Pain Med.2017 Jul;18(7):1264-1277

Pain and Cognitive Functioning in Adults with Down Syndrome

Nanda C. de Knegt, Frank Lobbezoo, Carlo Schuengel, Heleen M. Evenhuis, and Erik J.A. Scherder.

From the Department of Clinical Neuropsychology, VU University, Amsterdam, the Netherlands.

Correspondence should be addressed to Nanda C. de Knegt, Department of Clinical Neuropsychology, VU University, Van der Boechorststraat 1, 1081 BT Amsterdam, the Netherlands, E.mail: nc.de.knegt@vu.nl

 

Abstract

Objective. The aim of the present study was to examine whether cognitive functioning (i.e., memory and executive functioning) is related to self- reported presence of pain (i.e., affirmative answer to the question whether the individual feels pain) and experience of pain (i.e., intensity and affect) in adults with Down syndrome (DS).

Design, Setting, and Subjects. Cross-sectional study of 224 adults with DS (mean age 5 38.1 years, mild- severe intellectual disabilities) in the Netherlands.

Methods. File-based medical information was evaluated. Self-reported presence and experience of pain were assessed during a test session, both in rest and after movement (affect with the facial affective scale [FAS], intensity with the numeric rating scale [NRS]). Neuropsychological tests for memory and executive functioning were used.

Results. Participants with lower memory scores were more likely to report the presence of pain, while con- trolling for age, gender, physical conditions that may cause pain, language comprehension, and vocabulary (p = .030, 58.4% classification rate, n = 154). No statistically significant associations were found between executive functioning and self-reported presence of pain or between cognitive functioning and self-reported pain experience.

Conclusions. Memory seems to be related to the self-reported presence of pain in adults with DS after explicit inquiry, although the clinical use of this model is yet limited. Therefore, further research is needed for insight into the role of cognitive processes in self-report (e.g., involving aspects such as acquiescence and repeated measurements) to evaluate whether neuropsychological examination could contribute to pain assessment in DS.

Key Words. Down Syndrome; Pain Assessment; Cognitive Function; Clinical Significance

https://doi.org/10.1093/pm/pnw280  

 

Supplement:

Previous clinical studies and experimental studies have demonstrated a functional association between pain experience and cognitive functioning. The evidence in pain patients and elderly people with dementia shows both a negative association (i.e., worse cognitive functioning with a higher self-reported pain experience) (1–4) and a positive association (i.e., worse cognitive functioning with a lower self-reported pain experience) (5–8). It suggests that a change in cognitive functioning indicates a change in pain experience. However, this topic has not been studied in people with intellectual disabilities, while knowledge about such a functional association may contribute to pain assessment in for example Down syndrome (DS). This common genetic cause of intellectual disability (9) is characterised by a high risk for painful physical conditions (10–14) enhanced by an increased life expectancy (15), but also complex pain diagnostics. A delayed response to pain, a lower tendency to complain about pain, and a higher tendency to express medical problems as problematic behavior (16–18) necessitate timely detection of pain and a better understanding of pain experience.

Therefore, we examined in the present study whether cognitive functioning of adults with DS is associated with their self-reported presence and experience of pain. Our cross-sectional design contained a memory component, an executive functioning component, the participants’ answer to the question of whether they felt pain, and their chosen scale items of pain intensity (i.e., sensory dimension of severity (19)) as well as pain affect (perceived unpleasantness (19)).

The 224 adults with DS (mean age 38.1 years, mild- severe intellectual disabilities) were each assessed during one test session with both neuropsychological tests and scales to self-report pain in rest as well as movement. Tests were used to assess memory for words and abstract drawings, cognitive flexibility to copy alternating geometrical patterns, verbal fluency to name words quickly and efficiently, visual-spatial working memory to repeat series of circles in backward order, and planning to complete mazes. Pain or discomfort in muscles and joints was provoked during function by encouraging participants to push maximum limits of their movement capabilities while imitating active movements demonstrated by the researcher in a standardized order (i.e., legs, hips, neck, shoulders, elbows, wrists, fingers, back, and jaw). The Numeric Rating Scale (NRS) and Facial Affective Scale (FAS) to assess pain intensity and pain affect, respectively (20), were only used in participants who passed comprehension tests (i.e., NRS anchors and order of items in both scales). Other measures included the presence of potentially painful or discomforting conditions based on medical files and neuropsychological tests of language comprehension and vocabulary. Consent was obtained from both the Medical Ethical Committee of VU University Medical Center Amsterdam and participants or their legal representatives.

Participants who performed worse on memory tests were more likely to report the presence of pain, controlling for age, gender, painful/ discomforting conditions, language comprehension, and vocabulary. The most likely possible explanation for this finding is that DS adults with an impaired memory are less able during the test session to recall pain from the preceding week and pain during the movements and that this uncertainty may lead to the tendency to answer “yes” to questions (21). Therefore, it is recommended in clinical practice to use multiple assessments of the self-reported presence of pain (i.e., to reduce the appeal to memory) and to use additional sources for pain diagnostics such as an observational method of proxy report. Replication of the present study as a longitudinal study with repeated measurements would increase the chance of assessing pain from fluctuating painful conditions such as rheumatoid arthritis (22) and decrease the influence of a poor memory on pain recall (i.e., the individual only has to reflect on current pain) (23,24).

We were unable to find statistically significant associations between cognitive functioning and self-reported pain experience, controlling for age, gender, painful/discomforting conditions, and interactions of cognitive functioning with age or painful/discomforting conditions. Besides insufficient statistical power due to selection on participants who reported the presence of pain (58%), a possible explanation for this finding is an abnormal functional association between cognitive functioning and pain experience in DS. Structural differences (25), atypical patterns of brain activation (25), and abnormal or even inefficient brain organization for cognitive functions such as verbal memory (26) are found in DS, while neuroimaging studies of pain are lacking in this group.

Therefore, our study arises the fundamental question of whether the same brain areas for cognitive functioning and pain experience are involved and activated in DS as in the general population. Pain researchers (27,28) have suggested that: 1) cognitive functioning and pain compete for limited cognitive resources such as attention, 2) pain disturbs neurochemistry of brain areas, 3) pain disturbs neuroplasticity of brain areas, and 4) atrophy of brain areas involved in cognitive functioning as well as pain experience may disturb the functional association between the two. Whether these processes also occur in DS remains to be investigated in the novel research field that our study opened. By using acute painful stimuli (e.g., vaccinations or operations) and intervention studies (e.g., pain treatment) in combination with repeated measurements of cognitive functioning (e.g., including also attention and inhibition) and pain experience, more insight will be gained into the association between these two components in DS. This might also be a solution to control for the present study limitations in certainty about the actual presence of pain experience that arise by the use of a ‘pain and/or discomfort’ indication of physical conditions, the use of self-report, and insufficient information about the provocation by the movements.

In conclusion, the results suggest that adults with DS with impaired memory functioning are more likely to report pain during the test session, but that self-reported pain experience is unrelated to cognitive functioning. Besides gaining more insight into the association between cognitive functioning and pain, it is also recommended to extend assessment of intensity and affect to the impact of pain on the individual and to use this information to direct treatment and measure improvement. More than half of the participants (58%) reported pain during the test session and a majority (79%) comprehended at least one of the two self-reporting scales. When selecting only participants for each assessment situation (rest and the various movements) who reported pain in that specific situation, the scores were above cut-offs of moderate to substantial pain. These findings emphasize the clinical significance to call attention for pain diagnostics in individuals with intellectual disabilities, as well as the potential to involve them into pain assessment.

 

References

  1. Apkarian AV, Sosa Y, Krauss BR, Thomas PS, Fredrickson BE, Levy RE, et al. Chronic pain patients are impaired on an emotional decision-making task. Pain. 2004;108(1–2):129–36.
  2. Eccleston C. Chronic pain and distraction: An experimental investigation into the role of sustained and shifting attention in the processing of chronic persistent pain. Behav Res Ther. 1995;33(4):391–405.
  3. Oosterman JM, Derksen LC, Van Wijck AJM, Veldhuijzen DS, Kessels RPC. Memory functions in chronic pain: Examining contributions of attention and age to test performance. Clin J Pain. 2011;27(1):70–5.
  4. Weiner DK, Rudy TE, Morrow L, Slaboda J, Lieber S. The relationship between pain, neuropsychological performance, and physical function in community-dwelling older adults with chronic low back pain. Pain Med. 2006;7(1):60–70.
  5. Benedetti F, Vighetti S, Ricco C, Bergamasco B, Pinessi L, Rainero I. Pain threshold and tolerance in Alzheimer’s disease. Pain. 1999;80(1–2):377–82.
  6. Carlino E, Benedetti F, Rainero I, Asteggiano G, Cappa G, Tarenzi L, et al. Pain perception and tolerance in patients with frontotemporal dementia. Pain. 2010;151(3):783–9.
  7. Oosterman JM, De Vries K, Dijkerman HC, De Haan EHF, Scherder EJA. Exploring the relationship between cognition and self-reported pain in residents of homes for the elderly. Int psychogeriatrics. 2009;21(1):157–63.
  8. Scherder EJA, Eggermont L, Plooij B, Oudshoorn J, Vuijk PJ, Pickering G, et al. Relationship between chronic pain and cognition in cognitively intact older persons and in patients with Alzheimer’s disease: The need to control for mood. Gerontology. 2008;54(1):50–8.
  9. Rauch A, Hoyer J, Guth S, Zweier C, Kraus C, Becker C, et al. Diagnostic yield of various genetic approaches in patients with unexplained developmental delay or mental retardation. Am J Med Genet Part A. 2006;140A:2063–74.
  10. Amirfeyz R, Aspros D, Gargan M. Down syndrome. Curr Orthop. 2006;20(3):212–5.
  11. Hresko MT, McCarthy JC, Goldberg MJ. Hip disease in adults with Down syndrome. J Bone Jt Surg. 1993;75(B):604–7.
  12. Ali FE, Al-Bustan MA, Al-Busairi WA, Al-Mulla FA, Esbaita EY. Cervical spine abnormalities associated with Down syndrome. Int Orthop. 2006;30(4):284–9.
  13. Kamatani N, Yamanaka H, Totokawa S, Kashiwazaki S. Down syndrome with coexistent gout: Report of six patients and possible reasons for the scarcity of descriptions of this association. Ann Rheum Dis. 1996;55(9):649–50.
  14. Caselli M, Cohen-Sobel E, Thompson J, Adler J, Gonzalez L. Biomechanical management of children and adolescents with Down syndrome. J Am Podiatr Med Assoc. 1991;81(3):119–27.
  15. Glasson EJ, Sullivan SG, Hussain R, Petterson BA, Montgomery PD, Bittles AH. The changing survival profile of people with Down’s syndrome: Implications for genetic counselling. Clin Genet. 2002;62(14):390–3.
  16. Smith DS. Health care management of adults with Down syndrome. Am Fam Physician. 2001 Sep 15;64(6):1031–8.
  17. Defrin R, Pick CG, Peretz C, Carmeli E. A quantitative somatosensory testing of pain threshold in individuals with mental retardation. Pain. 2004;108(1–2):58–66.
  18. Hennequin M, Morin C, Feine JS. Pain expression and stimulus localisation in individuals with Down’s syndrome. Lancet. 2000;356(9245):1882–7.
  19. Rainville P, Duncan GH, Price DD, Carrier B, Bushnell C. Pain affect encoded in human anterior cingulate but not somatosensory cortex. Science. 1997;277(5328):968–71.
  20. McGrath PA, Seifert CE, Speechley KN, Booth JC, Stitt L, Gibson MC. A new analogue scale for assessing children’s pain: An initial validation study. Pain. 1996;64(3):435–43.
  21. Finlay WML, Lyons E. Acquiescence in interviews with people who have mental retardation. Ment Retard. 2002;40(1):14–29.
  22. Shariff F, Carter J, Dow C, Polley M, Salinas M, Ridge D. Mind and body management strategies for chronic pain and rheumatoid arthritis. Qual Health Res. 2009;19(8):1037–49.
  23. Scherder E, Bouma A, Slaets J, Ooms M, Ribbe M, Blok A, et al. Repeated pain assessment in Alzheimer’s disease. Dement Geriatr Cogn Disord. 2001;12(6):400–7.
  24. Farrell MJ, Katz B, Helme RD. Review Article The impact of dementia on the pain experience. Pain. 1996;67(1):7–15.
  25. Dierssen M. Down syndrome: The brain in trisomic mode. Nat Rev Neurosci. 2012;13(12):844–58.
  26. Menghini D, Costanzo F, Vicari S. Relationship between brain and cognitive processes in Down syndrome. Behav Genet. 2011;41(3):381–93.
  27. Moriarty O, McGuire BE, Finn DP. The effect of pain on cognitive function: A review of clinical and preclinical research. Prog Neurobiol. 2011;93(3):385–404.
  28. Scherder EJA, Sergeant JA, Swaab DF. Review – Pain processing in dementia and its relation to neuropathology. Lancet Neurol. 2003;2(11):677–86.