title: Small vessel disease, but neither amyloid load nor metabolic deficit, is dependent on age at onset in Alzheimer's disease.
abstract: BACKGROUND
  There is controversy concerning whether Alzheimer's disease (AD) with early onset is distinct from AD with late onset with regard to amyloid pathology and neuronal metabolic deficit. We hypothesized that compared with patients with early-onset AD, patients with late-onset AD have more comorbid small vessel disease (SVD) contributing to clinical severity, whereas there are no differences in amyloid pathology and neuronal metabolic deficit.
  
  
  METHODS
  The study included two groups of patients with probable AD dementia with evidence of the AD pathophysiologic process: 24 patients with age at onset <60 years old and 36 patients with age at onset >70 years old. Amyloid deposition was assessed using carbon-11-labeled Pittsburgh compound B positron emission tomography, comorbid SVD was assessed using magnetic resonance imaging, and neuronal metabolic deficit was assessed using fluorodeoxyglucose positron emission tomography. Group differences of global and regional distribution of pathology were explored using region of interest and voxel-based analyses, respectively, carefully controlling for the influence of dementia severity, apolipoprotein E genotype, and in particular SVD. The pattern of cognitive impairment was determined using z scores of the subtests of the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery.
  
  
  RESULTS
  Patients with late-onset AD showed a significantly greater amount of SVD. No statistically significant differences in global or regional amyloid deposition or neuronal metabolic deficit between the two groups were revealed. However, when not controlling for SVD, subtle differences in fluorodeoxyglucose uptake between early-onset AD and late-onset AD groups were detectable. There were no significant differences regarding cognitive functioning.
  
  
  CONCLUSIONS
  Age at onset does not influence amyloid deposition or neuronal metabolic deficit in AD. The greater extent of SVD in late-onset AD influences the association between neuronal metabolic deficit and clinical symptoms.
authors.affiliation: Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany. Electronic address: marion.ortner@lrz.tum.de.
authors.forename: Marion
authors.initials: M
authors.lastname: Ortner
authors.affiliation: Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kurz
authors.affiliation: Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Alexopoulos
authors.affiliation: Department Diagnostic and Interventional Neuroradiology, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Auer
authors.affiliation: Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
authors.forename: Janine
authors.initials: J
authors.lastname: Diehl-Schmid
authors.affiliation: Department of Nuclear Medicine, University Köln, Cologne, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Drzezga
authors.affiliation: Department Nuclear Medicine, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Förster
authors.affiliation: Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Förstl
authors.affiliation: Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany; Neuroepidemiology and Ageing Research Unit, School of Public Health, Faculty of Medicine, The Imperial College of Science, Technology, and Medicine, London; West London Cognitive Disorders Treatment and Research Unit, West London Mental Health Trust, London, United Kingdom.
authors.forename: Robert
authors.initials: R
authors.lastname: Perneczky
authors.affiliation: Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Sorg
authors.affiliation: Pharmaceutical Radiochemistry, Faculties of Chemistry and Medicine, Technische Universität München, Garching, Germany.
authors.forename: Behrooz H
authors.initials: BH
authors.lastname: Yousefi
authors.affiliation: Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
authors.forename: Timo
authors.initials: T
authors.lastname: Grimmer
mesh_terms: D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism*; D000682:Amyloid / Q000378:metabolism*; D000814:Aniline Compounds; D001057:Apolipoproteins E / Q000235:genetics; D052160:Benzothiazoles / Q000493:pharmacokinetics; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008659:Metabolic Diseases / Q000000981:diagnostic imaging / Q000209:etiology; D008875:Middle Aged; D011877:Radionuclide Imaging; D013844:Thiazoles; D014652:Vascular Diseases / Q000000981:diagnostic imaging / Q000209:etiology*
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000682:Amyloid; D000814:Aniline Compounds; D001057:Apolipoproteins E; D052160:Benzothiazoles; D013844:Thiazoles; D019788:Fluorodeoxyglucose F18
keywords: AD; Age at onset; Alzheimer’s disease; Amyloid load; Metabolic deficit; Small vessel disease