A systematic review and meta-analysis were performed to estimate the size and variability of the association between chronic pain (CP) and poorer cognitive test performances as a function of individual tests, pain sub-types, and study sources on 22 studies having (1) a control group, (2) reported means and standard deviations (SDs) and (3) tests studied at least 3 times.
Results:
CP patients performed significantly poorer with small to moderate effects (d = −.31 to −.57) on Digit Span Backward; STROOP Word; Color and Color-Word; Digit Symbol; Trail Making A and B; Rey Auditory Learning Immediate and Delayed Recall and Recognition. For these 10 measures, single effects (no interaction) were supported (I2 = 0%–8%) and Random and Fixed models yielded similar results. No group differences were found for Corsi Blocks Forward or Wisconsin Cart Sorting Test Categories Achieved, or Perseveration. Effects for the Rey Complex Figure Immediate and Delayed Recall were significant, but effect size was inconclusive, given moderate to high heterogeneity and lack of consistency between Random and Fixed models. For the Paced Auditory Serial Addition Test, there was a homogeneous (I2 = 0%) and significantly lower performance in fibromyalgia (d = −.47), but no effect in diagnostically undifferentiated pain samples, and wide variability across studies of whiplash (d = −.15 to −1.04, I2 = 60%).
Conclusion:
The magnitude and consistency of the CP – cognition effect depended on the test, pain subgroup and study source.
Summary points
Among tests showing a chronic pain (CP) – cognition effect, the magnitude of this association was consistently small to moderate across tests.
Effect size estimation was inconclusive for Digit Span Forwards, the Paced Auditory Serial Addition Test and the Rey Complex Figure Test.
Variance was too heterogeneous for testing cognitive domain specificity of the CP – cognition effect.
BerrymanCStantonTRBoweringJ. Evidence for working memory deficits in chronic pain: a systematic review and meta-analysis. Pain2013; 154: 1181–1196.
2.
BerrymanCStantonTRBoweringKJ. Do people with chronic pain have impaired executive function? A meta-analytical review. Clin Psychol Rev2014; 34: 563–579.
3.
HartRPMartelliMFZaslerND.Chronic pain and neuropsychological functioning. Neuropsychol Rev2000; 10(3): 131–149.
4.
KesselsRPCAlemanAVerhagenWIM. Cognitive functioning after whiplash injury: a meta-analysis. J Int Neuropsychol Soc2000; 6: 271–278.
5.
MoriartyOMcGuireBEFinnDP.The effect of pain on cognitive function: a review of clinical and preclinical research. Prog Neurobiol2011; 93: 385–404.
6.
ChapmanCR.Limbic processes and the affective dimension of pain. Prog Brain Res1996; 110: 63–81.
7.
KarzmarkPHallKEnglanderJ.Late-onset post-concussion symptoms after mild brain injury: the role of premorbid, injury-related, environmental and personality factors. Brain Inj1995; 9: 21–26.
8.
EmanuelsonIAndersson HolmkvistEBjörklundR. Quality of life and post-concussion symptoms in adults after mild traumatic brain injury: a population-based study in western Sweden. Acta Neurol Scand2003; 108(5): 332–338.
9.
BlockCCianfriniL.Neuropsychological and neuroanatomical sequelae of chronic non-malignant pain and opioid analgesia. NeuroRehabilitation2013; 33(2): 343–366.
10.
IversonGLMcCrackenLM.‘Postconcussive’ symptoms in persons with chronic pain. Brain Inj1997; 11(11): 783–790.
11.
KewmanDGVaishampayanNZaldD. Cognitive impairment in musculoskeletal pain patients. Int J Psychiatry Med1991; 21: 253–262.
12.
RadanovBPDi StefanoGSchnidrigA. Cognitive functioning after common whiplash: a controlled follow-up study. Arch Neurol1993; 50: 87–91.
13.
BeaupréMDe GuiseEMcKerralM.The association between pain-related variables, emotional factors, and attentional functioning following mild traumatic brain injury. Rehabil Res Pract2012; 2012: Article ID 924692 (10 pp.).
14.
ClarkMEBairMJBuckenmaierCC3rd. Pain and combat injuries in soldiers returning from Operations Enduring Freedom and Iraqi Freedom: implications for research and practice. J Rehabil Res Dev2007; 44(2): 179–194.
15.
CrombezGVan DammeSEcclestonC.Hypervigilance to pain: an experimental and clinical analysis. Pain2005; 116(1–2): 4–7.
16.
EcclestonC.Chronic pain and distraction: an experimental investigation into the role of sustained and shifting attention in the processing of chronic persistent pain. Behav Res Ther1995; 33: 391–405.
17.
EcclestonCCrombezG.Pain demands attention: a cognitive-affective model of the interruptive function of pain. Psychol Bull1999; 125: 356–366.
18.
KhatibiADehghaniMSharpeL. Selective attention towards painful faces among chronic pain patients: evidence from a modified version of the dot-probe. Pain2009; 142(1–2): 42–47.
19.
DeQuervinDJRoozendaalBMcGraughJL.Stress and glucocorticoids impair retrieval of long-term spatial memory. Nature1998; 394: 787–790.
20.
McDermottLMEbmeierKP.A meta-analysis of depression severity and cognitive function. J Affect Disord2009; 19: 1–8.
21.
DuricVMcCarsonKE.Persistent pain produces stress-like alterations in hippocampal neurogenesis and gene expression. J Pain2006; 7: 544–555.
22.
HuYYangJHuY. Amitriptyline rather than lornoxicam ameliorates neuropathic pain-induced deficits in abilities of spatial learning and memory. Eur J Anaesthesiol2010; 27(2): 162–168.
23.
ApkarianAVHashmiJABalikiMN.Pain and the brain: specificity and plasticity of the brain in clinical chronic pain. Pain2011; 152: S49–S64.
24.
Schmidt-WilckeTLeinischEStraubeA. Gray matter decrease in patients with chronic tension type headache. Neurology2005; 65: 1483–1486.
25.
Schmidt-WilckeTLeinischEGanssbauerS. Affective components and intensity of pain correlate with structural differences in gray matter in chronic back pain patients. Pain2006; 125(1–2): 89–97.
26.
Schmidt-WilckeTLuerdingRWeigandT. Striatal grey matter increase in patients suffering from fibromyalgia – a voxel-based morphometry study. Pain2007; 132(Suppl. 1): S109–S116.
CalandreEPBembibreJArnedoML. Cognitive disturbances and regional cerebral blood flow abnormalities in migraine patients: their relationship with the clinical manifestations of the illness. Cephalalgia2002; 22: 291–302.
29.
MartelliMFGraysonRZaslerND.Post traumatic headache: psychological and neuropsychological issues in assessment and treatment. J Head Trauma Rehabil1999; 14(1): 49–69.
30.
HigginsJPTThompsonSG. Quantifying heterogeneity in a meta-analysis. Stat Med2002; 21: 1539–1558.
31.
HigginsJPTThompsonSGDeeksJJ. Measuring inconsistency in meta-analyses. BMJ2003; 327(7414): 557–560.
32.
PetittiDB.Approaches to heterogeneity in meta-analysis. Stat Med2001; 20: 3625–3633.
33.
FieldAP.Is the meta-analysis of correlation coefficients accurate when population effect sizes vary?Psychol Meth2005; 10: 444–467.
34.
LeeRSCHermensDFMelanieA. A meta-analysis of cognitive deficits in first-episode Major Depressive Disorder. J Affect Disord2012; 140: 113–124.
35.
ScottJCMattGEWrocklageKM. A quantitative meta-analysis of neurocognitive functioning in posttraumatic stress disorder. Psychol Bull141: 105–140.
36.
The Cochrane Collaboration. Review Manager (RevMan) (Computer program), version 5.2. Copenhagen: The Nordic Cochrane Centre, 2014.
CohenJ.Set correlation and contingency tables. Appl Psychol Meas1988; 12(4): 425–434.
39.
MoherDLiberatiATetzlaffJ.; The PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med6(6): e1000097. DOI: 10.1371/journal.pmed1000097
40.
AnderssonGHaldrupD.Personalized pain words and Stroop interference in chronic pain patients. Eur J Pain2003; 7: 431–438.
41.
BosmaFKKesselsRP.Cognitive impairments, psychological dysfunction, and coping styles in patients with chronic whiplash syndrome. Neuropsychiatry Neuropsychol Behav Neurol2002; 15: 56–65.
DickBEcclestonCCrombezG.Attentional functioning in fibromyalgia, rheumatoid arthritis, and musculoskeletal pain patients. Arthritis Rheum2002; 47(6): 639–644.
44.
DickBDVerrierMJHarkenKT. Disruption of cognitive function in fibromyalgia syndrome. Pain2008; 139: 610–616.
45.
Di StefanoGRadanovBP. Course of attention and memory after common whiplash: a two-year prospective study with age, education and gender pair-matched patients. Acta Neurol Scand1995; 91: 346–352.
46.
GimseRBjorgenIATjellC. Reduced cognitive functions in a group of whiplash patients with demonstrated disturbances in the posture control system. J Clin Exp Neuropsychol1997; 19(6): 838–849.
47.
GraceGMNielsonWRHopkinsM. Concentration and memory deficits in patients with fibromyalgia syndrome. J Clin Exp Neuropsychol1999; 21: 477–487.
48.
GrisartJMVan der LindenM.Conscious and automatic uses of memory in chronic pain patients. Pain2001; 94: 305–313.
49.
KimS-HKimS-HKimS-K. Spatial versus verbal memory impairments in patients with fibromyalgia. Rheumatol Int2012; 32: 1135–1142.
50.
LandroNIStilesTCSletvoldH.Memory functioning in patients with primary fibromyalgia and major depression and healthy controls. J Psychosom Res1997; 42: 297–306.
51.
LeeDMPendletonNTajarA. Chronic widespread pain is associated with slower cognitive processing speed in middle-aged and older European men. Pain2010; 51: 30–36.
52.
OostermanJMDerksenLCvan WijckAJM. Memory functions in chronic pain: examining contributions of attention and age to test performance. Clin J Pain2011; 27: 70–75.
53.
OostermanJMDerksenLCvan WijckAJM. Executive and attentional functions in chronic pain: does performance decrease with increasing task load?Pain Res Manag2012; 17(3): 159–164.
54.
Roldán-TapiaLCánovas-LópezRCimadevillaJ. Cognition and perception deficits in fibromyalgia and rheumatoid arthritis. Reumatol Clin2007; 3: 101–109.
55.
SchmandBLindeboomJSchagenS. Cognitive complaints in patients after whiplash injury: the impact of malingering. J Neurol Neurosurg Psychiatr1998; 64: 339–343.
56.
ShurJA.Neuropsychological impairment in fibromyalgia: relation to depression, fatigue, and pain. J Psychosom Res2003; 55: 321–329.
57.
SjogrenPChristrupLLPetersenMA. Neuropsychological assessment of chronic non-malignant pain patients treated in a multidisciplinary pain centre. Eur J Pain2005; 9: 453–462.
58.
Verdejo-GarciaALopez-TorrecillasFCalandreEP. Executive function and decision-making in women with fibromyalgia. Arch Clin Neuropsychol2009; 24: 113–122.
59.
WalittBRoebuck-SpencerTBleibergJ. Automated neuropsychiatric measurements of information processing in fibromyalgia. Rheumatol Int2008; 28: 561–566.
60.
WalterosCSánchez-NavarroJPMuñozMA. Altered associative learning and emotional decision making in fibromyalgia. J Psychosom Res2011;70: 294–301.
61.
WeinerDKRudyTEMorrowL. The relationship between pain, neuropsychological performance, and physical function in community-dwelling older adults with chronic low back pain. Pain Med2006; 7: 60–70.
62.
TakkoucheBKhudyadovPCosta-BouzasJ. Confidence intervals for heterogeneity measures in meta-analysis. Am J Epidemiol2013; 178(6): 993–1004.
63.
ThorlandKImbergerGJohnstonBC. Evaluation of heterogeneity estimates and their 95% confidence intervals in large meta-analyses. PLoS ONE2012; 7(7): e39471–e39478.
64.
BrowningMFletcherPSharpeM.Can neuroimaging help us to understand and classify somatoform disorders? A systematic and critical review. Psychosom Med2011; 73: 173–184.
65.
LegrainVDammeSVEcclestonC. A neurocognitive model of attention to pain: behavioral and neuroimaging evidence. Pain2009; 144: 230–232.
66.
JongsmaMLAPostmaSAESourenP. Neurodegenerative properties of chronic pain: cognitive decline in patients with chronic pancreatitis. PLoS ONE2011; 6: e23363.
67.
LeurdingRWeigandTBogdahnU. Working memory performance is correlated with local brain morphology in the medial frontal and anterior cingulated cortex in fibromyalgia patients: structural correlates of pain-cognition interaction. Brain2008; 131: 3222–3231.
68.
MelkumovaKAPodchufarovaEVYakhnoNN.Characteristics of cognitive functions in patients with chronic spinal pain. Neurosci Behav Physiol2011; 41: 20–24.
