Pain Is a Prodromal Symptom, Correlate Rather Than Direct Cause of Dementia

Close up of daughter comforting pained mother
In patients with dementia, pain is a correlate or prodromal symptom rather than a direct cause of dementia.

In patients with dementia, pain may be prodromal symptom rather than a direct cause of dementia, or share a common causal mechanism, according to study results published in Pain.         

Previous data have indicated that permanent structural changes in brains of people with chronic pain are similar to those observed in dementia. Consequently, study researchers sought to analyze the temporal relationship between pain scores and incident dementia.

In this retrospective study, researchers used data from the ongoing Whitehall II population study ( identifier: NCT00005680). They included 9046 participants (2840 women; 6206 men) who participated in at least one of the pain measurement waves between 1991-1993 and had information on pain and covariates. Covariates such as sociodemographic factors at the time of pain evaluation were included. Additionally, study researchers evaluated health conditions from a multimorbidity index, depression, and pain medication use by using clinical examinations, questionnaire data, and health records. They collected data every 2 to 3 years and assessed pain using the body pain scale every 4 to 5 years. They then compared characteristics of the study population as a function of dementia status using the Pearson’s Chi square and analysis of variance (ANOVA) test through two sets of analysis: time to event analysis and retrospective analysis of 27 year pain trajectories.

Of the 9046 participants, 567 developed dementia by the age of 77.0 (Standard Deviation (SD) = 5.9) years throughout the average 25 years of follow-up. Of these, 56.1% were diagnosed in the previous 5 years of follow-up. At the first wave of pain measurement, patients with dementia had higher average pain scores (19.4 vs 15.7 for total pain, respectively; P <0.001). In the analysis not adjusted for health conditions, continuous pain was associated with increased hazard ratio (HR) of dementia; however, in the fully adjusted analysis, the association remained only at a mean follow-up of 10 years (HR per 10-increase=1.06; 95%CI, 1.01-1.11; P =0.03). The association between dementia and pain measures became more relevant as follow-up time decreased.

Over the 27 year follow-up, pain trajectories differed between patients with a dementia diagnoses and those without. Beginning 16 years before diagnosis, patients with dementia had higher total pain scores (difference=1.4; 95%CI, 0.1-2.7; P =0.04, corresponding to 7% of a SD of total pain score). This difference reached 5.5 at dementia diagnosis (95%CI, 2.5-8.4; P <0.001, corresponding to 28% of SD of the total pain score). Differences in probability began 11 years, 6 years, and 12 years before diagnosis at 2.5% (95%CI, 0.1%-4.8%; P =0.04) for total pain, 2.7% (95%CI, 0.0%-5.5%; P =0.05) for pain intensity, and 1.9% (95%CI, 0.1%-3.7%; P =0.03) for pain interference. Probability for total pain and pain diagnosis increased 5 times by dementia diagnosis.

Limitations present in the study include lack of data on characteristic, type, and location of pain, as well as the specific chronic conditions contributing to the association between pain and dementia. Additionally, the information regarding type or severity of dementia was not complete as patients were diagnosed using electronic health records.

Study researchers concluded that findings indicate “that pain is a prodromal symptom of dementia or both share common causal mechanisms rather than an important contributor to risk of dementia.” Additionally, the stronger association between pain inference and dementia emphasized the importance for pain management in older adults.


Kumaradev S, Fayosse A, Dugravot A et al. Timeline of Pain before Dementia Diagnosis. Pain. Published online Septemeber23, 2020. doi:10.1097/j.pain.0000000000002080

This article originally appeared on Neurology Advisor