Caviness, John N.

AbstractBackgroundPast research has demonstrated that clinical EEG is sensitive to dementia associated with Alzheimer's (AD) and Parkinson’s diseases (PD), and nonfluent/agrammatic Primary Progressive Aphasia (agPPA), but not Primary Progressive Apraxia of Speech (PPAOS). However, clinical EEG studies do not quantify interactions of multiple brain areas, or network activity. Graph theory (GT) simplifies analyzing and comparing complex brain networks. Studies have shown changes in EEG GT measures in AD and PD, but have not been studied in agPPA or PPAOS. The goal of this study was to use GT to characterize network‐level changes and associations with speech and language functioning in patients with agPPA and PPAOS.MethodsScalp EEGs of 14 agPPA and 7 PPAOS patients were collected during relaxed wakefulness (10‐20 positions, 256Hz sampling, 1–200Hz bandpass filter). Eight artifact‐free epochs were selected from non‐overlapping 1024‐point epochs. Via Brainwave software, GT weighted connectivity and minimum spanning tree (MST) measures were calculated for theta and alpha frequency bands. Differences in theta MST measures between agPPA and PPAOS were assessed with Wilcoxon rank‐sum tests. Spearman correlations were computed between behavioral and all network measures across all patients.ResultsTheta frequency MST diameter and eccentricity were significantly lower and leaf was significantly higher in agPPA compared to PPAOS patients; betweenness centrality did not differ. This indicates agPPA networks are more integrated (star‐like) than PPAOS. There were significant correlations between several network measures (e.g. kappa, lambda, PLI) and indices of speech‐language functioning.ConclusionsThe results provide EEG evidence of network alteration in agPPA and PPAOS patients. The GT measures and associations with behavioral measures provide support for reduced global efficiency, or network specificity, in these patients. The correlation of language measures with lambda (path length) in the theta frequency band suggests agPPA is associated with an inefficient path length and/or increased integration. The correlation between apraxia of speech (AOS) measures and MST eccentricity in the alpha frequency band suggests that more severe AOS is associated with reduced distance between two nodes. This study demonstrates potential for EEG GT measures to quantify network changes and distinguish network changes between related but different clinical syndromes.

PolyQ ATXN3 is a pharmacodynamic marker for SCA3, and a SNP associated with the expanded allele may serve to specifically target mutant ATXN3 .

Twelve cases (6 M, 6F; mean age 87.9) with incidental Lewy bodies (no clinical diagnosis of parkinsonism or dementia) had medical histories of supraventricular arrhythmia (6/12), dysphagia (5/12), depression (5/12) and falls (4/12). Standardized movement disorder assessments were performed antemortem on 6 cases. The mean Part III UPDRS score was 7 (range 2–14). Motor findings included kinetic tremor (5/6), rest tremor (3/6), postural instability (3/6), postural tremor (2/6), and voice tremor (2/6). Of these 6 cases one was considered to have a normal movement exam, 2 were diagnosed as essential tremor, and 3 as nonspecific tremor disorder. Mean MMSE score in 7 cases was 26.6 (range 23–30). Medical records review revealed 4/12 cases had cognitive impairment not meeting criteria for dementia. Of these 12 cases, 5 had received standardized cognitive assessments: 3 were categorized as cognitively normal and 2 as mild cognitive impairment. Our series of incidental Lewy body disease cases reveal a range of neurologic findings including tremor and cognitive impairment. Antemortem standardized evaluations suggest there may be early clinical markers for Lewy body disorders. Supported by the State of AZ Department of Health Services, NIA P30 AG19610 and the Prescott Family Parkinson's Initiative: a Partnership of the Michael J. Fox Foundation and the Arizona Parkinson's Disease Consortium.