Dual-Task Performance and Neurodegeneration: Correlations Between Timed Up-and-Go Dual-Task Test Outcomes and Alzheimer's Disease Cerebrospinal Fluid Biomarkers

Hanna Bozkurt Åhman, Vilmantas Giedraitis, Ylva Cedervall, Björn Lennhed, Lars Berglund, Kevin McKee, Lena Kilander, Erik Rosendahl, Martin Ingelsson, Anna Cristina Åberg, Hanna Bozkurt Åhman, Vilmantas Giedraitis, Ylva Cedervall, Björn Lennhed, Lars Berglund, Kevin McKee, Lena Kilander, Erik Rosendahl, Martin Ingelsson, Anna Cristina Åberg

Abstract

Background: Tools to identify individuals at preclinical stages of dementia disorders are needed to enable early interventions. Alterations in dual-task performance have been detected early in progressive neurodegenerative disorders. Hence, dual-task testing may have the potential to screen for cognitive impairment caused by neurodegeneration. Exploring correlations between dual-task performance and biomarkers of neurodegeneration is therefore of interest.

Objective: To investigate correlations between Timed Up-and-Go dual-task (TUGdt) outcomes and Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers amyloid-β 42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau).

Methods: This cross-sectional cohort study included 90 participants (age range 49-84 years) undergoing memory assessment, who were subsequently diagnosed with AD, other dementia disorders, mild cognitive impairment, or subjective cognitive impairment. TUG combined with "Naming Animals" (TUGdt NA) and "Months Backwards" (TUGdt MB), respectively, were used to assess dual-task performance. The number of correct words and time taken to complete the tests were measured. The CSF biomarkers were analysed by ELISA. Spearman's rank correlation was used for analyses between TUGdt outcomes (TUGdt NA and TUGdt MB), and CSF biomarkers, adjusted for age, gender, and educational level.

Results: The number of correct words, as well as the number of correct words/10 s during TUGdt NA correlated negatively to CSF t-tau and p-tau. No correlations were found between any time scores and CSF biomarkers.

Conclusion: The correlations between TUGdt NA and t-tau and p-tau may indicate that neurodegeneration affects dual-task performance. Longitudinal studies are needed to further explore dual-task testing in screening for cognitive impairment due to neurodegeneration.

Keywords: Alzheimer’s disease; attention; biomarkers; cerebrospinal fluid; dementia; executive function; gait; mild cognitive impairment; subjective cognitive impairment.

Conflict of interest statement

Authors’ disclosures available online (https://www.j-alz.com/manuscript-disclosures/18-1265r1).

Figures

Fig.1
Fig.1
Associations between A) t-tau concentration and number of correct words during Timed Up-and-Go dual-task naming animals (TUGdt NA); B) p-tau concentration and number of correct words during TUGdt NA; C) t-tau concentration and number of correct words per 10 s during TUGdt NA; D) p-tau concentration and number of correct words per 10 s during TUGdt NA.

References

    1. Laske C, Sohrabi HR, Frost SM, Lopez-de-Ipina K, Garrard P, Buscema M, Dauwels J, Soekadar SR, Mueller S, Linnemann C, Bridenbaugh SA, Kanagasingam Y, Martins RN, O’Bryant SE (2015) Innovative diagnostic tools for early detection of Alzheimer’s disease. Alzheimers Dement 11, 561–578.
    1. Yogev-Seligmann G, Hausdorff JM, Giladi N (2008) The role of executive function and attention in gait. Mov Disord 23, 329–342; quiz 472.
    1. Cullen S, Montero-Odasso M, Bherer L, Almeida Q, Fraser S, Muir-Hunter S, Li K, Liu-Ambrose T, McGibbon CA, McIlroy W, Middleton LE, Sarquis-Adamson Y, Beauchet O, McFadyen BJ, Morais JA, Camicioli R (2018) Guidelines for gait assessments in the Canadian Consortium on Neurodegeneration in Aging (CCNA). Can Geriatr J 21, 157–165.
    1. Pashler H (1994) Dual-task interference in simple tasks: Data and theory. Psychol Bull 116, 220–244.
    1. Bahureksa L, Najafi B, Saleh A, Sabbagh M, Coon D, Mohler MJ, Schwenk M (2017) The impact of mild cognitive impairment on gait and balance: A systematic review and meta-analysis of studies using instrumented assessment. Gerontology 63, 67–83.
    1. MacAulay RK, Wagner MT, Szeles D, Milano NJ (2017) Improving sensitivity to detect mild cognitive impairment: Cognitive load dual-task gait speed assessment. J Int Neuropsychol Soc 23, 493–501.
    1. Borges Sde M, Radanovic M, Forlenza OV (2015) Functional mobility in a divided attention task in older adults with cognitive impairment. J Mot Behav 47, 378–385.
    1. Belghali M, Chastan N, Cignetti F, Davenne D, Decker LM (2017) Loss of gait control assessed by cognitive-motor dual-tasks: Pros and cons in detecting people at risk of developing Alzheimer’s and Parkinson’s diseases. Geroscience 39, 305–329.
    1. Montero-Odasso MM, Sarquis-Adamson Y, Speechley M, Borrie MJ, Hachinski VC, Wells J, Riccio PM, Schapira M, Sejdic E, Camicioli RM, Bartha R, McIlroy WE, Muir-Hunter S (2017) Association of dual-task gait with incident dementia in mild cognitive impairment: Results from the Gait and Brain Study. JAMA Neurol 74, 857–865.
    1. Bridenbaugh SA, Kressig RW (2015) Motor cognitive dual tasking: Early detection of gait impairment, fall risk and cognitive decline. Z Gerontol Geriatr 48, 15–21.
    1. Lundin-Olsson L, Nyberg L, Gustafson Y (1997) “Stops walking when talking” as a predictor of falls in elderly people. Lancet 349, 617.
    1. Cedervall Y, Halvorsen K, Aberg AC (2014) A longitudinal study of gait function and characteristics of gait disturbance in individuals with Alzheimer’s disease. Gait Posture 39, 1022–1027.
    1. Montero-Odasso M, Speechley M, Muir-Hunter SW, Sarquis-Adamson Y, Sposato LA, Hachinski V, Borrie M, Wells J, Black A, Sejdic E, Bherer L, Chertkow H, Canadian Gait and Cognition Network (2018) Motor and cognitive trajectories before dementia: Results from Gait and Brain Study. J Am Geriatr Soc 66, 1676–1683.
    1. Nielsen MS, Simonsen AH, Siersma V, Hasselbalch SG, Hoegh P (2018) The diagnostic and prognostic value of a dual-tasking paradigm in a memory clinic. J Alzheimers Dis 61, 1189–1199.
    1. Al-Yahya E, Dawes H, Smith L, Dennis A, Howells K, Cockburn J (2011) Cognitive motor interference while walking: A systematic review and meta-analysis. Neurosci Biobehav Rev 35, 715–728.
    1. Klotzbier TJ, Schott N (2017) Cognitive-motor interference during walking in older adults with probable mild cognitive impairment. Front Aging Neurosci 9, 350.
    1. Blennow K, Dubois B, Fagan AM, Lewczuk P, de Leon MJ, Hampel H (2015) Clinical utility of cerebrospinal fluid biomarkers in the diagnosis of early Alzheimer’s disease. Alzheimers Dement 11, 58–69.
    1. Petersen RC, Aisen PS, Beckett LA, Donohue MC, Gamst AC, Harvey DJ, Jack CR Jr, Jagust WJ, Shaw LM, Toga AW, Trojanowski JQ, Weiner MW (2010) Alzheimer’s Disease Neuroimaging Initiative (ADNI): Clinical characterization. Neurology 74, 201–209.
    1. Tifratene K, Robert P, Metelkina A, Pradier C, Dartigues JF (2015) Progression of mild cognitive impairment to dementia due to AD in clinical settings. Neurology 85, 331–338.
    1. Garcia-Ptacek S, Eriksdotter M, Jelic V, Porta-Etessam J, Kareholt I, Manzano Palomo S (2016) Subjective cognitive impairment: Towards early identification of Alzheimer disease. Neurologia 31, 562–571.
    1. Mitchell AJ, Beaumont H, Ferguson D, Yadegarfar M, Stubbs B (2014) Risk of dementia and mild cognitive impairment in older people with subjective memory complaints: Meta-analysis. Acta Psychiatr Scand 130, 439–451.
    1. Palmqvist S, Zetterberg H, Mattsson N, Johansson P, Minthon L, Blennow K, Olsson M, Hansson O (2015) Detailed comparison of amyloid PET and CSF biomarkers for identifying early Alzheimer disease. Neurology 85, 1240–1249.
    1. Ritchie C, Smailagic N, Noel-Storr AH, Ukoumunne O, Ladds EC, Martin S (2017) CSF tau and the CSF tau/ABeta ratio for the diagnosis of Alzheimer’s disease dementia and other dementias in people with mild cognitive impairment (MCI). Cochrane Database Syst Rev 3, CD010803.
    1. Jack CR Jr, Holtzman DM (2013) Biomarker modeling of Alzheimer’s disease. Neuron 80, 1347–1358.
    1. Degerman Gunnarsson M, Ingelsson M, Blennow K, Basun H, Lannfelt L, Kilander L (2016) High tau levels in cerebrospinal fluid predict nursing home placement and rapid progression in Alzheimer’s disease. Alzheimers Res Ther 8, 22.
    1. Colijn MA, Grossberg GT (2015) Amyloid and tau biomarkers in subjective cognitive impairment. J Alzheimers Dis 47, 1–8.
    1. Blennow K, Zetterberg H, Minthon L, Lannfelt L, Strid S, Annas P, Basun H, Andreasen N (2007) Longitudinal stability of CSF biomarkers in Alzheimer’s disease. Neurosci Lett 419, 18–22.
    1. Mattsson N, Portelius E, Rolstad S, Gustavsson M, Andreasson U, Stridsberg M, Wallin A, Blennow K, Zetterberg H (2012) Longitudinal cerebrospinal fluid biomarkers over four years in mild cognitive impairment. J Alzheimers Dis 30, 767–778.
    1. Jack CR Jr., Knopman DS, Jagust WJ, Shaw LM, Aisen PS, Weiner MW, Petersen RC, Trojanowski JQ (2010) Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade. Lancet Neurol 9, 119–128.
    1. Belghali M, Chastan N, Davenne D, Decker LM (2017) Improving dual-task walking paradigms to detect prodromal Parkinson’s and Alzheimer’s diseases. Front Neurol 8, 207.
    1. Fritz NE, Kegelmeyer DA, Kloos AD, Linder S, Park A, Kataki M, Adeli A, Agrawal P, Scharre DW, Kostyk SK (2016) Motor performance differentiates individuals with Lewy body dementia, Parkinson’s and Alzheimer’s disease. Gait Posture 50, 1–7.
    1. Montero-Odasso M, Pieruccini-Faria F, Bartha R, Black SE, Finger E, Freedman M, Greenberg B, Grimes DA, Hegele RA, Hudson C, Kleinstiver PW, Lang AE, Masellis M, McLaughlin PM, Munoz DP, Strother S, Swartz RH, Symons S, Tartaglia MC, Zinman L, Strong MJ, McIlroy W (2017) Motor phenotype in neurodegenerative disorders: Gait and balance platform study design protocol for the Ontario Neurodegenerative Research Initiative (ONDRI). J Alzheimers Dis 59, 707–721.
    1. Tallberg IM, Ivachova E, Jones Tinghag K, Ostberg P (2008) Swedish norms for word fluency tests: FAS, animals and verbs. Scand J Psychol 49, 479–485.
    1. Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12, 189–198.
    1. Arevalo-Rodriguez I, Smailagic N, Roque IFM, Ciapponi A, Sanchez-Perez E, Giannakou A, Pedraza OL, Bonfill Cosp X, Cullum S (2015) Mini-Mental State Examination (MMSE) for the detection of Alzheimer’s disease and other dementias in people with mild cognitive impairment (MCI). Cochrane Database Syst Rev, CD010783.
    1. Podsiadlo D, Richardson S (1991) The timed “Up & Go”: A test of basic functional mobility for frail elderly persons. J Am Geriatr Soc 39, 142–148.
    1. Ries JD, Echternach JL, Nof L, Gagnon Blodgett M (2009) Test-retest reliability and minimal detectable change scores for the timed “up & go” test, the six-minute walk test, and gait speed in people with Alzheimer disease. Phys Ther 89, 569–579.
    1. Muir SW, Speechley M, Wells J, Borrie M, Gopaul K, Montero-Odasso M (2012) Gait assessment in mild cognitive impairment and Alzheimer’s disease: The effect of dual-task challenges across the cognitive spectrum. Gait Posture 35, 96–100.
    1. Meagher J, Leonard M, Donoghue L, O’Regan N, Timmons S, Exton C, Cullen W, Dunne C, Adamis D, Maclullich AJ, Meagher D (2015) Months backward test: A review of its use in clinical studies. World J Psychiatry 5, 305–314.
    1. Henry JD, Crawford JR, Phillips LH (2004) Verbal fluency performance in dementia of the Alzheimer’s type: A meta-analysis. Neuropsychologia 42, 1212–1222.
    1. Sheridan PL, Solomont J, Kowall N, Hausdorff JM (2003) Influence of executive function on locomotor function: Divided attention increases gait variability in Alzheimer’s disease. J Am Geriatr Soc 51, 1633–1637.
    1. Montero-Odasso M, Bergman H, Phillips NA, Wong CH, Sourial N, Chertkow H (2009) Dual-tasking and gait in people with mild cognitive impairment. The effect of working memory. BMC Geriatr 9, 41.
    1. Beauchet O, Dubost V, Aminian K, Gonthier R, Kressig RW (2005) Dual-task-related gait changes in the elderly: Does the type of cognitive task matter? J Mot Behav 37, 259–264.
    1. Vaughan RM, Coen RF, Kenny R, Lawlor BA (2018) Semantic and phonemic verbal fluency discrepancy in mild cognitive impairment: Potential predictor of progression to Alzheimer’s Disease. J Am Geriatr Soc 66, 755–759.
    1. Ostberg P, Hansson V, Haagg S (2012) Adult norms and test-retest reliability for the Months Backward test: Durational and response accuracy measures. Logoped Phoniatr Vocol 37, 11–17.
    1. Ostberg P, Fernaeus SE, Bogdanovic N, Wahlund LO (2008) Word sequence production in cognitive decline: Forward ever, backward never. Logoped Phoniatr Vocol 33, 126–135.
    1. Velickaite V, Giedraitis V, Strom K, Alafuzoff I, Zetterberg H, Lannfelt L, Kilander L, Larsson EM, Ingelsson M (2017) Cognitive function in very old men does not correlate to biomarkers of Alzheimer’s disease. BMC Geriatr 17, 208.
    1. Spillantini MG, Goedert M (2013) Tau pathology and neurodegeneration. Lancet Neurol 12, 609–622.
    1. Rogers SL, Friedman RB (2008) The underlying mechanisms of semantic memory loss in Alzheimer’s disease and semantic dementia. Neuropsychologia 46, 12–21.
    1. Beauchet O, Allali G, Poujol L, Barthelemy JC, Roche F, Annweiler C (2010) Decrease in gait variability while counting backward: A marker of “magnet effect”? J Neural Transm (Vienna) 117, 1171–1176.
    1. Rami L, Fortea J, Bosch B, Sole-Padulles C, Llado A, Iranzo A, Sanchez-Valle R, Molinuevo JL (2011) Cerebrospinal fluid biomarkers and memory present distinct associations along the continuum from healthy subjects to AD patients. J Alzheimers Dis 23, 319–326.
    1. Wallin AK, Blennow K, Andreasen N, Minthon L (2006) CSF biomarkers for Alzheimer’s Disease: Levels of beta-amyloid, tau, phosphorylated tau relate to clinical symptoms and survival. Dement Geriatr Cogn Disord 21, 131–138.
    1. Mirandez RM, Aprahamian I, Talib LL, Forlenza OV, Radanovic M (2017) Multiple category verbal fluency in mild cognitive impairment and correlation with CSF biomarkers for Alzheimer’s disease. Int Psychogeriatr 29, 949–958.
    1. Reijs BLR, Ramakers I, Kohler S, Teunissen CE, Koel-Simmelink M, Nathan PJ, Tsolaki M, Wahlund LO, Waldemar G, Hausner L, Vandenberghe R, Johannsen P, Blackwell A, Vanderstichele H, Verhey F, Visser PJ (2017) Memory correlates of Alzheimer’s disease cerebrospinal fluid markers: A longitudinal cohort study. J Alzheimers Dis 60, 1119–1128.
    1. Rolstad S, Berg AI, Bjerke M, Johansson B, Zetterberg H, Wallin A (2013) Cerebrospinal fluid biomarkers mirror rate of cognitive decline. J Alzheimers Dis 34, 949–956.

Source: PubMed

3
Předplatit