title: Measuring cerebral atrophy and white matter hyperintensity burden to predict the rate of cognitive decline in Alzheimer disease.
abstract: OBJECTIVE
  To determine if baseline measurements of cerebral atrophy and severity of white matter hyperintensity (WMH) predict the rate of future cognitive decline in patients with Alzheimer disease (AD).
  
  
  METHODS
  Data were drawn from the Predictors Study, a longitudinal study that enrolls patients with mild AD and reassesses them every 6 months with use of the Columbia modified Mini-Mental State (mMMS) examination (score range, 0-57). Magnetic resonance images were analyzed to determine the severity of WMH, using the Scheltens scale, and the degree of atrophy, using the bicaudate ratio. Generalized estimating equations were used to determine whether severity of baseline magnetic resonance image measurements and their interaction predicted the rate of mMMS score decline at subsequent visits.
  
  
  METHODS
  Three university-based AD centers in the United States.
  
  
  METHODS
  At baseline, 84 patients with AD from the Predictors Study received structural magnetic resonance imaging and were selected for analysis. They had a mean of 6 follow-up evaluations. Main Outcome Measure The mMMS score.
  
  
  RESULTS
  Generalized estimating equation models demonstrated that the degree of baseline atrophy (beta = -0.316; P = .04), the severity of WMH (beta = -0.173; P = .03), and their interaction (beta = -6.061; P = .02) predicted the rate of decline in mMMS scores.
  
  
  CONCLUSIONS
  Both degree of cerebral atrophy and severity of WMH are associated with the rapidity of cognitive decline in AD. Atrophy and WMH may have a synergistic effect on future decline in AD, such that patients with a high degree of both have a particularly precipitous cognitive course. These findings lend further support to the hypothesis that cerebrovascular pathological abnormalities contribute to the clinical syndrome of AD.
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, 630 W 168th St, Campus Box 16, New York, NY 10032, USA. amb2139@columbia.edu
authors.forename: Adam M
authors.initials: AM
authors.lastname: Brickman
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Honig
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Scarmeas
authors.forename: Oksana
authors.initials: O
authors.lastname: Tatarina
authors.forename: Linda
authors.initials: L
authors.lastname: Sanders
authors.forename: Marilyn S
authors.initials: MS
authors.lastname: Albert
authors.forename: Jason
authors.initials: J
authors.lastname: Brandt
authors.forename: Deborah
authors.initials: D
authors.lastname: Blacker
authors.forename: Yaakov
authors.initials: Y
authors.lastname: Stern
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology* / Q000523:psychology; D001284:Atrophy; D001921:Brain / Q000473:pathology*; D010054:Brief Psychiatric Rating Scale / Q000592:standards; D003072:Cognition Disorders / Q000473:pathology* / Q000523:psychology; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D019636:Neurodegenerative Diseases / Q000473:pathology / Q000523:psychology; D011237:Predictive Value of Tests; D012107:Research Design / Q000592:standards*
references.citation: Neurology. 2000 Aug 22;55(4):484-89
references.pmid: 10953178
references.citation: Arch Neurol. 1994 Mar;51(3):260-8
references.pmid: 8129637
references.citation: Arch Neurol. 2006 Feb;63(2):246-50
references.pmid: 16476813
references.citation: AJNR Am J Neuroradiol. 1997 Jan;18(1):115-23
references.pmid: 9010529
references.citation: Neurology. 2001 Nov 27;57(10):1756-63
references.pmid: 11723259
references.citation: Ann Neurol. 2008 Jan;63(1):72-80
references.pmid: 18157909
references.citation: Arch Neurol. 1990 May;47(5):524-7
references.pmid: 2334300
references.citation: Biol Psychiatry. 1993 Nov 1;34(9):612-21
references.pmid: 8292690
references.citation: Arch Gen Psychiatry. 2002 Sep;59(9):785-92
references.pmid: 12215077
references.citation: Neurology. 1999 May 12;52(8):1687-9
references.pmid: 10331700
references.citation: J Lipid Res. 1990 Mar;31(3):545-8
references.pmid: 2341813
references.citation: Neurology. 1978 Nov;28(11):1196-1200
references.pmid: 152416
references.citation: J Psychiatr Res. 1975 Nov;12(3):189-98
references.pmid: 1202204
references.citation: Stroke. 2000 Sep;31(9):2182-8
references.pmid: 10978049
references.citation: Stroke. 1999 Mar;30(3):529-36
references.pmid: 10066847
references.citation: Neuropsychology. 2000 Apr;14(2):224-32
references.pmid: 10791862
references.citation: J Gerontol A Biol Sci Med Sci. 1996 Jul;51(4):M179-84
references.pmid: 8681001
references.citation: JAMA. 1997 Mar 12;277(10):813-7
references.pmid: 9052711
references.citation: Ann N Y Acad Sci. 2002 Nov;977:411-5
references.pmid: 12480780
references.citation: Ann Neurol. 2004 Apr;55(4):570-5
references.pmid: 15048897
references.citation: Neurosci Lett. 2006 Oct 2;406(1-2):60-5
references.pmid: 16904823
references.citation: Neurobiol Aging. 2000 Jan-Feb;21(1):19-26
references.pmid: 10794844
references.citation: Neurology. 2005 May 10;64(9):1520-4
references.pmid: 15883311
references.citation: Neurobiol Aging. 2007 Mar;28(3):389-97
references.pmid: 16504345
references.citation: J Geriatr Psychiatry Neurol. 1994 Jan-Mar;7(1):13-7
references.pmid: 8192824
references.citation: Neuroradiology. 1999 Apr;41(4):261-4
references.pmid: 10344510
references.citation: Arch Neurol. 2005 Dec;62(12):1870-6
references.pmid: 16344345
references.citation: Dement Geriatr Cogn Disord. 2005;20(6):358-66
references.pmid: 16192726
references.citation: Neurology. 2004 Jul 13;63(1):108-14
references.pmid: 15249619
references.citation: Neurology. 2004 May 25;62(10):1862-4
references.pmid: 15159496
references.citation: Brain. 1992 Jun;115 ( Pt 3):735-48
references.pmid: 1628199
references.citation: Arch Neurol. 2002 Oct;59(10):1612-20
references.pmid: 12374500
references.citation: J Neurol Neurosurg Psychiatry. 2001 Jan;70(1):9-14
references.pmid: 11118240
references.citation: Neurology. 2005 May 24;64(10):1696-703
references.pmid: 15911793
references.citation: Neuroepidemiology. 1997;16(3):149-62
references.pmid: 9159770
references.citation: Neurology. 2006 Jan 10;66(1):23-9
references.pmid: 16401840
references.citation: AJR Am J Roentgenol. 1989 Jun;152(6):1257-62
references.pmid: 2785749
references.citation: Acta Neuropathol. 2002 May;103(5):481-7
references.pmid: 11935264
references.citation: Gerontology. 2004 Jul-Aug;50(4):242-6
references.pmid: 15258430
references.citation: Alzheimer Dis Assoc Disord. 1993 Spring;7(1):3-21
references.pmid: 8481224
references.citation: AJNR Am J Neuroradiol. 1994 May;15(5):929-37
references.pmid: 8059663
references.citation: J Neurol Sci. 1993 Jan;114(1):7-12
references.pmid: 8433101
references.citation: Neurology. 1984 Jul;34(7):939-44
references.pmid: 6610841
references.citation: Lancet. 1996 Jul 13;348(9020):94-7
references.pmid: 8676724
references.citation: Ann N Y Acad Sci. 2007 Feb;1097:215-24
references.pmid: 17413024
references.citation: Neurology. 2004 Sep 28;63(6):975-82
references.pmid: 15452286
references.citation: Alzheimer Dis Assoc Disord. 1993 Spring;7(1):22-32
references.pmid: 8481223
references.citation: J Neurol Neurosurg Psychiatry. 2001 Oct;71(4):441-7
references.pmid: 11561025
references.citation: J Neurol Neurosurg Psychiatry. 2004 Jun;75(6):822-7
references.pmid: 15145992
references.citation: Neurology. 2004 Feb 24;62(4):591-600
references.pmid: 14981176
references.citation: Dement Geriatr Cogn Disord. 1998 Jul;9 Suppl 1:6-12
references.pmid: 9716238
references.citation: Neurology. 1993 Sep;43(9):1683-9
references.pmid: 8414012