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

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.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.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.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.