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. Author manuscript; available in PMC: 2024 Oct 1.
Published in final edited form as: J Aging Health. 2023 Jan 21;35(9):643–650. doi: 10.1177/08982643231153459

Association of Osteoarthritis and Functional Limitations With Cognitive Impairment Among Older Adults in the United States

Maxwell J Rakutt 1, Ryan A Mace 2, Caitlin E W Conley 3, Austin V Stone 3, Stephen T Duncan 3, Jonathan Greenberg 2, David C Landy 3, Ana-Maria Vranceanu 2, Cale A Jacobs 4
PMCID: PMC10940858  NIHMSID: NIHMS1970806  PMID: 36680455

Abstract

Objective:

Given overlapping pathophysiology, this study sought to assess the association between osteoarthritis (OA), functional impairment, and cognitive impairment in the aging population.

Methods:

The National Health and Nutrition Examination Survey was used to identify participants >60 years of age. We analyzed multivariable associations of grouped participants that underwent cognitive function testing using linear and logistic regression, adjusting for sex, age, race, and ethnicity.

Results:

Of 2776 identified participants representing a population of 50,242,917, 40% did not report OA or functional limitations; 21% had OA but not functional limitations; 15% did not have OA but had functional limitations; 17% had OA and related functional limitations; and 7% had OA and non-arthritic functional limitations. OA was not independently associated with cognitive impairment. Contrarily, functional limitations were associated with cognitive impairment regardless of OA diagnosis.

Discussion:

Cognitive impairment is not associated with OA, but rather functional limitations, potentially guiding future intervention.

Keywords: osteoarthritis, cognitive impairment, functional limitations, aging, dementia

Introduction

Cognitive impairment involves deficits in one or more cognitive domains, often evidenced by impairments in short-term memory, attention, orientation, judgment, and/or problem-solving on neuropsychological testing (Hebben & Milberg, 2009). Many factors are associated with cognitive impairment, such as a history of stroke (Lo Coco et al., 2016), heart failure (Cannon et al., 2017; Jinawong et al., 2021), smoking (Amini et al., 2021; Campos et al., 2016), sepsis (Iwashyna et al., 2010; Seidel et al., 2020), or social isolation (Griffin et al., 2020). Importantly for this discussion, systemic inflammation has also been identified as a risk factor for cognitive impairment among older adults (Pan et al., 2019; Wichmann et al., 2014). Given the inflammatory nature of osteoarthritis (OA) (Berenbaum, 2013), there is considerable interest in the possible association between OA and cognitive impairment.

OA is the most common articular disease globally, and is the source of significant pain, disability, and cost (Glyn-Jones et al., 2015). The initiation and progression of OA involves both local and systemic inflammation (Berenbaum, 2013; Greene & Loeser, 2015), potentially contributing to cognitive impairment. Studies have investigated the association between OA and cognitive impairment (Berenbaum, 2013; Chen et al., 2018; Huang et al., 2015; Innes & Sambamoorthi, 2020a, 2020b; Li et al., 2020; Mayburd & Baranova, 2019; Wang et al., 2018; Weber et al., 2019); however, many cite functional limitations as a possible confounding factor (Huang et al., 2015; Innes & Sambamoorthi, 2020a; Li et al., 2020). Evidence for functional limitations as a confounding factor is supported by previous research linking physical inactivity and cognitive impairment (Abbott et al., 2004; Chang et al., 2010; Imtiaz et al., 2014; Kivipelto et al., 2006). Further, it is known that activity restriction secondary to OA is positively associated with depressive symptoms (Lee et al., 2017), a risk factor for cognitive impairment. While these preliminary investigations have identified potential associations between OA and cognitive impairment, none controlled for or evaluated the possible contribution of functional limitations.

Thus, it remains unclear whether OA is independently associated with cognitive impairment when controlling for other risk factors such as age (Flier & Scheltens, 2005), sex (Sohn et al., 2018), race, ethnicity (Weuve et al., 2018; Zhang et al., 2016), and functional limitations. The purpose of this study was to assess the association between cognitive impairment, OA, and functional limitations when controlling for demographic risk factors. We hypothesized that OA would be independently associated with cognitive impairment.

Methods

Design

We used the National Health and Nutrition Examination Survey (NHANES) dataset within a cross-sectional study design to test the above hypothesis and to further evaluate for related associations. As this retrospective review utilized an anonymized database, the requirement for informed consent was waived.

Data Source

The NHANES dataset includes both interviews and physical examinations conducted by the National Center for Health Statistics under the Centers for Disease Control and Prevention, and consists of a nationally representative sample of 5000 United States citizens.

Survey Components

The NHANES dataset from 2011 to 2014 includes a cognitive functioning component for adults 60 years and older. Special assessments within this component include the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) word list learning and delayed recall tests, an animal fluency test, and a digit symbol substitution test.

The CERAD word list learning test assessed learning ability (Moms et al., 1989) in 3-phases, each with recitation and immediate recollection of a 10-word list. In the current study, the score from the first recall of the 3-phase CERAD word list learning assessment was used for analysis. The animal fluency tests were used to assess verbal (Sebaldt et al., 2009) and executive functioning skills (Rofes et al., 2020). Participants were asked to name as many animals as possible within 1 minute. Working memory, attention, and processing speed (Jaeger, 2018) were assessed with the digit symbol substitution test. In this test, participants were asked to match symbols to a provided array of numbers according to a key at the top of the page. Finally, recall memory (Moms et al., 1989) was assessed using the CERAD delayed recall test where participants were asked to recite the 10 words learned during the CERAD word learning test. The CERAD word learning, CERAD delayed recall (Tsoi et al., 2017), animal fluency (Vonk et al., 2020), and digit symbol substitution (Jaeger, 2018) tests are widely accepted for the evaluation of neurodegeneration or dementia.

Study Population and Grouping

In total, 3181 of 3472 participants 60 years or older completed the cognitive functioning component of NHANES and were included in the study. Participants were first grouped by whether they reported a diagnosis of OA by a health care provider. A total of 405 participants with other types of arthritis (347) or insufficient data (58) were excluded. Participants were then grouped by whether they had functional limitations, defined here as difficulty standing for an extended period of time or walking a quarter mile, and further by whether this limitation was due to their OA. This resulted in the creation of the five distinct groups: those with no OA and no functional limitations, those with no OA but functional limitations not related to arthritis, those with OA but no functional limitations, those with OA and functional limitations not attributable to arthritis, and those with OA and functional limitations attributable to arthritis.

Data Analysis

Cognitive impairment was assessed as both a dichotomous and continuous measure. As a dichotomous measure, performance not conditioned on age, sex, or education within the bottom quartile of each cognitive performance assessment was used to define cognitive impairment. This method is in accordance with existing literature examining cognitive impairment using NHANES data (Blaum et al., 2002; Brody et al., 2019). As a continuous measure, raw scores from performance testing were used in statistical analyses. Multivariable associations of patient group with cognitive function testing were performed with linear and logistic regression used to adjust for sex, age, race, and ethnicity. All analyses were performed using survey-specific statistics with incorporation of weighting and survey design characteristics to produce nationally representative estimate.

Results

In total, our study population comprised of 2776 unique participants with data representing a population of 50,242,917. Of this population, 19,865,293 (40%) did not report OA or functional limitations; 10,526,296 (21%) had OA but not functional limitations; 7,690,136 (15%) did not have OA but had functional limitations; 8,558,546 (17%) had OA and related functional limitations; and 3,602,645 (7%) had OA and functional limitations unrelated to their OA (Table 1).

Table 1.

Characteristics of NHANES Participants With Cognitive Function Testing by OA and Functional Limitation Grouping.

Characteristic No OA, No
Functional Limit
 No OA, Functional
Limits
 OA, No Functional
Limit
 OA, Functional Limit,
Arthritic
 OA, Functional Limit,
Not Arthritic
 p
Na = 19,865,293
 Na = 7,690,136
 Na = 10,526,296
 Na = 3,602,645
 Na = 8,558,546
N (%) N (%) N (%) N (%) N (%)
Sex
 Female 9.22 M (46) 3.62 M (47) 6.05 M (58) 2.34 M (65) 6.04 M (71)
 Male 10.6 M (54) 4.07 M (53) 4.47 M (42) 1.26 M (35) 2.52 M (29) <.001
Age
 60–64 years 8.14 M (41) 1.84 M (24) 3.01 M (29) 0.633 M (18) 2.49 M (29)
 65–69 years 4.97 M (25) 1.41 M (18) 2.83 M (27) 0.925 M (26) 1.60 M (19)
 70–74 years 3.42 M (17) 1.61 M (21) 2.10 M (20) 0.728 M (20) 1.46 M (17)
 75–79 years 1.64 M (8) 0.904 M (12) 1.27 M (12) 0.506 M (14) 1.05 M (12)
 80 years or older 1.70 M (9) 1.92 M (25) 1.31 M (12) 0.811 M (23) 1.95 M (23) <.001
Race and ethnicity
 White, non-Hispanic 15.3 M (77) 5.91 M (77) 9.01 M (86) 2.85 M (79) 6.78 M (79)
 Black, non-Hispanic 1.64 M (8) 0.701 M (9) 0.685 M (7) 0.423 M (12) 0.780 M (9)
 Hispanic 1.51 M (8) 0.645 M (8) 0.545 M (5) 0.226 M (6) 0.708 M (8)
 Other 1.46 M (7) 0.434 M (6) 0.284 M (3) 0.106 M (3) 0.292 M (3) <.001
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Some participants refused or did not know; Million (M).

a

Frequencies weighted by year w/wtmec2yr adjusted for inclusion of two cycles.

Compared to participants with no OA and no functional limitations, those with OA and no functional limitations, had similar cognitive function on the CERAD first recall (0.09 words, p-value (p) = 0.397), CERAD delayed recall (0.17 words, p = .222), and animal fluency (0.21 names, p = .563) tests but higher cognitive function on the digit substitution (2.39 matches, p = .005) test. Compared to participants with no OA and no functional limitations, those with no OA and functional limitations, had lower cognitive function on the CERAD first recall (−0.34 words, p < .001), CERAD delayed recall (−0.54 words, p = .002), animal fluency (−1.86 names, p < .001), and digit substitution (−5.65 matches, p < .001) tests. Compared to participants with OA and no functional limitations, those with OA and functional limitations related to their OA, had lower cognitive function on the CERAD first recall (−0.25 words, p = .014), CERAD delayed recall (−0.30 words, p = .069), animal fluency (−2.09 names, p < .001), and digit substitution (−7.94 matches, p < .001) tests. Compared to participants with OA and functional limitations from their arthritis, those with OA and functional limitations unrelated to their OA had similar cognitive function on the CERAD first recall (0.02 words, p = .917), CERAD delayed recall (−0.24 words, p = .304), animal fluency (0.40 names, p = .541), and digit substitution (1.07 match, p = .554) tests. These results were largely consistent with those where cognitive function was dichotomized into cognitive impairment (Table 1).

When controlling for age, sex, race, and ethnicity, OA did not appear to be independently associated with cognitive impairment. On the contrary, functional limitations, whether related to OA or not, were independently associated with cognitive impairment (Table 2). The group with OA and no functional impairment demonstrated similar odds ratios (range = 0.8–1.1) to the group with neither OA nor functional limitations (Reference group, odds ratios = 1.0). Odds ratios were, however, greater for the groups that reported functional limitations regardless of OA diagnosis (Table 2).

Table 2.

Association of OA/Function With Cognitive Impairment, Adjusted for Age, Sex, and Race.

Cognitive Impairment (Defined as Lowest Quartile)
First Recall OR
(95% CI)		 Delayed Recall OR
(95% CI)		 Animal Fluency OR
(95% CI)		 Digit Substitution OR
(95% CI)
No OA
No functional limit		 1.0 (Ref) 1.0 (Ref) 1.0 (Ref) 1.0 (Ref)
No OA
Functional limits		 1.7 (1.2–2.3) 1.8 (1.3–2.5) 2.1 (1.7–2.7) 2.5 (1.8–3.5)
OA
No functional limit		 1.0 (0.7–1.4) 0.8 (0.6–1.1) 1.1 (0.9–1.5) 1.1 (0.8–1.5)
OA
Functional limit, arthritic		 1.5 (1.1–2.0) 1.1 (0.7–1.7) 2.2 (1.7–3.0) 2.9 (2.1–3.9)
OA
Functional limit, not arthritic		 0.9 (0.5–1.4) 1.8 (1.0–3.0) 2.0 (1.1–3.5) 2.7 (1.6–4.7)
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Discussion

While inflammation plays a critical role in the initiation and progression of both OA and cognitive impairment, the NHANES data when adjusted for sex, age, race, ethnicity, and functional limitations does not show a significant association between the two disease processes. The development of cognitive impairment in individuals is not necessarily a slow, linear progression towards debilitating dementia. Individuals in the early stages of these diagnoses progress and regress along the continuum of cognitive impairment, providing incentive for the discovery of actionable risk reduction interventions. Each year, 7–8% of individuals with subjective cognitive impairment progress to mild cognitive impairment, while up to 44% of those diagnosed with mild cognitive impairment regress to normal (Gauthier et al., 2006).

To date, many population-based studies have evaluated risk factors for progression including age, education, sex, systolic blood pressure, and/or physical activity (Abbott et al., 2004; Chang et al., 2010; Imtiaz et al., 2014; Kivipelto et al., 2006). Previous studies have also evaluated the association between OA and forms of cognitive impairment, some suggesting that functional limitations secondary to OA contributed to the association. Within many of these studies, however, the effect of functional limitations on this association was not explored. The results from our study indicate that functional limitations, whether related to OA or not, are potentially the driver of this association. A recent meta-analysis indicated an increased risk of dementia and cognitive impairment in patients with OA (Guo et al., 2022). Subgroup analyses were conducted to investigate the effect of known confounding factors such as age, alcohol use, and tobacco use, however, the effects of functional impairment were not examined. In a longitudinal study of U.S. Medicare beneficiaries, Innes et. al (Innes & Sambamoorthi, 2020a) concluded that OA was associated with an increased risk of Alzheimer’s related dementia but noted that physical inactivity was a possible confounder within the study design. A longitudinal cohort study from Taiwan discussed the potential influence of functional disability on the discovered association between OA and dementia but again did not incorporate this into the study design (Huang et al., 2015). Two more case-control studies were found to evaluate similar associations (Chen et al., 2018; Wang et al., 2018). Potentially due to limited data, analyses of the potential contribution of functional limitations have not been previously conducted. Our study adds to this literature by examining the effect of functional limitations on the potential correlation between cognitive impairment and OA.

In this nationally representative sample, older adults with functional limitations had approximately a one to three-fold greater odds of cognitive impairment evident on neuropsychological testing. This association was independent of OA diagnosis and demographic variables (age, sex, race, and ethnicity). Loss of independence is a hallmark of dementia and neurodegenerative disorders. The association between functional limitations and cognitive impairment has been widely documented at earlier stages of decline (Brown et al., 2011; Castilla-Rilo et al., 2007; Gold, 2012; Mansbach & Mace, 2019; Marshall et al., 2015; Royall et al., 2007). Our population-based study adds to this literature by providing further evidence that subtle functional limitations detectable in healthy older adults are associated with cognitive impairment (Andrews et al., 2017; Farias et al., 2013). Functional changes can occur 10 years before these diagnoses (Fauth et al., 2013; Pérès et al., 2008). Cognitive impairment and functional limitations in older adults are linked to several adverse outcomes, including greater disability (Farias et al., 2013), poorer quality of life (Andersen et al., 2004), overutilization (Andrews et al., 2017), and premature nursing home placement (Fogel et al., 2000). Taken together, earlier identification and treatment of co-occurring cognitive impairment and functional limitations may greatly benefit older patients.

These results highlight the need to study specific interventions that reduce functional limitations and improve physical activity amongst at-risk older adults, both with and without OA diagnosis. Older adults face several barriers to being more physically active, including chronic pain and other comorbidities, anxiety, depression, lack of social support, and limited access to equipment. Programs that gradually increase walking are safe, preferred by older adults (Prohaska et al., 2009; Stubbs et al., 2013), and beneficial for improving both physical and cognitive function (Brach & VanSwearingen, 2013; Falck et al., 2019), including those with OA (Talbot et al., 2003). Recent studies have attempted to maximize benefits from possible interventions. A meta-analysis conducted to determine whether programs combining physical and cognitive activity improved cognitive health more than physical activity alone suggested these interventions to be synergistic (Gheysen et al., 2018). The modalities investigated were broad and included dance and tai-chi which were suggested to be particularly beneficial as they combine both cognitive and physical activity. Mind-body practices can complement walking programs by teaching older adults skills to overcome behavioral challenges of cognitive impairment and functional limitations while reengaging in valued activities. The recently developed Active Brains (Mace, Gates, Bullard et al., 2021) program for older adults pairs mind-body skills with paced walking using a digital monitoring device, and has shown excellent feasibility and acceptability, as well as improvements in multimodal physical, cognitive, and emotional functioning (Mace, Doorley et al., 2021; Mace, Gates, Popok et al., 2021). A recent study utilizing input from experts and end-users compared various qualities of similar combined physical and cognitive activity programs (Marent et al., 2022) providing more specific guidance for new interventions. Future RCTs with long term follow-up are needed to determine whether increased physical activity during interventions can protect against future cognitive decline in at-risk older adults.

This study had several limitations. The study was cross-sectional and therefore unable to determine whether functional limitations predict cognitive decline or if modifying functional limitations could have a protective effect. Although we controlled for basic demographics, we were unable to comprehensively assess the influence of other important variables such as disease duration, disease modulators, depression, cardiovascular risk factors for cognitive decline, or family history of dementia. Although outside of the scope of the current study, further investigation into the effects of these demographics are warranted. During these cycles, NHANES did not include measures of systemic inflammation, so we were unable to incorporate such measures into our analyses. We included age and other factors as covariates but did not examine potential interaction effects. Although consistent with approaches within the literature (Blaum et al., 2002; Brody et al., 2019), the metric used to dichotomize results from performance testing served as an arbitrary metric to compare the various groups and was not recalculated after controlling for possible confounders. Clinical diagnoses related to cognitive impairment vary between patients and clinicians. The use of performance on accepted cognitive assessments is one of many modalities in de-termining this pathology and thus might introduce inherent bias. NHANES data utilized in the study relies on patient provided information, which might introduce bias especially in patients with severe arthritis, cognitive impairment, or functional limitations. These limitations were counterbalanced by the strengths of the study which included the large, nationally-representative sample and the use of multi-domain cognitive assessments given that memory and executive functioning show differential associations with different functional abilities (Mansbach & Mace, 2019).

Conclusion

OA, independent of functional limitations, does not appear to be overtly associated with cognitive impairment. Functional limitations are associated with cognitive impairment regardless of OA and independent of age, sex, race, and ethnicity. These results further support interventions to reduce functional limitations and improve physical activity amongst older adults, irrespective of OA diagnosis.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Ana-Maria Vranceanu, PhD –Support for this study comes from National Center for Complementary and Integrative Health (R34AT010370 [MPIs Jacobs and Vranceanu] and R01AG075899 [PI Vranceanu]); Cale A. Jacobs, PhD–Support for this study comes from R34AT010370 (MPIs Jacobs and Vranceanu).

Footnotes

Declaration of Conflicting Interests

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Austin V. Stone, PhD – American Orthopaedic Society for Sports Medicine and Arthroscopy Association of North America committee member. Consultee for Smith & Nephew and Allo-Source; Stephen T. Duncan – Consultee and research grantee for Smith & Nephew, consultee, and research grantee for BoneSupport, consultee for Heraeus, consultee for OrthAlign, stock owner of MiCare, research grantee for Medtronic, research grantee for Stryker, and research grantee for Zimmer/Biomet.

References

  1. Abbott RD, White LR, Ross GW, Masaki KH, Curb JD, & Petrovitch H (2004). Walking and dementia in physically capable elderly men. JAMA, 292(12), 1447–1453. 10.1001/jama.292.12.1447 [DOI] [PubMed] [Google Scholar]
  2. Amini R, Sahli M, & Ganai S (2021). Cigarette smoking and cognitive function among older adults living in the community. Neuropsychology, Development, and Cognition. Section B, Aging, Neuropsychology and Cognition, 28(4), 616–631. 10.1080/13825585.2020.1806199 [DOI] [PubMed] [Google Scholar]
  3. Andersen CK, Wittrup-Jensen KU, Lolk A, Andersen K, & Kragh-Sørensen P (2004). Ability to perform activities of daily living is the main factor affecting quality of life in patients with dementia. Health and Quality of Life Outcomes, 2(1), 52. 10.1186/1477-7525-2-52 [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Andrews JS, Desai U, Kirson NY, Enloe CJ, Ristovska L, King S, Birnbaum HG, Fleisher AS, Ye W, & Kahle-Wrobleski K (2017). Functional limitations and health care resource utilization for individuals with cognitive impairment without dementia: Findings from a United States population-based survey. Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring, 6(1), 65–74. 10.1016/j.dadm.2016.11.005 [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Berenbaum F. (2013). Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthritis and Cartilage, 21(1), 16–21. 10.1016/j.joca.2012.11.012 [DOI] [PubMed] [Google Scholar]
  6. Blaum CS, Ofstedal MB, & Liang J (2002). Low cognitive performance, comorbid disease, and task-specific disability: Findings from a nationally representative survey. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 57(8), M523–M531. 10.1093/gerona/57.8.M523 [DOI] [PubMed] [Google Scholar]
  7. Brach JS, & VanSwearingen JM (2013). Interventions to improve walking in older adults. Current Translational Geriatrics and Experimental Gerontology Reports, 2(4), 230–238. 10.1007/s13670-013-0059-0 [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Brody D, Kramarow E, Tayor C, & McGuire L (2019). Cognitive performance in adults aged 60 and over: National health and nutrition examination survey, 2011–2014 (p. 126). [PubMed] [Google Scholar]
  9. Brown PJ, Devanand DP, Liu X, & Caccappolo E Alzheimer’s Disease Neuroimaging Initiative. (2011). Functional impairment in elderly patients with mild cognitive impairment and mild Alzheimer disease. Archives of General Psychiatry, 68(6), 617–626. 10.1001/archgenpsychiatry.2011.57 [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Campos MW, Serebrisky D, & Castaldelli-Maia JM (2016). Smoking and cognition. Current Drug Abuse Reviews, 9(2), 76–79. 10.2174/1874473709666160803101633 [DOI] [PubMed] [Google Scholar]
  11. Cannon JA, Moffitt P, Perez-Moreno AC, Walters MR, Broomfield NM, McMurray JJV, & Quinn TJ (2017). Cognitive impairment and heart failure: Systematic review and meta-analysis. Journal of Cardiac Failure, 23(6), 464–475. 10.1016/j.cardfail.2017.04.007 [DOI] [PubMed] [Google Scholar]
  12. Castilla-Rilo J, López-Arrieta J, Bermejo-Pareja F, Ruiz M, Sánchez-Sánchez F, & Trincado R (2007). Instrumental activities of daily living in the screening of dementia in population studies: A systematic review and meta-analysis. International Journal of Geriatric Psychiatry, 22(9), 829–836. 10.1002/gps.1747 [DOI] [PubMed] [Google Scholar]
  13. Chang M, Jonsson PV, Snaedal J, Bjornsson S, Saczynski JS, Aspelund T, Eiriksdottir G, Jonsdottir MK, Lopez OL, Harris TB, Gudnason V, & Launer LJ (2010). The effect of midlife physical activity on cognitive function among older adults: AGES—Reykjavik study. The Journals of Gerontology: Series A, 65A(12), 1369–1374. 10.1093/gerona/glq152 [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Chen K-T, Chen Y-C, Fan Y-H, Lin W-X, Lin W-C, Wang Y-H, Lin L, Chiou J-Y, & Wei JC-C (2018). Rheumatic diseases are associated with a higher risk of dementia: A nation-wide, population-based, case-control study. International Journal of Rheumatic Diseases, 21(2), 373–380. 10.1111/1756-185X.13246 [DOI] [PubMed] [Google Scholar]
  15. Falck RS, Davis JC, Best JR, Crockett RA, & Liu-Ambrose T (2019). Impact of exercise training on physical and cognitive function among older adults: A systematic review and meta-analysis. Neurobiology of Aging, 79(3 Pt 2), 119–130. 10.1016/j.neurobiolaging.2019.03.007 [DOI] [PubMed] [Google Scholar]
  16. Farias ST, Chou E, Harvey DJ, Mungas D, Reed B, DeCarli C, Park LQ, & Beckett L (2013). Longitudinal trajectories of everyday function by diagnostic status. Psychology and Aging, 28(4), 1070–1075. 10.1037/a0034069 [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Fauth EB, Schwartz S, Tschanz JT, Østbye T, Corcoran C, & Norton MC (2013). Baseline disability in activities of daily living predicts dementia risk even after controlling for baseline global cognitive ability and depressive symptoms. International Journal of Geriatric Psychiatry, 28(6), 597–606. 10.1002/gps.3865 [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Flier WM van der., & Scheltens P (2005). Epidemiology and risk factors of dementia. Journal of Neurology, Neurosurgery & Psychiatry, 76(suppl 5), v2–v7. 10.1136/jnnp.2005.082867 [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Fogel JF, Hyman RB, Rock B, & Wolf-Klein G (2000). Predictors of hospital length of stay and nursing home placement in an elderly medical population. Journal of the American Medical Directors Association, 1(5), 202–210. [PubMed] [Google Scholar]
  20. Gauthier S, Reisberg B, Zaudig M, Petersen RC, Ritchie K, Broich K, Belleville S, Brodaty H, Bennett D, Chertkow G, Cummings JL, de Leon M, Feldman H, Ganguli M, Hampel H, Scheltens P, Tierney MC, Whitehouse P, & Winblad B International Psychogeriatric Association Expert Conference on mild cognitive impairment (2006). Mild cognitive impairment. Lancet, 367(9518), 1262–1270. 10.1016/S0140-6736(06)68542-5 [DOI] [PubMed] [Google Scholar]
  21. Gheysen F, Poppe L, DeSmet A, Swinnen S, Cardon G, De Bourdeaudhuij I, Chastin S, & Fias W (2018). Physical activity to improve cognition in older adults: Can physical activity programs enriched with cognitive challenges enhance the effects? A systematic review and meta-analysis. International Journal of Behavioral Nutrition and Physical Activity, 15(1), 63. 10.1186/s12966-018-0697-x [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Glyn-Jones S, Palmer AJR, Agricola R, Price AJ, Vincent TL, Weinans H, & Carr AJ (2015). Osteoarthritis. Lancet, 386(9991), 376–387. 10.1016/S0140-6736(14)60802-3 [DOI] [PubMed] [Google Scholar]
  23. Gold DA (2012). An examination of instrumental activities of daily living assessment in older adults and mild cognitive impairment. Journal of Clinical and Experimental Neuropsychology, 34(1), 11–34. 10.1080/13803395.2011.614598 [DOI] [PubMed] [Google Scholar]
  24. Greene MA, & Loeser RF (2015). Aging-related inflammation in osteoarthritis. Osteoarthritis and Cartilage, 23(11), 1966–1971. 10.1016/j.joca.2015.01.008 [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Griffin SC, Mezuk B, Williams AB, Perrin PB, & Rybarczyk BD (2020). Isolation, not loneliness or cynical hostility, predicts cognitive decline in older Americans. Journal of Aging and Health, 32(1–2), 52–60. 10.1177/0898264318800587 [DOI] [PubMed] [Google Scholar]
  26. Guo R, Ou Y-N, Hu H-Y, Ma Y-H, Tan L, & Yu J-T (2022). The association between osteoarthritis with risk of dementia and cognitive impairment: A meta-analysis and systematic review. Journal of Alzheimer’s Disease, 89(4), 1159–1172. 10.3233/JAD-220568 [DOI] [PubMed] [Google Scholar]
  27. Hebben N, & Milberg W (2009). Essentials of neuropsychological assessment. Wiley. [Google Scholar]
  28. Huang S-W, Wang W-T, Chou L-C, Liao C-D, Liou T-H, & Lin H-W (2015). Osteoarthritis increases the risk of dementia: A nationwide cohort study in Taiwan. Scientific Reports, 5(1), 10145. 10.1038/srep10145 [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Imtiaz B, Tolppanen A-M, Kivipelto M, & Soininen H (2014). Future directions in Alzheimer’s disease from risk factors to prevention. Biochemical Pharmacology, 88(4), 661–670. 10.1016/j.bcp.2014.01.003 [DOI] [PubMed] [Google Scholar]
  30. Innes KE, & Sambamoorthi U (2020a). The association of osteoarthritis and related pain burden to incident Alzheimer’s disease and related dementias: A retrospective cohort study of U.S. Medicare beneficiaries. Journal of Alzheimer’s Disease, 75(3), 789–805. 10.3233/JAD-191311 [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Innes KE, & Sambamoorthi U (2020b). The potential contribution of chronic pain and common chronic pain conditions to subsequent cognitive decline, new onset cognitive impairment, and incident dementia: A systematic review and conceptual model for future research. Journal of Alzheimer’s Disease, 78(3), 1177–1195. 10.3233/JAD-200960 [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Iwashyna TJ, Ely EW, Smith DM, & Langa KM (2010). Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA, 304(16), 1787–1794. 10.1001/jama.2010.1553 [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Jaeger J. (2018). Digit symbol substitution test: The case for sensitivity over specificity in neuropsychological testing. Journal of Clinical Psychopharmacology, 38(5), 513–519. 10.1097/JCP.0000000000000941 [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Jinawong K, Apaijai N, Chattipakorn N, & Chattipakorn SC (2021). Cognitive impairment in myocardial infarction and heart failure. Acta Physiologica, 232(1), Article e13642. 10.1111/apha.13642 [DOI] [PubMed] [Google Scholar]
  35. Kivipelto M, Ngandu T, Laatikainen T, Winblad B, Soininen H, & Tuomilehto J (2006). Risk score for the prediction of dementia risk in 20 years among middle aged people: A longitudinal, population-based study. Lancet Neurology, 5(9), 735–741. 10.1016/S1474-4422(06)70537-3 [DOI] [PubMed] [Google Scholar]
  36. Lee JE, Martire LM, Zarit SH, & Rovine MJ (2017). Activity restriction and depressive symptoms in older couples. Journal of Aging and Health, 29(7), 1251–1267. 10.1177/0898264316660413 [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Li X, Tong Q, Gao J, Liu C, & Liu Y (2020). Alzheimer’s disease neuroimaging initiative, & liu, YOsteoarthritis was associated with a faster decline in hippocampal volumes in cognitively normal older people. Frontiers in Aging Neuroscience, 12, 190. 10.3389/fnagi.2020.00190 [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Lo Coco D, Lopez G, & Corrao S (2016). Cognitive impairment and stroke in elderly patients. Vascular Health and Risk Management, 12, 105–116. 10.2147/VHRM.S75306 [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Mace RA, Doorley JD, Popok PJ, & Vranceanu A-M (2021a). Live video adaptations to a mind-body activity program for chronic pain and cognitive decline: Protocol for the virtual active Brains study. JMIR Research Protocols, 10(1), Article e25351. 10.2196/25351 [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Mace RA, Gates MV, Bullard B, Lester EG, Silverman H, Quiroz YT, & Vranceanu A-M (2021b). Development of a novel mind-body activity and pain management program for older adults with cognitive decline. The Gerontologist, 61(3), 449–459. 10.1093/geront/gnaa084 [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Mace RA, Gates MV, Popok PJ, Kulich R, Quiroz YT, & Vranceanu A-M (2021c). Feasibility trial of a mind-body activity pain management program for older adults with cognitive decline. The Gerontologist, 61(8), 1326–1337. 10.1093/geront/gnaa179 [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Mansbach WE, & Mace RA (2019). Predicting functional dependence in mild cognitive impairment: Differential contributions of memory and executive functions. The Gerontologist, 59(5), 925–935. 10.1093/geront/gny097 [DOI] [PubMed] [Google Scholar]
  43. Marent P-J, Vangilbergen A, Chastin S, Cardon G, van Uffelen JGZ, & Beeckman M (2022). Conceptualization of a cognitively enriched walking program for older adults: A co-design study with experts and end users. BMC Geriatrics, 22(1), 167. 10.1186/s12877-022-02823-z [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Marshall GA, Zoller AS, Lorius N, Amariglio RE, Locascio JJ, Johnson KA, Sperling RA, & Rentz DM (2015). Functional activities questionnaire items that best discriminate and predict progression from clinically normal to mild cognitive impairment. Current Alzheimer Research, 12(5), 493–502. 10.2174/156720501205150526115003 [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Mayburd AL, & Baranova A (2019). Increased lifespan, decreased mortality, and delayed cognitive decline in osteoarthritis. Scientific Reports, 9(1), 18639. 10.1038/s41598-019-54867-8 [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Moms JC, Heyman A, Mohs RC, Hughes JP, Belle G van, Fillenbaum G, Mellits ED, & Clark C (1989). The Consortium to establish a Registry for Alzheimer’s disease (CERAD). Part I. Clinical and neuropsychological assesment of Alzheimer’s disease. Neurology, 39(9), 1159–1159. 10.1212/WNL.39.9.1159 [DOI] [PubMed] [Google Scholar]
  47. Pan H, Huang X, Li F, Ren M, Zhang J, Xu M, & Wu M (2019). Association among plasma lactate, systemic inflammation, and mild cognitive impairment: A community-based study. Neurological Sciences, 40(8), 1667–1673. 10.1007/s10072-019-03900-9 [DOI] [PubMed] [Google Scholar]
  48. Pérès K, Helmer C, Amieva H, Orgogozo J-M, Rouch I, Dartigues J-F, & Barberger-Gateau P (2008). Natural history of decline in instrumental activities of daily living performance over the 10 years preceding the clinical diagnosis of dementia: A prospective population-based study. Journal of the American Geriatrics Society, 56(1), 37–44. 10.1111/j.1532-5415.2007.01499.x [DOI] [PubMed] [Google Scholar]
  49. Prohaska TR, Eisenstein AR, Satariano WA, Hunter R, Bayles CM, Kurtovich E, Kealey M, & Ivey SL (2009). Walking and the preservation of cognitive function in older populations. The Gerontologist, 49(S1), S86–S93. 10.1093/geront/gnp079 [DOI] [PubMed] [Google Scholar]
  50. Rofes A, de Aguiar V, Jonkers R, Oh SJ, DeDe G, & Sung JE (2020). What drives task performance during animal fluency in people with Alzheimer’s disease? Frontiers in Psychology, 11, 1485. 10.3389/fpsyg.2020.01485 [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Royall DR, Lauterbach EC, Kaufer D, Malloy P, Coburn KL, & Black KJ Committee on Research of the American Neuropsychiatric Association. (2007). The cognitive correlates of functional status: A review from the committee on research of the American Neuropsychiatric Association. The Journal of Neuropsychiatry and Clinical Neurosciences, 19(3), 249–265. 10.1176/jnp.2007.19.3.249 [DOI] [PubMed] [Google Scholar]
  52. Sebaldt R, Dalziel W, Massoud F, Tanguay A, Ward R, Thabane L, Melnyk P, Landry P-A, & Lescrauwaet B (2009). Detection of cognitive impairment and dementia using the animal fluency test: The DECIDE study. Canadian Journal of Neurological Sciences, 36(5), 599–604. 10.1017/S0317167100008106 [DOI] [PubMed] [Google Scholar]
  53. Seidel G, Gaser C, Götz T, Günther A, & Hamzei F (2020). Accelerated brain ageing in sepsis survivors with cognitive long-term impairment. The European Journal of Neuroscience, 52(10), 4395–4402. 10.1111/ejn.14850 [DOI] [PubMed] [Google Scholar]
  54. Sohn D, Shpanskaya K, Lucas JE, Petrella JR, Saykin AJ, Tanzi RE, Samatova NF, & Doraiswamy PM (2018). Sex differences in cognitive decline in subjects with high likelihood of mild cognitive impairment due to Alzheimer’s disease. Scientific Reports, 8(1), 7490. 10.1038/s41598-018-25377-w [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Stubbs B, Binnekade TT, Soundy A, Schofield P, Huijnen IPJ, & Eggermont LHP (2013). Are older adults with chronic musculoskeletal pain less active than older adults without pain? A systematic review and meta-analysis. Pain Medicine, 14(9), 1316–1331. 10.1111/pme.12154 [DOI] [PubMed] [Google Scholar]
  56. Talbot LA, Gaines JM, Huynh TN, & Metter EJ (2003). A home-based pedometer-driven walking program to increase physical activity in older adults with osteoarthritis of the knee: A preliminary study. Journal of the American Geriatrics Society, 51(3), 387–392. 10.1046/j.1532-5415.2003.51113.x [DOI] [PubMed] [Google Scholar]
  57. Tsoi KKF, Chan JYC, Hirai HW, Wong A, Mok VCT, Lam LCW, Kwok TCY, & Wong SYS (2017). Recall tests are effective to detect mild cognitive impairment: A systematic review and meta-analysis of 108 diagnostic studies. Journal of the American Medical Directors Association, 18(9), 807. 10.1016/j.jamda.2017.05.016 [DOI] [PubMed] [Google Scholar]
  58. Vonk JMJ, Twait EL, Scholten RJPM, & Geerlings MI (2020). Cross-sectional associations of amyloid burden with semantic cognition in older adults without dementia: A systematic review and meta-analysis. Mechanisms of Ageing and Development, 192, 111386. 10.1016/j.mad.2020.111386 [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Wang J-H, Wu Y-J, Tee BL, & Lo RY (2018). Medical comorbidity in Alzheimer’s disease: A nested case-control study. Journal of Alzheimer’s Disease, 63(2), 773–781. 10.3233/JAD-170786 [DOI] [PubMed] [Google Scholar]
  60. Weber A, Mak S hung, Berenbaum F, Sellam J, Zheng Y-P, Han Y, & Wen C (2019). Association between osteoarthritis and increased risk of dementia: A systemic review and meta-analysis. Medicine, 98(10), Article e14355. 10.1097/MD.0000000000014355 [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Weuve J, Barnes LL, Mendes de Leon CF, Rajan KB, Beck T, Aggarwal NT, Hebert LE, Bennett DA, Wilson RS, & Evans DA (2018). Cognitive aging in black and white Americans: Cognition, cognitive decline, and incidence of Alzheimer disease dementia. Epidemiology, 29(1), 151–159. 10.1097/EDE.0000000000000747 [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Wichmann MA, Cruickshanks KJ, Carlsson CM, Chappell R, Fischer ME, Klein BEK, Klein R, Tsai MY, & Schubert CR (2014). Long-term systemic inflammation and cognitive impairment in a population-based cohort. Journal of the American Geriatrics Society, 62(9), 1683–1691. 10.1111/jgs.12994 [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Zhang Z, Hayward MD, & Yu Y-L (2016). Life course pathways to racial disparities in cognitive impairment among older Americans. Journal of Health and Social Behavior, 57(2), 184–199. 10.1177/0022146516645925 [DOI] [PMC free article] [PubMed] [Google Scholar]

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