Clinical Rheumatology

, Volume 33, Issue 4, pp 511–521

Characterization of cognitive dysfunction in Sjögren’s syndrome patients

  • Lynn C. Epstein
  • Gina Masse
  • Jerold S. Harmatz
  • Tammy M. Scott
  • Athena S. Papas
  • David J. Greenblatt
Original Article

Abstract

Sjögren’s syndrome is an autoimmune disorder primarily affecting women, with decreased saliva and tear production as the principal characteristic. Cognitive, neurological, and psychiatric disorders also are associated with Sjögren’s. The present study addressed the hypothesis that patients with Sjögren’s syndrome differ significantly from matched controls in the prevalence and impact of a number of neuropsychiatric abnormalities. Sjögren’s patients and controls (n = 37 per group) underwent medical and psychiatric evaluation, demographic assessments, quality of life and symptom evaluation, and extensive testing of cognitive function and memory. Patients and controls were closely matched for age, gender distribution, verbal IQ, marital status, educational level, employment status, and current/past medical or psychiatric history. On most subjective self-ratings, Sjögren’s patients reported greater fatigue, impaired physical functioning, feeling depressed, and autonomic symptomatology compared to controls. Impaired memory was described mainly as loss of thought continuity in the midst of a task or activity. However, the majority of objective measures of cognition, psychomotor function, and memory showed minimal differences between groups. Sjögren’s patients rate themselves as impaired on multiple ratings of emotional, cognitive, and physical function, but objective measures of cognition reveal fewer substantive differences between patients and matched controls. Sjögren’s patients perceive deteriorated physical function over time, but they achieve a level of functioning comparable to controls despite the burden of their illness.

Keywords

Cognitive function Fatigue Memory Sjögren’s syndrome 

References

  1. 1.
    Anaya JM, Talal N (1999) Sjögren’s syndrome comes of age. Semin Arthritis Rheum 28:35–39CrossRefGoogle Scholar
  2. 2.
    Bayetto K, Logan RM (2010) Sjögren’s syndrome: a review of aetiology, pathogenesis, diagnosis and management. Aust Dent J 55(1Suppl):39–47PubMedCrossRefGoogle Scholar
  3. 3.
    Fox RI (2005) Sjögren’s Syndrome. Lancet 366:321–331PubMedCrossRefGoogle Scholar
  4. 4.
    Kassan SS, Moutsopoulos HM (2004) Clinical manifestations and early diagnosis of Sjögren’s syndrome. Arch Intern Med 164:1275–1284PubMedCrossRefGoogle Scholar
  5. 5.
    Cermak JM, Papas AS, Sullivan RM, Dana MR, Sullivan DA (2003) Nutrient intake in women with primary and secondary Sjögren’s syndrome. Eur J Clin Nutr 57:328–334PubMedCrossRefGoogle Scholar
  6. 6.
    Cummins MJ, Papas A, Kammer GM, Fox PC (2003) Treatment of primary Sjögren’s syndrome with low-dose human interferon alfa administered by the oromucosal route: combined phase III results. Arthritis Rheum 49:585–593PubMedCrossRefGoogle Scholar
  7. 7.
    Fox PC, Bowman SJ, Segal B et al (2008) Oral involvement in primary Sjögren syndrome. J Am ENT Assoc 139:1592–1601CrossRefGoogle Scholar
  8. 8.
    Papas AS, Fernancez MM, Castano RA, Gallagher SC, Trivedi M, Shrotriya RC (1998) Oral pilocarpine for symptomatic relief of dry mouth and dry eyes in patient with Sjögren’s syndrome. Adv Exp Med Biol 438:973–978PubMedCrossRefGoogle Scholar
  9. 9.
    Ramos-Casals M, Tzioufas AG, Stone JH, Sisó A, Bosch X (2010) Treatment of primary Sjögren Syndrome: a systematic review. JAMA 304:452–460PubMedCrossRefGoogle Scholar
  10. 10.
    Barendregt PJ, Visser MRM, Smets EMA, Tulen JHM, van den Meiracker AH, Boomsma F, Markusse HM (1998) Fatigue in primary Sjögren’s syndrome. Ann Rheum Dis 57:291–295PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Strombeck B, Ekdahl C, Manthorpe R, Wikstrom I, Jacobsson L (2000) Health-related quality of life in primary Sjögren’s syndrome, rheumatoid arthritis and fibromyalgia compared to normal population data using SF-36. Scand J Rheumatol 29:20–28PubMedCrossRefGoogle Scholar
  12. 12.
    Ng WF, Bowman SJ (2010) Primary Sjögren’s syndrome: too dry and too tired. Rheumatology 49:844–853PubMedCrossRefGoogle Scholar
  13. 13.
    Haldorsen K, Bjelland I, Bolstad AI, Jonsson R, Brun JG (2011) A five-year prospective study of fatigue in primary Sjögren’s syndrome. Arthritis Res Ther 13:R167PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Godaert GLR, Hartkamp A, Geenen R, Garssen A, Kruize AA, Bijlsma JMR, Derksen RHWM (2002) Fatigue in daily life in patients with primary Sjögren’s syndrome and systemic lupus erythematosus. Ann NY Acad Sci 966:320–326PubMedCrossRefGoogle Scholar
  15. 15.
    Valtysdottir ST, Gudbjornsson B, Lindqvist U, Hallgren R, Hetta J (2000) Anxiety and depression in patients with primary Sjögren’s syndrome. J Rheum 27:165–169PubMedGoogle Scholar
  16. 16.
    Valtysdottir ST, Gudbjornsson B, Hallgren R, Hetta J (2000) Psychological well-being in patients with primary Sjögren’s syndrome. Clin Exp Rheumatol 18:597–600PubMedGoogle Scholar
  17. 17.
    Delalande S, de Seze J, Fauchais A-L et al (2004) Neurologic manifestations in primary Sjögren syndrome: a study of 82 patients. Medicine 83:280–291PubMedCrossRefGoogle Scholar
  18. 18.
    Govoni M, Padovan M, Rizzo N, Trotta F (2001) CNS involvement in primary Sjögren’s syndrome: prevalence, clinical aspects, diagnostic assessment and therapeutic approach. CNS Drugs 15:597–607PubMedCrossRefGoogle Scholar
  19. 19.
    Mauch E, Voelk C, Kratzsch G, Krapf H et al (1994) Neurological and neuropsychiatric dysfunction in primary Sjögren’s syndrome. Acta Neurol Scand 89:31–35PubMedCrossRefGoogle Scholar
  20. 20.
    Alexander EL (1991) Central nervous system disease in Sjögren’s syndrome. New insights into immunopathogenesis. Rheum Dis clin North Am 18:637–672Google Scholar
  21. 21.
    DeBattista C, Doghramji K, Menza MA, Rosenthal MH, Fieve RR (2003) Modafinil in Depression Study Group. Adjunct modafinil for the short-term treatment of fatigue and sleepiness in patients with major depressive disorder: a preliminary double-blind, placebo-controlled study. J Clin Psychiatry 64:1057–1064PubMedCrossRefGoogle Scholar
  22. 22.
    Dinges DF, Weaver TE (2003) Effects of modafinil on sustained attention performance and quality of life in OSA patients with residual sleepiness while being treated with nCPAP. Sleep Med 4:393–402PubMedCrossRefGoogle Scholar
  23. 23.
    Johnstone B, Pepmueller PH, Vieth AZ, Komatireddy G (1996) Effective treatment of neuropsychological deficits in Sjögren’s syndrome. Appl Neuropsychol 3:122–127PubMedCrossRefGoogle Scholar
  24. 24.
    Le Guern V, Belin C, Henegar C et al (2010) Cognitive function and 99mTc-ECD brain SPECT are significantly correlated in patients with primary Sjögren syndrome: a case–control study. Ann Rheum Dis 69:132–137PubMedCrossRefGoogle Scholar
  25. 25.
    Cox PD, Hales RE (1999) CNS Sjögren’s syndrome: an under-recognized and underappreciated neuropsychiatric disorder. J Neuropsych Clin Neurosci 11:241–247Google Scholar
  26. 26.
    Wyszynski AA, Wyszynski B (1993) Treatment of depression with fluoxetine in corticosteroid-dependent central nervous system Sjögren’s syndrome. Psychosomatics: J Consult Liaison Psychiatry 34:173–177CrossRefGoogle Scholar
  27. 27.
    Shiboski SC, Shiboski CH, Criswell L, Baer A, Challacombe S, Lanfranchi H, Schiødt M, Umehara H, Vivino F, Zhao Y, Dong Y, Greenspan D, Heidenreich AM, Helin P, Kirkham B, Kitagawa K, Larkin G, Li M, Lietman T, Lindegaard J, McNamara N, Sack K, Shirlaw P, Sugai S, Vollenweider C, Whitcher J, Wu A, Zhang S, Zhang W, Greenspan J, Daniels T (2012) Sjögren’s International Collaborative Clinical Alliance (SICCA) Research Groups. Arthritis Care Res 64:475–487CrossRefGoogle Scholar
  28. 28.
    Greenblatt DJ, Harmatz JS, Shapiro L, Engelhardt N, Gouthro TA, Shader RI (1991) Sensitivity to triazolam in the elderly. N Engl J Med 324:1691–1698PubMedCrossRefGoogle Scholar
  29. 29.
    Kaplan GB, Greenblatt DJ, Ehrenberg BL, Goddard JE, Cotreau MM, Harmatz JS, Shader RI (1997) Dose dependent pharmacokinetics and psychomotor effects of caffeine in humans. J Clin Pharmacol 37:693–703PubMedCrossRefGoogle Scholar
  30. 30.
    Scavone JM, Greenblatt DJ, Harmatz JS, Engelhardt N, Shader RI (1998) Pharmacokinetics and pharmacodynamics of diphenhydramine 25 mg in young and elderly volunteers. J Clin Pharmacol 38:603–609PubMedCrossRefGoogle Scholar
  31. 31.
    Spitzer RL, Williams JB, Gibbon M, First MB (1992) The structured clinical interview for DSM-III-R (SCID). I: History, rationale, and description. Arch Gen Psychiatry 49:624–629PubMedCrossRefGoogle Scholar
  32. 32.
    Spitzer RL, Williams JBW, Gibbon M, First MB. Structured clinical interview for DSM-III-R, patient edition/non-patient edition, (SCID-P/SCID-NP), Washington, D.C.: American Psychiatric Press, Inc., 1990Google Scholar
  33. 33.
    Small GW (2002) The Memory Bible: an innovative strategy for keeping the brain young. Penguin, LondonGoogle Scholar
  34. 34.
    Holmes TH, Rahe RH (1967) Holmes-Rahe social readjustment rating scale. J Psychosom Res 11:213–218PubMedCrossRefGoogle Scholar
  35. 35.
    Hollingshead AB (1975) Four factor index of social status. Yale University, New HavenGoogle Scholar
  36. 36.
    Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD (1989) The fatigue severity scale: application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol 46:1121–1123PubMedCrossRefGoogle Scholar
  37. 37.
    Ware JEJ, Snow KK, Kosinski M, Gandek B (1993) SF-36 Health survey: manual and interpretation guide. The Health Institute, New England Medical CenterGoogle Scholar
  38. 38.
    Radloff LS, Teri L (1986) Use of the center for epidemiological studies—depression scale with older adults. Clin Gerontol 5:119–136CrossRefGoogle Scholar
  39. 39.
    Greenblatt DJ, Harmatz JS, Engelhardt N, Shader RI (1989) Pharmacokinetic determinants of dynamic differences among three benzodiazepine hypnotics: flurazepam, temazepam, and triazolam. Arch Gen Psychiatry 46:326–332PubMedCrossRefGoogle Scholar
  40. 40.
    Greeenblatt DJ, Harmatz J, Dorsey C, Shader RI (1988) Comparative single-dose kinetics and dynamics of lorazepam, alprazolam, prazepam, and placebo. Clin Pharmacol Ther 44:326–334CrossRefGoogle Scholar
  41. 41.
    Curtis-Prior PB (1996) Computerized methods of neuropsychological assessment. Br J Hosp Med 56:445–449PubMedGoogle Scholar
  42. 42.
    Sahakian BJ, Owen AM (1992) Computerized assessment in neuropsychiatry using CANTAB. J R Soc Med 85:399–402PubMedCentralPubMedGoogle Scholar
  43. 43.
    Fray PJ, Robbins TW (1996) CANTAB battery: proposed utility in neurotoxicology. Neurotoxicol Teratol 18:499–504PubMedCrossRefGoogle Scholar
  44. 44.
    Bright P, Jaldow E, Kopelman MD (2002) The National Adult Reading Test as a measure of premorbid intelligence: a comparison with estimates derived from demographic variables. J Int Neuropsychol Soc 8:847–854PubMedCrossRefGoogle Scholar
  45. 45.
    Gladsjo JA, Heaton RK, Palmer BW, Taylor MJ, Jeste DV (1999) Use of oral reading to estimate premorbid intellectual and neuropsychological functioning. J Int Neuro Psychol Soc 5:247–254Google Scholar
  46. 46.
    Birnbaum J (2010) Peripheral nervous system manifestations of Sjögren’s syndrome: clinical patterns, diagnostic paradigms, etiopathogenesis, and therapeutic strategies. Neurologist 16:287–297PubMedCrossRefGoogle Scholar
  47. 47.
    Segal BM, Pogatchnik B, Holker E, Liu H, Sloan J, Rhodus N, Moser KL (2012) Primary Sjögren's syndrome: cognitive symptoms, mood, and cognitive performance. Acta Neurol Scand 125:272–278PubMedCentralPubMedCrossRefGoogle Scholar
  48. 48.
    Segal B, Bowman SJ, Fox PC et al (2009) Primary Sjögren’s syndrome: health experiences and predictors of health quality among patients in the United States. Health Qual Life Outcomes 7:46PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Clinical Rheumatology 2013

Authors and Affiliations

  • Lynn C. Epstein
    • 1
  • Gina Masse
    • 2
  • Jerold S. Harmatz
    • 2
  • Tammy M. Scott
    • 1
  • Athena S. Papas
    • 3
  • David J. Greenblatt
    • 1
    • 2
  1. 1.Department of PsychiatryTufts University School of Medicine and Tufts Medical CenterBostonUSA
  2. 2.Integrative Physiology and PathobiologyTufts University School of Medicine and Tufts Medical CenterBostonUSA
  3. 3.Division of General DentistryTufts University School of Dental MedicineBostonUSA

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