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Aspirin moderates the association between cardiovascular risk, brain white matter hyperintensity total lesion volume and processing speed in normal ageing

      Highlights

      • The role of white matter hyperintensity on cognition in older adults with cardiovascular risk varied by aspirin use.
      • Aspirin use exacerbated the negative effect of white matter hyperintensity burden on cognition.
      • The underlying pathways to cognitive decline may differ among aspirin users.
      • Considering aspirin use in addition to white matter hyperintensity and cardiovascular risk could improve the prediction of cognition in older adults.

      Abstract

      Objectives

      Cardiovascular risk is associated with cognitive decline and this effect is attributed to brain pathology, including white matter hyperintensity (WMH) burden. Low-dose aspirin is frequently recommended for reducing vascular events. We investigated the effect of taking aspirin on the association between cardiovascular risk, WMH burden and cognitive function.

      Study design

      The study sample was drawn from 318 dementia-free adults aged 67–71 years. Brain magnetic resonance imaging (MRI) scans were acquired from 239 participants.

      Main outcome measures

      WMH total lesion volumes (TLV) were extracted using the automated lesion segmentation algorithm. We measured cardiovascular risk by calculating ASSIGN score. Cognitive ability was measured using a test of processing speed. We developed structural equation models to test our hypothesis.

      Results

      Sixty-eight participants (47.1 % male, mean age = 68.8 years) reported that they took aspirin. The demographic measures did not differ significantly by aspirin use. Among aspirin users, there was a strong negative association between WMH TLV and cognition (β = −0.43, p-value < 0.001), while in non-users of aspirin the only significant predictor of poorer cognition was cardiovascular risk (β = −0.17, p-value = 0.001).

      Conclusions

      Aspirin use moderates the negative effect of WMH burden on cognition. Considering WMH burden in addition to cardiovascular risk could improve the prediction of cognitive decline in older adults with aspirin use.

      Keywords

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      References

      1. Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients.
        BMJ. 2002; 324: 71-86
        • Qiu C.
        • Fratiglioni L.
        A major role for cardiovascular burden in age-related cognitive decline.
        Nat. Rev. Cardiol. 2015; 12: 267-277
        • Robertson M.
        • Seaton A.
        • Whalley L.J.
        Can we reduce the risk of dementia?.
        QJM. 2015; 108: 93-97
        • Kang J.H.
        • Cook N.
        • Manson J.
        • Buring J.E.
        • Grodstein F.
        Low dose aspirin and cognitive function in the women’s health study cognitive cohort.
        BMJ. 2007; 334 (BMJ Publishing Group Ltd): 987
        • Kelley B.J.
        • McClure L.A.
        • Unverzagt F.W.
        • Kissela B.
        • Kleindorfer D.
        • Howard G.
        • et al.
        Regular aspirin use does not reduce risk of cognitive decline.
        J. Am. Geriatr. Soc. 2015; 63: 390-392
        • Price J.F.
        • Stewart M.C.
        • Deary I.J.
        • Murray G.D.
        • Sandercock P.
        • Butcher I.
        • et al.
        Low dose aspirin and cognitive function in middle aged to elderly adults: randomised controlled trial.
        BMJ. 2008; 337: a1198
        • Wardlaw J.M.
        • Smith C.
        • Dichgans M.
        Mechanisms of sporadic cerebral small vessel disease: insights from neuroimaging.
        Lancet Neurol. 2013; 12: 483-497
        • Murray A.D.
        • Staff R.T.
        • Shenkin S.D.
        • Deary I.J.
        • Starr J.M.
        • Whalley L.J.
        Brain white matter hyperintensities: relative importance of vascular risk factors in nondemented elderly people.
        Radiology. 2005; 237: 251-257
        • Breteler M.M.
        • van Swieten J.C.
        • Bots M.L.
        • Grobbee D.E.
        • Claus J.J.
        • van den Hout J.H.
        • et al.
        Cerebral white matter lesions, vascular risk factors, and cognitive function in a population-based study: the Rotterdam Study.
        Neurology. 1994; 44: 1246-1252
        • De Groot J.C.
        • De Leeuw F.E.
        • Oudkerk M.
        • Van Gijn J.
        • Hofman A.
        • Jolles J.
        • et al.
        Periventricular cerebral white matter lesions predict rate of cognitive decline.
        Ann. Neurol. 2002; 52: 335-341
        • Vernooij M.W.
        • Haag M.D.
        • van der Lugt A.
        • Hofman A.
        • Krestin G.P.
        • Stricker B.H.
        • et al.
        Use of antithrombotic drugs and the presence of cerebral microbleeds: the Rotterdam scan Study.
        Arch. Neurol. 2009; 66: 714-720
        • Sato H.
        • Koretsune Y.
        • Fukunami M.
        • Kodama K.
        • Yamada Y.
        • Fujii K.
        • et al.
        Aspirin attenuates the incidence of silent brain lesions in patients with nonvalvular atrial fibrillation.
        Circ. J. 2004; 68: 410-416
        • Holcombe A.
        • Ammann E.
        • Espeland M.A.
        • Kelley B.J.
        • Manson J.E.
        • Wallace R.
        • et al.
        Chronic use of aspirin and total white matter lesion volume: results from the women’s health initiative memory study of magnetic resonance imaging study.
        J. Stroke Cerebrovasc. Dis. 2017; 26: 2128-2136
        • Salthouse T.A.
        The processing-speed theory of adult age differences in cognition.
        Psychol. Rev. 1996; 103: 403-428
        • Papp K.V.
        • Kaplan R.F.
        • Springate B.
        • Moscufo N.
        • Wakefield D.B.
        • Guttmann C.R.G.
        • et al.
        Processing speed in normal aging: effects of white matter hyperintensities and hippocampal volume loss. Neuropsychology, development, and cognition.
        Sect. B Aging Neuropsychol. Cogn. 2014; 21: 197-213
        • van Dijk E.J.
        • Prins N.D.
        • Vrooman H.A.
        • Hofman A.
        • Koudstaal P.J.
        • Breteler M.M.
        Progression of cerebral small vessel disease in relation to risk factors and cognitive consequences: rotterdam scan study.
        Stroke. 2008; 39: 2712-2719
        • van den Heuvel D.M.
        • ten Dam V.H.
        • de Craen A.J.
        • Admiraal-Behloul F.
        • Olofsen H.
        • Bollen E.L.
        • et al.
        Increase in periventricular white matter hyperintensities parallels decline in mental processing speed in a non-demented elderly population.
        J. Neurol. Neurosurg. Psychiatry. 2006; 77: 149-153
      2. Wechsler D. WAIS-III: Administration and Scoring Manual: Wechsler Adult Intelligence Scale. Psychological Corporation, New York1997
        • Whalley L.J.
        • Murray A.D.
        • Staff R.T.
        • Starr J.M.
        • Deary I.J.
        • Fox H.C.
        • et al.
        How the 1932 and 1947 mental surveys of Aberdeen schoolchildren provide a framework to explore the childhood origins of late onset disease and disability.
        Maturitas. 2011; 69: 365-372
        • Woodward M.
        • Brindle P.
        • Tunstall-Pedoe H.
        SIGN group on risk estimation. Adding social deprivation and family history to cardiovascular risk assessment: the ASSIGN score from the Scottish Heart Health Extended Cohort (SHHEC).
        Heart. 2007; 93: 172-176
        • Murray A.D.
        • Staff R.T.
        • McNeil C.J.
        • Salarirad S.
        • Starr J.M.
        • Deary I.J.
        • et al.
        Brain lesions, hypertension and cognitive ageing in the 1921 and 1936 Aberdeen birth cohorts.
        Age. 2012; 34: 451-459
        • Schmidt P.
        • Gaser C.
        • Arsic M.
        • Buck D.
        • Forschler A.
        • Berthele A.
        • et al.
        An automated tool for detection of FLAIR-hyperintense white-matter lesions in Multiple Sclerosis.
        Neuroimage. 2012; 59: 3774-3783
        • Hu L.
        • Bentler P.M.
        Cutoff criteria for fit indexes in covariance structure analysis: conventional criteria versus new alternatives.
        Struct. Equ. Model. A Multidiscip. J. 1999; 6: 1-55
        • Antithrombotic Trialists’ (ATT) Collaboration
        • Baigent C.
        • Blackwell L.
        • Collins R.
        • Emberson J.
        • Godwin J.
        • et al.
        Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials.
        Lancet. 2009; 373: 1849-1860
        • McNeil C.J.
        • Myint P.K.
        • Sandu A.L.
        • Potter J.F.
        • Staff R.
        • Whalley L.J.
        • et al.
        Increased diastolic blood pressure is associated with MRI biomarkers of dementia-related brain pathology in normative ageing.
        Age Ageing. 2018; 47: 95-100
        • Gottesman R.F.
        • Schneider A.L.C.
        • Albert M.
        • Alonso A.
        • Bandeen-Roche K.
        • Coker L.
        • et al.
        Midlife hypertension and 20-year cognitive change: the atherosclerosis risk in communities neurocognitive study.
        JAMA Neurol. 2014; 71: 1218-1227
        • Duron E.
        • Hanon O.
        Vascular risk factors, cognitive decline, and dementia.
        Vasc. Health Risk Manag. 2008; 4: 363-381
        • Iadecola C.
        • Yaffe K.
        • Biller J.
        • Bratzke L.C.
        • Faraci F.M.
        • Gorelick P.B.
        • et al.
        Impact of hypertension on cognitive function: a scientific statement from the american heart association.
        Hypertension. 2016; 68: e67-94
        • Anstey K.J.
        • von Sanden C.
        • Salim A.
        • O’Kearney R.
        Smoking as a risk factor for dementia and cognitive decline: a meta-analysis of prospective studies.
        Am. J. Epidemiol. 2007; 166: 367-378
        • Ward S.A.
        • Raniga P.
        • Ferris N.J.
        • Woods R.L.
        • Storey E.
        • Bailey M.J.
        • et al.
        ASPREE-NEURO study protocol: a randomized controlled trial to determine the effect of low-dose aspirin on cerebral microbleeds, white matter hyperintensities, cognition, and stroke in the healthy elderly.
        Int. J. Stroke. 2016;