Skip to main content

Advertisement

Log in

Progression of Atrophy in Alzheimer’s Disease and Related Disorders

  • Published:
Neurotoxicity Research Aims and scope Submit manuscript

Abstract

Longitudinal MRI is a powerful tool that allows the assessment of progression of brain changes over multiple imaging time-points and has been increasingly employed in the study of neurodegenerative dementias, particularly Alzheimer’s disease (AD). Early studies demonstrated that AD was associated with increased rates of whole brain loss and hippocampal atrophy. A number of sophisticated voxel-level techniques have now been developed that have provided additional information describing regional atrophy over time in the temporal, parietal, and frontal lobes in AD. Studies have also focused on subjects in the prodromal phase of AD in order to describe the earliest changes that are occurring in the brain. Atrophy has been shown to start in the medial temporal lobes and fusiform gyrus at least 3 years before subjects reach a diagnosis of AD, and then spread to the posterior temporal lobes and parietal lobes, and then eventually the frontal lobes. These patterns of atrophy correlate well with the progression of neurofibrillary tangles observed on pathology. Rates of atrophy have also been shown to accelerate over the course of the disease as a subject progresses from cognitively normal to a diagnosis of AD. Similar techniques have also been applied to other neurodegenerative diseases, such as frontotemporal dementia which show higher rates of atrophy and different patterns of progression to those observed in AD. Hence, longitudinal MRI shows promise as a biomarker of disease progression in neurodegenerative disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Barnes J, Whitwell JL, Frost C, Josephs KA, Rossor M, Fox NC (2006) Measurements of the amygdala and hippocampus in pathologically confirmed Alzheimer disease and frontotemporal lobar degeneration. Arch Neurol 63:1434–1439

    Article  PubMed  Google Scholar 

  • Baron JC, Chetelat G, Desgranges B, Perchey G, Landeau B, de la Sayette V et al (2001) In vivo mapping of gray matter loss with voxel-based morphometry in mild Alzheimer’s disease. Neuroimage 14:298–309

    Article  CAS  PubMed  Google Scholar 

  • Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol (Berl) 82:239–259

    Article  CAS  Google Scholar 

  • Brambati SM, Renda NC, Rankin KP, Rosen HJ, Seeley WW, Ashburner J et al (2007) A tensor based morphometry study of longitudinal gray matter contraction in FTD. Neuroimage 35:998–1003

    Article  PubMed  Google Scholar 

  • Brambati SM, Rankin KP, Narvid J, Seeley WW, Dean D, Rosen HJ et al (2009) Atrophy progression in semantic dementia with asymmetric temporal involvement: a tensor-based morphometry study. Neurobiol Aging 30:103–111

    Article  CAS  PubMed  Google Scholar 

  • Carlson NE, Moore MM, Dame A, Howieson D, Silbert LC, Quinn JF et al (2008) Trajectories of brain loss in aging and the development of cognitive impairment. Neurology 70:828–833

    Article  CAS  PubMed  Google Scholar 

  • Carmichael OT, Kuller LH, Lopez OL, Thompson PM, Dutton RA, Lu A et al (2007) Cerebral ventricular changes associated with transitions between normal cognitive function, mild cognitive impairment, and dementia. Alzheimer Dis Assoc Disord 21:14–24

    Article  PubMed  Google Scholar 

  • Chan D, Fox NC, Scahill RI, Crum WR, Whitwell JL, Leschziner G et al (2001) Patterns of temporal lobe atrophy in semantic dementia and Alzheimer’s disease. Ann Neurol 49:433–442

    Article  CAS  PubMed  Google Scholar 

  • Chan D, Janssen JC, Whitwell JL, Watt HC, Jenkins R, Frost C et al (2003) Change in rates of cerebral atrophy over time in early-onset Alzheimer’s disease: longitudinal MRI study. Lancet 362:1121–1122

    Article  PubMed  Google Scholar 

  • Chetelat G, Desgranges B, De La Sayette V, Viader F, Eustache F, Baron JC (2002) Mapping gray matter loss with voxel-based morphometry in mild cognitive impairment. Neuroreport 13:1939–1943

    Article  PubMed  Google Scholar 

  • Chetelat G, Landeau B, Eustache F, Mezenge F, Viader F, de la Sayette V et al (2005) Using voxel-based morphometry to map the structural changes associated with rapid conversion in MCI: a longitudinal MRI study. Neuroimage 27:934–946

    Article  CAS  PubMed  Google Scholar 

  • Czarnecki K, Duffy JR, Nehl CR, Cross SA, Molano JR, Jack CR Jr et al (2008) Very early semantic dementia with progressive temporal lobe atrophy: an 8-year longitudinal study. Arch Neurol 65:1659–1663

    Article  PubMed  Google Scholar 

  • Desikan RS, Fischl B, Cabral HJ, Kemper TL, Guttmann CR, Blacker D et al (2008) MRI measures of temporoparietal regions show differential rates of atrophy during prodromal AD. Neurology 71:819–825

    Article  CAS  PubMed  Google Scholar 

  • Driscoll I, Davatzikos C, An Y, Wu X, Shen D, Kraut M et al (2009) Longitudinal pattern of regional brain volume change differentiates normal aging from MCI. Neurology 72:1906–1913

    Article  CAS  PubMed  Google Scholar 

  • Du AT, Schuff N, Amend D, Laakso MP, Hsu YY, Jagust WJ et al (2001) Magnetic resonance imaging of the entorhinal cortex and hippocampus in mild cognitive impairment and Alzheimer’s disease. J Neurol Neurosurg Psychiatry 71:441–447

    Article  CAS  PubMed  Google Scholar 

  • Engler H, Forsberg A, Almkvist O, Blomquist G, Larsson E, Savitcheva I et al (2006) Two-year follow-up of amyloid deposition in patients with Alzheimer’s disease. Brain 129:2856–2866

    Article  PubMed  Google Scholar 

  • Fox NC, Freeborough PA (1997) Brain atrophy progression measured from registered serial MRI: validation and application to Alzheimer’s disease. J Magn Reson Imaging 7:1069–1075

    Article  CAS  PubMed  Google Scholar 

  • Fox NC, Freeborough PA, Rossor MN (1996) Visualisation and quantification of rates of atrophy in Alzheimer’s disease. Lancet 348:94–97

    Article  CAS  PubMed  Google Scholar 

  • Fox NC, Scahill RI, Crum WR, Rossor MN (1999a) Correlation between rates of brain atrophy and cognitive decline in AD. Neurology 52:1687–1689

    CAS  PubMed  Google Scholar 

  • Fox NC, Warrington EK, Freeborough PA, Hartikainen P, Kennedy AM, Stevens JM et al (1999b) Presymptomatic hippocampal atrophy in Alzheimer’s disease. A longitudinal MRI study. Brain 119(Pt 6):2001–2007

    Google Scholar 

  • Fox NC, Crum WR, Scahill RI, Stevens JM, Janssen JC, Rossor MN (2001) Imaging of onset and progression of Alzheimer’s disease with voxel-compression mapping of serial magnetic resonance images. Lancet 358:201–205

    Article  CAS  PubMed  Google Scholar 

  • Fox NC, Black RS, Gilman S, Rossor MN, Griffith SG, Jenkins L et al (2005) Effects of Abeta immunization (AN1792) on MRI measures of cerebral volume in Alzheimer disease. Neurology 64:1563–1572

    Article  CAS  PubMed  Google Scholar 

  • Gorno-Tempini ML, Murray RC, Rankin KP, Weiner MW, Miller BL (2004) Clinical, cognitive and anatomical evolution from nonfluent progressive aphasia to corticobasal syndrome: a case report. Neurocase 10:426–436

    Article  PubMed  Google Scholar 

  • Hashimoto M, Kazui H, Matsumoto K, Nakano Y, Yasuda M, Mori E (2005) Does donepezil treatment slow the progression of hippocampal atrophy in patients with Alzheimer’s disease? Am J Psychiatry 162:676–682

    Article  PubMed  Google Scholar 

  • Hebert LE, Scherr PA, Bienias JL, Bennett DA, Evans DA (2003) Alzheimer disease in the US population: prevalence estimates using the 2000 census. Arch Neurol 60:1119–1122

    Article  PubMed  Google Scholar 

  • Jack CR Jr, Petersen RC, O’Brien PC, Tangalos EG (1992) MR-based hippocampal volumetry in the diagnosis of Alzheimer’s disease. Neurology 42:183–188

    PubMed  Google Scholar 

  • Jack CR Jr, Petersen RC, Xu Y, O’Brien PC, Smith GE, Ivnik RJ et al (2000) Rates of hippocampal atrophy correlate with change in clinical status in aging and AD. Neurology 55:484–489

    PubMed  Google Scholar 

  • Jack CR Jr, Slomkowski M, Gracon S, Hoover TM, Felmlee JP, Stewart K et al (2003) MRI as a biomarker of disease progression in a therapeutic trial of milameline for AD. Neurology 60:253–260

    Article  PubMed  Google Scholar 

  • Jack CR Jr, Shiung MM, Gunter JL, O’Brien PC, Weigand SD, Knopman DS et al (2004) Comparison of different MRI brain atrophy rate measures with clinical disease progression in AD. Neurology 62:591–600

    PubMed  Google Scholar 

  • Jack CR Jr, Shiung MM, Weigand SD, O’Brien PC, Gunter JL, Boeve BF et al (2005) Brain atrophy rates predict subsequent clinical conversion in normal elderly and amnestic MCI. Neurology 65:1227–1231

    Article  PubMed  Google Scholar 

  • Jack CR Jr, Petersen RC, Grundman M, Jin S, Gamst A, Ward CP et al (2008a) Longitudinal MRI findings from the vitamin E and donepezil treatment study for MCI. Neurobiol Aging 29:1285–1295

    Article  CAS  PubMed  Google Scholar 

  • Jack CR Jr, Weigand SD, Shiung MM, Przybelski SA, O’Brien PC, Gunter JL et al (2008b) Atrophy rates accelerate in amnestic mild cognitive impairment. Neurology 70:1740–1752

    Article  PubMed  Google Scholar 

  • Jack CR Jr, Lowe VJ, Weigand SD, Wiste HJ, Senjem ML, Knopman DS et al (2009) Serial PIB and MRI in normal, mild cognitive impairment and Alzheimer’s disease: implications for sequence of pathological events in Alzheimer’s disease. Brain 132:1355–1365

    Article  PubMed  Google Scholar 

  • Janke AL, de Zubicaray G, Rose SE, Griffin M, Chalk JB, Galloway GJ (2001) 4D deformation modeling of cortical disease progression in Alzheimer’s dementia. Magn Reson Med 46:661–666

    Article  CAS  PubMed  Google Scholar 

  • Janssen JC, Schott JM, Cipolotti L, Fox NC, Scahill RI, Josephs KA et al (2005) Mapping the onset and progression of atrophy in familial frontotemporal lobar degeneration. J Neurol Neurosurg Psychiatry 76:162–168

    Article  CAS  PubMed  Google Scholar 

  • Jicha GA, Parisi JE, Dickson DW, Johnson K, Cha R, Ivnik RJ et al (2006) Neuropathologic outcome of mild cognitive impairment following progression to clinical dementia. Arch Neurol 63:674–681

    Article  PubMed  Google Scholar 

  • Josephs KA, Whitwell JL, Ahmed Z, Shiung MM, Weigand SD, Knopman DS et al (2008a) Beta-amyloid burden is not associated with rates of brain atrophy. Ann Neurol 63:204–212

    Article  PubMed  Google Scholar 

  • Josephs KA, Whitwell JL, Vemuri P, Senjem ML, Boeve BF, Knopman DS et al (2008b) The anatomic correlate of prosopagnosia in semantic dementia. Neurology 71:1628–1633

    Article  CAS  PubMed  Google Scholar 

  • Karas GB, Scheltens P, Rombouts SA, Visser PJ, van Schijndel RA, Fox NC et al (2004) Global and local gray matter loss in mild cognitive impairment and Alzheimer’s disease. Neuroimage 23:708–716

    Article  CAS  PubMed  Google Scholar 

  • Klunk WE, Engler H, Nordberg A, Wang Y, Blomqvist G, Holt DP et al (2004) Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B. Ann Neurol 55:306–319

    Article  CAS  PubMed  Google Scholar 

  • Knopman DS, Jack CR Jr, Kramer JH, Boeve BF, Caselli RJ, Graff-Radford NR et al (2009) Brain and ventricular volumetric changes in frontotemporal lobar degeneration over 1 year. Neurology 72:1843–1849

    Article  CAS  PubMed  Google Scholar 

  • Krueger CE, Dean DL, Rosen HJ, Halabi C, Weiner M, Miller BL et al (2010) Longitudinal rates of lobar atrophy in frontotemporal dementia, semantic dementia, and Alzheimer’s disease. Alzheimer Dis Assoc Disord 24:43–48

    Article  PubMed  Google Scholar 

  • Leow AD, Yanovsky I, Parikshak N, Hua X, Lee S, Toga AW et al (2009) Alzheimer’s disease neuroimaging initiative: a one-year follow up study using tensor-based morphometry correlating degenerative rates, biomarkers and cognition. Neuroimage 45:645–655

    Article  PubMed  Google Scholar 

  • McDonald CR, McEvoy LK, Gharapetian L, Fennema-Notestine C, Hagler DJ Jr, Holland D et al (2009) Regional rates of neocortical atrophy from normal aging to early Alzheimer disease. Neurology 73:457–465

    Article  CAS  PubMed  Google Scholar 

  • McKeith IG, Dickson DW, Lowe J, Emre M, O’Brien JT, Feldman H et al (2005) Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology 65:1863–1872

    Article  CAS  PubMed  Google Scholar 

  • McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 34:939–944

    CAS  PubMed  Google Scholar 

  • Mintun MA, Larossa GN, Sheline YI, Dence CS, Lee SY, Mach RH et al (2006) [11C]PIB in a nondemented population: potential antecedent marker of Alzheimer disease. Neurology 67:446–452

    Article  CAS  PubMed  Google Scholar 

  • Mungas D, Harvey D, Reed BR, Jagust WJ, DeCarli C, Beckett L et al (2005) Longitudinal volumetric MRI change and rate of cognitive decline. Neurology 65:565–571

    Article  CAS  PubMed  Google Scholar 

  • Neary D, Snowden JS, Gustafson L, Passant U, Stuss D, Black S et al (1998) Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 51:1546–1554

    CAS  PubMed  Google Scholar 

  • Nordberg A (2004) PET imaging of amyloid in Alzheimer’s disease. Lancet Neurol 3:519–527

    Article  CAS  PubMed  Google Scholar 

  • O’Brien JT, Paling S, Barber R, Williams ED, Ballard C, McKeith IG et al (2001) Progressive brain atrophy on serial MRI in dementia with Lewy bodies, AD, and vascular dementia. Neurology 56:1386–1388

    PubMed  Google Scholar 

  • Pennanen C, Testa C, Laakso MP, Hallikainen M, Helkala EL, Hanninen T et al (2005) A voxel based morphometry study on mild cognitive impairment. J Neurol Neurosurg Psychiatry 76:11–14

    Article  CAS  PubMed  Google Scholar 

  • Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E (1999) Mild cognitive impairment: clinical characterization and outcome. Arch Neurol 56:303–308

    Article  CAS  PubMed  Google Scholar 

  • Ridha BH, Barnes J, Bartlett JW, Godbolt A, Pepple T, Rossor MN et al (2006) Tracking atrophy progression in familial Alzheimer’s disease: a serial MRI study. Lancet Neurol 5:828–834

    Article  PubMed  Google Scholar 

  • Ridha BH, Anderson VM, Barnes J, Boyes RG, Price SL, Rossor MN et al (2008) Volumetric MRI and cognitive measures in Alzheimer disease: comparison of markers of progression. J Neurol 255:567–574

    Article  PubMed  Google Scholar 

  • Rohrer JD, McNaught E, Foster J, Clegg SL, Barnes J, Omar R et al (2008) Tracking progression in frontotemporal lobar degeneration: serial MRI in semantic dementia. Neurology 71:1445–1451

    Article  CAS  PubMed  Google Scholar 

  • Rosen HJ, Kramer JH, Gorno-Tempini ML, Schuff N, Weiner M, Miller BL (2002) Patterns of cerebral atrophy in primary progressive aphasia. Am J Geriatr Psychiatry 10:89–97

    PubMed  Google Scholar 

  • Scahill RI, Schott JM, Stevens JM, Rossor MN, Fox NC (2002) Mapping the evolution of regional atrophy in Alzheimer’s disease: unbiased analysis of fluid-registered serial MRI. Proc Natl Acad Sci USA 99:4703–4707

    Article  CAS  PubMed  Google Scholar 

  • Schott JM, Crutch SJ, Frost C, Warrington EK, Rossor MN, Fox NC (2008) Neuropsychological correlates of whole brain atrophy in Alzheimer’s disease. Neuropsychologia 46:1732–1737

    Article  CAS  PubMed  Google Scholar 

  • Schuff N, Woerner N, Boreta L, Kornfield T, Shaw LM, Trojanowski JQ et al (2009) MRI of hippocampal volume loss in early Alzheimer’s disease in relation to ApoE genotype and biomarkers. Brain 132:1067–1077

    Article  CAS  PubMed  Google Scholar 

  • Silbert LC, Quinn JF, Moore MM, Corbridge E, Ball MJ, Murdoch G et al (2003) Changes in premorbid brain volume predict Alzheimer’s disease pathology. Neurology 61:487–492

    CAS  PubMed  Google Scholar 

  • Sluimer JD, van der Flier WM, Karas GB, van Schijndel R, Barnes J, Boyes RG et al (2009) Accelerating regional atrophy rates in the progression from normal aging to Alzheimer’s disease. Eur Radiol 19:2826–2833

    Article  PubMed  Google Scholar 

  • Spulber G, Niskanen E, Macdonald S, Smilovici O, Chen K, Reiman EM et al (2008) Whole brain atrophy rate predicts progression from MCI to Alzheimer’s disease. Neurobiol Aging. Sept 29 [Epub ahead of print]

  • Thompson PM, Hayashi KM, de Zubicaray G, Janke AL, Rose SE, Semple J et al (2003) Dynamics of gray matter loss in Alzheimer’s disease. J Neurosci 23:994–1005

    CAS  PubMed  Google Scholar 

  • Thompson PM, Hayashi KM, Dutton RA, Chiang MC, Leow AD, Sowell ER et al (2007) Tracking Alzheimer’s disease. Ann N Y Acad Sci 1097:183–214

    Article  PubMed  Google Scholar 

  • van de Pol LA, van der Flier WM, Korf ES, Fox NC, Barkhof F, Scheltens P (2007) Baseline predictors of rates of hippocampal atrophy in mild cognitive impairment. Neurology 69:1491–1497

    Article  PubMed  Google Scholar 

  • Wang PN, Liu HC, Lirng JF, Lin KN, Wu ZA (2009) Accelerated hippocampal atrophy rates in stable and progressive amnestic mild cognitive impairment. Psychiatry Res 171:221–231

    Article  PubMed  Google Scholar 

  • Whitwell JL, Anderson VM, Scahill RI, Rossor MN, Fox NC (2004) Longitudinal patterns of regional change on volumetric MRI in frontotemporal lobar degeneration. Dement Geriatr Cogn Disord 17:307–310

    Article  PubMed  Google Scholar 

  • Whitwell JL, Jack CR Jr, Parisi JE, Knopman DS, Boeve BF, Petersen RC et al (2007a) Rates of cerebral atrophy differ in different degenerative pathologies. Brain 130:1148–1158

    Article  PubMed  Google Scholar 

  • Whitwell JL, Przybelski S, Weigand SD, Knopman DS, Boeve BF, Petersen RC et al (2007b) 3D maps from multiple MRI illustrate changing atrophy patterns as subjects progress from MCI to AD. Brain 130:1777–1786

    Article  PubMed  Google Scholar 

  • Whitwell JL, Jack CR Jr, Pankratz VS, Parisi JE, Knopman DS, Boeve BF et al (2008a) Rates of brain atrophy over time in autopsy-proven frontotemporal dementia and Alzheimer disease. Neuroimage 39:1034–1040

    Article  PubMed  Google Scholar 

  • Whitwell JL, Josephs KA, Murray ME, Kantarci K, Przybelski SA, Weigand SD et al (2008b) MRI correlates of neurofibrillary tangle pathology at autopsy: a voxel-based morphometry study. Neurology 71:743–749

    Article  CAS  PubMed  Google Scholar 

  • Whitwell JL, Shiung MM, Przybelski SA, Weigand SD, Knopman DS, Boeve BF et al (2008c) MRI patterns of atrophy associated with progression to AD in amnestic mild cognitive impairment. Neurology 70:512–520

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jennifer L. Whitwell.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Whitwell, J.L. Progression of Atrophy in Alzheimer’s Disease and Related Disorders. Neurotox Res 18, 339–346 (2010). https://doi.org/10.1007/s12640-010-9175-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12640-010-9175-1

Keywords

Navigation