Early cerebral small vessel disease and brain volume, cognition, and gait

Objective Decline in cognitive function begins by the 40s, and may be related to future dementia risk. We used data from a community‐representative study to determine whether there are age‐related differences in simple cognitive and gait tests by the 40s, and whether these differences were associate...

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Veröffentlicht in:	Annals of neurology Jg. 77; H. 2; S. 251 - 261
Hauptverfasser:	Smith, Eric E., O'Donnell, Martin, Dagenais, Gilles, Lear, Scott A., Wielgosz, Andreas, Sharma, Mukul, Poirier, Paul, Stotts, Grant, Black, Sandra E., Strother, Stephen, Noseworthy, Michael D., Benavente, Oscar, Modi, Jayesh, Goyal, Mayank, Batool, Saima, Sanchez, Karla, Hill, Vanessa, McCreary, Cheryl R., Frayne, Richard, Islam, Shofiqul, DeJesus, Jane, Rangarajan, Sumathy, Teo, Koon, Yusuf, Salim
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States Blackwell Publishing Ltd 01.02.2015 Wiley Subscription Services, Inc
Schlagworte:	Adult Aged Atrophy - pathology Brain - pathology Canada - epidemiology Cerebral Small Vessel Diseases - diagnosis Cerebral Small Vessel Diseases - physiopathology Cerebral Small Vessel Diseases - psychology Cognition - physiology Early Diagnosis Female Gait - physiology Humans Magnetic Resonance Imaging - methods Male Middle Aged Organ Size Population Surveillance - methods Prospective Studies Canada
ISSN:	0364-5134, 1531-8249, 1531-8249
Online-Zugang:	Volltext
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Abstract	Objective Decline in cognitive function begins by the 40s, and may be related to future dementia risk. We used data from a community‐representative study to determine whether there are age‐related differences in simple cognitive and gait tests by the 40s, and whether these differences were associated with covert cerebrovascular disease on magnetic resonance imaging (MRI). Methods Between 2010 and 2012, 803 participants aged 40 to 75 years in the Prospective Urban Rural Epidemiological (PURE) study, recruited from prespecified postal code regions centered on 4 Canadian cities, underwent brain MRI and simple tests of cognition and gait as part of a substudy (PURE‐MIND). Results Mean age was 58 ± 8 years. Linear decreases in performance on the Montreal Cognitive Assessment, Digit Symbol Substitution Test (DSST), and Timed Up and Go test of gait were seen with each age decade from the 40s to the 70s. Silent brain infarcts were observed in 3% of 40‐ to 49‐year‐olds, with increasing prevalence up to 18.9% in 70‐year‐olds. Silent brain infarcts were associated with slower timed gait and lower volume of supratentorial white matter. Higher volume of supratentorial MRI white matter hyperintensity was associated with slower timed gait and worse performance on DSST, and lower volumes of the supratentorial cortex and white matter, and cerebellum. Interpretation Covert cerebrovascular disease and its consequences on cognitive and gait performance and brain atrophy are manifest in some clinically asymptomatic persons as early as the 5th decade of life. Ann Neurol 2015;77:251–261
AbstractList	Decline in cognitive function begins by the 40s, and may be related to future dementia risk. We used data from a community-representative study to determine whether there are age-related differences in simple cognitive and gait tests by the 40s, and whether these differences were associated with covert cerebrovascular disease on magnetic resonance imaging (MRI).OBJECTIVEDecline in cognitive function begins by the 40s, and may be related to future dementia risk. We used data from a community-representative study to determine whether there are age-related differences in simple cognitive and gait tests by the 40s, and whether these differences were associated with covert cerebrovascular disease on magnetic resonance imaging (MRI).Between 2010 and 2012, 803 participants aged 40 to 75 years in the Prospective Urban Rural Epidemiological (PURE) study, recruited from prespecified postal code regions centered on 4 Canadian cities, underwent brain MRI and simple tests of cognition and gait as part of a substudy (PURE-MIND).METHODSBetween 2010 and 2012, 803 participants aged 40 to 75 years in the Prospective Urban Rural Epidemiological (PURE) study, recruited from prespecified postal code regions centered on 4 Canadian cities, underwent brain MRI and simple tests of cognition and gait as part of a substudy (PURE-MIND).Mean age was 58 ± 8 years. Linear decreases in performance on the Montreal Cognitive Assessment, Digit Symbol Substitution Test (DSST), and Timed Up and Go test of gait were seen with each age decade from the 40s to the 70s. Silent brain infarcts were observed in 3% of 40- to 49-year-olds, with increasing prevalence up to 18.9% in 70-year-olds. Silent brain infarcts were associated with slower timed gait and lower volume of supratentorial white matter. Higher volume of supratentorial MRI white matter hyperintensity was associated with slower timed gait and worse performance on DSST, and lower volumes of the supratentorial cortex and white matter, and cerebellum.RESULTSMean age was 58 ± 8 years. Linear decreases in performance on the Montreal Cognitive Assessment, Digit Symbol Substitution Test (DSST), and Timed Up and Go test of gait were seen with each age decade from the 40s to the 70s. Silent brain infarcts were observed in 3% of 40- to 49-year-olds, with increasing prevalence up to 18.9% in 70-year-olds. Silent brain infarcts were associated with slower timed gait and lower volume of supratentorial white matter. Higher volume of supratentorial MRI white matter hyperintensity was associated with slower timed gait and worse performance on DSST, and lower volumes of the supratentorial cortex and white matter, and cerebellum.Covert cerebrovascular disease and its consequences on cognitive and gait performance and brain atrophy are manifest in some clinically asymptomatic persons as early as the 5th decade of life.INTERPRETATIONCovert cerebrovascular disease and its consequences on cognitive and gait performance and brain atrophy are manifest in some clinically asymptomatic persons as early as the 5th decade of life. Decline in cognitive function begins by the 40s, and may be related to future dementia risk. We used data from a community-representative study to determine whether there are age-related differences in simple cognitive and gait tests by the 40s, and whether these differences were associated with covert cerebrovascular disease on magnetic resonance imaging (MRI). Between 2010 and 2012, 803 participants aged 40 to 75 years in the Prospective Urban Rural Epidemiological (PURE) study, recruited from prespecified postal code regions centered on 4 Canadian cities, underwent brain MRI and simple tests of cognition and gait as part of a substudy (PURE-MIND). Mean age was 58 ± 8 years. Linear decreases in performance on the Montreal Cognitive Assessment, Digit Symbol Substitution Test (DSST), and Timed Up and Go test of gait were seen with each age decade from the 40s to the 70s. Silent brain infarcts were observed in 3% of 40- to 49-year-olds, with increasing prevalence up to 18.9% in 70-year-olds. Silent brain infarcts were associated with slower timed gait and lower volume of supratentorial white matter. Higher volume of supratentorial MRI white matter hyperintensity was associated with slower timed gait and worse performance on DSST, and lower volumes of the supratentorial cortex and white matter, and cerebellum. Covert cerebrovascular disease and its consequences on cognitive and gait performance and brain atrophy are manifest in some clinically asymptomatic persons as early as the 5th decade of life. Objective Decline in cognitive function begins by the 40s, and may be related to future dementia risk. We used data from a community‐representative study to determine whether there are age‐related differences in simple cognitive and gait tests by the 40s, and whether these differences were associated with covert cerebrovascular disease on magnetic resonance imaging (MRI). Methods Between 2010 and 2012, 803 participants aged 40 to 75 years in the Prospective Urban Rural Epidemiological (PURE) study, recruited from prespecified postal code regions centered on 4 Canadian cities, underwent brain MRI and simple tests of cognition and gait as part of a substudy (PURE‐MIND). Results Mean age was 58 ± 8 years. Linear decreases in performance on the Montreal Cognitive Assessment, Digit Symbol Substitution Test (DSST), and Timed Up and Go test of gait were seen with each age decade from the 40s to the 70s. Silent brain infarcts were observed in 3% of 40‐ to 49‐year‐olds, with increasing prevalence up to 18.9% in 70‐year‐olds. Silent brain infarcts were associated with slower timed gait and lower volume of supratentorial white matter. Higher volume of supratentorial MRI white matter hyperintensity was associated with slower timed gait and worse performance on DSST, and lower volumes of the supratentorial cortex and white matter, and cerebellum. Interpretation Covert cerebrovascular disease and its consequences on cognitive and gait performance and brain atrophy are manifest in some clinically asymptomatic persons as early as the 5th decade of life. Ann Neurol 2015;77:251–261 Objective Decline in cognitive function begins by the 40s, and may be related to future dementia risk. We used data from a community-representative study to determine whether there are age-related differences in simple cognitive and gait tests by the 40s, and whether these differences were associated with covert cerebrovascular disease on magnetic resonance imaging (MRI). Methods Between 2010 and 2012, 803 participants aged 40 to 75 years in the Prospective Urban Rural Epidemiological (PURE) study, recruited from prespecified postal code regions centered on 4 Canadian cities, underwent brain MRI and simple tests of cognition and gait as part of a substudy (PURE-MIND). Results Mean age was 58 plus or minus 8 years. Linear decreases in performance on the Montreal Cognitive Assessment, Digit Symbol Substitution Test (DSST), and Timed Up and Go test of gait were seen with each age decade from the 40s to the 70s. Silent brain infarcts were observed in 3% of 40- to 49-year-olds, with increasing prevalence up to 18.9% in 70-year-olds. Silent brain infarcts were associated with slower timed gait and lower volume of supratentorial white matter. Higher volume of supratentorial MRI white matter hyperintensity was associated with slower timed gait and worse performance on DSST, and lower volumes of the supratentorial cortex and white matter, and cerebellum. Interpretation Covert cerebrovascular disease and its consequences on cognitive and gait performance and brain atrophy are manifest in some clinically asymptomatic persons as early as the 5th decade of life. Ann Neurol 2015; 77:251-261 Objective Decline in cognitive function begins by the 40s, and may be related to future dementia risk. We used data from a community-representative study to determine whether there are age-related differences in simple cognitive and gait tests by the 40s, and whether these differences were associated with covert cerebrovascular disease on magnetic resonance imaging (MRI). Methods Between 2010 and 2012, 803 participants aged 40 to 75 years in the Prospective Urban Rural Epidemiological (PURE) study, recruited from prespecified postal code regions centered on 4 Canadian cities, underwent brain MRI and simple tests of cognition and gait as part of a substudy (PURE-MIND). Results Mean age was 58±8 years. Linear decreases in performance on the Montreal Cognitive Assessment, Digit Symbol Substitution Test (DSST), and Timed Up and Go test of gait were seen with each age decade from the 40s to the 70s. Silent brain infarcts were observed in 3% of 40- to 49-year-olds, with increasing prevalence up to 18.9% in 70-year-olds. Silent brain infarcts were associated with slower timed gait and lower volume of supratentorial white matter. Higher volume of supratentorial MRI white matter hyperintensity was associated with slower timed gait and worse performance on DSST, and lower volumes of the supratentorial cortex and white matter, and cerebellum. Interpretation Covert cerebrovascular disease and its consequences on cognitive and gait performance and brain atrophy are manifest in some clinically asymptomatic persons as early as the 5th decade of life. Ann Neurol 2015;77:251-261
Author	Lear, Scott A. Black, Sandra E. O'Donnell, Martin Batool, Saima Poirier, Paul McCreary, Cheryl R. Teo, Koon Smith, Eric E. Goyal, Mayank Wielgosz, Andreas Sharma, Mukul Islam, Shofiqul Sanchez, Karla Rangarajan, Sumathy Yusuf, Salim Modi, Jayesh Hill, Vanessa Strother, Stephen Dagenais, Gilles Stotts, Grant Benavente, Oscar Noseworthy, Michael D. Frayne, Richard DeJesus, Jane
Author_xml	– sequence: 1 givenname: Eric E. surname: Smith fullname: Smith, Eric E. email: eesmith@ucalgary.ca organization: Hotchkiss Brain Institute – sequence: 2 givenname: Martin surname: O'Donnell fullname: O'Donnell, Martin organization: Population Health Research Institute, McMaster University, Ontario, Hamilton – sequence: 3 givenname: Gilles surname: Dagenais fullname: Dagenais, Gilles organization: Quebec Heart and Lung Institute, Laval University, Quebec, Quebec City – sequence: 4 givenname: Scott A. surname: Lear fullname: Lear, Scott A. organization: Faculty of Health Sciences, Simon Fraser University, British Columbia, Burnaby – sequence: 5 givenname: Andreas surname: Wielgosz fullname: Wielgosz, Andreas organization: Department of Medicine, University of Ottawa, Ontario, Ottawa – sequence: 6 givenname: Mukul surname: Sharma fullname: Sharma, Mukul organization: Population Health Research Institute, McMaster University, Ontario, Hamilton – sequence: 7 givenname: Paul surname: Poirier fullname: Poirier, Paul organization: Quebec Heart and Lung Institute, Laval University, Quebec, Quebec City – sequence: 8 givenname: Grant surname: Stotts fullname: Stotts, Grant organization: Department of Medicine, University of Ottawa, Ontario, Ottawa – sequence: 9 givenname: Sandra E. surname: Black fullname: Black, Sandra E. organization: Division of Neurology, University of Toronto, Ontario, Toronto – sequence: 10 givenname: Stephen surname: Strother fullname: Strother, Stephen organization: Rotman Research Institute, Ontario, Baycrest – sequence: 11 givenname: Michael D. surname: Noseworthy fullname: Noseworthy, Michael D. organization: Department of Electrical and Computer, Engineering, McMaster University, Ontario, Hamilton – sequence: 12 givenname: Oscar surname: Benavente fullname: Benavente, Oscar organization: Department of Neurology, University of British Columbia, British Columbia, Vancouver, Canada – sequence: 13 givenname: Jayesh surname: Modi fullname: Modi, Jayesh organization: Department of Radiology – sequence: 14 givenname: Mayank surname: Goyal fullname: Goyal, Mayank organization: Hotchkiss Brain Institute – sequence: 15 givenname: Saima surname: Batool fullname: Batool, Saima organization: Department of Radiology – sequence: 16 givenname: Karla surname: Sanchez fullname: Sanchez, Karla organization: Department of Clinical Neurosciences – sequence: 17 givenname: Vanessa surname: Hill fullname: Hill, Vanessa organization: Department of Clinical Neurosciences – sequence: 18 givenname: Cheryl R. surname: McCreary fullname: McCreary, Cheryl R. organization: Department of Clinical Neurosciences – sequence: 19 givenname: Richard surname: Frayne fullname: Frayne, Richard organization: Hotchkiss Brain Institute – sequence: 20 givenname: Shofiqul surname: Islam fullname: Islam, Shofiqul organization: Population Health Research Institute, McMaster University, Ontario, Hamilton – sequence: 21 givenname: Jane surname: DeJesus fullname: DeJesus, Jane organization: Population Health Research Institute, McMaster University, Ontario, Hamilton – sequence: 22 givenname: Sumathy surname: Rangarajan fullname: Rangarajan, Sumathy organization: Population Health Research Institute, McMaster University, Ontario, Hamilton – sequence: 23 givenname: Koon surname: Teo fullname: Teo, Koon organization: Population Health Research Institute, McMaster University, Ontario, Hamilton – sequence: 24 givenname: Salim surname: Yusuf fullname: Yusuf, Salim organization: Population Health Research Institute, McMaster University, Ontario, Hamilton
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/25428654$$D View this record in MEDLINE/PubMed
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Copyright	2014 The Authors Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association. 2015 The Authors Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. 2015 American Neurological Association 2014 The Authors Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association. 2014
Copyright_xml	– notice: 2014 The Authors Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association. – notice: 2015 The Authors Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. – notice: 2015 American Neurological Association – notice: 2014 The Authors Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association. 2014
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Association between lower digit symbol substitution test score and slower gait and greater risk of mortality and of developing incident disability in well-functioning older adults. J Am Geriatr Soc 2008;56:1618-1625. Maillard P, Seshadri S, Beiser A, et al. Effects of systolic blood pressure on white-matter integrity in young adults in the Framingham Heart Study: a cross-sectional study. Lancet Neurol 2012;11:1039-1047. Ikram MA, Vernooij MW, Vrooman HA, et al. Brain tissue volumes and small vessel disease in relation to the risk of mortality. Neurobiol Aging 2009;30:450-456. Kaplan E, Fein D, Morris R, Delis D. The WAIS-R as a neuropsychological instrument. San Antonio, TX: Psychological Corporation, 1991. Hoogendam YY, van der Geest JN, van der Lijn F, et al. Determinants of cerebellar and cerebral volume in the general elderly population. Neurobiol Aging 2012;33:2774-2781. Hachinski V, Iadecola C, Petersen RC, et al. National Institute of Neurological Disorders and Stroke-Canadian Stroke Network vascular cognitive impairment harmonization standards. Stroke 2006;37:2220-2241. Kohara K, Fujisawa M, Ando F, et al. MTHFR gene polymorphism as a risk factor for silent brain infarcts and white matter lesions in the Japanese general population: the NILS-LSA Study. Stroke 2003;34:1130-1135. Schmidt R, Ropele S, Enzinger C, et al. White matter lesion progression, brain atrophy, and cognitive decline: the Austrian Stroke Prevention study. Ann Neurol 2005;58:610-616. Debette S, Beiser A, DeCarli C, et al. Association of MRI markers of vascular brain injury with incident stroke, mild cognitive impairment, dementia, and mortality: the Framingham Offspring Study. Stroke 2010;41:600-606. Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol 2010;9:689-701. Han X, Jovicich J, Salat D, et al. Reliability of MRI-derived measurements of human cerebral cortical thickness: the effects of field strength, scanner upgrade and manufacturer. Neuroimage 2006;32:180-194. Vermeer SE, Longstreth WT Jr, Koudstaal PJ. Silent brain infarcts: a systematic review. Lancet Neurol 2007;6:611-619. Bohannon RW. Comfortable and maximum walking speed of adults aged 20-79 years: reference values and determinants. Age Ageing 1997;26:15-19. Hoyer WJ, Stawski RS, Wasylyshyn C, Verhaeghen P. Adult age and digit symbol substitution performance: a meta-analysis. Psychol Aging 2004;19:211-214. Wardlaw JM, Smith EE, Biessels GJ, et al. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol 2013;12:822-838. Genovese CR, Lazar NA, Nichols T. Thresholding of statistical maps in functional neuroimaging using the false discovery rate. Neuroimage 2002;15:870-878. Bohannon RW. 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References_xml	– reference: Hachinski V, Iadecola C, Petersen RC, et al. National Institute of Neurological Disorders and Stroke-Canadian Stroke Network vascular cognitive impairment harmonization standards. Stroke 2006;37:2220-2241. – reference: Desikan RS, Segonne F, Fischl B, et al. An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. Neuroimage 2006;31:968-980. – reference: Schmidt R, Ropele S, Enzinger C, et al. White matter lesion progression, brain atrophy, and cognitive decline: the Austrian Stroke Prevention study. Ann Neurol 2005;58:610-616. – reference: Kohara K, Fujisawa M, Ando F, et al. MTHFR gene polymorphism as a risk factor for silent brain infarcts and white matter lesions in the Japanese general population: the NILS-LSA Study. Stroke 2003;34:1130-1135. – reference: Hoyer WJ, Stawski RS, Wasylyshyn C, Verhaeghen P. Adult age and digit symbol substitution performance: a meta-analysis. Psychol Aging 2004;19:211-214. – reference: Maillard P, Seshadri S, Beiser A, et al. Effects of systolic blood pressure on white-matter integrity in young adults in the Framingham Heart Study: a cross-sectional study. Lancet Neurol 2012;11:1039-1047. – reference: Hoogendam YY, van der Geest JN, van der Lijn F, et al. Determinants of cerebellar and cerebral volume in the general elderly population. Neurobiol Aging 2012;33:2774-2781. – reference: Singh-Manoux A, Kivimaki M, Glymour MM, et al. Timing of onset of cognitive decline: results from Whitehall II prospective cohort study. BMJ 2012;344:d7622. – reference: Genovese CR, Lazar NA, Nichols T. Thresholding of statistical maps in functional neuroimaging using the false discovery rate. Neuroimage 2002;15:870-878. – reference: Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol 2010;9:689-701. – reference: DeCarli C, Massaro J, Harvey D, et al. Measures of brain morphology and infarction in the Framingham heart study: establishing what is normal. Neurobiol Aging 2005;26:491-510. – reference: Debette S, Beiser A, DeCarli C, et al. Association of MRI markers of vascular brain injury with incident stroke, mild cognitive impairment, dementia, and mortality: the Framingham Offspring Study. Stroke 2010;41:600-606. – reference: Nasreddine ZS, Phillips NA, Bedirian V, et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 2005;53:695-699. – reference: Mortamet B, Bernstein MA, Jack CR Jr, et al. Automatic quality assessment in structural brain magnetic resonance imaging. Magn Reson Med 2009;62:365-372. – reference: Kenny RA, Coen RF, Frewen J, et al. Normative values of cognitive and physical function in older adults: findings from the Irish Longitudinal Study on Ageing. J Am Geriatr Soc 2013;61(suppl 2):S279-S290. – reference: Ikram MA, Vernooij MW, Vrooman HA, et al. Brain tissue volumes and small vessel disease in relation to the risk of mortality. Neurobiol Aging 2009;30:450-456. – reference: Bohannon RW. Comfortable and maximum walking speed of adults aged 20-79 years: reference values and determinants. Age Ageing 1997;26:15-19. – reference: Rosano C, Newman AB, Katz R, et al. Association between lower digit symbol substitution test score and slower gait and greater risk of mortality and of developing incident disability in well-functioning older adults. J Am Geriatr Soc 2008;56:1618-1625. – reference: van Velsen EF, Vernooij MW, Vrooman HA, et al. Brain cortical thickness in the general elderly population: the Rotterdam Scan Study. Neurosci Lett 2013;550:189-194. – reference: Yusuf S, Islam S, Chow CK, et al. Use of secondary prevention drugs for cardiovascular disease in the community in high-income, middle-income, and low-income countries (the PURE Study): a prospective epidemiological survey. Lancet 2011;378:1231-1243. – reference: Fischl B, Salat DH, Busa E, et al. Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron 2002;33:341-355. – reference: LADIS Study Group. 2001-2011: a decade of the LADIS (Leukoaraiosis And DISability) Study: what have we learned about white matter changes and small-vessel disease? Cerebrovasc Dis 2011;32:577-588. – reference: Vermeer SE, Longstreth WT Jr, Koudstaal PJ. Silent brain infarcts: a systematic review. Lancet Neurol 2007;6:611-619. – reference: Wardlaw JM, Smith EE, Biessels GJ, et al. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol 2013;12:822-838. – reference: Vermeer SE, Den Heijer T, Koudstaal PJ, et al. Incidence and risk factors of silent brain infarcts in the population-based Rotterdam Scan Study. Stroke 2003;34:392-396. – reference: Gunter JL, Bernstein MA, Borowski BJ, et al. Measurement of MRI scanner performance with the ADNI phantom. Med Phys 2009;36:2193-2205. – reference: Pendlebury ST, Cuthbertson FC, Welch SJ, et al. Underestimation of cognitive impairment by Mini-Mental State Examination versus the Montreal Cognitive Assessment in patients with transient ischemic attack and stroke: a population-based study. Stroke 2010;41:1290-1293. – reference: Han X, Jovicich J, Salat D, et al. Reliability of MRI-derived measurements of human cerebral cortical thickness: the effects of field strength, scanner upgrade and manufacturer. Neuroimage 2006;32:180-194. – reference: Kaplan E, Fein D, Morris R, Delis D. The WAIS-R as a neuropsychological instrument. San Antonio, TX: Psychological Corporation, 1991. – reference: Bohannon RW. Reference values for the timed up and go test: a descriptive meta-analysis. J Geriatr Phys Ther 2006;29:64-68. – volume: 32 start-page: 577 year: 2011 end-page: 588 article-title: 2001–2011: a decade of the LADIS (Leukoaraiosis And DISability) Study: what have we learned about white matter changes and small‐vessel disease? publication-title: Cerebrovasc Dis – volume: 56 start-page: 1618 year: 2008 end-page: 1625 article-title: Association between lower digit symbol substitution test score and slower gait and greater risk of mortality and of developing incident disability in well‐functioning older adults publication-title: J Am Geriatr Soc – volume: 11 start-page: 1039 year: 2012 end-page: 1047 article-title: Effects of systolic blood pressure on white‐matter integrity in young adults in the Framingham Heart Study: a cross‐sectional study publication-title: Lancet Neurol – volume: 550 start-page: 189 year: 2013 end-page: 194 article-title: Brain cortical thickness in the general elderly population: the Rotterdam Scan Study publication-title: Neurosci Lett – volume: 12 start-page: 822 year: 2013 end-page: 838 article-title: Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration publication-title: Lancet Neurol – volume: 58 start-page: 610 year: 2005 end-page: 616 article-title: White matter lesion progression, brain atrophy, and cognitive decline: the Austrian Stroke Prevention study publication-title: Ann Neurol – volume: 34 start-page: 1130 year: 2003 end-page: 1135 article-title: MTHFR gene polymorphism as a risk factor for silent brain infarcts and white matter lesions in the Japanese general population: the NILS‐LSA Study publication-title: Stroke – volume: 9 start-page: 689 year: 2010 end-page: 701 article-title: Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges publication-title: Lancet Neurol – volume: 33 start-page: 2774 year: 2012 end-page: 2781 article-title: Determinants of cerebellar and cerebral volume in the general elderly population publication-title: Neurobiol Aging – volume: 26 start-page: 15 year: 1997 end-page: 19 article-title: Comfortable and maximum walking speed of adults aged 20–79 years: reference values and determinants publication-title: Age Ageing – volume: 36 start-page: 2193 year: 2009 end-page: 2205 article-title: Measurement of MRI scanner performance with the ADNI phantom publication-title: Med Phys – volume: 32 start-page: 180 year: 2006 end-page: 194 article-title: Reliability of MRI‐derived measurements of human cerebral cortical thickness: the effects of field strength, scanner upgrade and manufacturer publication-title: Neuroimage – volume: 34 start-page: 392 year: 2003 end-page: 396 article-title: Incidence and risk factors of silent brain infarcts in the population‐based Rotterdam Scan Study publication-title: Stroke – volume: 37 start-page: 2220 year: 2006 end-page: 2241 article-title: National Institute of Neurological Disorders and Stroke‐Canadian Stroke Network vascular cognitive impairment harmonization standards publication-title: Stroke – volume: 33 start-page: 341 year: 2002 end-page: 355 article-title: Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain publication-title: Neuron – volume: 61 start-page: S279 issue: suppl 2 year: 2013 end-page: S290 article-title: Normative values of cognitive and physical function in older adults: findings from the Irish Longitudinal Study on Ageing publication-title: J Am Geriatr Soc – volume: 29 start-page: 64 year: 2006 end-page: 68 article-title: Reference values for the timed up and go test: a descriptive meta‐analysis publication-title: J Geriatr Phys Ther – volume: 15 start-page: 870 year: 2002 end-page: 878 article-title: Thresholding of statistical maps in functional neuroimaging using the false discovery rate publication-title: Neuroimage – volume: 41 start-page: 600 year: 2010 end-page: 606 article-title: Association of MRI markers of vascular brain injury with incident stroke, mild cognitive impairment, dementia, and mortality: the Framingham Offspring Study publication-title: Stroke – volume: 41 start-page: 1290 year: 2010 end-page: 1293 article-title: Underestimation of cognitive impairment by Mini‐Mental State Examination versus the Montreal Cognitive Assessment in patients with transient ischemic attack and stroke: a population‐based study publication-title: Stroke – volume: 30 start-page: 450 year: 2009 end-page: 456 article-title: Brain tissue volumes and small vessel disease in relation to the risk of mortality publication-title: Neurobiol Aging – volume: 378 start-page: 1231 year: 2011 end-page: 1243 article-title: Use of secondary prevention drugs for cardiovascular disease in the community in high‐income, middle‐income, and low‐income countries (the PURE Study): a prospective epidemiological survey publication-title: Lancet – volume: 53 start-page: 695 year: 2005 end-page: 699 article-title: The Montreal Cognitive 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Snippet	Objective Decline in cognitive function begins by the 40s, and may be related to future dementia risk. We used data from a community‐representative study to... Decline in cognitive function begins by the 40s, and may be related to future dementia risk. We used data from a community-representative study to determine... Objective Decline in cognitive function begins by the 40s, and may be related to future dementia risk. We used data from a community-representative study to...
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SubjectTerms	Adult Aged Atrophy - pathology Brain - pathology Canada - epidemiology Cerebral Small Vessel Diseases - diagnosis Cerebral Small Vessel Diseases - physiopathology Cerebral Small Vessel Diseases - psychology Cognition - physiology Early Diagnosis Female Gait - physiology Humans Magnetic Resonance Imaging - methods Male Middle Aged Organ Size Population Surveillance - methods Prospective Studies
Title	Early cerebral small vessel disease and brain volume, cognition, and gait
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