title: Long-term effects of amyloid, hypometabolism, and atrophy on neuropsychological functions.
abstract: OBJECTIVE
  To assess how amyloid deposition, glucose hypometabolism, and cerebral atrophy affect neuropsychological performance in patients with Alzheimer disease (AD) dementia, patients with mild cognitive impairment (MCI), and controls over time.
  
  
  METHODS
  A total of 41 patients with AD dementia, 28 patients with MCI, and 19 controls underwent [(11)C]-Pittsburgh compound B ((11)C-PiB) and [(18)F]-2-fluoro-2-deoxy-d-glucose ((18)F-FDG)-PET and MRI scans at baseline. We extracted global binding potential for (11)C-PiB, the number of abnormal voxels for (18)F-FDG, and gray matter volumes using SIENAX for MRI as measures of amyloid, hypometabolism, and atrophy. In addition, repeat neuropsychological testing was performed, including memory, attention, language, and executive tasks (mean follow-up 2.2 ± 0.7 years). Cross-sectional and longitudinal relationships between imaging markers and cognition were assessed using linear mixed models, including terms for the imaging markers, time, sex, age, diagnosis, and interactions for imaging marker × time and imaging marker × time × diagnosis.
  
  
  RESULTS
  Linear mixed models showed that baseline hypometabolism and atrophy were associated with poorer baseline performance on attention and executive functions (p < 0.05), whereas amyloid was not related to baseline cognition. Hypometabolism and amyloid were strongly associated with longitudinal decline in essentially all cognitive domains (pinteraction < 0.05), whereas atrophy was related specifically to future decline in Mini-Mental State Examination and memory (pinteraction < 0.05).
  
  
  CONCLUSIONS
  Glucose hypometabolism and brain atrophy were associated with concurrent cognitive function, whereas brain amyloid was not. Amyloid deposition and glucose hypometabolism were predictors for decline of a wide variety of cognitive functions, while brain atrophy specifically predicted memory deterioration.
authors.affiliation: From the Department of Radiology & Nuclear Medicine (R.O., S.C.J.V., H.V., A.V., R.A.v.S., S.M.A., M.D.Z., R.B., A.D.W., F.B., A.A.L., B.N.M.v.B.), Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam (R.O., W.M.v.d.F., S.A.S., S.M.A., M.D.Z., P.S.), and Department of Epidemiology & Biostatistics (W.M.v.d.F., S.A.S., J.T.), VU University Medical Center, Amsterdam, the Netherlands. r.ossenkoppele@vumc.nl.
authors.forename: Rik
authors.initials: R
authors.lastname: Ossenkoppele
authors.affiliation: From the Department of Radiology & Nuclear Medicine (R.O., S.C.J.V., H.V., A.V., R.A.v.S., S.M.A., M.D.Z., R.B., A.D.W., F.B., A.A.L., B.N.M.v.B.), Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam (R.O., W.M.v.d.F., S.A.S., S.M.A., M.D.Z., P.S.), and Department of Epidemiology & Biostatistics (W.M.v.d.F., S.A.S., J.T.), VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Wiesje M
authors.initials: WM
authors.lastname: van der Flier
authors.affiliation: From the Department of Radiology & Nuclear Medicine (R.O., S.C.J.V., H.V., A.V., R.A.v.S., S.M.A., M.D.Z., R.B., A.D.W., F.B., A.A.L., B.N.M.v.B.), Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam (R.O., W.M.v.d.F., S.A.S., S.M.A., M.D.Z., P.S.), and Department of Epidemiology & Biostatistics (W.M.v.d.F., S.A.S., J.T.), VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Sander C J
authors.initials: SC
authors.lastname: Verfaillie
authors.affiliation: From the Department of Radiology & Nuclear Medicine (R.O., S.C.J.V., H.V., A.V., R.A.v.S., S.M.A., M.D.Z., R.B., A.D.W., F.B., A.A.L., B.N.M.v.B.), Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam (R.O., W.M.v.d.F., S.A.S., S.M.A., M.D.Z., P.S.), and Department of Epidemiology & Biostatistics (W.M.v.d.F., S.A.S., J.T.), VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Hugo
authors.initials: H
authors.lastname: Vrenken
authors.affiliation: From the Department of Radiology & Nuclear Medicine (R.O., S.C.J.V., H.V., A.V., R.A.v.S., S.M.A., M.D.Z., R.B., A.D.W., F.B., A.A.L., B.N.M.v.B.), Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam (R.O., W.M.v.d.F., S.A.S., S.M.A., M.D.Z., P.S.), and Department of Epidemiology & Biostatistics (W.M.v.d.F., S.A.S., J.T.), VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Adriaan
authors.initials: A
authors.lastname: Versteeg
authors.affiliation: From the Department of Radiology & Nuclear Medicine (R.O., S.C.J.V., H.V., A.V., R.A.v.S., S.M.A., M.D.Z., R.B., A.D.W., F.B., A.A.L., B.N.M.v.B.), Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam (R.O., W.M.v.d.F., S.A.S., S.M.A., M.D.Z., P.S.), and Department of Epidemiology & Biostatistics (W.M.v.d.F., S.A.S., J.T.), VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Ronald A
authors.initials: RA
authors.lastname: van Schijndel
authors.affiliation: From the Department of Radiology & Nuclear Medicine (R.O., S.C.J.V., H.V., A.V., R.A.v.S., S.M.A., M.D.Z., R.B., A.D.W., F.B., A.A.L., B.N.M.v.B.), Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam (R.O., W.M.v.d.F., S.A.S., S.M.A., M.D.Z., P.S.), and Department of Epidemiology & Biostatistics (W.M.v.d.F., S.A.S., J.T.), VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Sietske A
authors.initials: SA
authors.lastname: Sikkes
authors.affiliation: From the Department of Radiology & Nuclear Medicine (R.O., S.C.J.V., H.V., A.V., R.A.v.S., S.M.A., M.D.Z., R.B., A.D.W., F.B., A.A.L., B.N.M.v.B.), Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam (R.O., W.M.v.d.F., S.A.S., S.M.A., M.D.Z., P.S.), and Department of Epidemiology & Biostatistics (W.M.v.d.F., S.A.S., J.T.), VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Jos
authors.initials: J
authors.lastname: Twisk
authors.affiliation: From the Department of Radiology & Nuclear Medicine (R.O., S.C.J.V., H.V., A.V., R.A.v.S., S.M.A., M.D.Z., R.B., A.D.W., F.B., A.A.L., B.N.M.v.B.), Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam (R.O., W.M.v.d.F., S.A.S., S.M.A., M.D.Z., P.S.), and Department of Epidemiology & Biostatistics (W.M.v.d.F., S.A.S., J.T.), VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Sofie M
authors.initials: SM
authors.lastname: Adriaanse
authors.affiliation: From the Department of Radiology & Nuclear Medicine (R.O., S.C.J.V., H.V., A.V., R.A.v.S., S.M.A., M.D.Z., R.B., A.D.W., F.B., A.A.L., B.N.M.v.B.), Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam (R.O., W.M.v.d.F., S.A.S., S.M.A., M.D.Z., P.S.), and Department of Epidemiology & Biostatistics (W.M.v.d.F., S.A.S., J.T.), VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Marissa D
authors.initials: MD
authors.lastname: Zwan
authors.affiliation: From the Department of Radiology & Nuclear Medicine (R.O., S.C.J.V., H.V., A.V., R.A.v.S., S.M.A., M.D.Z., R.B., A.D.W., F.B., A.A.L., B.N.M.v.B.), Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam (R.O., W.M.v.d.F., S.A.S., S.M.A., M.D.Z., P.S.), and Department of Epidemiology & Biostatistics (W.M.v.d.F., S.A.S., J.T.), VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Ronald
authors.initials: R
authors.lastname: Boellaard
authors.affiliation: From the Department of Radiology & Nuclear Medicine (R.O., S.C.J.V., H.V., A.V., R.A.v.S., S.M.A., M.D.Z., R.B., A.D.W., F.B., A.A.L., B.N.M.v.B.), Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam (R.O., W.M.v.d.F., S.A.S., S.M.A., M.D.Z., P.S.), and Department of Epidemiology & Biostatistics (W.M.v.d.F., S.A.S., J.T.), VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Albert D
authors.initials: AD
authors.lastname: Windhorst
authors.affiliation: From the Department of Radiology & Nuclear Medicine (R.O., S.C.J.V., H.V., A.V., R.A.v.S., S.M.A., M.D.Z., R.B., A.D.W., F.B., A.A.L., B.N.M.v.B.), Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam (R.O., W.M.v.d.F., S.A.S., S.M.A., M.D.Z., P.S.), and Department of Epidemiology & Biostatistics (W.M.v.d.F., S.A.S., J.T.), VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.affiliation: From the Department of Radiology & Nuclear Medicine (R.O., S.C.J.V., H.V., A.V., R.A.v.S., S.M.A., M.D.Z., R.B., A.D.W., F.B., A.A.L., B.N.M.v.B.), Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam (R.O., W.M.v.d.F., S.A.S., S.M.A., M.D.Z., P.S.), and Department of Epidemiology & Biostatistics (W.M.v.d.F., S.A.S., J.T.), VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.affiliation: From the Department of Radiology & Nuclear Medicine (R.O., S.C.J.V., H.V., A.V., R.A.v.S., S.M.A., M.D.Z., R.B., A.D.W., F.B., A.A.L., B.N.M.v.B.), Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam (R.O., W.M.v.d.F., S.A.S., S.M.A., M.D.Z., P.S.), and Department of Epidemiology & Biostatistics (W.M.v.d.F., S.A.S., J.T.), VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Lammertsma
authors.affiliation: From the Department of Radiology & Nuclear Medicine (R.O., S.C.J.V., H.V., A.V., R.A.v.S., S.M.A., M.D.Z., R.B., A.D.W., F.B., A.A.L., B.N.M.v.B.), Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam (R.O., W.M.v.d.F., S.A.S., S.M.A., M.D.Z., P.S.), and Department of Epidemiology & Biostatistics (W.M.v.d.F., S.A.S., J.T.), VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Bart N M
authors.initials: BN
authors.lastname: van Berckel
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000378:metabolism / Q000523:psychology; D000682:Amyloid / Q000378:metabolism*; D001284:Atrophy / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D001288:Attention; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D003071:Cognition; D060825:Cognitive Dysfunction / Q000175:diagnosis* / Q000378:metabolism / Q000523:psychology; D003704:Dementia / Q000175:diagnosis* / Q000378:metabolism / Q000523:psychology; D018450:Disease Progression; D056344:Executive Function; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011877:Radionuclide Imaging
chemical_list: D000682:Amyloid; D005947:Glucose