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Abstract
Objective To examine whether domain-specific patterns of cognitive impairment and trajectories of decline differed in patients with clinically diagnosed Parkinson disease dementia (PDD) (N = 29) and autopsy-confirmed dementia with Lewy bodies (DLB) (N = 58) or Alzheimer disease (AD) (N = 174) and to determine the impact of pooling patients with PDD and DLB in clinical trials targeting cognition.
Methods Patients were matched on demographics and level of global cognitive impairment. Patterns of cross-sectional performance and longitudinal decline were examined in 4 cognitive domains: Visuospatial, Memory, Executive, and Language. Power analyses were performed to determine the numbers of participants needed to adequately power a hypothetical clinical trial to slow cognitive decline in pure PDD, pure DLB, or a mixed PDD/DLB group.
Results Both DLB and PDD were more impaired and declined more rapidly than AD in the Visuospatial domain. Patients with PDD exhibited the most impairment and fastest decline in Executive, although patients with DLB also declined faster than AD. Memory was more impaired in AD than DLB and in both compared with PDD; however, all 3 groups declined at comparable rates. In contrast, PDD declined at a slower rate on Language measures than DLB or AD. Power analyses suggest that Visuospatial and Executive outcome measures would be most sensitive in PDD, but Memory and Language in DLB.
Conclusion DLB and PDD differ from each other, and from AD, in a cognitive domain-specific manner. As such, different outcome measures may be most sensitive to detecting changes in DLB vs PDD, suggesting that the 2 should be analyzed separately in clinical trials.
Glossary
- ADRC=
- Alzheimer's Disease Research Center;
- AD=
- Alzheimer disease;
- CDR=
- Clinical Dementia Rating;
- CERAD=
- Consortium to Establish a Registry for Alzheimer's Disease;
- DLB=
- dementia with Lewy bodies;
- H&E=
- hematoxylin-eosin;
- LBD=
- Lewy body disease;
- MMRM=
- mixed models with repeated measures;
- POD=
- Pfeffer Outpatient Disability;
- PCA=
- principal component analysis;
- PD=
- Parkinson disease;
- PDD=
- Parkinson disease dementia;
- UCSD=
- University of California, San Diego;
- UPDRS=
- Uniform Parkinson's Disease Rating Scale;
- WAIS-R=
- Wechsler Adult Intelligence Scale–Revised;
- WMS=
- Wechsler Memory Scale
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Editorial, page 858
CME Course: NPub.org/cmelist
- Received September 6, 2019.
- Accepted in final form December 3, 2019.
- © 2020 American Academy of Neurology
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