O4‐03‐03: Clinical Characterization of Mild Cognitive Impairment Associated With Eventual Lewy Body Disease Pathology
Year: 2019
Type: article
Study design: Observational Study
Abstract: The clinical characteristics of prodromal Lewy body disease (LBD) preceding the phenotype of dementia with Lewy bodies (DLB) are still being defined. Antemortem data were analyzed from autopsied patients with either limbic-transitional or diffuse-neocortical LBD diagnosed with mild cognitive impairment (MCI) and followed prospectively through the Mayo Alzheimer's Disease Research Center. Patients were compared based on absence vs. presence of neocortical neurofibrillary tangles (NFT) (Braak stages 0 to 3 vs. stages 4 to 6). The sample included 74 patients (34 transitional, 40 diffuse). There were no clinical or demographic differences based on distribution of Lewy-related pathology. At the first MCI evaluation, the mean MMSE was 27±2, age of cognitive decline onset was 71±9 years, and death age was 81±8 years. During the MCI stage, 69% had at least one core DLB feature and 45% had two features. Probable REM sleep behavior disorder (RBD) was evident in 55%, parkinsonism in 35%, visual hallucinations in 24%, and fluctuations in 26%. When distinguished by the absence (n=36) vs. presence (n=38) of neocortical NFT, the latter group had greater amyloid-β neuritic plaque density (p<0.01) and fewer males (58% vs. 86%, p<0.01). One or more core DLB features during the MCI stage was more likely in LBD without neocortical NFT (83% vs. 55%, p<0.01). Specifically, before dementia was diagnosed, those without neocortical NFT were more likely to have RBD (72% vs. 40%, p=0.005), parkinsonism (47% vs. 24%, p=0.03), and visual hallucinations (36% vs. 13%, p=0.02) but fluctuations were equally likely (31% vs. 21%, p=0.35). All but 5 patients developed dementia with a mean duration from MCI to dementia of 2±1 years. By the end of life, 92% had at least one core DLB feature, and 80% had two or more core features, with greater frequency in LBD without comorbid neocortical NFT (97% vs. 63%, p<0.01). In the MCI stage of evolving DLB, 69% had at least one core DLB feature. Patients with neocortical NFT were less likely to have core features in the pre-dementia stage. These findings underscore the need for biomarkers that are sensitive and specific to Lewy-related pathology.
Source: Alzheimer s & Dementia
Authors: Bradley F. Boeve, Tanis J. Ferman, Neill R. Graff-Radford, David S. Knopman, Jonathan Graff-Radford, Rodolfo Savica, David T. Jones, Daniel A. Drubach, Julie A. Fields, Mary M. Machulda, John A. Lucas, Leah K. Forsberg, Toji Miyagawa, Laura A. Allen, Kejal Kantarci, Melissa E. Murray, Joseph E. Parisi, Dennis W. Dickson, Ronald C. Petersen
Institutions: Mayo Clinic, Mayo Clinic in Florida
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2980824356