title: Relation between subcortical grey matter atrophy and conversion from mild cognitive impairment to Alzheimer's disease.
abstract: OBJECTIVE
  To investigate whether subcortical grey matter atrophy predicts progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD), and to compare subcortical volumes between AD, MCI and controls. To assess the correlation between subcortical grey matter volumes and severity of cognitive impairment.
  
  
  METHODS
  We included 773 participants with three-dimensional T1-weighted MRI at 3 T, made up of 181 controls, who had subjective memory symptoms with normal cognition, 201 MCIs and 391 AD. During follow-up (2.0 ± 0.9 years), 35 MCIs converted to AD (progressive MCI) and 160 MCIs remained stable (stable MCI). We segmented volumes of six subcortical structures of the amygdala, thalamus, caudate nucleus, putamen, globus pallidus and nucleus accumbens, and of the hippocampus, using FMRIBs integrated registration and segmentation tool.
  
  
  RESULTS
  Analysis of variances, adjusted for sex and age, showed that all structures, except the globus pallidus, were smaller in AD than in controls. In addition, the amygdala, thalamus, putamen, nucleus accumbens and hippocampus were smaller in MCIs than in controls. Across groups, all subcortical greymatter volumes, except the globus pallidus, showed a positive correlation with cognitive function, as measured by Mini Mental State Examination (MMSE) (0.16<r<0.28, all p<0.05). Cox proportional hazards analyses adjusted for age, sex, education, Cambridge Cognitive Examination-Revised (CAMCOG-R) and MMSE showed that smaller volumes of the hippocampus and nucleus accumbens were associated with increased risk of progression from MCI to AD (HR (95% CI) 1.60 (1.15 to 2.21); 1.60 (1.09 to 2.35), p<0.05).
  
  
  CONCLUSIONS
  In addition to the hippocampus, the nucleus accumbens volume loss was also associated with increased risk of progression from MCI to AD. Furthermore, volume loss of subcortical grey matter structures was associated with severity of cognitive impairment.
authors.affiliation: Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands Department of Neurology, Keimyung University School of Medicine, Daegu, South Korea.
authors.forename: Hyon-Ah
authors.initials: HA
authors.lastname: Yi
authors.affiliation: Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Christiane
authors.initials: C
authors.lastname: Möller
authors.affiliation: Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands Department of Radiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Nikki
authors.initials: N
authors.lastname: Dieleman
authors.affiliation: Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Femke H
authors.initials: FH
authors.lastname: Bouwman
authors.affiliation: Department of Radiology & Nuclear Medicine, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.affiliation: Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.affiliation: Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands Department of Epidemiology & Biostatistics, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Wiesje M
authors.initials: WM
authors.lastname: van der Flier
authors.affiliation: Department of Radiology & Nuclear Medicine, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands Department of Physics & Medical Technology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Hugo
authors.initials: H
authors.lastname: Vrenken
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology* / Q000523:psychology; D001284:Atrophy; D060825:Cognitive Dysfunction / Q000473:pathology* / Q000523:psychology; D018450:Disease Progression; D004522:Educational Status; D005260:Female; D066128:Gray Matter / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory; D008875:Middle Aged; D009483:Neuropsychological Tests; D012737:Sex Factors
keywords: ALZHEIMER'S DISEASE; MRI