title: ¹⁸F-FDG PET for the early diagnosis of Alzheimer's disease dementia and other dementias in people with mild cognitive impairment (MCI).
abstract: BACKGROUND
  ¹⁸F-FDFG uptake by brain tissue as measured by positron emission tomography (PET) is a well-established method for assessment of brain function in people with dementia. Certain findings on brain PET scans can potentially predict the decline of mild cognitive Impairment (MCI) to Alzheimer's disease dementia or other dementias.
  
  
  OBJECTIVE
  To determine the diagnostic accuracy of the ¹⁸F-FDG PET index test for detecting people with MCI at baseline who would clinically convert to Alzheimer's disease dementia or other forms of dementia at follow-up.
  
  
  METHODS
  We searched the Cochrane Register of Diagnostic Test Accuracy Studies, MEDLINE, EMBASE, Science Citation Index, PsycINFO, BIOSIS previews, LILACS, MEDION, (Meta-analyses van Diagnostisch Onderzoek), DARE (Database of Abstracts of Reviews of Effects), HTA (Health Technology Assessment Database), ARIF (Aggressive Research Intelligence Facility) and C-EBLM (International Federation of Clinical Chemistry and Laboratory Medicine Committee for Evidence-based Laboratory Medicine) databases to January 2013. We checked the reference lists of any relevant studies and systematic reviews for additional studies.
  
  
  METHODS
  We included studies that evaluated the diagnostic accuracy of ¹⁸F-FDG PET to determine the conversion from MCI to Alzheimer's disease dementia or to other forms of dementia, i.e. any or all of vascular dementia, dementia with Lewy bodies, and fronto-temporal dementia. These studies necessarily employ delayed verification of conversion to dementia and are sometimes labelled as 'delayed verification cross-sectional studies'.
  
  
  METHODS
  Two blinded review authors independently extracted data, resolving disagreement by discussion, with the option to involve a third review author as arbiter if necessary. We extracted and summarised graphically the data for two-by-two tables. We conducted exploratory analyses by plotting estimates of sensitivity and specificity from each study on forest plots and in receiver operating characteristic (ROC) space. When studies had mixed thresholds, we derived estimates of sensitivity and likelihood ratios at fixed values (lower quartile, median and upper quartile) of specificity from the hierarchical summary ROC (HSROC) models.
  
  
  RESULTS
  We included 14 studies (421 participants) in the analysis. The sensitivities for conversion from MCI to Alzheimer's disease dementia were between 25% and 100% while the specificities were between 15% and 100%. From the summary ROC curve we fitted we estimated that the sensitivity was 76% (95% confidence interval (CI): 53.8 to 89.7) at the included study median specificity of 82%. This equates to a positive likelihood ratio of 4.03 (95% CI: 2.97 to 5.47), and a negative likelihood ratio of 0.34 (95% CI: 0.15 to 0.75). Three studies recruited participants from the same Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort but only the largest ADNI study (Herholz 2011) is included in the meta-analysis. In order to demonstrate whether the choice of ADNI study or discriminating brain region (Chételat 2003) or reader assessment (Pardo 2010) make a difference to the pooled estimate, we performed five additional analyses. At the median specificity of 82%, the estimated sensitivity was between 74% and 76%. There was no impact on our findings. In addition to evaluating Alzheimer's disease dementia, five studies evaluated the accuracy of ¹⁸F-FDG PET for all types of dementia. The sensitivities were between 46% and 95% while the specificities were between 29% and 100%; however, we did not conduct a meta-analysis because of too few studies, and those studies which we had found recruited small numbers of participants. Our findings are based on studies with poor reporting, and the majority of included studies had an unclear risk of bias, mainly for the reference standard and participant selection domains. According to the assessment of Index test domain, more than 50% of studies were of poor methodological quality.
  
  
  CONCLUSIONS
  It is difficult to determine to what extent the findings from the meta-analysis can be applied to clinical practice. Given the considerable variability of specificity values and lack of defined thresholds for determination of test positivity in the included studies, the current evidence does not support the routine use of ¹⁸F-FDG PET scans in clinical practice in people with MCI. The ¹⁸F-FDG PET scan is a high-cost investigation, and it is therefore important to clearly demonstrate its accuracy and to standardise the process of ¹⁸F-FDG PET diagnostic modality prior to its being widely used. Future studies with more uniform approaches to thresholds, analysis and study conduct may provide a more homogeneous estimate than the one available from the included studies we have identified.
authors: Institute of Public Health, University of Cambridge, Forvie Site, Robinson Way, Cambridge, UK, CB2 0SR.
authors: Nadja
authors: N
authors: Smailagic
authors: Marco
authors: M
authors: Vacante
authors: Chris
authors: C
authors: Hyde
authors: Steven
authors: S
authors: Martin
authors: Obioha
authors: O
authors: Ukoumunne
authors: Christos
authors: C
authors: Sachpekidis
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging*; D001921:Brain / Q000000981:diagnostic imaging; D060825:Cognitive Dysfunction / Q000150:complications / Q000000981:diagnostic imaging*; D003704:Dementia / Q000000981:diagnostic imaging*; D018450:Disease Progression; D042241:Early Diagnosis; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008875:Middle Aged; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D012680:Sensitivity and Specificity
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
references: Eur J Neurol. 2005 Apr;12(4):254-63
references: 15804241
references: Neurobiol Aging. 2012 Nov;33(11):2533-50
references: 22365486
references: Ann Intern Med. 2008 Dec 16;149(12):889-97
references: 19075208
references: Curr Alzheimer Res. 2010 Jun;7(4):287-94
references: 19939228
references: Eur J Nucl Med Mol Imaging. 2008 Dec;35(12):2191-202
references: 18648805
references: Alzheimers Dement. 2011 May;7(3):263-9
references: 21514250
references: J Neurol Neurosurg Psychiatry. 1994 Apr;57(4):416-8
references: 8163988
references: PLoS One. 2012;7(3):e33182
references: 22457741
references: Int Psychogeriatr. 2004 Jun;16(2):129-40
references: 15318760
references: Acta Neuropathol. 1991;82(4):239-59
references: 1759558
references: Neurology. 2009 Jan 6;72(1):56-62
references: 19122031
references: J Am Geriatr Soc. 2008 Aug;56(8):1424-33
references: 18662209
references: J Intern Med. 2004 Sep;256(3):183-94
references: 15324362
references: J Nucl Med. 2011 Aug;52(8):1218-26
references: 21764801
references: Ann Neurol. 2012 Oct;72(4):578-86
references: 23109153
references: Alzheimers Dement. 2011 May;7(3):270-9
references: 21514249
references: Neuroimage. 2002 Sep;17(1):302-16
references: 12482085
references: Ann Neurol. 2005 Apr;57(4):480-8
references: 15786453
references: Neuroimage. 2010 Jun;51(2):654-64
references: 20202480
references: Lancet Neurol. 2007 Aug;6(8):734-46
references: 17616482
references: Psychiatry Res. 2007 Jul 15;155(2):147-54
references: 17524628
references: Arch Neurol. 1999 Mar;56(3):303-8
references: 10190820
references: Ann Intern Med. 2011 Oct 18;155(8):529-36
references: 22007046
references: Eur J Nucl Med Mol Imaging. 2009 Dec;36(12):2103-10
references: 19838705
references: Alzheimers Dement. 2010 Jul;6(4):326-33
references: 20447873
references: Arch Neurol. 2011 Oct;68(10):1257-66
references: 21670386
references: Dement Geriatr Cogn Disord. 1999 Nov-Dec;10(6):494-504
references: 10559566
references: BMJ Open. 2012 Apr 24;2(2):e000773
references: 22535791
references: Neurology. 2010 Jan 19;74(3):201-9
references: 20042704
references: Eur J Nucl Med Mol Imaging. 2013 Oct;40(10):1567-72
references: 23801168
references: J Mol Neurosci. 2001 Oct;17(2):101-18
references: 11816784
references: Neurocase. 2005 Feb;11(1):14-25
references: 15804920
references: Cochrane Database Syst Rev. 2006 Apr 19;(2):CD003154
references: 16625572
references: Neurology. 1998 Dec;51(6):1546-54
references: 9855500
references: J Nucl Med. 2012 Dec;53(12):1916-25
references: 23143086
references: Neurology. 2010 Jul 20;75(3):230-8
references: 20592257
references: Arch Neurol. 2009 Dec;66(12):1447-55
references: 20008648
references: Neurobiol Aging. 2010 Aug;31(8):1443-51, 1451.e1
references: 20541287
references: Neurology. 2003 Apr 22;60(8):1374-7
references: 12707450
references: Neurology. 2012 Sep 25;79(13):1349-55
references: 22972646
references: Cochrane Database Syst Rev. 2006 Jan 25;(1):CD005593
references: 16437532
references: Neuroimage. 2012 Mar;60(1):221-9
references: 22236449
references: Arch Neurol. 2005 Nov;62(11):1728-33
references: 16286547
references: J Nucl Med. 2005 Oct;46(10):1625-32
references: 16204712
references: JAMA. 2009 Jul 22;302(4):385-93
references: 19622817
references: AJNR Am J Neuroradiol. 2010 Feb;31(2):347-54
references: 20075088
references: Am J Alzheimers Dis Other Demen. 2010 Jun;25(4):324-32
references: 20539026
references: Neurology. 1993 Feb;43(2):250-60
references: 8094895
references: Alzheimers Dement. 2010 May;6(3):257-64
references: 20451874
references: Lancet Neurol. 2010 Nov;9(11):1118-27
references: 20934914
references: Acta Neurol Scand. 2000 Mar;101(3):172-6
references: 10705939
references: Neurobiol Aging. 2008 Oct;29(10):1456-65
references: 17499392
references: Neurology. 2013 Jul 30;81(5):487-500
references: 23897875
references: J Nucl Med. 2002 Feb;43(2):253-66
references: 11850493
references: Am J Psychiatry. 1995 Dec;152(12):1757-64
references: 8526242
references: J Neurol. 2010 Dec;257(12):2004-14
references: 20632026
references: Lancet. 2011 Mar 19;377(9770):1019-31
references: 21371747
references: J Nucl Med. 2000 Nov;41(11):1920-8
references: 11079505
references: J Alzheimers Dis. 2012;29(3):641-8
references: 22297644
references: J Nucl Med. 1995 Jul;36(7):1238-48
references: 7790950
references: JAMA. 2001 Nov 7;286(17):2120-7
references: 11694153
references: Neurology. 2007 Aug 28;69(9):871-7
references: 17724289
references: Neurobiol Aging. 2010 Aug;31(8):1364-74
references: 20570399
references: Alzheimer Dis Assoc Disord. 2005 Oct-Dec;19 Suppl 1:S3-6
references: 16317256
references: J Alzheimers Dis. 2006;9(3 Suppl):417-23
references: 16914880
references: J Psychiatr Res. 1999 Jan-Feb;33(1):7-16
references: 10094234
references: BMJ. 2002 Feb 23;324(7335):477-80
references: 11859054
references: Am J Psychiatry. 1984 Nov;141(11):1356-64
references: 6496779
references: Int J Alzheimers Dis. 2010 Sep 20;2011:
references: 20885966
references: Nat Rev Drug Discov. 2010 Jul;9(7):560-74
references: 20592748
references: Biol Psychiatry. 2004 Aug 15;56(4):279-83
references: 15312816
references: Neuroreport. 2001 Mar 26;12(4):851-5
references: 11277595
references: J Nucl Med. 2001 Apr;42(4):548-57
references: 11337540
references: Am J Psychiatry. 1982 Sep;139(9):1136-9
references: 7114305
references: Dement Geriatr Cogn Disord. 2005;19(5-6):383-9
references: 15802914
references: Eur J Nucl Med Mol Imaging. 2010 Jan;37(1):36-45
references: 19662411
references: Arch Neurol. 1986 Sep;43(9):882-5
references: 3488728
references: Neurology. 1996 Nov;47(5):1113-24
references: 8909416
references: Alzheimers Dement. 2013 Jul;9(4):414-21
references: 23164552
references: Neurology. 1984 Jul;34(7):939-44
references: 6610841
references: Cochrane Database Syst Rev. 2013 Sep 11;(9):MR000022
references: 24022476
references: Neurology. 2008 Oct 21;71(17):1342-9
references: 18936426
references: Eur J Nucl Med Mol Imaging. 2012 Jun;39(6):990-1000
references: 22441582
references: Eur J Nucl Med Mol Imaging. 2003 Aug;30(8):1104-13
references: 12764551
references: Neuron. 2004 Aug 5;43(3):321-32
references: 15294141
references: Neurobiol Aging. 2011 Jul;32(7):1207-18
references: 19660834
references: Neurology. 2004 Dec 28;63(12):2332-40
references: 15623696
references: Alzheimers Dement. 2010 May;6(3):221-9
references: 20451870
references: Neurology. 1986 Jul;36(7):879-87
references: 3487046
references: Fam Pract. 2004 Feb;21(1):4-10
references: 14760036
references: Arch Neurol. 2001 Dec;58(12):1985-92
references: 11735772
references: Neurology. 2006 Oct 10;67(7):1201-7
references: 17030753
references: Q J Nucl Med Mol Imaging. 2009 Dec;53(6):646-57
references: 20016455
references: Lancet. 2005 Dec 17;366(9503):2112-7
references: 16360788
references: Int Psychogeriatr. 2009 Feb;21(1):148-56
references: 19040787
references: Neurobiol Aging. 2012 Jan;33(1):198.e1-14
references: 20688420
references: J Nucl Med. 2012 Jan;53(1):59-71
references: 22173840
references: J Intern Med. 2004 Sep;256(3):240-6
references: 15324367
references: Dement Geriatr Cogn Disord. 2010;29(3):213-23
references: 20332639
references: Stat Med. 2001 Oct 15;20(19):2865-84
references: 11568945
references: Eur J Nucl Med Mol Imaging. 2008 Jul;35(7):1357-66
references: 18418593
references: Psychiatry Res. 2007 Jul 15;155(2):167-71
references: 17531450
references: Neurology. 1993 Nov;43(11):2412-4
references: 8232972
references: J Nucl Med. 1999 May;40(5):737-46
references: 10319744
references: Eur J Nucl Med Mol Imaging. 2002 Oct;29(10):BP43-8
references: 12436498
references: Cochrane Database Syst Rev. 2014 Apr 10;(4):CD010079
references: 24719028
references: Alzheimers Dement. 2011 May;7(3):280-92
references: 21514248
references: J Nucl Med. 1997 Jul;38(7):1095-101
references: 9225797
references: Cochrane Database Syst Rev. 2015 Jan 28;1:CD010632
references: 25629415
references: J Alzheimers Dis. 2010;20(2):547-60
references: 20164554
references: Neuroimage. 2009 Oct 1;47(4):1196-206
references: 19463961