Persistent Pain and Cognitive Decline in Older Adults

A Systematic Review and Meta-analysis From Longitudinal Studies

Gabriella Pequeno Costa Gomes de Aguiar; Marcos Daniel Saraiva; Eugênia Jatene Bou Khazaal; Daniel Ciampi de Andrade; Wilson Jacob-Filho; Claudia Kimie Suemoto


Pain. 2020;161(10):2236-2247. 

In This Article

Abstract and Introduction


Both persistent pain and cognitive decline prevalence increase with advancing age and are associated with functional decline. However, the association of pain and cognitive decline has not been evaluated yet by a systematic assessment of longitudinal studies. We aimed to assess the association of persistent pain as a risk factor for cognitive decline in community older adults, using data from longitudinal studies in a systematic review and meta-analysis. Publications were identified using a systematic search on PubMed, EMBASE, and Cochrane Library databases from inception to June 2019. Because heterogeneity across studies was high, we used random-effects meta-analysis to calculate the pooled relative risk (RR) for the association between persistent pain and cognitive decline incidence. We investigated sources of heterogeneity among studies using meta-regression and stratified analyses. We included 10 prospective longitudinal studies with 57,495 participants with a mean age at the baseline ranging from 61.8 to 88.4 years and mean follow-up times ranging from 2.75 to 11.8 years. Persistent pain at baseline was not associated with the development of cognitive decline during the follow-up (pooled RR = 1.05, 95% confidence interval = 0.92–1.21). In sensitivity analyses, only length of follow-up time ≤4.5 years was associated with a higher risk of cognitive impairment (pooled RR = 1.19, 95% confidence interval = 1.10–1.28). Persistent pain was not associated with the incidence of cognitive decline.


Pain is common among older people, with a prevalence varying from 25% to 50% in community dwelling older adults.[53,55] Persistent pain is defined as a painful experience that can be the sole or a leading complaint, and persists or recurs for more than 3 months.[55] Persistent pain is associated with several adverse outcomes in older adults, such as functional loss, frailty, depression, anxiety, social isolation, gait change, falls, weight loss, sleep disorder, polypharmacy, low quality of life, and higher health costs.[47,53]

Cognitive decline is characterized as a decrease in cognition involving one or more cognitive domains (learning and memory, language, executive function, complex attention, perceptual-motor, and social cognition) and is also related with functional decline and increased health-related costs.[34,46] Overall, approximately 85% of dementia cases are diagnosed in older adults aged 75 years or older, and the Lancet Commission estimated that approximately 35% of dementia cases are attributable to a combination of 9 potentially modifiable risk factors as follows: low educational attainment, midlife hypertension, midlife obesity, hearing loss, late-life depression, diabetes, smoking, physical inactivity, and social isolation.[34]

Once both persistent pain and cognitive decline affects functional independence and quality of life, the association between them deserves further attention. Cross-sectional studies have shown important changes in attention, memory, executive planning, and information processing in older patients with persistent pain.[32] Ferreira et al. have conducted a case-control study and concluded that patients with chronic pain had a poorer performance in a brief assessment of cognitive impairment, not related to confounding variables such as comorbidities and medications used for pain.[13] A recent prospective longitudinal cohort study described an absolute 2.2% increase in the likelihood of dementia in older adults who had persistent pain.[59] Moreover, a meta-analysis of longitudinal studies showed that headache was associated with a 24% greater risk of all-cause dementia.[57]

The relation between pain and cognitive decline is likely multifactorial and may directly impair cognition by several mechanisms.[32] The most accepted theories hypothesized that pain may directly compete for cognitive processing resources and, as a consequence, lead to diverting attention.[26,48] In neuropathological studies, pain seems to be associated with a reduction of gray matter in key structures for cognition, such as the insular cortex, the hippocampus,[32,56] and ventromedial and dorsolateral region of the prefrontal cortex.[24] Finally, the affective stress of persistent pain may be implicated in faster cognitive decline also through putative cortisol-based pathways.[38]

Because pain is a treatable condition, defining whether it is a risk factor for cognitive decline or dementia can pave the way for targeted screening, preventive interventions, and therapeutic interventions. We hypothesize that persistent pain is a risk factor for cognitive decline in older adults. Therefore, to assess the longitudinal association of persistent pain and cognitive decline, we reviewed data from longitudinal studies, randomized clinical trials, systematic reviews, and meta-analyses that included community older adults with and without persistent pain at the baseline and assessed cognitive decline during the follow-up.