Association Between Knee Extension Strength and Cognitive Function in Older Adults With Type 2 Diabetes: a cross sectional study. Running Title

Association Between Knee Extension Strength and Cognitive Function in Older Adults With Type 2 Diabetes: a cross sectional study. 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Running Title Takahiro Nonaka, Kono Kenichi, Go Owari, Yuto Watabe, Minoru Takemoto, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8728780/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Cognitive impairment is a frequent and clinically important complication in older adults with type 2 diabetes. Reduced muscle strength is common in this population and may be associated with cognitive function; however, evidence from routine clinical settings remains limited. Methods: This cross-sectional study included 42 older adults with type 2 diabetes. Knee extension strength normalized to body weight was assessed using a handheld dynamometer. Cognitive function was evaluated using a standardized cognitive assessment. Multivariable linear regression analyses were performed to examine the association between knee extension strength and cognitive function after adjusting for relevant demographic and clinical confounders. Results: Knee extension strength was significantly associated with cognitive function. In multivariable regression analysis, knee extension strength remained independently associated with cognitive performance after adjustment for potential confounders. The inclusion of knee extension strength substantially improved the explanatory power of the regression model. Conclusions: Lower knee extension strength was independently associated with poorer cognitive function in older adults with type 2 diabetes. Assessment of lower extremity muscle strength may provide clinically relevant information when evaluating cognitive health in this population. Type 2 diabetes cognitive function muscle strength sarcopenia aging Introduction Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cognitive impairment and dementia in older adults [1–3]. Proposed mechanisms include chronic hyperglycemia, insulin resistance, vascular dysfunction, and systemic inflammation [4–6]. However, these metabolic factors alone do not fully explain individual differences in cognitive outcomes among people with T2DM [7]. Muscle strength, particularly in the lower extremities, is a key determinant of mobility, physical function, and metabolic health in older adults [8,9]. Emerging evidence suggests that muscle strength may also be linked to brain health through multiple pathways, including improved insulin sensitivity, reduced inflammation, and increased secretion of neurotrophic factors such as brain-derived neurotrophic factor (BDNF) [10–12]. Importantly, muscle strength relative to body weight may be more functionally relevant than absolute strength, especially in older adults with heterogeneous body composition and adiposity [13]. However, few studies have examined the association between relative lower-limb muscle strength and cognitive function in older adults with T2DM. Therefore, the aim of this study was to investigate whether knee extension strength relative to body weight is independently associated with cognitive function in older adults with T2DM, after accounting for age, glycemic control, and visceral adiposity. Methods Study Design and Participants This cross-sectional study included 42 older adults with diagnosed T2DM. Participants were recruited from outpatient clinical settings. Individuals with severe neurological disorders or inability to complete physical or cognitive assessments were excluded. Measurements Cognitive Function Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA), a widely used screening tool for mild cognitive impairment [14]. Muscle Strength and Physical Performance Knee extension strength was measured using standardized procedures and normalized to body weight (knee extension strength/body weight). Physical performance was assessed using the Short Physical Performance Battery (SPPB) and the six-minute walk test. Metabolic and Body Composition Measures HbA1c, fasting blood glucose, C-peptide, estimated glomerular filtration rate (eGFR), and visceral fat area were obtained using standard clinical and imaging methods. Statistical Analysis Continuous variables were summarized as mean ± standard deviation or median [interquartile range], depending on distribution. Hierarchical multiple regression analyses were performed with MoCA score as the dependent variable. Models were constructed sequentially: age-only model, muscle-adjusted model, metabolic-adjusted model (HbA1c), and visceral fat model. Statistical significance was set at p < 0.05. Ethics and Approval Statement This study was approved by the Ethics Committee of the International University of Health and Welfare Narita Hospital (approval number: 25-CN-011). The study was conducted in accordance with the Declaration of Helsinki, and written informed consent was obtained from all participants, or the study was carried out based on publicly available information, as approved by the ethics committee. Clinical trial number: not applicable. Results Baseline characteristics of participants are shown in Table 1. Participants had a mean age of 72.8 years, with a median diabetes duration of 9 years. The median MoCA score was 22, indicating a high prevalence of cognitive impairment. Results of the hierarchical regression analyses are presented in Table 2. Age was significantly associated with cognitive function in all models. After adjusting for age, knee extension strength/body weight was positively associated with MoCA score (β = 8.34, p = 0.032). This association remained significant after further adjustment for HbA1c (β = 8.32, p = 0.034). HbA1c itself was not significantly associated with cognitive function. Visceral fat area showed a trend toward a negative association with MoCA score, but this did not reach statistical significance. Discussion The present study demonstrated that knee extension strength relative to body weight was independently associated with cognitive function in older adults with type 2 diabetes. Notably, the inclusion of knee extension strength substantially improved the explanatory power of the regression model, suggesting that lower-limb muscle strength may play an important role in cognitive health beyond traditional diabetes-related factors. One plausible mechanism is that greater muscle strength reflects higher levels of habitual physical activity, which has been shown to improve cerebral blood flow and cognitive performance in older adults [15,16]. Additionally, skeletal muscle functions as an endocrine organ, releasing myokines such as irisin and BDNF that exert neuroprotective effects [11,17]. The lack of a significant association between HbA1c and cognitive function in this study aligns with previous findings indicating that long-term metabolic burden and physical function may be more relevant determinants of late-life cognitive outcomes than short-term glycemic control [18,19]. The observed trend toward a negative association between visceral fat area and cognitive function further supports the role of adiposity-related inflammation and insulin resistance in cognitive decline [20]. From a clinical perspective, these findings suggest that interventions aimed at preserving or improving lower-limb muscle strength—such as resistance training—may represent a feasible and effective strategy to mitigate cognitive decline in older adults with T2DM [21,22]. Limitations The cross-sectional design precludes causal inference, and longitudinal studies are warranted to confirm the directionality of these associations [23]. Declarations Conflicts of Interest No potential conflict of interest relevant to this article was reported. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Author Contribution T.N contributed to the conception and design of the study; acquisition, analysis, and interpretation of the data; drafting of the manuscript; and final approval of the version to be published.K.K, Y.N, and M.T contributed to the conception and design of the study and critically revised the manuscript for important intellectual content.Y.W and G.O contributed to data acquisition.K.K and Y. N also provided methodological and statistical advice during data analysis and interpretation.M. T, as a medical doctor, was responsible for patient safety and clinical oversight throughout the study.All authors approved the final manuscript and agree to be accountable for all aspects of the work. Acknowledgments None. Data Availability The datasets generated and/or analyzed during the current study are not publicly available due to ethical restriction and the protection of participant privacy, but are available from the corresponding author on reasonable request. References Biessels GJ, Staekenborg S, Brunner E, Brayne C, Scheltens P. Risk of dementia in diabetes mellitus: A systematic review. Lancet Neurol 2006;5:64–74. Cheng G, Huang C, Deng H, Wang H. Diabetes as a risk factor for dementia and mild cognitive impairment: A meta-analysis of longitudinal studies. Neurology 2012;79:1132–1139. Crane PK, Walker R, Hubbard RA, Li G, Nathan DM, Zheng H, et al. Glucose levels and risk of dementia. N Engl J Med 2013;369:540–548. Strachan MWJ, Reynolds RM, Marioni RE, Price JF. Cognitive function, dementia and type 2 diabetes mellitus in the elderly. Diabetologia 2011;54:1681–1690. Kullmann S, Heni M, Fritsche A, Preissl H. Insulin action in the human brain: Evidence from neuroimaging studies. Nat Rev Endocrinol 2016;12:723–735. Craft S. Insulin resistance and Alzheimer’s disease pathogenesis: Potential mechanisms and implications for treatment. Lancet Neurol 2009;8:778–788. Exalto LG, Biessels GJ, Karter AJ, Huang ES, Quesenberry CP Jr, Whitmer RA. Risk score for prediction of 10-year dementia risk in individuals with type 2 diabetes: A cohort study. Diabetes Care 2014;37:2240–2247. Newman AB, Kupelian V, Visser M, Simonsick EM, Goodpaster BH, Nevitt M, et al. Strength, but not muscle mass, is associated with mortality in the Health, Aging and Body Composition Study cohort. J Am Geriatr Soc 2006;54:173–181. Bohannon RW. Hand-grip dynamometry predicts future outcomes in aging adults. J Geriatr Phys Ther 2008;31:3–10. Cotman CW, Berchtold NC. Exercise: A behavioral intervention to enhance brain health and plasticity. Trends Neurosci 2007;30:464–472. Pedersen BK. Muscle as a secretory organ. Physiol Rev 2012;92:1379–1406. Erickson KI, Voss MW, Prakash RS, Basak C, Szabo A, Chaddock L, et al. Exercise training increases size of hippocampus and improves memory. Proc Natl Acad Sci U S A 2011;108:3017–3022. Newman AB, Haggerty CL, Goodpaster B, Harris T, Kritchevsky S, Nevitt M, et al. Strength and muscle quality in a well-functioning cohort of older adults: The Health, Aging and Body Composition Study. J Gerontol A Biol Sci Med Sci 2003;58:M431–M437. Nasreddine ZS, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I, et al. The Montreal Cognitive Assessment, MoCA: A brief screening tool for mild cognitive impairment. J Am Geriatr Soc 2005;53:695–699. Colcombe S, Kramer AF. Fitness effects on the cognitive function of older adults: A meta-analytic study. Psychol Sci 2003;14:125–130. Barnes DE, Yaffe K, Satariano WA, Tager IB. A longitudinal study of cardiorespiratory fitness and cognitive function in healthy older adults. Arch Neurol 2003;60:135–140. Wrann CD, White JP, Salogiannnis J, Laznik-Bogoslavski D, Wu J, Ma D, et al. Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway. Cell Metab 2013;18:649–659. Yaffe K, Falvey CM, Hamilton N, Schwartz AV, Simonsick EM, Satterfield S, et al. Diabetes, glucose control, and 9-year cognitive decline among older adults without dementia. Arch Neurol 2012;69:1170–1175. Ravona-Springer R, Schnaider-Beeri M. The association of diabetes and dementia and possible implications for nondiabetic populations. Expert Rev Neurother 2011;11:1609–1617. Gustafson DR. Adiposity and cognitive decline: Underlying mechanisms. Int J Obes (Lond) 2008;32 Suppl 6:S53–S58. Liu-Ambrose T, Nagamatsu LS, Graf P, Beattie BL, Ashe MC, Handy TC. Resistance training and executive functions: A 12-month randomized controlled trial. Arch Intern Med 2010;170:170–178. Cassilhas RC, Viana VAR, Grassmann V, Santos RT, Santos RF, Tufik S, et al. The impact of resistance exercise on the cognitive function of the elderly. Med Sci Sports Exerc 2007;39:1401–1407. Sabia S, Dugravot A, Dartigues JF, Abell J, Elbaz A, Kivimäki M, et al. Physical activity, cognitive decline, and risk of dementia: 28-year follow-up of Whitehall II cohort study. BMJ 2017;356:i6536. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8728780","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":587243469,"identity":"4d0883e9-44ae-489c-9a33-b2c7b3c0856c","order_by":0,"name":"Takahiro Nonaka","email":"data:image/png;base64,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","orcid":"","institution":"International University of Health and Welfare Narita Hospital","correspondingAuthor":true,"prefix":"","firstName":"Takahiro","middleName":"","lastName":"Nonaka","suffix":""},{"id":587243470,"identity":"d7d0868f-5406-43b5-a534-0ccdc875e6e4","order_by":1,"name":"Kono Kenichi","email":"","orcid":"","institution":"International University of Health and Welfare Okawa Campus","correspondingAuthor":false,"prefix":"","firstName":"Kono","middleName":"","lastName":"Kenichi","suffix":""},{"id":587243471,"identity":"485cfcad-bfa5-4797-b63b-d2399885d648","order_by":2,"name":"Go Owari","email":"","orcid":"","institution":"International University of Health and Welfare Narita Hospital","correspondingAuthor":false,"prefix":"","firstName":"Go","middleName":"","lastName":"Owari","suffix":""},{"id":587243472,"identity":"764f2e33-0ffa-497f-a516-188616f6897a","order_by":3,"name":"Yuto Watabe","email":"","orcid":"","institution":"International University of Health and Welfare Narita Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yuto","middleName":"","lastName":"Watabe","suffix":""},{"id":587243473,"identity":"08fa66b4-4432-4208-af68-01fd290d7cb2","order_by":4,"name":"Minoru Takemoto","email":"","orcid":"","institution":"International University of Health and Welfare Narita Hospital","correspondingAuthor":false,"prefix":"","firstName":"Minoru","middleName":"","lastName":"Takemoto","suffix":""},{"id":587243474,"identity":"6c04c238-33ec-4bad-8f74-2d28c0fd54c5","order_by":5,"name":"Yusuke Nishida","email":"","orcid":"","institution":"International University of Health and Welfare Narita Campus","correspondingAuthor":false,"prefix":"","firstName":"Yusuke","middleName":"","lastName":"Nishida","suffix":""}],"badges":[],"createdAt":"2026-01-29 08:08:38","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8728780/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8728780/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":102397203,"identity":"041b77a4-2503-49ac-a141-097f846b363a","added_by":"auto","created_at":"2026-02-11 10:10:22","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":412542,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8728780/v1/e60b479a-c97e-407d-b76e-6c18e2d8d9dd.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Association Between Knee Extension Strength and Cognitive Function in Older Adults With Type 2 Diabetes: a cross sectional study. Running Title","fulltext":[{"header":"Introduction","content":"\u003cp\u003eType 2 diabetes mellitus (T2DM) is associated with an increased risk of cognitive impairment and dementia in older adults [1\u0026ndash;3]. Proposed mechanisms include chronic hyperglycemia, insulin resistance, vascular dysfunction, and systemic inflammation [4\u0026ndash;6]. However, these metabolic factors alone do not fully explain individual differences in cognitive outcomes among people with T2DM [7].\u003c/p\u003e \u003cp\u003eMuscle strength, particularly in the lower extremities, is a key determinant of mobility, physical function, and metabolic health in older adults [8,9]. Emerging evidence suggests that muscle strength may also be linked to brain health through multiple pathways, including improved insulin sensitivity, reduced inflammation, and increased secretion of neurotrophic factors such as brain-derived neurotrophic factor (BDNF) [10\u0026ndash;12].\u003c/p\u003e \u003cp\u003eImportantly, muscle strength relative to body weight may be more functionally relevant than absolute strength, especially in older adults with heterogeneous body composition and adiposity [13]. However, few studies have examined the association between relative lower-limb muscle strength and cognitive function in older adults with T2DM.\u003c/p\u003e \u003cp\u003eTherefore, the aim of this study was to investigate whether knee extension strength relative to body weight is independently associated with cognitive function in older adults with T2DM, after accounting for age, glycemic control, and visceral adiposity.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design and Participants\u003c/h2\u003e \u003cp\u003eThis cross-sectional study included 42 older adults with diagnosed T2DM. Participants were recruited from outpatient clinical settings. Individuals with severe neurological disorders or inability to complete physical or cognitive assessments were excluded.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eMeasurements\u003c/h3\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eCognitive Function\u003c/h2\u003e \u003cp\u003eCognitive function was assessed using the Montreal Cognitive Assessment (MoCA), a widely used screening tool for mild cognitive impairment [14].\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eMuscle Strength and Physical Performance\u003c/h3\u003e\n\u003cp\u003eKnee extension strength was measured using standardized procedures and normalized to body weight (knee extension strength/body weight). Physical performance was assessed using the Short Physical Performance Battery (SPPB) and the six-minute walk test.\u003c/p\u003e\n\u003ch3\u003eMetabolic and Body Composition Measures\u003c/h3\u003e\n\u003cp\u003eHbA1c, fasting blood glucose, C-peptide, estimated glomerular filtration rate (eGFR), and visceral fat area were obtained using standard clinical and imaging methods.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eContinuous variables were summarized as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or median [interquartile range], depending on distribution. Hierarchical multiple regression analyses were performed with MoCA score as the dependent variable. Models were constructed sequentially: age-only model, muscle-adjusted model, metabolic-adjusted model (HbA1c), and visceral fat model. Statistical significance was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eEthics and Approval Statement\u003c/h3\u003e\n\u003cp\u003e This study was approved by the Ethics Committee of the International University of Health and Welfare Narita Hospital (approval number: 25-CN-011). The study was conducted in accordance with the Declaration of Helsinki, and written informed consent was obtained from all participants, or the study was carried out based on publicly available information, as approved by the ethics committee.\u003c/p\u003e \u003cp\u003eClinical trial number: not applicable.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eBaseline characteristics of participants are shown in Table\u0026nbsp;1. Participants had a mean age of 72.8 years, with a median diabetes duration of 9 years. The median MoCA score was 22, indicating a high prevalence of cognitive impairment.\u003c/p\u003e \u003cp\u003eResults of the hierarchical regression analyses are presented in Table\u0026nbsp;2. Age was significantly associated with cognitive function in all models. After adjusting for age, knee extension strength/body weight was positively associated with MoCA score (β\u0026thinsp;=\u0026thinsp;8.34, p\u0026thinsp;=\u0026thinsp;0.032). This association remained significant after further adjustment for HbA1c (β\u0026thinsp;=\u0026thinsp;8.32, p\u0026thinsp;=\u0026thinsp;0.034). HbA1c itself was not significantly associated with cognitive function. Visceral fat area showed a trend toward a negative association with MoCA score, but this did not reach statistical significance.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe present study demonstrated that knee extension strength relative to body weight was independently associated with cognitive function in older adults with type 2 diabetes. Notably, the inclusion of knee extension strength substantially improved the explanatory power of the regression model, suggesting that lower-limb muscle strength may play an important role in cognitive health beyond traditional diabetes-related factors.\u003c/p\u003e \u003cp\u003eOne plausible mechanism is that greater muscle strength reflects higher levels of habitual physical activity, which has been shown to improve cerebral blood flow and cognitive performance in older adults [15,16]. Additionally, skeletal muscle functions as an endocrine organ, releasing myokines such as irisin and BDNF that exert neuroprotective effects [11,17].\u003c/p\u003e \u003cp\u003eThe lack of a significant association between HbA1c and cognitive function in this study aligns with previous findings indicating that long-term metabolic burden and physical function may be more relevant determinants of late-life cognitive outcomes than short-term glycemic control [18,19]. The observed trend toward a negative association between visceral fat area and cognitive function further supports the role of adiposity-related inflammation and insulin resistance in cognitive decline [20].\u003c/p\u003e \u003cp\u003eFrom a clinical perspective, these findings suggest that interventions aimed at preserving or improving lower-limb muscle strength\u0026mdash;such as resistance training\u0026mdash;may represent a feasible and effective strategy to mitigate cognitive decline in older adults with T2DM [21,22].\u003c/p\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eThe cross-sectional design precludes causal inference, and longitudinal studies are warranted to confirm the directionality of these associations [23].\u003c/p\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eConflicts of Interest\u003c/h2\u003e \u003cp\u003eNo potential conflict of interest relevant to this article was reported.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eT.N contributed to the conception and design of the study; acquisition, analysis, and interpretation of the data; drafting of the manuscript; and final approval of the version to be published.K.K, Y.N, and M.T contributed to the conception and design of the study and critically revised the manuscript for important intellectual content.Y.W and G.O contributed to data acquisition.K.K and Y. N also provided methodological and statistical advice during data analysis and interpretation.M. T, as a medical doctor, was responsible for patient safety and clinical oversight throughout the study.All authors approved the final manuscript and agree to be accountable for all aspects of the work.\u003c/p\u003e\u003ch2\u003eAcknowledgments\u003c/h2\u003e \u003cp\u003eNone.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets generated and/or analyzed during the current study are not publicly available due to ethical restriction and the protection of participant privacy, but are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003e Biessels GJ, Staekenborg S, Brunner E, Brayne C, Scheltens P. Risk of dementia in diabetes mellitus: A systematic review. Lancet Neurol 2006;5:64\u0026ndash;74.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Cheng G, Huang C, Deng H, Wang H. Diabetes as a risk factor for dementia and mild cognitive impairment: A meta-analysis of longitudinal studies. Neurology 2012;79:1132\u0026ndash;1139.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Crane PK, Walker R, Hubbard RA, Li G, Nathan DM, Zheng H, et al. Glucose levels and risk of dementia. N Engl J Med 2013;369:540\u0026ndash;548.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Strachan MWJ, Reynolds RM, Marioni RE, Price JF. Cognitive function, dementia and type 2 diabetes mellitus in the elderly. Diabetologia 2011;54:1681\u0026ndash;1690.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Kullmann S, Heni M, Fritsche A, Preissl H. Insulin action in the human brain: Evidence from neuroimaging studies. Nat Rev Endocrinol 2016;12:723\u0026ndash;735.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Craft S. Insulin resistance and Alzheimer\u0026rsquo;s disease pathogenesis: Potential mechanisms and implications for treatment. Lancet Neurol 2009;8:778\u0026ndash;788.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Exalto LG, Biessels GJ, Karter AJ, Huang ES, Quesenberry CP Jr, Whitmer RA. Risk score for prediction of 10-year dementia risk in individuals with type 2 diabetes: A cohort study. Diabetes Care 2014;37:2240\u0026ndash;2247.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Newman AB, Kupelian V, Visser M, Simonsick EM, Goodpaster BH, Nevitt M, et al. Strength, but not muscle mass, is associated with mortality in the Health, Aging and Body Composition Study cohort. J Am Geriatr Soc 2006;54:173\u0026ndash;181.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Bohannon RW. Hand-grip dynamometry predicts future outcomes in aging adults. J Geriatr Phys Ther 2008;31:3\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Cotman CW, Berchtold NC. Exercise: A behavioral intervention to enhance brain health and plasticity. Trends Neurosci 2007;30:464\u0026ndash;472.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Pedersen BK. Muscle as a secretory organ. Physiol Rev 2012;92:1379\u0026ndash;1406.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Erickson KI, Voss MW, Prakash RS, Basak C, Szabo A, Chaddock L, et al. Exercise training increases size of hippocampus and improves memory. Proc Natl Acad Sci U S A 2011;108:3017\u0026ndash;3022.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Newman AB, Haggerty CL, Goodpaster B, Harris T, Kritchevsky S, Nevitt M, et al. Strength and muscle quality in a well-functioning cohort of older adults: The Health, Aging and Body Composition Study. 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BMJ 2017;356:i6536.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Type 2 diabetes, cognitive function, muscle strength, sarcopenia, aging","lastPublishedDoi":"10.21203/rs.3.rs-8728780/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8728780/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground:\u003c/h2\u003e \u003cp\u003eCognitive impairment is a frequent and clinically important complication in older adults with type 2 diabetes. Reduced muscle strength is common in this population and may be associated with cognitive function; however, evidence from routine clinical settings remains limited.\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e \u003cp\u003eThis cross-sectional study included 42 older adults with type 2 diabetes. Knee extension strength normalized to body weight was assessed using a handheld dynamometer. Cognitive function was evaluated using a standardized cognitive assessment. Multivariable linear regression analyses were performed to examine the association between knee extension strength and cognitive function after adjusting for relevant demographic and clinical confounders.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e \u003cp\u003eKnee extension strength was significantly associated with cognitive function. In multivariable regression analysis, knee extension strength remained independently associated with cognitive performance after adjustment for potential confounders. The inclusion of knee extension strength substantially improved the explanatory power of the regression model.\u003c/p\u003e\u003ch2\u003eConclusions:\u003c/h2\u003e \u003cp\u003eLower knee extension strength was independently associated with poorer cognitive function in older adults with type 2 diabetes. Assessment of lower extremity muscle strength may provide clinically relevant information when evaluating cognitive health in this population.\u003c/p\u003e","manuscriptTitle":"Association Between Knee Extension Strength and Cognitive Function in Older Adults With Type 2 Diabetes: a cross sectional study. 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