Voxel Level Survival Analysis of Grey Matter Volume and Incident Mild Cognitive Impairment or Alzheimer's Disease

被引:20
作者
Zeifman, Lubov E. [1 ,4 ]
Eddy, William F. [1 ,2 ,3 ,4 ]
Lopez, Oscar L. [3 ]
Kuller, Lewis H. [6 ]
Raji, Cyrus [9 ]
Thompson, Paul M. [10 ,11 ,12 ]
Becker, James T. [5 ,7 ,8 ]
机构
[1] Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA
[2] Carnegie Mellon Univ, Dept Machine Learning, Pittsburgh, PA 15213 USA
[3] Carnegie Mellon Univ, Dept Biol Sci, Pittsburgh, PA 15213 USA
[4] Carnegie Mellon Univ, Dept Ctr Neural Basis Cognit, Pittsburgh, PA 15213 USA
[5] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA
[6] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA
[7] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA
[8] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA
[9] Univ Calif Los Angeles, Dept Radiol, Los Angeles, CA USA
[10] Univ So Calif, Imaging Genet Ctr, Los Angeles, CA USA
[11] Keck USC Sch Med, Dept Neurol, Dept Psychiat, Dept Radiol,Dept Pediat,Dept Engn, Los Angeles, CA USA
[12] Keck USC Sch Med, Dept Ophthalmol, Los Angeles, CA USA
基金
美国国家科学基金会;
关键词
Alzheimer's disease; Cox survival model; incidence; mild cognitive impairment; MRI; MEDIAL TEMPORAL-LOBE; SMALL VESSEL DISEASE; CARDIOVASCULAR HEALTH; WHITE-MATTER; VASCULAR DEMENTIA; OLDER-ADULTS; HYPOTHETICAL MODEL; BLOOD-PRESSURE; MRI FINDINGS; RISK-FACTORS;
D O I
10.3233/JAD-150047
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The purpose of this study was to identify, at the voxel level, brain regions associated with the time to develop mild cognitive impairment (MCI) or Alzheimer's disease (AD) from normal cognition. We analyzed incident MCI (n = 58) or AD (n = 151) in 292 cognitively normal participants in the Cardiovascular Health Study-Cognition Study (mean age = 79.2 +/- 3.6 years). We used segmented, modulated grey matter maps from 3D (spoiled gradient echo) MRI scans obtained in 1998/99 (with clinical follow-up through 2012) that were smoothed with a 3-D 4mm Gaussian filter. We fit approximately 1.92 million voxel-level Cox proportional hazard models to examine the grey matter volume effect on time to event, adjusting for age, sex, and diabetes. We used the significance threshold of p < 0.005 with contiguity threshold of at least 68 voxels (false detection probability < 2.5x10(-8)). Areas within the mesial temporal lobe (MTL), anterior temporal lobe, hippocampus, and posterior cingulate gyrus were associated with time to MCI or AD. The presence of white matter lesions (a marker of small vessel disease in the brain) was associated with the volumes of the MTL and precuneus; MRI-identified infarcts also predicted MTL volume. These findings are important because we identified critical brain regions that predict a person's increased likelihood of developing MCI or AD over a decade prior to the onset of clinical symptoms; these critical brain regions were themselves affected by the presence of vascular disease.
引用
收藏
页码:167 / 178
页数:12
相关论文
共 77 条
[1]   SCREENING FOR DEPRESSION IN WELL OLDER ADULTS - EVALUATION OF A SHORT-FORM OF THE CES-D [J].
ANDRESEN, EM ;
MALMGREN, JA ;
CARTER, WB ;
PATRICK, DL .
AMERICAN JOURNAL OF PREVENTIVE MEDICINE, 1994, 10 (02) :77-84
[2]  
[Anonymous], 1994, DSM 4
[3]  
[Anonymous], 1981, Wechsler Adult Intelligence Scale-Revised
[4]  
[Anonymous], 2012, The WHO application of ICD-10 to deaths during pregnancy, childbirth and the puerperium: IDC-MM
[5]   Three-dimensional patterns of hippocampal atrophy in mild cognitive impairment [J].
Becker, JT ;
Davis, SW ;
Hayashi, KM ;
Meltzer, CC ;
Toga, AW ;
Lopez, OL ;
Thompson, PM .
ARCHIVES OF NEUROLOGY, 2006, 63 (01) :97-101
[6]  
Berent S, 1999, J PSYCHIAT RES, V33, P7
[7]   Intensity non-uniformity correction using N3 on 3-T scanners with mutichannel phased array coils [J].
Boyes, Richard G. ;
Gunter, Jeff L. ;
Frost, Chris ;
Janke, Andrew L. ;
Yeatman, Thomas ;
Hill, Derek L. G. ;
Bernstein, Matt A. ;
Thompson, Paul M. ;
Weiner, Michael W. ;
Schuff, Norbert ;
Alexander, Gene E. ;
Killiany, Ronald J. ;
DeCarli, Charles ;
Jack, Clifford R. ;
Fox, Nick C. .
NEUROIMAGE, 2008, 39 (04) :1752-1762
[8]  
Brandt, 1988, NEUROPSY NEUROPSY BE, V1, P111, DOI DOI 10.1001/ARCHNEUR.1993.00540060039014
[9]  
BRYAN RN, 1994, AM J NEURORADIOL, V15, P1625
[10]   Molecular, structural, and functional characterization of Alzheimer's disease: Evidence for a relationship between default activity, amyloid, and memory [J].
Buckner, RL ;
Snyder, AZ ;
Shannon, BJ ;
LaRossa, G ;
Sachs, R ;
Fotenos, AF ;
Sheline, YI ;
Klunk, WE ;
Mathis, CA ;
Morris, JC ;
Mintun, MA .
JOURNAL OF NEUROSCIENCE, 2005, 25 (34) :7709-7717