Dementia and Neurocognitive Disorders (대한치매학회지)

Korean Dementia Association (대한치매학회)
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Detection of Prodromal Alzheimer's Disease in Patients with Depression and Mild Cognitive Impairment Using $^{11}C$-PIB PET: Preliminary Study

Detection of Prodromal Alzheimer's Disease in Patients with Depression and Mild Cognitive Impairment Using 11C-PIB PET: Preliminary Study

  • Kim, Hee-Young (Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Jeong, Eun-Hye (Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Kim, Jae-Seung (Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Lee, Su-Na (Department of Neurology, Kyung Hee University College of Medicine) ;
  • Lee, Jae-Hong (Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine)
  • Published : 2011.12.31
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Abstract

Background: There is increasing evidence of an empirical link between late-life depression and cognitive impairment. Depressive symptoms may be the earliest identifiable clinical stage of dementia. In contrast, depression may represent an independent risk factor predisposing to dementia disorders, including Alzheimer's disease (AD). Among individuals with amnestic mild cognitive impairment and depression (aMCID), it is largely unknown who has brain amyloid deposition and will progress to AD. We employed the amyloid PET imaging using $^{11}C$-Pittsburgh Compound B ($^{11}C$-PiB) to determine the presence of AD pathology in patients with aMCID. We examined differences in the clinical or radiological features between subjects with aMCID with amyloid deposition and those without. Methods: Twelve patients with aMCID (10 multiple-domain aMCID, 2 single-domain aMCID) underwent $^{11}C$-PiB PET, brain MRI, and neuropsychological test. Depressive symptoms were measured with the Geriatric Depression Scale (GDS) and those with the GDS score being 18 and over were designated as aMCID. By calculating the mean cortical PiB uptake ratio, we divided patients with aMCID into PiB-positive and PiB-negative groups. Results: Eight (66.7%) of 12 patients with aMCID were positive for cortical PiB binding. There was a significant difference between PiB-positive and PiB-negative groups in terms of the apolipoprotein E (ApoE) ${\varepsilon}4$ allele frequency (100% vs. 0%, p=0.006) and GDS score (24.2 vs. 28.2, p=0.03). The neuropsychological assessment revealed that patients with $^{11}C$-PiB-negative aMCID performed better on the recognition of visual memory test than those with PiB-positive. Conclusions: In patients with aMCID, the presence of cortical amyloid was strongly associated with the APOE ${\varepsilon}4$ allele. This finding suggests that those with aMCID and ApoE4 genotype may be a prodromal state to AD.

Keywords

References

  1. Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol 1999; 56: 303-8. https://doi.org/10.1001/archneur.56.3.303
  2. Bozoki A, Giordani B, Heidebrink JL, Berent S, Foster NL. Mild cognitive impairments predict dementia in nondemented elderly patients with memory loss. Arch Neurol 2001; 58: 411-6. https://doi.org/10.1001/archneur.58.3.411
  3. Palmer K, Backman L, Winblad B, Fratiglioni L. Detection of Alzheimer's disease and dementia in the preclinical phase: population based cohort study. BMJ 2003; 326: 245. https://doi.org/10.1136/bmj.326.7383.245
  4. Palmer K, Wang HX, Backman L, Winblad B, Fratiglioni L. Differential evolution of cognitive impairment in nondemented older persons: results from the Kungsholmen Project. Am J Psychiatry 2002; 159: 436-42. https://doi.org/10.1176/appi.ajp.159.3.436
  5. Ritchie K, Artero S, Touchon J. Classification criteria for mild cognitive impairment: a population-based validation study. Neurology 2001; 56: 37-42. https://doi.org/10.1212/WNL.56.1.37
  6. Monastero R, Palmer K, Qiu C, Winblad B, Fratiglioni L. Heterogeneity in risk factors for cognitive impairment, no dementia: population-based longitudinal study from the Kungsholmen Project. Am J Geriatr Psychiatry 2007; 15: 60-9. https://doi.org/10.1097/01.JGP.0000229667.98607.34
  7. Apostolova LG, Cummings JL. Neuropsychiatric manifestations in mild cognitive impairment: a systematic review of the literature. Dement Geriatr Cogn Disord 2008; 25: 115-26. https://doi.org/10.1159/000112509
  8. Alexopoulos GS, Meyers BS, Young RC, Kakuma T, Silbersweig D, Charlson M. Clinically defined vascular depression. Am J Psychiatry 1997; 154: 562-5. https://doi.org/10.1176/ajp.154.4.562
  9. Alexopoulos GS, Meyers BS, Young RC, Campbell S, Silbersweig D, Charlson M. 'Vascular depression' hypothesis. Arch Gen Psychiat 1997; 54: 915-22. https://doi.org/10.1001/archpsyc.1997.01830220033006
  10. Alexopoulos GS, Meyers BS, Young RC, Mattis S, Kakuma T. The Course of Geriatric Depression with Reversible Dementia - a Controlled-Study. Am J Psychiat 1993; 150: 1693-9. https://doi.org/10.1176/ajp.150.11.1693
  11. Klunk WE, Wang Y, Huang GF, Debnath ML, Holt DP, Mathis CA. Uncharged thioflavin-T derivatives bind to amyloid-beta protein with high affinity and readily enter the brain. Life Sci 2001; 69: 1471-84. https://doi.org/10.1016/S0024-3205(01)01232-2
  12. Mathis CA, Bacskai BJ, Kajdasz ST, McLellan ME, Frosch MP, Hyman BT, et al. A lipophilic thioflavin-T derivative for positron emission tomography (PET) imaging of amyloid in brain. Bioorg Med Chem Lett 2002; 12: 295-8. https://doi.org/10.1016/S0960-894X(01)00734-X
  13. Mathis CA, Wang Y, Holt DP, Huang GF, Debnath ML, Klunk WE. Synthesis and evaluation of 11C-labeled 6-substituted 2-arylbenzothiazoles as amyloid imaging agents. J Med Chem 2003; 46: 2740-54. https://doi.org/10.1021/jm030026b
  14. Bae JN, Cho MJ. Development of the Korean version of the Geriatric Depression Scale and its short form among elderly psychiatric patients. J Psychosom Res 2004; 57: 297-305. https://doi.org/10.1016/j.jpsychores.2004.01.004
  15. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 1984; 34: 939-44. https://doi.org/10.1212/WNL.34.7.939
  16. Kang Y, Na DL. Seoul Neuropsychological Screening Battery:Professional Manual. Seoul: Human Brain Research & Consulting Co; 2003.
  17. Seo SW, Im K, Lee JM, Kim YH, Kim ST, Kim SY, et al. Cortical thickness in single- versus multiple-domain amnestic mild cognitive impairment. Neuroimage 2007; 36: 289-97. https://doi.org/10.1016/j.neuroimage.2007.02.042
  18. Scheltens P, Leys D, Barkhof F, Huglo D, Weinstein HC, Vermersch P, et al. Atrophy of medial temporal lobes on MRI in "probable" Alzheimer's disease and normal ageing: diagnostic value and neuropsychological correlates. J Neurol Neurosurg Psychiatry 1992; 55:967-72. https://doi.org/10.1136/jnnp.55.10.967
  19. Lee JH, Kim SH, Kim GH, Seo SW, Park HK, Oh SJ, et al. Identification of pure subcortical vascular dementia using 11C-Pittsburgh compound B. Neurology 2011; 77: 18-25. https://doi.org/10.1212/WNL.0b013e318221acee
  20. Bertram L, Tanzi RE. Thirty years of Alzheimer's disease genetics: the implications of systematic meta-analyses. Nat Rev Neurosci 2008; 9: 768-78. https://doi.org/10.1038/nrn2494
  21. Brayne C, Harrington CR, Wischik CM, Huppert FA, Chi LY, Xuereb JH, et al. Apolipoprotein E genotype in the prediction of cognitive decline and dementia in a prospectively studied elderly population. Dementia 1996; 7: 169-74.
  22. Kim J, Basak JM, Holtzman DM. The role of apolipoprotein E in Alzheimer's disease. Neuron 2009; 63: 287-303. https://doi.org/10.1016/j.neuron.2009.06.026
  23. Haan MN, Shemanski L, Jagust WJ, Manolio TA, Kuller L. The role of APOE epsilon4 in modulating effects of other risk factors for cognitive decline in elderly persons. JAMA 1999; 282: 40-6. https://doi.org/10.1001/jama.282.1.40
  24. Butters MA, Young JB, Lopez O, Aizenstein HJ, Mulsant BH, Reynolds CF 3rd, et al. Pathways linking late-life depression to persistent cognitive impairment and dementia. Dialogues Clin Neurosci 2008; 10: 345-57.
  25. Fuhrer R, Dufouil C, Dartigues JF. Exploring sex differences in the relationship between depressive symptoms and dementia incidence: prospective results from the PAQUID Study. J Am Geriatr Soc 2003; 51: 1055-63. https://doi.org/10.1046/j.1532-5415.2003.51352.x
  26. Dal Forno G, Palermo MT, Donohue JE, Karagiozis H, Zonderman AB, Kawas CH. Depressive symptoms, sex, and risk for Alzheimer's disease. Ann Neurol 2005; 57: 381-7. https://doi.org/10.1002/ana.20405
  27. Ownby RL, Crocco E, Acevedo A, John V, Loewenstein D. Depression and risk for Alzheimer disease: systematic review, meta-analysis, and metaregression analysis. Arch Gen Psychiatry 2006; 63: 530-8. https://doi.org/10.1001/archpsyc.63.5.530
  28. Wolk DA, Price JC, Saxton JA, Snitz BE, James JA, Lopez OL, et al. Amyloid imaging in mild cognitive impairment subtypes. Ann Neurol 2009; 65: 557-68. https://doi.org/10.1002/ana.21598