title: Depressive symptoms accelerate cognitive decline in amyloid-positive MCI patients.
abstract: OBJECTIVE
  Late-life depression even in subsyndromal stages is strongly associated with Alzheimer's disease (AD). Furthermore, brain amyloidosis is an early biomarker in subjects who subsequently suffer from AD and can be sensitively detected by amyloid PET. Therefore, we aimed to compare amyloid load and glucose metabolism in subsyndromally depressed subjects with mild cognitive impairment (MCI).
  
  
  METHODS
  [(18)F]AV45 PET, [(18)F]FDG PET and MRI were performed in 371 MCI subjects from the Alzheimer's Disease Neuroimaging Initiative Subjects were judged β-amyloid-positive (Aβ+; 206 patients) or β-amyloid-negative (Aβ-; 165 patients) according to [(18)F]AV45 PET. Depressive symptoms were assessed by the Neuropsychiatric Inventory Questionnaire depression item 4. Subjects with depressive symptoms (65 Aβ+, 41 Aβ-) were compared with their nondepressed counterparts. Conversion rates to AD were analysed (mean follow-up time 21.5 ± 9.1 months) with regard to coexisting depressive symptoms and brain amyloid load.
  
  
  RESULTS
  Aβ+ depressed subjects showed large clusters with a higher amyloid load in the frontotemporal and insular cortices (p < 0.001) with coincident hypermetabolism (p < 0.001) in the frontal cortices than nondepressed subjects. Faster progression to AD was observed in subjects with depressive symptoms (p < 0.005) and in Aβ+ subjects (p < 0.001). Coincident depressive symptoms additionally shortened the conversion time in all Aβ+ subjects (p < 0.005) and to a greater extent in those with a high amyloid load (p < 0.001).
  
  
  CONCLUSIONS
  Our results clearly indicate that Aβ+ MCI subjects with depressive symptoms have an elevated amyloid load together with relative hypermetabolism of connected brain areas compared with cognitively matched nondepressed individuals. MCI subjects with high amyloid load and coexistent depressive symptoms are at high risk of faster conversion to AD.
authors: Department of Nuclear Medicine, University of Munich, Munich, Germany.
authors: Matthias
authors: M
authors: Brendel
authors: Oliver
authors: O
authors: Pogarell
authors: Guoming
authors: G
authors: Xiong
authors: Andreas
authors: A
authors: Delker
authors: Peter
authors: P
authors: Bartenstein
authors: Axel
authors: A
authors: Rominger
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D060825:Cognitive Dysfunction / Q000150:complications / Q000000981:diagnostic imaging*; D003863:Depression / Q000150:complications*; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008297:Male; D058225:Plaque, Amyloid / Q000150:complications / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
references: Psychiatry Investig. 2010 Sep;7(3):208-14
references: 20927310
references: Arch Gen Psychiatry. 1997 Oct;54(10):915-22
references: 9337771
references: Lancet Neurol. 2013 Apr;12(4):357-67
references: 23477989
references: Int J Geriatr Psychiatry. 2009 Aug;24(8):798-808
references: 19173332
references: J Neuropsychiatry Clin Neurosci. 2013 Fall;25(4):302-7
references: 24247857
references: Alzheimers Dement. 2014 Nov;10(6):743-751.e1
references: 24589436
references: Int J Geriatr Psychiatry. 2013 Apr;28(4):417-23
references: 22740289
references: J Alzheimers Dis. 2014;40(3):551-61
references: 24496075
references: Biol Psychiatry. 2012 May 1;71(9):814-21
references: 22322105
references: Neuroimage. 2005 Jul 1;26(3):839-51
references: 15955494
references: Alzheimers Dement. 2013 Jan;9(1):e-1-16
references: 23360977
references: Acta Neuropathol. 1991;82(4):239-59
references: 1759558
references: Am J Geriatr Psychiatry. 2009 Jun;17(6):493-502
references: 19472439
references: Brain. 2013 Jul;136(Pt 7):2228-38
references: 23775979
references: Biol Psychiatry. 2009 Aug 1;66(3):259-66
references: 19368900
references: Alzheimers Dement. 2008 Sep;4(5):316-23
references: 18790458
references: Eur J Nucl Med Mol Imaging. 2014 Apr;41(4):714-22
references: 24233127
references: Sci Transl Med. 2014 May 14;6(236):236re4
references: 24828079
references: Neuropsychopharmacology. 2010 Jan;35(1):192-216
references: 19693001
references: Neuropsychopharmacology. 2004 Dec;29(12):2242-50
references: 15354182
references: Neurology. 1998 Feb;50(2):380-3
references: 9484357
references: Br J Psychiatry. 2014;204:400-1
references: 24526746
references: Am J Geriatr Psychiatry. 2002 Mar-Apr;10(2):129-41
references: 11925274
references: Neurology. 2012 Oct 16;79(16):1645-52
references: 23071163
references: J Magn Reson Imaging. 2008 Apr;27(4):685-91
references: 18302232
references: Arch Gen Psychiatry. 2008 May;65(5):542-50
references: 18458206
references: J Cereb Blood Flow Metab. 1992 Jul;12(4):571-83
references: 1618936
references: J Alzheimers Dis. 2012;31(2):265-75
references: 22543846
references: Biol Psychiatry. 2005 Feb 15;57(4):412-21
references: 15705358
references: Alzheimer Dis Assoc Disord. 2008 Jul-Sep;22(3):261-8
references: 18580591
references: J Neurol Neurosurg Psychiatry. 2014 Aug;85(8):930-5
references: 24421287
references: Expert Rev Neurother. 2012 Nov;12(11):1339-50
references: 23234395
references: Neurobiol Aging. 2012 Oct;33(10):2334-42
references: 22192243
references: Arch Gen Psychiatry. 2006 May;63(5):530-8
references: 16651510
references: Am J Geriatr Psychiatry. 2006 Jul;14(7):625-8
references: 16816017
references: J Neuropsychiatry Clin Neurosci. 2000 Spring;12(2):233-9
references: 11001602
references: Synapse. 2009 Jan;63(1):1-6
references: 18925655
references: J Neurol Neurosurg Psychiatry. 2014 Apr;85(4):449-55
references: 24133289
references: Am J Geriatr Psychiatry. 2008 Feb;16(2):168-74
references: 18239198
references: Dement Geriatr Cogn Disord. 2010;29(1):37-45
references: 20110699
references: Arch Gen Psychiatry. 2006 Feb;63(2):161-7
references: 16461859