- Email: [email protected]
Cognitive Impairment and Community Integration Outcomes in Individuals Living With Multiple Sclerosis
Accepted Manuscript Cognitive Impairment and Community Integration Outcomes in Individuals Living with Multiple Sclerosis Abbey J. Hughes, PhD, Narineh Hartoonian, PhD, Brett Parmenter, PhD, Jodie K. Haselkorn, MD, MPH, Jesus F. Lovera, MSPH, MD, Dennis Bourdette, MD, Aaron P. Turner, PhD PII:
S0003-9993(15)00561-4
DOI:
10.1016/j.apmr.2015.07.003
Reference:
YAPMR 56247
To appear in:
ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
Received Date: 9 April 2015 Revised Date:
30 June 2015
Accepted Date: 6 July 2015
Please cite this article as: Hughes AJ, Hartoonian N, Parmenter B, Haselkorn JK, Lovera JF, Bourdette D, Turner AP, Cognitive Impairment and Community Integration Outcomes in Individuals Living with Multiple Sclerosis, ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION (2015), doi: 10.1016/ j.apmr.2015.07.003. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Running Head: Cognitive Impairment & Community Integration in MS Cognitive Impairment and Community Integration Outcomes in Individuals Living with
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Multiple Sclerosis
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Abbey J. Hughes, PhD1, 2
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Narineh Hartoonian, PhD2
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Brett Parmenter, PhD3
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Jodie K. Haselkorn, MD, MPH1,2,4
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Jesus F. Lovera, MSPH, MD5
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Dennis Bourdette, MD6,7
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Aaron P. Turner, PhD1, 2
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Department of Rehabilitation Medicine, University of Washington, Seattle, WA
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Multiple Sclerosis Center of Excellence West, Veterans Affairs Puget Sound Health Care
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System, Seattle Division, Seattle, WA
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Veterans Affairs Puget Sound Health Care System, American Lake Division, Tacoma, WA
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Department of Epidemiology, University of Washington, Seattle, WA
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Department of Neurology, Louisiana State University Health Science Center, New Orleans, LA
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Multiple Sclerosis Center of Excellence West, Veterans Affairs Portland Health Care System,
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Portland, OR
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Department of Neurology, School of Medicine, Oregon Health & Science University, Portland,
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Acknowledgements
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The work conducted in this manuscript has not been previously published, nor is it under
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consideration for publication elsewhere. However, we plan to present (poster presentation) the
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results in February 2015 at the annual Rehabilitation Psychology Conference in San Diego, CA.
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The contents of this article were developed under grants from the Department of Veterans
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Affairs, Office of Research and Development, Rehabilitation Research and Development, Grant
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B4368R. The contents of this paper do not represent the view of the Department of Veterans
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Affairs of the US Government. In addition, the work reported in this manuscript was supported
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by a mentor-based fellowship grant from the National Multiple Sclerosis Society to Turner (PI),
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Grant MB 0026.
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10 Conflict of Interest
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We certify that no party having a direct interest in the results of the research supporting this
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article has or will confer a benefit on the authors or on any organization with which they are
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associated and we certify that all financial and material support for this research and work are
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clearly identified in the title page of the manuscript.
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Correspondence and reprint requests should be addressed to:
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Abbey J. Hughes, PhD
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NMSS Postdoctoral Research Fellow
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Department of Rehabilitation Medicine
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University of Washington
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325 Ninth Avenue, Box 359612
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Seattle, Washington 98104
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Email: [email protected]
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Telephone: (206) 221-5688
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Cognitive Impairment and Community Integration Outcomes in Individuals Living with
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Multiple Sclerosis
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Objective. To determine the association between unique domains of cognitive impairment and
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community integration in individuals with multiple sclerosis (MS), and to determine the
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contributions of cognitive impairment to community integration beyond the influence of
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demographic and clinical variables.
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Design. Cross-sectional analysis of objective neuropsychological assessment and self-report
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data. Data were collected during baseline assessment of a randomized multi-site controlled trial
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of ginkgo biloba for cognitive impairment in MS. Hierarchical regression analyses examined the
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association between subjective and objective measures of cognitive impairment and three
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domains of community integration, adjusting for relevant covariates.
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Setting. Two VA medical center MS clinics.
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Participants. 121 adults (ages 24 to 65) with a confirmed MS diagnosis.
Interventions. Not applicable.
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Main Outcome Measures. Primary outcomes were scores on the Home Integration (CIQ-H),
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Social Integration (CIQ-S), and Productivity (CIQ-P) domains of the Community Integration
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Questionnaire (CIQ).
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Results. Cognitive impairment was associated with lower scores on the CIQ-H and CIQ-S, but
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not the CIQ-P. Greater levels of subjective cognitive impairment were associated with lower
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scores on the CIQ-H and CIQ-S. Greater levels of objective cognitive impairment, specifically
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slower processing speed and poorer inhibitory control, were related to lower CIQ-S scores.
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Subjective and objective measures of cognitive impairment were significantly and independently
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associated with CIQ-S.
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Conclusions. Objective cognitive impairment may interfere with participation in social
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activities. Subjective cognitive impairment is also important to assess, because individuals who
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perceive themselves to be cognitively impaired may be less likely to participate in both home
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and social activities. Clinical interventions to enhance community integration in individuals with
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MS may benefit from addressing objective and subjective cognitive impairment by integrating
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cognitive rehabilitation approaches with self-efficacy-enhancing strategies.
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Key words: multiple sclerosis, cognitive impairment, community integration
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List of Abbreviations: BDI = Beck Depression Inventory – II; CIQ = Community Integration
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Questionnaire; CIQ-H = CIQ – Home Integration; CIQ-S = CIQ – Social Integration; CIQ-P =
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CIQ – Productivity; COWAT = Controlled Oral Word Association Test; CVLT = California
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Verbal Learning Test – II; EDSS = Expanded Disability Status Scale; FSS = Fatigue Severity
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Scale; MS = multiple sclerosis; RRMS = relapsing-remitting MS subtype; PASAT = Paced
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Auditory Serial Addition Test; PDQ = Perceived Deficits Questionnaire; PMS = Progressive MS
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subtype; VSCWT = Victoria Stroop Color-Word Test.
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Participation in daily roles, relationships, and activities, commonly known as community
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integration, is an important outcome among neurorehabilitation populations, including
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individuals with multiple sclerosis (MS).1-6 Community integration significantly contributes to
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quality of life in people living with physical disabilities, even after controlling for disease and
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disability severity.7 To date, research on community integration in MS has predominately
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focused on employment,8-10 with few studies investigating other domains such as home, social,
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educational, and vocational activities.11 Factors such as cognitive impairment may contribute to
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diminished community integration in MS; however the relationship between cognitive
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impairment and community integration remains poorly understood.
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Cognitive impairment affects 43 to 70% of individuals with MS12,13 and impacts a number of
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cognitive domains, including information processing speed, memory, verbal fluency, attention,
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working memory, and executive functions (e.g., inhibitory control). 12,14-24 Rao and colleagues
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demonstrated that MS patients who were impaired on a neuropsychological assessment battery
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were less likely to be employed than those without cognitive impairment. Although their work
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was among the first to demonstrate a relationship between objective cognitive impairment and
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community integration, the relationship between subjective cognitive impairment (i.e., an
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individual’s perceptions and beliefs about their cognitive impairment) and community
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integration has not been investigated. Moreover, it remains unclear whether there are differences
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in community integration outcomes across different objective and subjective cognitive measures
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and across different aspects of community integration.
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Willer and colleagues developed the Community Integration Questionnaire (CIQ)25 to assess
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three domains of community integration: participation in activities within a home-like setting
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(Home Integration [CIQ-H]), integration into social relationships (Social Integration [CIQ-S]),
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and regular performance of productive educational or vocational activities (Productivity [CIQ-
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P]). The CIQ provides a brief, validated self-report assessment tool for evaluating total
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community integration, as well as unique aspects of community integration in rehabilitation
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populations.26 A study investigating the scope, nature, and impact of pain in MS found that
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greater pain was significantly associated with lower scores on the CIQ-P, but not the CIQ-H or
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CIQ-S subscale.11 Although the CIQ also yields a total score, results from this study of pain in
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MS suggest it may be more clinically useful to examine each CIQ domain separately. Despite the
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CIQ’s potential utility, no studies to date have examined the relationship between cognitive
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impairment and each domain of the CIQ in MS.
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The purpose of this study was to assess whether objective and subjective cognitive impairments
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are associated with lower levels of community integration on each subscale of the CIQ, after
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controlling for relevant demographics and clinical characteristics. Understanding differences in
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community integration outcomes across different cognitive domains and measurement modalities
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will help inform the design of future clinical interventions to enhance community integration and
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ultimately promote quality of life in MS.
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Methods
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Participants and Procedures
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This study was performed at two VA Medical Centers. Study procedures were approved by both
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sites’ Institutional Review Boards. Participants were recruited as part of a previously reported
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trial comparing the effects of ginkgo biloba versus placebo in individuals with MS.27 The present
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data were collected from participants at baseline, prior to randomization. Participants were
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recruited from both sites’ MS clinics, their affiliated university clinics, and their local
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communities. All participants provided written informed consent. Eligible participants were
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required to have a physician-confirmed diagnosis of MS, disease stability for at least 30 days,
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and a score of at least one standard deviation below the mean of the normative sample on at least
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one objective cognitive test. Exclusion criteria included: severe depression symptoms, defined by
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a score greater than 28 on the Beck Depression Inventory – II (BDI),28 color-blindness, poor
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visual acuity, and current use of medications contraindicated for ginkgo biloba (e.g.,
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anticoagulant medications including coumadin).29 A total of 173 individuals were evaluated for
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eligibility. Of those, 52 were excluded due to meeting one or more exclusion criteria or declining
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participation after enrollment, yielding a final sample of 121 participants.
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Measures
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Cognitive impairment. The following objective measures were selected to assess the most
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common cognitive impairments observed in MS: the 2-second Paced Auditory Serial Addition
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Test (PASAT),30 a test of auditory working memory, attention, and processing speed; the long-
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delay free recall trial of the California Verbal Learning Test – II (CVLT),31 a measure of verbal
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memory; the Controlled Oral Word Association Test (COWAT),32 a speeded test of verbal
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ability and phonemic fluency; and the Color-Word subtest of the Victoria Stroop Color-Word
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Test (VSCWT),33 a measure of attention, processing speed, and inhibitory control. Participants’
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scores were converted to Z scores (M = 0, SD = 1.0) based on an age-matched normative
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sample, with higher scores indicating better performance. Subjective cognitive impairment was
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assessed using the Perceived Deficits Questionnaire (PDQ),34 a twenty-item Likert-type scale
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that assesses how often various cognitive problems occurred in the past four weeks. This
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measure has been validated for individuals with MS and demonstrates good internal consistency
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(Cronbach’s α = .93).35 Scores range from 0 to 80, with higher scores associated with greater
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subjective cognitive impairment. Although the PDQ does not reliably correlate with objective
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measures of verbal memory and processing speed, the PDQ assesses important ways in which
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individuals perceive their cognitive impairment.36
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Community integration. Community integration was assessed using the CIQ,25,26 a fifteen-item
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self-report scale that assesses the how often and how independently an individual participates in
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various activities. The CIQ yields three subscale scores: Home Integration (i.e., participation in
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home-based activities; CIQ-H), Social Integration (i.e., participation in social activities; CIQ-S),
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and Productivity (i.e., participation in educational or vocational activities; CIQ-P). Although this
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measure also yields a total CIQ score, the authors elected to examine the three subscales in order
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to better understand which aspects of community integration are related to cognitive impairment
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in MS. This measure has been validated in individuals with physical disabilities, including MS,
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and demonstrates adequate internal consistency (Cronbach’s α = .75) and excellent test-retest
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reliability (r = .91).37 Scores range from 0 to 10 for Home Integration, 0 to 12 for Social
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Integration, and 0 to 7 for Productivity, with higher scores associated with greater community
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integration. At present, a recommended cutoff score or minimally clinically important difference
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in scores has not been established.
143 Demographics. Participants were asked to report their age in years, sex (“Male” or “Female”),
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and education level (i.e., “Less than or Equal to High School Diploma,” “Some College or
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College Degree,” and “Greater than or Equal to Some Graduate School”).
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Clinical characteristics. Participants were asked to report their MS subtype and disease
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duration. MS subtype was categorized as either relapsing-remitting (RRMS) or progressive
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(PMS). Disease severity was determined by the Expanded Disability Status Scale (EDSS),38 a
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quantitative measure of disability that ranges from 0 (no disability) to 10 (death due to MS).
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Fatigue was assessed using the Fatigue Severity Scale (FSS),39 a nine-item Likert-type scale that
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assesses the degree to which fatigue interferes with daily activities. This measure has been
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recommended for use by the Multiple Sclerosis Taskforce of the American Physical Therapy
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Association and has excellent internal consistency (Cronbach’s α = .94).40,41 Scores range from 9
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to 63, with higher scores associated with greater levels of fatigue. Depressive symptoms were
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measured using the BDI, a 21-item self-report measure corresponding to the criteria for clinical
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depression as outlined in the Diagnosis and Statistical Manual of Mental Disorders – IV – Text
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Revision.28 This measure demonstrates excellent internal consistency (Cronbach’s α = .92).42
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Scores on this measure range from 0 to 63, with higher total summary score reflecting greater
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depressive symptom severity. Due to exclusion criteria, scores on this measure for the present
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study ranged from 0 to 27 (Cronbach’s α = .86).
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Data Analysis
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Statistical analyses were carried out using IBM SPSS Statistics version 22. No univariate or
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multivariate outliers were detected using histograms and Mahalanobis’ and Cooks’ distance
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analyses respectively and assumptions regarding the normality of sampling distributions were
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met using the Kolmogorov-Smirnov test (all ps >.05). Multicollinearity among variables in each
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model was assessed using Tolerance (T) values and Variance Inflation Factor (VIF = 1/T) values
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(critical value of 2.5).43 No VIF values exceeded 1.5.
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Correlational analyses were performed between potential covariates (i.e., demographics and
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clinical characteristics), cognitive measures, and each CIQ outcome. Covariates that significantly
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correlated with cognitive measures or CIQ outcomes (p < .05) were included in subsequent
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hierarchical regression analyses. Only CIQ outcomes that correlated with at least one cognitive
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measure were entered as outcome variables in hierarchical regression analyses. Significant
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covariates were entered into the first step, significant objective cognitive measures (i.e., PASAT,
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CVLT, COWAT, and/or VSCWT) were entered into the second step, and the PDQ (if
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significant) was entered into the third step.
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Results
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Participants
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Descriptive statistics for all variables assessed are presented in Table 1. Fifty-five percent of the
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sample was female and participants ranged between the ages of 24 and 65. Participants were
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generally highly educated, with the majority completing at least some college. Disease durations
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ranged from 1 to 47 years. The majority of participants were ambulatory without requiring
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mobility assistance (EDSS < 4.5). On average, the sample endorsed low levels of depression and
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moderate levels of fatigue. Participants’ mean scores on objective cognitive measures (i.e., the
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PASAT, CVLT, COWAT, and VSCWT) were below those of the normative sample. PDQ
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ratings indicated moderate levels of subjective cognitive impairment.
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[insert Table 1 here]
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Correlation Analyses
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Correlations between potential covariates, cognitive impairment measures, and CIQ outcomes
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are shown in Table 2. Female sex and the RRMS subtype were significantly associated with
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higher scores on the CIQ-H (all ps < .01). Female sex, lower EDSS ratings, and lower scores on
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the BDI and FSS were significantly associated with higher scores on the CIQ-S (all ps < .01).
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Lower EDSS ratings were also associated with higher scores on the CVLT. Younger age and
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shorter disease durations were significantly correlated with higher scores on the CIQ-P (i.e.,
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greater integration in educational or vocational activities; all ps < .05). Higher scores on the BDI
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and FSS were significantly related to higher scores on the PDQ (all ps < .001). Higher PDQ
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scores were associated with lower participation scores on the CIQ-H and CIQ-S. Higher PASAT
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scores were associated with higher CIQ-H scores, and higher VSCWT scores were associated
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with higher CIQ-S scores. No cognitive measures significantly correlated with CIQ-P outcomes.
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Thus, CIQ-P was not examined as an outcome in hierarchical regression analyses.
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[insert Table 2 here]
211 Hierarchical Regression Analyses
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The relationship between cognitive impairment and community integration outcomes differed
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across domains (Table 3).
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After controlling for sex, MS subtype, BDI, and FSS, the relationship between the PASAT and
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CIQ-H was no longer significant (β = .15, t = 1.13, p = .260). The addition of the PASAT did not
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significantly add to the variance in CIQ-H (∆R2 = .021, ∆F(1, 114) = 3.21, p = .076). The
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addition of the PDQ accounted for an additional 3.7% of the variance in CIQ-H (∆R2 = .037,
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∆F(1, 113) = 5.85, p = .017). In the final model, PDQ was the only cognitive impairment
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measure significantly associated with CIQ-H, where a 4-point increase on the PDQ was
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associated with a 1-point decrease on the CIQ-H (β = -.23, t = -2.42, p = .017). The final model
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was statistically significant and explained 28.4% of the variance in CIQ-H (R2 = .284, F(6, 113)
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= 7.47, p < .001).
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After controlling for sex, EDSS, BDI, and FSS, the addition of the VSCWT explained an
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additional 6.8% of the variance in CIQ-S (∆R2 = ..068, ∆F(1, 115) = 10.29, p = .002). Higher
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scores on the VSCWT were associated with higher scores on the CIQ-S (β = .27, t = 3.21, p =
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.002). The addition of the PDQ accounted for an additional 3.8% of the variance in CIQ-S (∆R2 =
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.038, ∆F(1, 114) = 6.09, p = .015). In the final model, both the VSCWT and the PDQ were
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significantly associated with CIQ-S, where higher scores on the VSCWT and lower scores on the
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on the PDQ were associated with higher scores on the CIQ-S (VSCWT: β = .26, t = 3.25, p =
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.002; PDQ: β = -.23, t = -2.47, p = .015). The final model was statistically significant and
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explained 28.4% of the variance in CIQ-S (R2 = .284, F(6, 114) = 7.52, p < .001).
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DISCUSSION
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This study investigated the relationship between cognitive impairment and community
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integration in individuals with MS. Participants were assessed on four measures of objective
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cognitive impairment, one measure of subjective cognitive impairment, and three domains of
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community integration. Although results generally supported previous findings that cognitive
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impairment is significantly associated with lower levels of community integration MS, this
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relationship varied across domains of these constructs.
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Higher levels of subjective cognitive impairment on the PDQ were significantly associated with
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less participation in activities within the home on the CIQ-H. No objective cognitive measures
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were related to this domain of community integration. With regard to participation in social
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activities, higher levels of impairment on the PDQ and worse objective cognitive performance on
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the VSCWT were significantly associated with less social participation on the CIQ-S. No
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cognitive measures were related to participation in educational or vocational activities on the
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CIQ-P. Results suggest that after taking into account demographic and clinical characteristics,
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objective cognitive impairments in processing speed and inhibitory control are related to
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diminished social integration, and subjective cognitive impairment is strongly associated with
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diminished home and social integration. Additional research is needed to determine whether the
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moderate effect sizes observed for these relationships warrant clinical significance.
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Similar to Rao’s findings,44 cognitive impairment was associated with disturbances in
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community integration; however, none of the cognitive measures in the present study were
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associated with participation in educational or vocational activities. For the present study, only
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disease duration and age were related to CIQ-P. These results demonstrate that each domain of
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the CIQ is distinct and should be assessed separately. A similar conclusion was supported in a
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more recent study examining the subjective frequency and importance of community integration
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among individuals with MS.5
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Results underscore the importance of incorporating baseline cognitive assessments in future
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interventions aimed at improving community integration. For clinicians working with this
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population, such assessments may help to: 1) identify cognitive impairment as a potential risk
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factor for suboptimal treatment outcomes; and 2) encourage the use of cognitive rehabilitation or
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compensatory strategies to mitigate the negative impact of cognitive impairment on community
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integration outcomes. Given that cognitive remediation strategies can lead to improved
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community integration and ultimately enhance everyday functional skills in individuals with
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traumatic brain injury,45,46 researchers have also begun to investigate cognitive impairment as a
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modifiable risk factor in MS.12,47 A 2011 Cochrane review demonstrated that cognitive
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rehabilitation interventions can support modest improvements in memory span, working
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memory, and visual memory.48 Although it remains to be seen whether these improvements
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might also facilitate improvements in other domains of functioning, including community
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integration, results from this study support a link between cognitive function and community
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integration, and future research may help clarify whether community integration is modifiable
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through improvements in cognitive function. For clinicians working to enhance community
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integration among patients with cognitive impairment, a focus on strategies that match the
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patient’s current level of function, and encourage cognitive rehabilitation strategies may be an
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effective target.
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This study afforded several major strengths. It featured a multi-site design with a large sample of
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community-dwelling individuals with MS. Unlike prior studies,44 this study employed validated
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measures of subjective cognitive impairment, objective cognitive impairment, and community
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integration. Given that community integration is increasingly being recognized as an important,
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multidimensional outcome in MS, the present study adds to the present literature by identifying
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cognitive impairment, particularly subjective cognitive impairment, as a potential risk factor for
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diminished community integration. These results may translate to better clinical practice, where
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early assessment of cognitive impairment and interventions aimed at promoting self-efficacy for
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managing cognitive impairment may promote home and social integration.
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This study’s participants and measures comprised additional strengths. The study featured a
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heterogeneous sample with regard to demographics and clinical characteristics. Although males
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are typically underrepresented in MS research, this study provided roughly equal proportions of
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men and women. Additionally, the inclusion of covariate measures provided the opportunity to
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assess the unique contributions of cognitive impairment to community integration beyond the
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contributions of demographics and clinical characteristics.
303 Limitations
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This study included a few limitations. First, participants in this sample had lower levels of
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depression and lower levels of physical disability than have previously been reported in the MS
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literature.49,50 Additionally, the sample was pre-selected for cognitive impairment. Given the
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restricted ranges for these variables, results may not reflect those of the full MS population, and
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underestimate the strength of the relationship between cognitive impairment and community
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integration. Future research is needed to examine this relationship in samples with the full
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spectrum of cognitive impairment and depressive symptoms. Second, this study featured a cross-
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sectional design with correlational and regression analyses. Therefore, definitive causation
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cannot be determined from this study. Third, this study employed univariate methods for pre-
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selecting the variables to be included in hierarchical regression analyses. Despite its practical
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advantages (e.g., elimination of unnecessary predictors, reduced computational burden), chance
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associations and model overfitting may have occurred.51 Finally, because symptom validity and
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performance validity measures were not included in this study, participant engagement and effort
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during testing could not be fully assessed.52 Despite these limitations, this study has important
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implications for the assessment of cognitive impairment and community integration and for the
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design of future intervention trials.
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Conclusions
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For individuals with MS, subjective cognitive impairment was strongly correlated with home and
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social activities. Objective impairments in processing speed and inhibitory control were strongly
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correlated with social activities. Importantly, these relationships were independent of the effects
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of demographics and clinical characteristics. Clinical interventions to enhance community
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integration in individuals with MS may benefit from addressing objective and subjective
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cognitive impairment by integrating cognitive rehabilitation approaches with self-efficacy-
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enhancing strategies.
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Bush SS, Ruff RM, Tröster AI, et al. Symptom validity assessment: Practice issues and medical necessity: NAN Policy & Planning Committee. Archives of Clinical Neuropsychology. 2005;20(4):419-426.
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Table 1 Descriptive statistics for demographics, clinical characteristics, cognitive impairment measures, and community integration outcomes %
Min
Demographics 24
Sex (Female)
66
54.5
7
5.8
87
71.9
27
22.3
≤ High School Some College/College Degree ≥ Some Graduate School Clinical Characteristics
RRMS PMS
65
52.08
9.08
78
64.5
43
35.5 1
47
20.10
11.71
0
7.5
4.10
1.92
0
27
9.77
6.71
9
63
49.50
11.05
PASAT
-3.37
1.63
-1.31
0.88
CVLT
-4.00
2.00
-0.52
1.19
COWAT
-2.81
1.77
-0.92
1.00
BDI FSS
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EDSS
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Disease Duration (years)
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MS Subtype
SD
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Education Level
M
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Age
Max
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n
Objective Cognitive Impairment
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VSCWT
-6.14
1.50
-1.00
1.49
9
71
37.79
12.49
PDQ Community Integration
0
CIQ-S
3
CIQ-P
0
10
5.72
2.82
12
8.17
2.05
7
3.22
1.80
SC
CIQ-H
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Subjective Cognitive Impairment
Note. n = 121.
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Abbreviations: BDI = Beck Depression Inventory – II; CIQ = Community Integration Questionnaire; CIQ-H = CIQ – Home Integration; CIQ-S = CIQ – Social Integration; CIQ-P = CIQ – Productivity; COWAT = Controlled Oral Word Association Test; CVLT = California Verbal Learning Test – II; EDSS = Expanded Disability Status Scale; FSS = Fatigue Severity
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Scale; RRMS = relapsing-remitting MS subtype; PASAT = Paced Auditory Serial Addition Test; PDQ = Perceived Deficits Questionnaire; PMS = Progressive MS subtype; VSCWT =
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Victoria Stroop Color-Word Test.
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Table 2
PASAT
CVLT
COWAT
VSCWT
SC
Covariates
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Correlations between potential covariates, cognitive impairment measures, and community integration outcomes Cognitive Impairment Measures CIQ Outcomes PDQ
CIQ-H
CIQ-S
CIQ-P
-.05
.25†
.05
-.07
-.17
.02
.03
-.19*
Sex (Female = 0, Male = 1)
-.01
-.01
-.12
.07
-.01
-.41‡
-.25†
-.09
.05
.02
.01
-.05
.03
.08
.06
.06
-.16
-.12
-.11
-.19*
-.02
-.25†
-.01
-.12
Education Levela Clinical Characteristics
BDI FSS Cognitive Impairment Measures PASAT CVLT
.25†
.22
-.09
-.03
-.09
.07
-.28†
-.16
-.20*
-.10
-.08
.12
-.17
-.21*
-.17
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EDSS
.02
-.03
-.06
.04
-.19*
.40‡
-.17
-.27†
-.07
.03
.02
.11
-.01
.47‡
-.07
-.27†
-.01
.18*
-.04
.16
.07
.12
.04
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Disease Duration (years)
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MS Subtype (RRMS = 0, PMS = 1)
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Age
.
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.04
.05
-.17
VSCWT
.14
.29†
.05
-.23†
-.34‡
-.10
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COWAT
PDQ Note. n = 121; * p < .05 † p < .01; ‡ p < .001.
Spearmen’s rank-order correlations (otherwise Pearson’s product-moment correlations).
SC
a
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Abbreviations: BDI = Beck Depression Inventory – II; CIQ = Community Integration Questionnaire; CIQ-H = CIQ Home Integration; CIQ-S = CIQ Social Integration; CIQ-P = CIQ Productivity; COWAT = Controlled Oral Word Association Test; CVLT = California Verbal Learning Test – II; EDSS = Expanded Disability Status Scale; FSS = Fatigue Severity Scale; RRMS = Relapsing Remitting MS subtype; PASAT = Paced Auditory Serial Addition Test; PDQ = Perceived Deficits Questionnaire; PMS = Progressive MS
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subtype; VSCWT = Victoria Stroop Color-Word Test.
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Table 3 Hierarchical regression of covariates and cognitive impairment measures on community
CIQ-H Step 1 (Covariates)
df
F
4, 115
8.38‡
MS Subtype (RRMS = 0, PMS = 1)
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BDI FSS
Step 2 (Objective Cognitive Impairment) PASAT
CIQ-S
∆F
.23
8.38‡
6, 113
4, 116
7.47‡
7.47‡
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-.36‡
-.15 -.01
.25
3.21 .15
.28
5.85* -.24*
6.27‡
.18
6.27‡ -.21*
Sex (Female = 0, Male = 1) EDSS
β
-.21*
EP
Step 1 (Covariates)
5, 114
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Step 3 (Subjective Cognitive Impairment) PDQ
R2
SC
Sex (Female = 0, Male = 1)
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integration outcomes
-.14
BDI
-.17
FSS
-.19*
Step 2 (Cognitive Impairment Predictors)
5, 115
7.48‡
.25
10.29† .27†
VSCWT Step 3 (Subjective Cognitive Impairment)
6, 114
7.52‡
.28
6.09*
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-.23*
PDQ Note. n = 121; * p < .05 † p < .01; ‡ p < .001. Abbreviations: BDI = Beck Depression Inventory – II; CIQ = Community Integration
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Questionnaire; CIQ-H = CIQ – Home Integration; CIQ-S = CIQ – Social Integration; CIQ-P = CIQ – Productivity; COWAT = Controlled Oral Word Association Test; CVLT = California Verbal Learning Test – II; EDSS = Expanded Disability Status Scale; FSS = Fatigue Severity
SC
Scale; RRMS = relapsing-remitting MS; PASAT = Paced Auditory Serial Addition Test; PDQ = Perceived Deficits Questionnaire; PMS = Progressive MS; VSCWT = Victoria Stroop Color-
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Word Test.
S0003-9993(15)00561-4
DOI:
10.1016/j.apmr.2015.07.003
Reference:
YAPMR 56247
To appear in:
ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
Received Date: 9 April 2015 Revised Date:
30 June 2015
Accepted Date: 6 July 2015
Please cite this article as: Hughes AJ, Hartoonian N, Parmenter B, Haselkorn JK, Lovera JF, Bourdette D, Turner AP, Cognitive Impairment and Community Integration Outcomes in Individuals Living with Multiple Sclerosis, ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION (2015), doi: 10.1016/ j.apmr.2015.07.003. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Running Head: Cognitive Impairment & Community Integration in MS Cognitive Impairment and Community Integration Outcomes in Individuals Living with
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Multiple Sclerosis
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Abbey J. Hughes, PhD1, 2
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Narineh Hartoonian, PhD2
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Brett Parmenter, PhD3
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Jodie K. Haselkorn, MD, MPH1,2,4
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Jesus F. Lovera, MSPH, MD5
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Dennis Bourdette, MD6,7
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Aaron P. Turner, PhD1, 2
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Department of Rehabilitation Medicine, University of Washington, Seattle, WA
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2
Multiple Sclerosis Center of Excellence West, Veterans Affairs Puget Sound Health Care
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System, Seattle Division, Seattle, WA
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Veterans Affairs Puget Sound Health Care System, American Lake Division, Tacoma, WA
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Department of Epidemiology, University of Washington, Seattle, WA
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Department of Neurology, Louisiana State University Health Science Center, New Orleans, LA
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Multiple Sclerosis Center of Excellence West, Veterans Affairs Portland Health Care System,
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Portland, OR
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OR
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Department of Neurology, School of Medicine, Oregon Health & Science University, Portland,
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Acknowledgements
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The work conducted in this manuscript has not been previously published, nor is it under
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consideration for publication elsewhere. However, we plan to present (poster presentation) the
3
results in February 2015 at the annual Rehabilitation Psychology Conference in San Diego, CA.
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The contents of this article were developed under grants from the Department of Veterans
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Affairs, Office of Research and Development, Rehabilitation Research and Development, Grant
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B4368R. The contents of this paper do not represent the view of the Department of Veterans
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Affairs of the US Government. In addition, the work reported in this manuscript was supported
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by a mentor-based fellowship grant from the National Multiple Sclerosis Society to Turner (PI),
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Grant MB 0026.
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10 Conflict of Interest
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We certify that no party having a direct interest in the results of the research supporting this
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article has or will confer a benefit on the authors or on any organization with which they are
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associated and we certify that all financial and material support for this research and work are
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clearly identified in the title page of the manuscript.
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Correspondence and reprint requests should be addressed to:
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Abbey J. Hughes, PhD
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NMSS Postdoctoral Research Fellow
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Department of Rehabilitation Medicine
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University of Washington
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325 Ninth Avenue, Box 359612
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Seattle, Washington 98104
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Email: [email protected]
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Telephone: (206) 221-5688
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Cognitive Impairment and Community Integration Outcomes in Individuals Living with
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Multiple Sclerosis
3 Abstract
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Objective. To determine the association between unique domains of cognitive impairment and
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community integration in individuals with multiple sclerosis (MS), and to determine the
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contributions of cognitive impairment to community integration beyond the influence of
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demographic and clinical variables.
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Design. Cross-sectional analysis of objective neuropsychological assessment and self-report
12
data. Data were collected during baseline assessment of a randomized multi-site controlled trial
13
of ginkgo biloba for cognitive impairment in MS. Hierarchical regression analyses examined the
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association between subjective and objective measures of cognitive impairment and three
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domains of community integration, adjusting for relevant covariates.
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Setting. Two VA medical center MS clinics.
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Participants. 121 adults (ages 24 to 65) with a confirmed MS diagnosis.
Interventions. Not applicable.
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Main Outcome Measures. Primary outcomes were scores on the Home Integration (CIQ-H),
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Social Integration (CIQ-S), and Productivity (CIQ-P) domains of the Community Integration
25
Questionnaire (CIQ).
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Results. Cognitive impairment was associated with lower scores on the CIQ-H and CIQ-S, but
28
not the CIQ-P. Greater levels of subjective cognitive impairment were associated with lower
29
scores on the CIQ-H and CIQ-S. Greater levels of objective cognitive impairment, specifically
30
slower processing speed and poorer inhibitory control, were related to lower CIQ-S scores.
31
Subjective and objective measures of cognitive impairment were significantly and independently
32
associated with CIQ-S.
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27
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Conclusions. Objective cognitive impairment may interfere with participation in social
35
activities. Subjective cognitive impairment is also important to assess, because individuals who
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perceive themselves to be cognitively impaired may be less likely to participate in both home
37
and social activities. Clinical interventions to enhance community integration in individuals with
38
MS may benefit from addressing objective and subjective cognitive impairment by integrating
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cognitive rehabilitation approaches with self-efficacy-enhancing strategies.
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Key words: multiple sclerosis, cognitive impairment, community integration
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List of Abbreviations: BDI = Beck Depression Inventory – II; CIQ = Community Integration
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Questionnaire; CIQ-H = CIQ – Home Integration; CIQ-S = CIQ – Social Integration; CIQ-P =
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CIQ – Productivity; COWAT = Controlled Oral Word Association Test; CVLT = California
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Verbal Learning Test – II; EDSS = Expanded Disability Status Scale; FSS = Fatigue Severity
47
Scale; MS = multiple sclerosis; RRMS = relapsing-remitting MS subtype; PASAT = Paced
48
Auditory Serial Addition Test; PDQ = Perceived Deficits Questionnaire; PMS = Progressive MS
49
subtype; VSCWT = Victoria Stroop Color-Word Test.
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Participation in daily roles, relationships, and activities, commonly known as community
52
integration, is an important outcome among neurorehabilitation populations, including
53
individuals with multiple sclerosis (MS).1-6 Community integration significantly contributes to
54
quality of life in people living with physical disabilities, even after controlling for disease and
55
disability severity.7 To date, research on community integration in MS has predominately
56
focused on employment,8-10 with few studies investigating other domains such as home, social,
57
educational, and vocational activities.11 Factors such as cognitive impairment may contribute to
58
diminished community integration in MS; however the relationship between cognitive
59
impairment and community integration remains poorly understood.
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Cognitive impairment affects 43 to 70% of individuals with MS12,13 and impacts a number of
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cognitive domains, including information processing speed, memory, verbal fluency, attention,
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working memory, and executive functions (e.g., inhibitory control). 12,14-24 Rao and colleagues
64
demonstrated that MS patients who were impaired on a neuropsychological assessment battery
65
were less likely to be employed than those without cognitive impairment. Although their work
66
was among the first to demonstrate a relationship between objective cognitive impairment and
67
community integration, the relationship between subjective cognitive impairment (i.e., an
68
individual’s perceptions and beliefs about their cognitive impairment) and community
69
integration has not been investigated. Moreover, it remains unclear whether there are differences
70
in community integration outcomes across different objective and subjective cognitive measures
71
and across different aspects of community integration.
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Willer and colleagues developed the Community Integration Questionnaire (CIQ)25 to assess
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three domains of community integration: participation in activities within a home-like setting
75
(Home Integration [CIQ-H]), integration into social relationships (Social Integration [CIQ-S]),
76
and regular performance of productive educational or vocational activities (Productivity [CIQ-
77
P]). The CIQ provides a brief, validated self-report assessment tool for evaluating total
78
community integration, as well as unique aspects of community integration in rehabilitation
79
populations.26 A study investigating the scope, nature, and impact of pain in MS found that
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greater pain was significantly associated with lower scores on the CIQ-P, but not the CIQ-H or
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CIQ-S subscale.11 Although the CIQ also yields a total score, results from this study of pain in
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MS suggest it may be more clinically useful to examine each CIQ domain separately. Despite the
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CIQ’s potential utility, no studies to date have examined the relationship between cognitive
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impairment and each domain of the CIQ in MS.
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The purpose of this study was to assess whether objective and subjective cognitive impairments
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are associated with lower levels of community integration on each subscale of the CIQ, after
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controlling for relevant demographics and clinical characteristics. Understanding differences in
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community integration outcomes across different cognitive domains and measurement modalities
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will help inform the design of future clinical interventions to enhance community integration and
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ultimately promote quality of life in MS.
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Methods
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Participants and Procedures
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This study was performed at two VA Medical Centers. Study procedures were approved by both
98
sites’ Institutional Review Boards. Participants were recruited as part of a previously reported
99
trial comparing the effects of ginkgo biloba versus placebo in individuals with MS.27 The present
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data were collected from participants at baseline, prior to randomization. Participants were
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recruited from both sites’ MS clinics, their affiliated university clinics, and their local
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communities. All participants provided written informed consent. Eligible participants were
103
required to have a physician-confirmed diagnosis of MS, disease stability for at least 30 days,
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and a score of at least one standard deviation below the mean of the normative sample on at least
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one objective cognitive test. Exclusion criteria included: severe depression symptoms, defined by
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a score greater than 28 on the Beck Depression Inventory – II (BDI),28 color-blindness, poor
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visual acuity, and current use of medications contraindicated for ginkgo biloba (e.g.,
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anticoagulant medications including coumadin).29 A total of 173 individuals were evaluated for
109
eligibility. Of those, 52 were excluded due to meeting one or more exclusion criteria or declining
110
participation after enrollment, yielding a final sample of 121 participants.
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Measures
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Cognitive impairment. The following objective measures were selected to assess the most
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common cognitive impairments observed in MS: the 2-second Paced Auditory Serial Addition
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Test (PASAT),30 a test of auditory working memory, attention, and processing speed; the long-
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delay free recall trial of the California Verbal Learning Test – II (CVLT),31 a measure of verbal
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memory; the Controlled Oral Word Association Test (COWAT),32 a speeded test of verbal
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ability and phonemic fluency; and the Color-Word subtest of the Victoria Stroop Color-Word
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Test (VSCWT),33 a measure of attention, processing speed, and inhibitory control. Participants’
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scores were converted to Z scores (M = 0, SD = 1.0) based on an age-matched normative
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sample, with higher scores indicating better performance. Subjective cognitive impairment was
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assessed using the Perceived Deficits Questionnaire (PDQ),34 a twenty-item Likert-type scale
123
that assesses how often various cognitive problems occurred in the past four weeks. This
124
measure has been validated for individuals with MS and demonstrates good internal consistency
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(Cronbach’s α = .93).35 Scores range from 0 to 80, with higher scores associated with greater
126
subjective cognitive impairment. Although the PDQ does not reliably correlate with objective
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measures of verbal memory and processing speed, the PDQ assesses important ways in which
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individuals perceive their cognitive impairment.36
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Community integration. Community integration was assessed using the CIQ,25,26 a fifteen-item
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self-report scale that assesses the how often and how independently an individual participates in
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various activities. The CIQ yields three subscale scores: Home Integration (i.e., participation in
133
home-based activities; CIQ-H), Social Integration (i.e., participation in social activities; CIQ-S),
134
and Productivity (i.e., participation in educational or vocational activities; CIQ-P). Although this
135
measure also yields a total CIQ score, the authors elected to examine the three subscales in order
136
to better understand which aspects of community integration are related to cognitive impairment
137
in MS. This measure has been validated in individuals with physical disabilities, including MS,
138
and demonstrates adequate internal consistency (Cronbach’s α = .75) and excellent test-retest
139
reliability (r = .91).37 Scores range from 0 to 10 for Home Integration, 0 to 12 for Social
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Integration, and 0 to 7 for Productivity, with higher scores associated with greater community
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integration. At present, a recommended cutoff score or minimally clinically important difference
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in scores has not been established.
143 Demographics. Participants were asked to report their age in years, sex (“Male” or “Female”),
145
and education level (i.e., “Less than or Equal to High School Diploma,” “Some College or
146
College Degree,” and “Greater than or Equal to Some Graduate School”).
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Clinical characteristics. Participants were asked to report their MS subtype and disease
149
duration. MS subtype was categorized as either relapsing-remitting (RRMS) or progressive
150
(PMS). Disease severity was determined by the Expanded Disability Status Scale (EDSS),38 a
151
quantitative measure of disability that ranges from 0 (no disability) to 10 (death due to MS).
152
Fatigue was assessed using the Fatigue Severity Scale (FSS),39 a nine-item Likert-type scale that
153
assesses the degree to which fatigue interferes with daily activities. This measure has been
154
recommended for use by the Multiple Sclerosis Taskforce of the American Physical Therapy
155
Association and has excellent internal consistency (Cronbach’s α = .94).40,41 Scores range from 9
156
to 63, with higher scores associated with greater levels of fatigue. Depressive symptoms were
157
measured using the BDI, a 21-item self-report measure corresponding to the criteria for clinical
158
depression as outlined in the Diagnosis and Statistical Manual of Mental Disorders – IV – Text
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Revision.28 This measure demonstrates excellent internal consistency (Cronbach’s α = .92).42
160
Scores on this measure range from 0 to 63, with higher total summary score reflecting greater
161
depressive symptom severity. Due to exclusion criteria, scores on this measure for the present
162
study ranged from 0 to 27 (Cronbach’s α = .86).
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Data Analysis
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Statistical analyses were carried out using IBM SPSS Statistics version 22. No univariate or
166
multivariate outliers were detected using histograms and Mahalanobis’ and Cooks’ distance
167
analyses respectively and assumptions regarding the normality of sampling distributions were
168
met using the Kolmogorov-Smirnov test (all ps >.05). Multicollinearity among variables in each
169
model was assessed using Tolerance (T) values and Variance Inflation Factor (VIF = 1/T) values
170
(critical value of 2.5).43 No VIF values exceeded 1.5.
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Correlational analyses were performed between potential covariates (i.e., demographics and
173
clinical characteristics), cognitive measures, and each CIQ outcome. Covariates that significantly
174
correlated with cognitive measures or CIQ outcomes (p < .05) were included in subsequent
175
hierarchical regression analyses. Only CIQ outcomes that correlated with at least one cognitive
176
measure were entered as outcome variables in hierarchical regression analyses. Significant
177
covariates were entered into the first step, significant objective cognitive measures (i.e., PASAT,
178
CVLT, COWAT, and/or VSCWT) were entered into the second step, and the PDQ (if
179
significant) was entered into the third step.
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181 182 183
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Results
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Participants
185
Descriptive statistics for all variables assessed are presented in Table 1. Fifty-five percent of the
186
sample was female and participants ranged between the ages of 24 and 65. Participants were
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generally highly educated, with the majority completing at least some college. Disease durations
188
ranged from 1 to 47 years. The majority of participants were ambulatory without requiring
189
mobility assistance (EDSS < 4.5). On average, the sample endorsed low levels of depression and
190
moderate levels of fatigue. Participants’ mean scores on objective cognitive measures (i.e., the
191
PASAT, CVLT, COWAT, and VSCWT) were below those of the normative sample. PDQ
192
ratings indicated moderate levels of subjective cognitive impairment.
193 194
[insert Table 1 here]
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Correlation Analyses
197
Correlations between potential covariates, cognitive impairment measures, and CIQ outcomes
198
are shown in Table 2. Female sex and the RRMS subtype were significantly associated with
199
higher scores on the CIQ-H (all ps < .01). Female sex, lower EDSS ratings, and lower scores on
200
the BDI and FSS were significantly associated with higher scores on the CIQ-S (all ps < .01).
201
Lower EDSS ratings were also associated with higher scores on the CVLT. Younger age and
202
shorter disease durations were significantly correlated with higher scores on the CIQ-P (i.e.,
203
greater integration in educational or vocational activities; all ps < .05). Higher scores on the BDI
204
and FSS were significantly related to higher scores on the PDQ (all ps < .001). Higher PDQ
205
scores were associated with lower participation scores on the CIQ-H and CIQ-S. Higher PASAT
206
scores were associated with higher CIQ-H scores, and higher VSCWT scores were associated
207
with higher CIQ-S scores. No cognitive measures significantly correlated with CIQ-P outcomes.
208
Thus, CIQ-P was not examined as an outcome in hierarchical regression analyses.
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209
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210
[insert Table 2 here]
211 Hierarchical Regression Analyses
213
The relationship between cognitive impairment and community integration outcomes differed
214
across domains (Table 3).
216
[insert Table 3 here]
217
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After controlling for sex, MS subtype, BDI, and FSS, the relationship between the PASAT and
219
CIQ-H was no longer significant (β = .15, t = 1.13, p = .260). The addition of the PASAT did not
220
significantly add to the variance in CIQ-H (∆R2 = .021, ∆F(1, 114) = 3.21, p = .076). The
221
addition of the PDQ accounted for an additional 3.7% of the variance in CIQ-H (∆R2 = .037,
222
∆F(1, 113) = 5.85, p = .017). In the final model, PDQ was the only cognitive impairment
223
measure significantly associated with CIQ-H, where a 4-point increase on the PDQ was
224
associated with a 1-point decrease on the CIQ-H (β = -.23, t = -2.42, p = .017). The final model
225
was statistically significant and explained 28.4% of the variance in CIQ-H (R2 = .284, F(6, 113)
226
= 7.47, p < .001).
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After controlling for sex, EDSS, BDI, and FSS, the addition of the VSCWT explained an
229
additional 6.8% of the variance in CIQ-S (∆R2 = ..068, ∆F(1, 115) = 10.29, p = .002). Higher
230
scores on the VSCWT were associated with higher scores on the CIQ-S (β = .27, t = 3.21, p =
231
.002). The addition of the PDQ accounted for an additional 3.8% of the variance in CIQ-S (∆R2 =
232
.038, ∆F(1, 114) = 6.09, p = .015). In the final model, both the VSCWT and the PDQ were
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significantly associated with CIQ-S, where higher scores on the VSCWT and lower scores on the
234
on the PDQ were associated with higher scores on the CIQ-S (VSCWT: β = .26, t = 3.25, p =
235
.002; PDQ: β = -.23, t = -2.47, p = .015). The final model was statistically significant and
236
explained 28.4% of the variance in CIQ-S (R2 = .284, F(6, 114) = 7.52, p < .001).
238 239
DISCUSSION
240
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This study investigated the relationship between cognitive impairment and community
242
integration in individuals with MS. Participants were assessed on four measures of objective
243
cognitive impairment, one measure of subjective cognitive impairment, and three domains of
244
community integration. Although results generally supported previous findings that cognitive
245
impairment is significantly associated with lower levels of community integration MS, this
246
relationship varied across domains of these constructs.
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Higher levels of subjective cognitive impairment on the PDQ were significantly associated with
249
less participation in activities within the home on the CIQ-H. No objective cognitive measures
250
were related to this domain of community integration. With regard to participation in social
251
activities, higher levels of impairment on the PDQ and worse objective cognitive performance on
252
the VSCWT were significantly associated with less social participation on the CIQ-S. No
253
cognitive measures were related to participation in educational or vocational activities on the
254
CIQ-P. Results suggest that after taking into account demographic and clinical characteristics,
255
objective cognitive impairments in processing speed and inhibitory control are related to
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256
diminished social integration, and subjective cognitive impairment is strongly associated with
257
diminished home and social integration. Additional research is needed to determine whether the
258
moderate effect sizes observed for these relationships warrant clinical significance.
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Similar to Rao’s findings,44 cognitive impairment was associated with disturbances in
261
community integration; however, none of the cognitive measures in the present study were
262
associated with participation in educational or vocational activities. For the present study, only
263
disease duration and age were related to CIQ-P. These results demonstrate that each domain of
264
the CIQ is distinct and should be assessed separately. A similar conclusion was supported in a
265
more recent study examining the subjective frequency and importance of community integration
266
among individuals with MS.5
267
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Results underscore the importance of incorporating baseline cognitive assessments in future
269
interventions aimed at improving community integration. For clinicians working with this
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population, such assessments may help to: 1) identify cognitive impairment as a potential risk
271
factor for suboptimal treatment outcomes; and 2) encourage the use of cognitive rehabilitation or
272
compensatory strategies to mitigate the negative impact of cognitive impairment on community
273
integration outcomes. Given that cognitive remediation strategies can lead to improved
274
community integration and ultimately enhance everyday functional skills in individuals with
275
traumatic brain injury,45,46 researchers have also begun to investigate cognitive impairment as a
276
modifiable risk factor in MS.12,47 A 2011 Cochrane review demonstrated that cognitive
277
rehabilitation interventions can support modest improvements in memory span, working
278
memory, and visual memory.48 Although it remains to be seen whether these improvements
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might also facilitate improvements in other domains of functioning, including community
280
integration, results from this study support a link between cognitive function and community
281
integration, and future research may help clarify whether community integration is modifiable
282
through improvements in cognitive function. For clinicians working to enhance community
283
integration among patients with cognitive impairment, a focus on strategies that match the
284
patient’s current level of function, and encourage cognitive rehabilitation strategies may be an
285
effective target.
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286
This study afforded several major strengths. It featured a multi-site design with a large sample of
288
community-dwelling individuals with MS. Unlike prior studies,44 this study employed validated
289
measures of subjective cognitive impairment, objective cognitive impairment, and community
290
integration. Given that community integration is increasingly being recognized as an important,
291
multidimensional outcome in MS, the present study adds to the present literature by identifying
292
cognitive impairment, particularly subjective cognitive impairment, as a potential risk factor for
293
diminished community integration. These results may translate to better clinical practice, where
294
early assessment of cognitive impairment and interventions aimed at promoting self-efficacy for
295
managing cognitive impairment may promote home and social integration.
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This study’s participants and measures comprised additional strengths. The study featured a
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heterogeneous sample with regard to demographics and clinical characteristics. Although males
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are typically underrepresented in MS research, this study provided roughly equal proportions of
300
men and women. Additionally, the inclusion of covariate measures provided the opportunity to
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301
assess the unique contributions of cognitive impairment to community integration beyond the
302
contributions of demographics and clinical characteristics.
303 Limitations
305
This study included a few limitations. First, participants in this sample had lower levels of
306
depression and lower levels of physical disability than have previously been reported in the MS
307
literature.49,50 Additionally, the sample was pre-selected for cognitive impairment. Given the
308
restricted ranges for these variables, results may not reflect those of the full MS population, and
309
underestimate the strength of the relationship between cognitive impairment and community
310
integration. Future research is needed to examine this relationship in samples with the full
311
spectrum of cognitive impairment and depressive symptoms. Second, this study featured a cross-
312
sectional design with correlational and regression analyses. Therefore, definitive causation
313
cannot be determined from this study. Third, this study employed univariate methods for pre-
314
selecting the variables to be included in hierarchical regression analyses. Despite its practical
315
advantages (e.g., elimination of unnecessary predictors, reduced computational burden), chance
316
associations and model overfitting may have occurred.51 Finally, because symptom validity and
317
performance validity measures were not included in this study, participant engagement and effort
318
during testing could not be fully assessed.52 Despite these limitations, this study has important
319
implications for the assessment of cognitive impairment and community integration and for the
320
design of future intervention trials.
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Conclusions
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For individuals with MS, subjective cognitive impairment was strongly correlated with home and
324
social activities. Objective impairments in processing speed and inhibitory control were strongly
325
correlated with social activities. Importantly, these relationships were independent of the effects
326
of demographics and clinical characteristics. Clinical interventions to enhance community
327
integration in individuals with MS may benefit from addressing objective and subjective
328
cognitive impairment by integrating cognitive rehabilitation approaches with self-efficacy-
329
enhancing strategies.
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Table 1 Descriptive statistics for demographics, clinical characteristics, cognitive impairment measures, and community integration outcomes %
Min
Demographics 24
Sex (Female)
66
54.5
7
5.8
87
71.9
27
22.3
≤ High School Some College/College Degree ≥ Some Graduate School Clinical Characteristics
RRMS PMS
65
52.08
9.08
78
64.5
43
35.5 1
47
20.10
11.71
0
7.5
4.10
1.92
0
27
9.77
6.71
9
63
49.50
11.05
PASAT
-3.37
1.63
-1.31
0.88
CVLT
-4.00
2.00
-0.52
1.19
COWAT
-2.81
1.77
-0.92
1.00
BDI FSS
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Disease Duration (years)
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SD
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Education Level
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Age
Max
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Objective Cognitive Impairment
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VSCWT
-6.14
1.50
-1.00
1.49
9
71
37.79
12.49
PDQ Community Integration
0
CIQ-S
3
CIQ-P
0
10
5.72
2.82
12
8.17
2.05
7
3.22
1.80
SC
CIQ-H
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Subjective Cognitive Impairment
Note. n = 121.
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Abbreviations: BDI = Beck Depression Inventory – II; CIQ = Community Integration Questionnaire; CIQ-H = CIQ – Home Integration; CIQ-S = CIQ – Social Integration; CIQ-P = CIQ – Productivity; COWAT = Controlled Oral Word Association Test; CVLT = California Verbal Learning Test – II; EDSS = Expanded Disability Status Scale; FSS = Fatigue Severity
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Scale; RRMS = relapsing-remitting MS subtype; PASAT = Paced Auditory Serial Addition Test; PDQ = Perceived Deficits Questionnaire; PMS = Progressive MS subtype; VSCWT =
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Victoria Stroop Color-Word Test.
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Table 2
PASAT
CVLT
COWAT
VSCWT
SC
Covariates
RI PT
Correlations between potential covariates, cognitive impairment measures, and community integration outcomes Cognitive Impairment Measures CIQ Outcomes PDQ
CIQ-H
CIQ-S
CIQ-P
-.05
.25†
.05
-.07
-.17
.02
.03
-.19*
Sex (Female = 0, Male = 1)
-.01
-.01
-.12
.07
-.01
-.41‡
-.25†
-.09
.05
.02
.01
-.05
.03
.08
.06
.06
-.16
-.12
-.11
-.19*
-.02
-.25†
-.01
-.12
Education Levela Clinical Characteristics
BDI FSS Cognitive Impairment Measures PASAT CVLT
.25†
.22
-.09
-.03
-.09
.07
-.28†
-.16
-.20*
-.10
-.08
.12
-.17
-.21*
-.17
EP
EDSS
.02
-.03
-.06
.04
-.19*
.40‡
-.17
-.27†
-.07
.03
.02
.11
-.01
.47‡
-.07
-.27†
-.01
.18*
-.04
.16
.07
.12
.04
AC C
Disease Duration (years)
TE D
MS Subtype (RRMS = 0, PMS = 1)
M AN U
Age
.
ACCEPTED MANUSCRIPT
.04
.05
-.17
VSCWT
.14
.29†
.05
-.23†
-.34‡
-.10
RI PT
COWAT
PDQ Note. n = 121; * p < .05 † p < .01; ‡ p < .001.
Spearmen’s rank-order correlations (otherwise Pearson’s product-moment correlations).
SC
a
M AN U
Abbreviations: BDI = Beck Depression Inventory – II; CIQ = Community Integration Questionnaire; CIQ-H = CIQ Home Integration; CIQ-S = CIQ Social Integration; CIQ-P = CIQ Productivity; COWAT = Controlled Oral Word Association Test; CVLT = California Verbal Learning Test – II; EDSS = Expanded Disability Status Scale; FSS = Fatigue Severity Scale; RRMS = Relapsing Remitting MS subtype; PASAT = Paced Auditory Serial Addition Test; PDQ = Perceived Deficits Questionnaire; PMS = Progressive MS
AC C
EP
TE D
subtype; VSCWT = Victoria Stroop Color-Word Test.
ACCEPTED MANUSCRIPT
Table 3 Hierarchical regression of covariates and cognitive impairment measures on community
CIQ-H Step 1 (Covariates)
df
F
4, 115
8.38‡
MS Subtype (RRMS = 0, PMS = 1)
M AN U
BDI FSS
Step 2 (Objective Cognitive Impairment) PASAT
CIQ-S
∆F
.23
8.38‡
6, 113
4, 116
7.47‡
7.47‡
AC C
-.36‡
-.15 -.01
.25
3.21 .15
.28
5.85* -.24*
6.27‡
.18
6.27‡ -.21*
Sex (Female = 0, Male = 1) EDSS
β
-.21*
EP
Step 1 (Covariates)
5, 114
TE D
Step 3 (Subjective Cognitive Impairment) PDQ
R2
SC
Sex (Female = 0, Male = 1)
RI PT
integration outcomes
-.14
BDI
-.17
FSS
-.19*
Step 2 (Cognitive Impairment Predictors)
5, 115
7.48‡
.25
10.29† .27†
VSCWT Step 3 (Subjective Cognitive Impairment)
6, 114
7.52‡
.28
6.09*
ACCEPTED MANUSCRIPT
-.23*
PDQ Note. n = 121; * p < .05 † p < .01; ‡ p < .001. Abbreviations: BDI = Beck Depression Inventory – II; CIQ = Community Integration
RI PT
Questionnaire; CIQ-H = CIQ – Home Integration; CIQ-S = CIQ – Social Integration; CIQ-P = CIQ – Productivity; COWAT = Controlled Oral Word Association Test; CVLT = California Verbal Learning Test – II; EDSS = Expanded Disability Status Scale; FSS = Fatigue Severity
SC
Scale; RRMS = relapsing-remitting MS; PASAT = Paced Auditory Serial Addition Test; PDQ = Perceived Deficits Questionnaire; PMS = Progressive MS; VSCWT = Victoria Stroop Color-
AC C
EP
TE D
M AN U
Word Test.