title: Prediction of dementia in MCI patients based on core diagnostic markers for Alzheimer disease.
abstract: OBJECTIVE
  The current model of Alzheimer disease (AD) stipulates that brain amyloidosis biomarkers turn abnormal earliest, followed by cortical hypometabolism, and finally brain atrophy ones. The aim of this study is to provide clinical evidence of the model in patients with mild cognitive impairment (MCI).
  
  
  METHODS
  A total of 73 patients with MCI from 3 European memory clinics were included. Brain amyloidosis was assessed by CSF Aβ42 concentration, cortical metabolism by an index of temporoparietal hypometabolism on FDG-PET, and brain atrophy by automated hippocampal volume. Patients were divided into groups based on biomarker positivity: 1) Aβ42- FDG-PET- Hippo-, 2) Aβ42+ FDG-PET- Hippo-, 3) Aβ42 + FDG-PET + Hippo-, 4) Aβ42 + FDG-PET+ Hippo+, and 5) any other combination not in line with the model. Measures of validity were prevalence of group 5, increasing incidence of progression to dementia with increasing biological severity, and decreasing conversion time.
  
  
  RESULTS
  When patients with MCI underwent clinical follow-up, 29 progressed to dementia, while 44 remained stable. A total of 26% of patients were in group 5. Incident dementia was increasing with greater biological severity in groups 1 to 5 from 4% to 27%, 64%, and 100% (p for trend < 0.0001), and occurred increasingly earlier (p for trend = 0.024).
  
  
  CONCLUSIONS
  The core biomarker pattern is in line with the current pathophysiologic model of AD. Fully normal and fully abnormal pattern is associated with exceptional and universal development of dementia. Cases not in line might be due to atypical neurobiology or inaccurate thresholds for biomarker (ab)normality.
authors: LENITEM-Laboratory of Epidemiology Neuroimaging and Telemedicine, IRCCS Centro San Giovanni di Dio FBF, Brescia, Italy.
authors: Annapaola
authors: A
authors: Prestia
authors: Anna
authors: A
authors: Caroli
authors: Wiesje M
authors: WM
authors: van der Flier
authors: Rik
authors: R
authors: Ossenkoppele
authors: Bart
authors: B
authors: Van Berckel
authors: Frederik
authors: F
authors: Barkhof
authors: Charlotte E
authors: CE
authors: Teunissen
authors: Anders E
authors: AE
authors: Wall
authors: Stephen F
authors: SF
authors: Carter
authors: Michael
authors: M
authors: Schöll
authors: Il Han
authors: IH
authors: Choo
authors: Agneta
authors: A
authors: Nordberg
authors: Philip
authors: P
authors: Scheltens
authors: Giovanni B
authors: GB
authors: Frisoni
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D001284:Atrophy; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000473:pathology; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000473:pathology*; D003704:Dementia / Q000175:diagnosis / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D011237:Predictive Value of Tests; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins