Baseline multimodal imaging to predict longitudinal clinical decline in atypical Alzheimer's disease.

There are recognized neuroimaging regions of interest in typical Alzheimer's disease which have been used to track disease progression and aid prognostication. However, there is a need for validated baseline imaging markers to predict clinical decline in atypical Alzheimer's Disease. We aimed to address this need by producing models from baseline imaging features using penalized regression and evaluating their predictive performance on various clinical measures. Baseline multimodal imaging data, in combination with clinical testing data at two time points from 46 atypical Alzheimer's Disease patients with a diagnosis of logopenic progressive aphasia (N = 24) or posterior cortical atrophy (N = 22), were used to generate our models. An additional 15 patients (logopenic progressive aphasia = 7, posterior cortical atrophy = 8), whose data were not used in our original analysis, were used to test our models. Patients underwent MRI, FDG-PET and Tau-PET imaging and a full neurologic battery at two time points. The Schaefer functional atlas was used to extract network-based and regional gray matter volume or PET SUVR values from baseline imaging. Penalized regression (Elastic Net) was used to create models to predict scores on testing at Time 2 while controlling for baseline performance, education, age, and sex. In addition, we created models using clinical or Meta Region of Interested (ROI) data to serve as comparisons. We found the degree of baseline involvement on neuroimaging was predictive of future performance on cognitive testing while controlling for the above measures on all three imaging modalities. In many cases, model predictability improved with the addition of network-based neuroimaging data to clinical data. We also found our network-based models performed superiorly to the comparison models comprised of only clinical or a Meta ROI score. Creating predictive models from imaging studies at a baseline time point that are agnostic to clinical diagnosis as we have described could prove invaluable in both the clinical and research setting, particularly in the development and implementation of future disease modifying therapies.

Refractory Obstructive Sleep Apnea Secondary to Vagal Nerve Stimulation.

Vagal nerve stimulator (VNS) devices are commonly used as a non-pharmacologic option for improved seizure control in patients with refractory epilepsy. However, a side effect associated with VNS device placement includes sleep-disordered breathing, which is complicated by the fact that a significant minority of patients with epilepsy have sleep-disordered breathing. We describe a patient with iatrogenically worsened refractory obstructive sleep apnea (OSA) secondary to VNS device placement, which resolved upon turning off the VNS device. This case highlights the need to screen for OSA in patients who are candidates for VNS device placement, as iatrogenic sleep-disordered breathing could place the patient at risk for adverse clinical outcomes, as well as paradoxically worsen seizure control due to poor quality sleep.

Dysexecutive Alzheimer's Disease with Lewy Body Disease Co-Pathology.

BACKGROUND: Alzheimer's disease can present atypically as a progressive dysexecutive syndrome (dAD), an entity that preferentially affects younger individuals and is frequently misdiagnosed, highlighting the imperative for additional research. OBJECTIVE: The objective of this study is to characterize the clinical, antemortem neuroimaging, and postmortem neuropathologic features of two cases of young-onset dAD who displayed evidence of Lewy body disease (LBD) co-pathology at autopsy. METHODS: Clinical histories, antemortem MRI and PET imaging, and postmortem neuropathologic data were reviewed for each patient. CASE PRESENTATION: Canonical features of dAD were observed in both cases, including progressive and predominant impairment in tasks related to working memory and cognitive flexibility, a lack of major behavioral/personality changes, and evidence of abnormal amyloid and tau deposition by antemortem amyloid and tau PET and postmortem neuropathology. Relative sparing of hippocampal involvement was observed in both individuals, in keeping with many cases of clinically atypical AD. One of the patients developed subtle parkinsonian signs as well as paranoia and irritability in the years prior to passing. In both cases, transitional (brainstem and limbic) LBD co-pathology was observed at autopsy. RESULTS AND DISCUSSION: Although LBD co-pathology is not uncommon in AD overall, the presence of LBD pathology in these young-onset cases of dAD (including a case with apparent symptomatic correlate) warrants further investigation for broader frequency and underlying pathophysiology. CONCLUSION: A better understanding of which specific young-onset AD phenotypes are associated with LBD co-pathology would have important implications for counseling, treatment, clinical trial enrollment, and knowledge on disease mechanisms.