Metabolic Topology of Neurodegenerative Disorders: Influence of Cognitive and Motor Deficits

J Nucl Med. 2015 Dec;56(12):1916-21. doi: 10.2967/jnumed.115.156067. Epub 2015 Sep 17.

Abstract

Parkinson disease with and without dementia (PDD and PD, respectively), dementia with Lewy bodies (DLB), and Alzheimer dementia (AD) traditionally have been viewed as distinct clinical and pathologic entities. However, intriguing overlaps in biochemical, clinical, and imaging findings question the concept of distinct entities and suggest a continuous spectrum in which individual patients express PD-typical patterns and AD-typical patterns to a variable degree.

Methods: Following this concept, we built a topological map based on regional patterns of the cerebral metabolic rate of glucose as measured with (18)F-FDG PET to rank and localize single subjects' disease status according to PD-typical (PD vs. controls) and AD-typical (AD vs. controls) pattern expression in patients clinically characterized as PD, PDD, DLB, amnestic mild cognitive impairment, and AD.

Results: The topology generally confirmed an indivisible spectrum of disease manifestation according to 2 separable expression patterns. The expression values derived from the first pattern were highly correlated with individual cognitive, but not motor, disability. The opposite was found for the corresponding expression values of the second pattern.

Conclusion: The metabolic imaging analysis supports the notion that there is a continuous spectrum of neurodegeneration between AD and PD. Furthermore, PDD and DLB may in fact represent 1 overlapping disease entity, characterized by the presence of mixed neuropathology and only different by the time course.

Keywords: Alzheimer; FDG PET; Parkinson; dementia; motor deficits.

MeSH terms

  • Aged
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / psychology
  • Brain Mapping
  • Cognition*
  • Cognitive Dysfunction / diagnostic imaging
  • Cognitive Dysfunction / metabolism
  • Cognitive Dysfunction / psychology
  • Female
  • Fluorodeoxyglucose F18
  • Humans
  • Image Processing, Computer-Assisted
  • Lewy Body Disease / diagnostic imaging
  • Lewy Body Disease / metabolism
  • Lewy Body Disease / psychology
  • Male
  • Movement Disorders / diagnostic imaging
  • Movement Disorders / metabolism*
  • Movement Disorders / psychology*
  • Neurodegenerative Diseases / diagnostic imaging
  • Neurodegenerative Diseases / metabolism*
  • Neurodegenerative Diseases / psychology*
  • Parkinson Disease / diagnostic imaging
  • Parkinson Disease / metabolism
  • Parkinson Disease / psychology
  • Parkinson Disease, Postencephalitic / diagnostic imaging
  • Parkinson Disease, Postencephalitic / metabolism
  • Parkinson Disease, Postencephalitic / psychology
  • Radionuclide Imaging
  • Radiopharmaceuticals

Substances

  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18