Grip Strength, Gait Speed and Plasma Markers of Neurodegeneration in Asymptomatic Middle-aged and Older Adults
Tóm tắt
Pragmatic biomarkers of preclinical dementia would allow for easy and large-scale screening of risk in populations. Physical function measures like grip strength and gait speed are potential predictive biomarkers but their relationship with plasma markers of Alzheimer’s Disease and neurodegeneration have not been elucidated. To examine association between physical function measures and plasma markers of Alzheimer’s Disease (AD) and neurodegeneration. Cross-sectional and longitudinal analyses. Community-based cohort in the city of Framingham, Massachusetts. 2336 participants of the Framingham Heart Study Offspring cohort with an average age of 61. Plasma Aβ40 and Aβ42 were measured in 1998–2001 (Exam-7) and plasma total tau measured 5 years later (Exam-8). Grip strength, fast walk speed and chair stand speed were measured at both exams. Quantification of Aβ isoforms in plasma was performed using INNO-BIA assays and plasma total-tau was measured using Quanterix Simoa HD-1 assay. Confounder-adjusted linear regression models examined associations between physical function and plasma markers. Grip strength at Exam-7 was associated with plasma Aβ40 (β −0.006, p-value 0.032) at Exam-7 and plasma total-tau (β −0.010, p-value 0.001) at Exam-8. Grip strength and fast walk speed at Exam-8 were associated with plasma total-tau at Exam-8 (GS: β −0.009, p 0.0005; FWS: β −0.226, p-value <0.0001). Chair stand speed was not associated with plasma markers; Aβ42 was not associated with function. Grip strength and fast walk speed are associated with plasma markers of neurodegeneration in dementia-free middle aged and older individuals. Both these measures could be used as potential screening tools for identifying individuals at a higher risk for AD and related dementias alongside other validated markers.
Tài liệu tham khảo
Fantoni ER, Chalkidou A, JT OB, Farrar G, Hammers A. A Systematic Review and Aggregated Analysis on the Impact of Amyloid PET Brain Imaging on the Diagnosis, Diagnostic Confidence, and Management of Patients being Evaluated for Alzheimer’s Disease. J Alzh Dis. 2018;63(2):783–96.
Aschenbrenner AJ, Gordon BA, Benzinger TLS, Morris JC, Hassenstab JJ. Influence of tau PET, amyloid PET, and hippocampal volume on cognition in Alzheimer disease. Neurology. 2018;91(9):e859–e66.
Jack CR, Jr., Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et al. NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease. Alzheimers Dement. 2018;14(4):535–62.
Albers MW, Gilmore GC, Kaye J, Murphy C, Wingfield A, Bennett DA, et al. At the interface of sensory and motor dysfunctions and Alzheimer’s disease. Alzheimers Dement. 2015;11(1):70–98.
Beauchet O, Allali G, Launay C, Herrmann FR, Annweiler C. Gait variability at fast-pace walking speed: a biomarker of mild cognitive impairment? The journal of nutrition, health & aging. 2013;17(3):235–9.
Verghese J, Wang C, Lipton RB, Holtzer R. Motoric cognitive risk syndrome and the risk of dementia. J Gerontol A Biol Sci Med Sci. 2013;68(4):412–8.
Dumurgier J, Artaud F, Touraine C, Rouaud O, Tavernier B, Dufouil C, et al. Gait Speed and Decline in Gait Speed as Predictors of Incident Dementia. J Gerontol A Biol Sci Med Sci: Series A. 2017;72(5):655–61.
Buracchio T, Dodge HH, Howieson D, Wasserman D, Kaye J. The trajectory of gait speed preceding mild cognitive impairment. Arch Neurol. 2010;67(8):980–6.
Camargo EC, Weinstein G, Beiser AS, Tan ZS, DeCarli C, Kelly-Hayes M, et al. Association of Physical Function with Clinical and Subclinical Brain Disease: The Framingham Offspring Study. J Alzh Res. 2016;53(4):1597–608.
del Campo N, Payoux P, Djilali A, Delrieu J, Hoogendijk EO, Rolland Y, et al. Relationship of regional brain β-amyloid to gait speed. Neurology. 2016;86(1):36–43.
Lalonde R, Fukuchi K, Strazielle C. Neurologic and motor dysfunctions in APP transgenic mice. Rev Neurosci. 2012;23(4):363–79.
Wang H, He J, Zhang R, Zhu S, Wang J, Kong L, et al. Sensorimotor gating and memory deficits in an APP/PS1 double transgenic mouse model of Alzheimer’s disease. Behavioural brain research. 2012;233(1):237–43.
Wennberg AMV, Savica R, Hagen CE, Roberts RO, Knopman DS, Hollman JH, et al. Cerebral Amyloid Deposition Is Associated with Gait Parameters in the Mayo Clinic Study of Aging. J Am Geriatr Soc. 2017;65(4):792–9.
Wennberg AMV, Lesnick TG, Schwarz CG, Savica R, Hagen CE, Roberts RO, et al. Longitudinal Association Between Brain Amyloid-Beta and Gait in the Mayo Clinic Study of Aging. J Gerontol A Biol Sci Med Sci. 2018;73(9):1244–50.
Nadkarni NK, Perera S, Snitz BE, Mathis CA, Price J, Williamson JD, et al. Association of Brain Amyloid-beta With Slow Gait in Elderly Individuals Without Dementia: Influence of Cognition and Apolipoprotein E epsilon4 Genotype. JAMA neurology. 2017;74(1):82–90.
Nakamura T, Kawarabayashi T, Seino Y, Hirohata M, Nakahata N, Narita S, et al. Aging and APOE-epsilon4 are determinative factors of plasma Abeta42 levels. Ann Clin Transl Neurol. 2018;5(10):1184–91.
Janelidze S, Stomrud E, Palmqvist S, Zetterberg H, van Westen D, Jeromin A, et al. Plasma beta-amyloid in Alzheimer’s disease and vascular disease. Sci Rep. 2016;6:26801.
Fan LY, Tzen KY, Chen YF, Chen TF, Lai YM, Yen RF, et al. The Relation Between Brain Amyloid Deposition, Cortical Atrophy, and Plasma Biomarkers in Amnesic Mild Cognitive Impairment and Alzheimer’s Disease. Front Aging Neurosci. 2018;10:175.
Koyama A, Okereke OI, Yang T, Blacker D, Selkoe DJ, Grodstein F. Plasma amyloid-β as a predictor of dementia and cognitive decline: a systematic review and meta-analysis. Archives of neurology. 2012;69(7):824–31.
Chouraki V, Beiser A, Younkin L, Preis SR, Weinstein G, Hansson O, et al. Plasma amyloid-β and risk of Alzheimer’s disease in the Framingham Heart Study. Alzheimer’s & dementia: the journal of the Alzheimer’s Association. 2015;11(3):249–57.e1.
Roeben B, Maetzler W, Vanmechelen E, Schulte C, Heinzel S, Stellos K, et al. Association of Plasma Aβ40 Peptides, But Not Aβ42, with Coronary Artery Disease and Diabetes Mellitus. J Alzh Dis. 2016;52(1):161–9.
Gabelle A, Schraen S, Gutierrez LA, Pays C, Rouaud O, Buée L, et al. Plasma β-amyloid 40 levels are positively associated with mortality risks in the elderly. Alzheimers Dement. 2015;11(6):672–80.
Gomis M, Sobrino T, Ois A, Millán M, Rodríguez-Campello A, Pérez de la Ossa N, et al. Plasma beta-amyloid 1–40 is associated with the diffuse small vessel disease subtype. Stroke. 2009;40(10):3197–201.
van der Kant R, Goldstein LSB, Ossenkoppele R. Amyloid-β-independent regulators of tau pathology in Alzheimer disease. Nat Rev Neurosci. 2020;21(1):21–35.
Blennow K, Dubois B, Fagan AM, Lewczuk P, de Leon MJ, Hampel H. Clinical utility of cerebrospinal fluid biomarkers in the diagnosis of early Alzheimer’s disease. Alzheimers Dement. 2015;11(1):58–69.
Buerger K, Ewers M, Pirttilä T, Zinkowski R, Alafuzoff I, Teipel SJ, et al. CSF phosphorylated tau protein correlates with neocortical neurofibrillary pathology in Alzheimer’s disease. Brain. 2006;129(Pt 11):3035–41.
Chen Z, Mengel D, Keshavan A, Rissman RA, Billinton A, Perkinton M, et al. Learnings about the complexity of extracellular tau aid development of a blood-based screen for Alzheimer’s disease. Alzheimers Dement. 2019;15(3):487–96.
Zetterberg H, Wilson D, Andreasson U, Minthon L, Blennow K, Randall J, et al. Plasma tau levels in Alzheimer’s disease. Alzheimers Res Ther. 2013;5(2):9.
Fossati S, Ramos Cejudo J, Debure L, Pirraglia E, Sone JY, Li Y, et al. Plasma tau complements CSF tau and P-tau in the diagnosis of Alzheimer’s disease. Alzheimers Dement (Amst). 2019;11:483–92.
Pase MP, Beiser AS, Himali JJ, Satizabal CL, Aparicio HJ, DeCarli C, et al. Assessment of Plasma Total Tau Level as a Predictive Biomarker for Dementia and Related Endophenotypes. JAMA Neurol. 2019;76(5):598–606.
Verghese J, Annweiler C, Ayers E, Barzilai N, Beauchet O, Bennett DA, et al. Motoric cognitive risk syndrome: multicountry prevalence and dementia risk. Neurology. 2014;83(8):718–26.
Schirinzi T, Madeo G, Martella G, Maltese M, Picconi B, Calabresi P, et al. Early synaptic dysfunction in Parkinson’s disease: Insights from animal models. Movement Disorders. 2016;31(6):802–13.
Schirinzi T, Di Lorenzo F, Sancesario GM, Di Lazzaro G, Ponzo V, Pisani A, et al. Amyloid-Mediated Cholinergic Dysfunction in Motor Impairment Related to Alzheimer’s Disease. J Alzh Dis. 2018;64:525–32.
Pozueta J, Lefort R, Shelanski ML. Synaptic changes in Alzheimer’s disease and its models. Neuroscience. 2013;251:51–65.
Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R, et al. Physical basis of cognitive alterations in Alzheimer’s disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol. 1991;30(4):572–80.
Schirinzi T, Canevelli M, Suppa A, Bologna M, Marsili L. The continuum between neurodegeneration, brain plasticity, and movement: a critical appraisal. Rev Neurosci. 2020;31(7):723–42.
Shaughnessy KA, Hackney KJ, Clark BC, Kraemer WJ, Terbizan DJ, Bailey RR, et al. A Narrative Review of Handgrip Strength and Cognitive Functioning: Bringing a New Characteristic to Muscle Memory. J Alzh Dis. 2020;73(4):1265–78.
Carson RG. Get a grip: individual variations in grip strength are a marker of brain health. Neurobiol Aging. 2018;71:189–222.
De Cock AM, Fransen E, Perkisas S, Verhoeven V, Beauchet O, Remmen R, et al. Gait characteristics under different walking conditions: Association with the presence of cognitive impairment in community-dwelling older people. PLoS One. 2017;12(6):e0178566.
Palmqvist S, Janelidze S, Quiroz YT, Zetterberg H, Lopera F, Stomrud E, et al. Discriminative Accuracy of Plasma Phospho-tau217 for Alzheimer Disease vs Other Neurodegenerative Disorders. Jama. 2020;324(8):772–81.