 to -0.39), with a stronger effect in males. However, nociplastic pain severity was not associated with a faster rate of executive function decline. Abnormal sleep duration, anxiety, pain intensity, and neuropathic pain features partially mediated the cross-sectional association.

CONCLUSIONS

Nociplastic pain severity is associated with worse executive function but reassuringly does not suggest worse cognitive decline. Abnormal sleep duration, anxiety, and pain intensity are highlighted as potential intervention targets.