Original Study| Volume 22, ISSUE 10, P2079-2086.e5, October 2021

Uncontrolled Pain and Risk for Depression and Behavioral Symptoms in Residents With Dementia



      Limited cohort studies have assessed the association between uncontrolled pain and risk for behavioral and psychological symptoms of dementia (BPSDs). We conducted a longitudinal cohort study to examine whether associations exist between uncontrolled pain and risk for 2 common BPSDs—depression and behavioral symptoms—among long-term care (LTC) residents with Alzheimer disease and related dementia (ADRD).


      This retrospective cohort study analyzed quarterly data from the 5% Medicare sample linked to Minimum Data Set (MDS) 3.0 between January 1, 2011, and December 31, 2015.

      Setting and Participants

      LTC residents aged 50 years or older with ADRD who had chronic pain and at least 2 quarterly MDS 3.0 assessments.


      LTC residents were followed up quarterly from first observed quarterly MDS 3.0 until first outcome event or last observed quarterly MDS 3.0. Uncontrolled pain was defined as numerical rating scale >4, verbal descriptor scale of moderate or severe pain, or ≥1 pain indicators on the Checklist of Nonverbal Pain Indicators. Depression was defined as ≥10 on the Patient Health Questionnaire 9; behavioral symptoms were defined as the presence of psychotic (delusions or hallucinations) or disruptive behaviors (rejection of care, or physical, verbal, or other aggressive behaviors). Generalized linear models (GLMs) with marginal structural modeling (MSM) stabilized weights were used to examine uncontrolled pain and outcome risk.


      The incidence rate of depression and behavioral symptoms during follow-up was 9.4 and 23.1 per 100 resident-years, respectively. Results from the MSM-GLMs showed that LTC residents with uncontrolled pain had a higher risk than those with controlled pain for developing depression [hazard ratio 1.67, 95% confidence interval (CI) 1.54–1.81] and behavioral symptoms (hazard ratio 1.28, 95% CI 1.19–1.37).

      Conclusions and Implications

      Uncontrolled pain was associated with elevated risk for depressive and behavioral symptoms in dementia, underscoring the importance of pain assessment and control among LTC residents with ADRD.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of the American Medical Directors Association
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Malara A.
        • De Biase G.A.
        • Bettarini F.
        • et al.
        Pain assessment in elderly with behavioral and psychological symptoms of dementia.
        J Alzheimers Dis. 2016; 50: 1217-1225
        • Gaugler J.E.
        • Yu F.
        • Krichbaum K.
        • et al.
        Predictors of nursing home admission for persons with dementia.
        Med Care. 2009; 47: 191-198
        • Lyketsos C.G.
        • Lopez O.
        • Jones B.
        • et al.
        Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: results from the cardiovascular health study.
        JAMA. 2002; 288: 1475-1483
        • Kales H.C.
        • Gitlin L.N.
        • Lyketsos C.G.
        Assessment and management of behavioral and psychological symptoms of dementia.
        BMJ. 2015; 350: h369
        • Kales H.C.
        • Gitlin L.N.
        • Lyketsos C.G.
        • et al.
        Management of neuropsychiatric symptoms of dementia in clinical settings: recommendations from a multidisciplinary expert panel.
        J Am Geriatr Soc. 2014; 62: 762-769
        • Livingston G.
        • Sommerlad A.
        • Orgeta V.
        • et al.
        Dementia prevention, intervention, and care.
        Lancet. 2017; 390: 2673-2734
        • Hodgson N.
        • Gitlin L.N.
        • Winter L.
        • et al.
        Caregiver's perceptions of the relationship of pain to behavioral and psychiatric symptoms in older community-residing adults with dementia.
        Clin J Pain. 2014; 30: 421-427
        • Tosato M.
        • Lukas A.
        • van der Roest H.G.
        • et al.
        Association of pain with behavioral and psychiatric symptoms among nursing home residents with cognitive impairment: results from the SHELTER study.
        Pain. 2012; 153: 305-310
        • Ishii S.
        • Streim J.E.
        • Saliba D.
        A conceptual framework for rejection of care behaviors: review of literature and analysis of role of dementia severity.
        J Am Med Dir Assoc. 2012; 13 (e11–e12): 11-23
        • Ahn H.
        • Horgas A.
        The relationship between pain and disruptive behaviors in nursing home residents with dementia.
        BMC Geriatr. 2013; 13: 14
        • Kunik M.E.
        • Snow A.L.
        • Davila J.A.
        • et al.
        Causes of aggressive behavior in patients with dementia.
        J Clin Psychiatry. 2010; 71: 1145-1152
        • Sampson E.L.
        • White N.
        • Lord K.
        • et al.
        Pain, agitation, and behavioural problems in people with dementia admitted to general hospital wards: a longitudinal cohort study.
        Pain. 2015; 156: 675-683
        • Volicer L.
        • Frijters D.H.
        • Van der Steen J.T.
        Relationship between symptoms of depression and agitation in nursing home residents with dementia.
        Int J Geriatr Psychiatry. 2012; 27: 749-754
        • Erdal A.
        • Flo E.
        • Selbaek G.
        • et al.
        Associations between pain and depression in nursing home patients at different stages of dementia.
        J Affect Disord. 2017; 218: 8-14
        • Mansournia M.A.
        • Etminan M.
        • Danaei G.
        • et al.
        Handling time varying confounding in observational research.
        BMJ. 2017; 359: j4587
        • Rahman A.N.
        • Applebaum R.A.
        The nursing home Minimum Data Set assessment instrument: manifest functions and unintended consequences--past, present, and future.
        Gerontologist. 2009; 49: 727-735
        • The Centers for Medicare & Medicaid Services (CMS)
        Chronic Conditions Data Warehouse 2020.
        (Available at:)
        • Levis B.
        • Benedetti A.
        • Thombs B.D.
        • et al.
        Accuracy of Patient Health Questionnaire-9 (PHQ-9) for screening to detect major depression: individual participant data meta-analysis.
        BMJ. 2019; 365: l1476
        • Kroenke K.
        • Spitzer R.L.
        • Williams J.B.
        The PHQ-9: validity of a brief depression severity measure.
        J Gen Intern Med. 2001; 16: 606-613
        • Gruber-Baldini A.L.
        • Boustani M.
        • Sloane P.D.
        • et al.
        Behavioral symptoms in residential care/assisted living facilities: prevalence, risk factors, and medication management.
        J Am Geriatr Soc. 2004; 52: 1610-1617
        • Galik E.
        • Resnick B.
        • Vigne E.
        • et al.
        Reliability and validity of the resistiveness to care scale among cognitively impaired older adults.
        J Am Med Dir Assoc. 2017; 18: 59-64
        • Saliba D.
        • Buchanan J.
        Rand Corporation Health: Development & validation of a revised nursing home assessment tool: MDS 3.0 health.
        (Available at:)
        • Allan C.E.
        • Valkanova V.
        • Ebmeier K.P.
        Depression in older people is underdiagnosed.
        Practitioner. 2014; 258 (19–22): 12-13
        • Saliba D.
        • Buchanan J.
        Making the investment count: Revision of the Minimum Data Set for nursing homes, MDS 3.0.
        J Am Med Dir Assoc. 2012; 13: 602-610
        • Farrington C.P.
        Interval censored survival data: A generalized linear modelling approach.
        Stat Med. 1996; 15: 283-292
        • Robins J.M.
        • Hernan M.A.
        • Brumback B.
        Marginal structural models and causal inference in epidemiology.
        Epidemiology. 2000; 11: 550-560
        • Williamson T.
        • Ravani P.
        Marginal structural models in clinical research: When and how to use them?.
        Nephrol Dial Transplant. 2017; 32: ii84-ii90
        • Cole S.R.
        • Hernan M.A.
        Constructing inverse probability weights for marginal structural models.
        Am J Epidemiol. 2008; 168: 656-664
        • Zeger S.L.
        • Liang K.Y.
        Longitudinal data analysis for discrete and continuous outcomes.
        Biometrics. 1986; 42: 121-130
        • The Centers for Medicare & Medicaid Services (CMS)
        Long-Term Care Facility Resident Assessment Instrument 3.0 User’s Manual, Version 1.17.1 2019.
        (Available at:)
        • Husebo B.S.
        • Ballard C.
        • Sandvik R.
        • et al.
        Efficacy of treating pain to reduce behavioural disturbances in residents of nursing homes with dementia: Cluster randomised clinical trial.
        BMJ. 2011; 343: d4065
        • Husebo B.S.
        • Ballard C.
        • Fritze F.
        • et al.
        Efficacy of pain treatment on mood syndrome in patients with dementia: A randomized clinical trial.
        Int J Geriatr Psychiatry. 2014; 29: 828-836
        • IsHak W.W.
        • Wen R.Y.
        • Naghdechi L.
        • et al.
        Pain and depression: A systematic review.
        Harv Rev Psychiatry. 2018; 26: 352-363
        • Payne J.L.
        • Sheppard J.M.
        • Steinberg M.
        • et al.
        Incidence, prevalence, and outcomes of depression in residents of a long-term care facility with dementia.
        Int J Geriatr Psychiatry. 2002; 17: 247-253
        • Platt R.W.
        • Delaney J.A.
        • Suissa S.
        The positivity assumption and marginal structural models: The example of warfarin use and risk of bleeding.
        Eur J Epidemiol. 2012; 27: 77-83
        • Wei Y.J.
        • Solberg L.
        • Chen C.
        • et al.
        Pain assessments in MDS 3.0: Agreement with vital sign pain records of nursing home residents.
        J Am Geriatr Soc. 2019; 67: 2421-2422
        • Wei Y.J.
        • Solberg L.
        • Chen C.
        • et al.
        Agreement of Minimum Data Set 3.0 depression and behavioral symptoms with clinical diagnosis in a nursing home.
        Aging Ment Health. 2020 May 25; ([E-pub ahead of print])
        • Fillingim R.B.
        • King C.D.
        • Ribeiro-Dasilva M.C.
        • et al.
        Sex, gender, and pain: A review of recent clinical and experimental findings.
        J Pain. 2009; 10: 447-485
        • Cowan R.L.
        • Beach P.A.
        • Atalla S.W.
        • et al.
        Sex differences in the psychophysical response to contact heat in moderate cognitive impairment Alzheimer's disease: A cross-sectional brief report.
        J Alzheimers Dis. 2017; 60: 1633-1640
      1. Obesity: preventing and managing the global epidemic. Report of a WHO consultation.
        World Health Organ Tech Rep Ser. 2000; 894: 1-253
        • Downer B.
        • Thomas K.S.
        • Mor V.
        • et al.
        Cognitive status of older adults on admission to a skilled nursing facility according to a hospital discharge diagnosis of dementia.
        J Am Med Dir Assoc. 2017; 18: 726-728
        • Mehta H.B.
        • Kuo Y.F.
        • Raji M.
        • et al.
        Time trends in opioid use by dementia severity in long-term care nursing home residents.
        J Am Med Dir Assoc. 2021; 22: 124-131.e121
        • Shao J.
        • Zhong B.
        Last observation carry-forward and last observation analysis.
        Stat Med. 2003; 22: 2429-2441
        • Masnoon N.
        • Shakib S.
        • Kalisch-Ellett L.
        • et al.
        What is polypharmacy? A systematic review of definitions.
        BMC Geriatr. 2017; 17: 230