Mild cognitive impairment with suspected nonamyloid pathology (SNAP) Prediction of progression

被引:111
作者
Caroli, Anna [1 ]
Prestia, Annapaola [2 ]
Galluzzi, Samantha [2 ]
Ferrari, Clarissa [2 ]
van der Flier, Wiesje M. [3 ,4 ,5 ]
Ossenkoppele, Rik [3 ,4 ]
Van Berckel, Bart [6 ]
Barkhof, Frederik [6 ]
Teunissen, Charlotte [7 ,8 ]
Wall, Anders E. [9 ]
Carter, Stephen F. [10 ,11 ]
Schoell, Michael [10 ,12 ]
Choo, Il Han [10 ,13 ]
Grimmer, Timo [14 ]
Redolfi, Alberto [2 ]
Nordberg, Agneta [10 ,15 ]
Scheltens, Philip [3 ,4 ]
Drzezga, Alexander [16 ]
Frisoni, Giovanni B. [2 ,17 ,18 ]
机构
[1] IRCCS Ist Ric Farmacol Mario Negri, Dept Biomed Engn, Med Imaging Unit, Bergamo, Italy
[2] IRCCS Ctr San Giovanni Dio Fatebenefratelli, LENITEM Lab Epidemiol Neuroimaging & Telemed, Brescia, Italy
[3] Vrije Univ Amsterdam, Med Ctr, Alzheimer Ctr, Amsterdam, Netherlands
[4] Vrije Univ Amsterdam, Med Ctr, Dept Neurol, Amsterdam, Netherlands
[5] Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, Amsterdam, Netherlands
[6] Vrije Univ Amsterdam, Med Ctr, Dept Radiol & Nucl Med, Amsterdam, Netherlands
[7] Vrije Univ Amsterdam, Med Ctr, Neurochem Lab, Amsterdam, Netherlands
[8] Vrije Univ Amsterdam, Med Ctr, Biobank, Dept Clin Chem, Amsterdam, Netherlands
[9] Uppsala Univ, Dept Radiol Oncol & Radiat Sci, PET Ctr, Sect Nucl Med & PET, S-75105 Uppsala, Sweden
[10] Karolinska Inst, Alzheimer Neurobiol Ctr, Stockholm, Sweden
[11] Univ Manchester, Wolfson Mol Imaging Ctr, Manchester M13 9PL, Lancs, England
[12] Univ Gothenburg, Sahlgrenska Univ Hosp, MedTech West, Gothenburg, Sweden
[13] Chosun Univ, Sch Med, Dept Neuropsychiat, Kwangju, South Korea
[14] Tech Univ Munich, Klinikum Rechts Isar, Dept Psychiat & Psychotherapy, D-80290 Munich, Germany
[15] Karolinska Univ Hosp Huddinge, Dept Geriatr Med, Stockholm, Sweden
[16] Univ Cologne, Dept Nucl Med, Cologne, Germany
[17] Univ Hosp, Dept Internal Med, Geneva, Switzerland
[18] Univ Hosp, Dept Psychiat, Geneva, Switzerland
基金
加拿大健康研究院; 瑞典研究理事会;
关键词
CEREBROSPINAL-FLUID BIOMARKERS; ALZHEIMERS-DISEASE; NATIONAL INSTITUTE; BETA; RECOMMENDATIONS; ACCURACY; DEMENTIA; MARKERS; TANGLE; PIB;
D O I
10.1212/WNL.0000000000001209
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Objectives:The aim of this study was to investigate predictors of progressive cognitive deterioration in patients with suspected non-Alzheimer disease pathology (SNAP) and mild cognitive impairment (MCI).Methods:We measured markers of amyloid pathology (CSF -amyloid 42) and neurodegeneration (hippocampal volume on MRI and cortical metabolism on [F-18]-fluorodeoxyglucose-PET) in 201 patients with MCI clinically followed for up to 6 years to detect progressive cognitive deterioration. We categorized patients with MCI as A+/A- and N+/N- based on presence/absence of amyloid pathology and neurodegeneration. SNAPs were A-N+ cases.Results:The proportion of progressors was 11% (8/41), 34% (14/41), 56% (19/34), and 71% (60/85) in A-N-, A+N-, SNAP, and A+N+, respectively; the proportion of APOE epsilon 4 carriers was 29%, 70%, 31%, and 71%, respectively, with the SNAP group featuring a significantly different proportion than both A+N- and A+N+ groups (p 0.005). Hypometabolism in SNAP patients was comparable to A+N+ patients (p = 0.154), while hippocampal atrophy was more severe in SNAP patients (p = 0.002). Compared with A-N-, SNAP and A+N+ patients had significant risk of progressive cognitive deterioration (hazard ratio = 2.7 and 3.8, p = 0.016 and p < 0.001), while A+N- patients did not (hazard ratio = 1.13, p = 0.771). In A+N- and A+N+ groups, none of the biomarkers predicted time to progression. In the SNAP group, lower time to progression was correlated with greater hypometabolism (r = 0.42, p = 0.073).Conclusions:Our findings support the notion that patients with SNAP MCI feature a specific risk progression profile.
引用
收藏
页码:508 / 515
页数:8
相关论文
共 30 条
[1]   The significance of medial temporal lobe atrophy [J].
Barkhof, F. ;
Polvikoski, T. M. ;
Van Straaten, E. C. W. ;
Kalaria, R. N. ;
Sulkava, R. ;
Aronen, H. J. ;
Niinisto, L. ;
Rastas, S. ;
Oinas, M. ;
Scheltens, P. ;
Erkinjuntti, T. .
NEUROLOGY, 2007, 69 (15) :1521-1527
[2]   Clinical and Biomarker Changes in Dominantly Inherited Alzheimer's Disease [J].
Bateman, Randall J. ;
Xiong, Chengjie ;
Benzinger, Tammie L. S. ;
Fagan, Anne M. ;
Goate, Alison ;
Fox, Nick C. ;
Marcus, Daniel S. ;
Cairns, Nigel J. ;
Xie, Xianyun ;
Blazey, Tyler M. ;
Holtzman, David M. ;
Santacruz, Anna ;
Buckles, Virginia ;
Oliver, Angela ;
Moulder, Krista ;
Aisen, Paul S. ;
Ghetti, Bernardino ;
Klunk, William E. ;
McDade, Eric ;
Martins, Ralph N. ;
Masters, Colin L. ;
Mayeux, Richard ;
Ringman, John M. ;
Rossor, Martin N. ;
Schofield, Peter R. ;
Sperling, Reisa A. ;
Salloway, Stephen ;
Morris, John C. .
NEW ENGLAND JOURNAL OF MEDICINE, 2012, 367 (09) :795-804
[3]   Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer Disease Centers, 2005-2010 [J].
Beach, Thomas G. ;
Monsell, Sarah E. ;
Phillips, Leslie E. ;
Kukull, Walter .
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2012, 71 (04) :266-273
[4]  
Blennow K, 2014, ALZHEIMERS DEMENT EP
[5]   Fluid Biomarkers in Alzheimer Disease [J].
Blennow, Kaj ;
Zetterberg, Henrik ;
Fagan, Anne M. .
COLD SPRING HARBOR PERSPECTIVES IN MEDICINE, 2012, 2 (09)
[6]  
Chételat G, 2013, NAT REV NEUROL, V9, P123, DOI [10.1038/nrneurol.2013.21, 10.1038/nrneurol.2013.21-c2]
[7]  
del Campo M, 2012, BIOMARK MED, V6, P419, DOI [10.2217/BMM.12.46, 10.2217/bmm.12.46]
[8]   Biomarker-based prediction of progression in MCI: comparison of AD signature and hippocampal volume with spinal fluid amyloid-β and tau [J].
Dickerson, Bradford C. ;
Wolk, David A. .
FRONTIERS IN AGING NEUROSCIENCE, 2013, 5
[9]   Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer's disease [J].
Giannakopoulos, P ;
Herrmann, FR ;
Bussière, T ;
Bouras, C ;
Kövari, E ;
Perl, DP ;
Morrison, JH ;
Gold, G ;
Hof, PR .
NEUROLOGY, 2003, 60 (09) :1495-1500
[10]   Discrimination between Alzheimer dementia and controls by automated analysis of multicenter FDG PET [J].
Herholz, K ;
Salmon, E ;
Perani, D ;
Baron, JC ;
Holthoff, V ;
Frölich, L ;
Schönknecht, P ;
Ito, K ;
Mielke, R ;
Kalbe, E ;
Zündorf, G ;
Delbeuck, X ;
Pelati, O ;
Anchisi, D ;
Fazio, F ;
Kerrouche, N ;
Desgranges, B ;
Eustache, F ;
Beuthien-Baumann, B ;
Menzel, C ;
Schröder, J ;
Kato, T ;
Arahata, Y ;
Henze, M ;
Heiss, WD .
NEUROIMAGE, 2002, 17 (01) :302-316