Amyloid deposition and CBF patterns predict conversion of mild cognitive impairment to dementia
Mild cognitive impairment (MCI) can include the transition from a normal state to dementia. To explore biomarkers for the development of dementia, we performed an 18-month follow-up study in 28 patients with amnestic MCI. Amyloid deposition was examined using PiB PET, and cerebral blood flow (CBF) was examined using SPECT. Cognitive function was periodically assessed. The rate of conversion to dementia was higher in the PiB-positive/equivocal group (74%) than in the PiB-negative group (33%) (p = 0.041). Perfusion SPECT was performed in 16 patients. MCI patients with an AD-characteristic pattern of reduced CBF had a higher PiB-positive/equivocal rate (82%) than those with a non-AD pattern (20%) (p = 0.018), and patients with an AD pattern had a higher conversion rate (82%) than those with a non-AD pattern (40%) (p = 0.094). Clinically, all PiB-positive converters were diagnosed as having Alzheimer’s disease (AD), whereas PiB-negative converters were thought to have some form of dementia other than AD. Amyloid PET is useful for predicting conversion to AD in MCI patients. A pattern analysis of perfusion SPECT findings might also be helpful for predicting conversion to AD, but with a lower specificity.
KeywordsAlzheimer’s disease Mild cognitive impairment Pittsburg compound B Positron emission tomography Perfusion SPECT
All the authors have approved the manuscript and agree with its submission.
Compliance with ethical standards
The present clinical study design was approved by the research ethics committee of the Osaka City University Graduate School of Medicine (IRB# 689). Written consent was obtained from all the study participants or from their next of kin.
Conflict of interest
The authors declare that they have no conflicts of interest.
- 3.Klunk WE, Engler H, Nordberg A, Wang Y, Blomqvist G, Holt DP, Bergstrom M, Savitcheva I, Huang GF, Estrada S, Ausen B, Debnath ML, Barletta J, Price JC, Sandell J, Lopresti BJ, Wall A, Koivisto P, Antoni G, Mathis CA, Langstrom B (2004) Imaging brain amyloid in Alzheimer’s disease with Pittsburgh compound-B. Ann Neurol 55(3):306–319CrossRefPubMedGoogle Scholar
- 4.Ikonomovic MD, Klunk WE, Abrahamson EE, Mathis CA, Price JC, Tsopelas ND, Lopresti BJ, Ziolko S, Bi W, Paljug WR, Debnath ML, Hope CE, Isanski BA, Hamilton RL, DeKosky ST (2008) Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer’s disease. Brain 131(Pt 6):1630–1645CrossRefPubMedPubMedCentralGoogle Scholar
- 9.Okello A, Koivunen J, Edison P, Archer HA, Turkheimer FE, Nagren K, Bullock R, Walker Z, Kennedy A, Fox NC, Rossor MN, Rinne JO, Brooks DJ (2009) Conversion of amyloid positive and negative MCI to AD over 3 years: an 11C-PIB PET study. Neurology 73(10):754–760CrossRefPubMedPubMedCentralGoogle Scholar
- 13.Winblad B, Palmer K, Kivipelto M, Jelic V, Fratiglioni L, Wahlund LO, Nordberg A, Backman L, Albert M, Almkvist O, Arai H, Basun H, Blennow K, de Leon M, DeCarli C, Erkinjuntti T, Giacobini E, Graff C, Hardy J, Jack C, Jorm A, Ritchie K, van Duijn C, Visser P, Petersen RC (2004) Mild cognitive impairment—beyond controversies, towards a consensus: report of the international working group on mild cognitive impairment. J Intern Med 256(3):240–246CrossRefPubMedGoogle Scholar
- 14.McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, Mohs RC, Morris JC, Rossor MN, Scheltens P, Carrillo MC, Thies B, Weintraub S, Phelps CH (2011) The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 7(3):263–269CrossRefPubMedPubMedCentralGoogle Scholar
- 15.T. Mino, H. Saito, J. Takeuchi, K. Ito, A. Takeda, S. Ataka, S. Shiomi, Y. Wada, Y. Watanabe, Y. Itoh (2016) Cerebral blood flow abnormality in clinically diagnosed Alzheimer’s disease patients with or without amyloid β accumulation on positron emission tomography. Neurol Clin Neurosci 5(2):55–59CrossRefGoogle Scholar
- 16.Jagust WJ, Bandy D, Chen K, Foster NL, Landau SM, Mathis CA, Price JC, Reiman EM, Skovronsky D, Koeppe RA, I. Alzheimer’s Disease Neuroimaging (2010) The Alzheimer’s disease neuroimaging initiative positron emission tomography core. Alzheimers Dement 6(3):221–229CrossRefPubMedPubMedCentralGoogle Scholar
- 17.Silverman DH, Small GW, Chang CY, Lu CS, Kung De Aburto MA, Chen W, Czernin J, Rapoport SI, Pietrini P, Alexander GE, Schapiro MB, Jagust WJ, Hoffman JM, Welsh-Bohmer KA, Alavi A, Clark CM, Salmon E, de Leon MJ, Mielke R, Cummings JL, Kowell AP, Gambhir SS, Hoh CK, Phelps ME (2001) Positron emission tomography in evaluation of dementia: regional brain metabolism and long-term outcome. JAMA 286(17):2120–2127CrossRefPubMedGoogle Scholar
- 18.Johnson KA, Minoshima S, Bohnen NI, Donohoe KJ, Foster NL, Herscovitch P, Karlawish JH, Rowe CC, Carrillo MC, Hartley DM, Hedrick S, Pappas V, Thies WH (2013) Appropriate use criteria for amyloid PET: a report of the amyloid imaging task force, the Society of Nuclear Medicine and Molecular Imaging, and the Alzheimer’s Association. J Nucl Med 54(3):476–490CrossRefPubMedGoogle Scholar
- 23.Alegret M, Cuberas-Borros G, Vinyes-Junque G, Espinosa A, Valero S, Hernandez I, Roca I, Ruiz A, Rosende-Roca M, Mauleon A, Becker JT, Castell-Conesa J, Tarraga L, Boada M (2012) A two-year follow-up of cognitive deficits and brain perfusion in mild cognitive impairment and mild Alzheimer’s disease. J Alzheimers Dis 30(1):109–120CrossRefPubMedPubMedCentralGoogle Scholar