Assessment of dementia risk in aging adults using both FDG-PET and FDDNP-PET imaging

Int J Geriatr Psychiatry. 2012 Oct;27(10):1017-27. doi: 10.1002/gps.2816. Epub 2012 Mar 1.

Abstract

Background: In a previous study, positron emission tomography (PET) with 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile (FDDNP), a molecule that binds to plaques and tangles in vitro, identified three subgroups of non-demented subjects according to FDDNP binding patterns: low global (LG) binding; high frontal, parietal, medial temporal binding (HF/PA); and high medial and lateral temporal and posterior cingulate (HT/PC) binding. In this follow-up investigation, we compared 2-deoxy-2-[F-18]fluoro- d-glucose (FDG)-PET cerebral metabolic patterns in the three FDDNP-PET binding subgroups.

Methods: Fifty-four subjects with normal aging (N = 28) or amnestic forms of mild cognitive impairment (N = 26) underwent FDDNP-PET and FDG-PET scanning. Subjects in the LG, HF/PA, and HT/PC FDDNP subgroups were compared according to visual ratings, statistical parametric mapping, and automated region of interest analyses of their FDG-PET data.

Results: The FDDNP-PET subgroups demonstrated different glucose metabolic patterns according to visual ratings, region of interest, and statistical parametric mapping analyses of FDG-PET data. The LG FDDNP subgroup showed no areas of significant hypometabolism relative to the other subgroups and had low Alzheimer's disease risk by FDG-PET standards. The HF/PA FDDNP subgroup demonstrated hypometabolism in bilateral inferior parietal/parietotemporal, bilateral posterior cingulate, perisylvian, mid-temporal gyrus, and dorsolateral prefrontal regions, which is a pattern suggestive of high Alzheimer's disease risk. The HT/PC FDDNP subgroup demonstrated heterogeneous FDG-PET patterns with predominant anterior frontal and anterior temporal hypometabolism, suggestive of mixed etiologies, including fronto-temporal dementia risk.

Conclusions: The FDG-PET data provided independent validation that different patterns of FDDNP-PET binding in non-demented individuals may be associated with differential dementia risk.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cerebellum / diagnostic imaging*
  • Cerebellum / metabolism
  • Cluster Analysis
  • Cognitive Dysfunction / diagnostic imaging*
  • Cognitive Dysfunction / metabolism
  • Dementia / diagnosis*
  • Dementia / metabolism
  • Female
  • Fluorodeoxyglucose F18* / pharmacokinetics
  • Humans
  • Male
  • Middle Aged
  • Neurofibrillary Tangles / diagnostic imaging
  • Neurofibrillary Tangles / metabolism
  • Nitriles* / pharmacokinetics
  • Plaque, Amyloid / diagnostic imaging
  • Plaque, Amyloid / metabolism
  • Positron-Emission Tomography / methods*
  • Radiopharmaceuticals* / pharmacokinetics
  • Risk Assessment
  • Risk Factors

Substances

  • 2-(1-(6-((2-fluoroethyl)(methyl)amino)-2-naphthyl)ethylidene)malononitrile
  • Nitriles
  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18