LBD Duration Shortens with Co-existing Alzheimer’s Disease

The rate of progression in Lewy body dementia (LBD) is hard to predict at the time of diagnosis. New research indicates the presence of a second neurodegenerative disease process, Alzheimer’s disease (AD), has an impact on one’s prognosis.

Researchers from five academic centers pooled clinical and autopsy data from 213 individuals with both clinical and autopsy-confirmed diagnoses of Parkinson’s disease dementia or dementia with Lewy bodies (DLB). The subjects were then divided into groups according to the amount of co-existing Alzheimer’s disease pathology: none (23%), low-level (26%), intermediate level (21%) and high level (30%).

As the level of Alzheimer’s disease pathology rose, so did the level of Lewy body pathology in the brain’s cerebrum. This suggests a synergistic effect between the two disease processes. Higher levels of AD pathology were associated with older age at the onset of motor symptoms, dementia and death. Compared to those with no AD pathology, individuals with the highest level had a shortened time (an average of 7 years) between the onset of parkinsonism and dementia, regardless of which symptom started first. Individuals with dementia with Lewy bodies were more likely in the higher level group than those with Parkinson’s disease dementia.

The study included analysis of 4 known genetic variations (SNCA, MAPT, GBA, APOE) associated with an increased risk for Lewy body dementia. Researchers found the presence of the GBA genetic variation was related to decreasing levels of Alzheimer’s disease pathology. In contrast, APOE gene variation, a known risk factor for both LBD and Alzheimer’s disease, was only associated with the presence of Alzheimer’s disease pathology, not the amount of it.

In summary, the presence of both disease processes results in a worse prognosis, especially as the levels of the pathologies increase. This study highlights several key opportunities in clinical trial design and therapeutics:

  • By assessing the presence of AD pathology and APOE gene variations in participants of clinical trials targeting Lewy body pathology, research may shed light on treatment response differences.
  • New treatments for AD pathology may directly benefit those with LBD by slowing down the disease course

This article was published in The Lancet in January, 2017 and funding was provided by the National Institutes of Health. The following co-authors are member of the Lewy Body Dementia Association’s Scientific Advisory Council: David J. Irwin, MD, Daniel Weintraub, MD, John E. Duda, MD, Oscar L. Lopez, MD, James B. Leverenz, MD, Debby Tsuang, MD, and Cyrus P. Zabetian, MD.