title: Risk of dementia in MCI: combined effect of cerebrovascular disease, volumetric MRI, and 1H MRS.
abstract: OBJECTIVE
  To investigate the combined ability of hippocampal volumes, 1H magnetic resonance spectroscopy (MRS) metabolites, and cerebrovascular disease to predict the risk of progression to dementia in mild cognitive impairment (MCI).
  
  
  METHODS
  We identified 151 consecutively recruited subjects with MCI from the Mayo Clinic Alzheimer's Disease Research Center and Patient Registry who underwent MRI and 1H MRS studies at baseline and were followed up with approximately annual clinical examinations. A multivariable proportional hazards model that considered all imaging predictors simultaneously was used to determine whether hippocampal volumes, posterior cingulate gyrus 1H MRS metabolites, white matter hyperintensity load, and presence of cortical and subcortical infarctions are complementary in predicting the risk of progression from MCI to dementia.
  
  
  RESULTS
  Seventy-five subjects with MCI progressed to dementia by last follow-up. The model that best predicted progression to dementia included age, sex, hippocampal volumes, N-acetylaspartate (NAA)/creatine (Cr) on 1H MRS, and cortical infarctions. Based on age- and sex-adjusted Kaplan-Meier plots, we estimated that by 3 years, 26% of the MCI patients with normal hippocampal volumes, NAA/Cr ratios >1 SD, and no cortical infarctions will progress to dementia, compared with 78% of the MCI patients with hippocampal atrophy, low NAA/Cr (< or =1 SD), and cortical infarction.
  
  
  CONCLUSIONS
  Multiple magnetic resonance (MR) markers of underlying dementia pathologies improve the ability to identify patients with prodromal dementia over a single MR marker, supporting the concept that individuals with multiple brain pathologies have increased odds of dementia compared with individuals with a single pathology.
authors.affiliation: Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA. kantarci.kejal@mayo.edu
authors.forename: K
authors.initials: K
authors.lastname: Kantarci
authors.forename: S D
authors.initials: SD
authors.lastname: Weigand
authors.forename: S A
authors.initials: SA
authors.lastname: Przybelski
authors.forename: M M
authors.initials: MM
authors.lastname: Shiung
authors.forename: J L
authors.initials: JL
authors.lastname: Whitwell
authors.forename: S
authors.initials: S
authors.lastname: Negash
authors.forename: D S
authors.initials: DS
authors.lastname: Knopman
authors.forename: B F
authors.initials: BF
authors.lastname: Boeve
authors.forename: P C
authors.initials: PC
authors.lastname: O'Brien
authors.forename: R C
authors.initials: RC
authors.lastname: Petersen
authors.forename: C R
authors.initials: CR
authors.lastname: Jack
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism; D001284:Atrophy / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002561:Cerebrovascular Disorders / Q000150:complications / Q000175:diagnosis*; D003072:Cognition Disorders / Q000175:diagnosis* / Q000378:metabolism* / Q000503:physiopathology; D015331:Cohort Studies; D003401:Creatine / Q000032:analysis / Q000378:metabolism; D003704:Dementia / Q000175:diagnosis* / Q000378:metabolism* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D001224:Aspartic Acid; C000179:N-acetylaspartate; D003401:Creatine