Premium
IC‐P‐159: AMYLOID‐BETA ACCUMULATION AFFECTS IN VIVO STAGING OF TAU DEPOSITION IN COGNITIVELY IMPAIRED INDIVIDUALS
Author(s) -
Aksman Leon M.,
Alexander Daniel C.,
Barkhof Frederik,
Altmann Andre
Publication year - 2019
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2019.06.4274
Subject(s) - tau pathology , cognitive impairment , white matter , abnormality , psychology , standardized uptake value , neuroimaging , pathology , amyloid (mycology) , disease , medicine , nuclear medicine , neuroscience , oncology , positron emission tomography , alzheimer's disease , magnetic resonance imaging , psychiatry , radiology
Background: The default mode network (DMN) and the salience network (SN) exhibit aberrant functional connectivity in Alzheimer’s disease (AD) and behavioral variant frontotemporal dementia (bvFTD), respectively. Moreover, these networks are anti-correlated. In this double-blind randomized trial, we tested the effect of electrical stimulation of these networks on clinical and functional connectivity measures in AD and bvFTD patients. Methods: AD patients (n1⁄420) were equally randomized to two arms: anodal stimulation of the DMN or cathodal stimulation of the anti-correlated network (SN) using transcranial direct current stimulation (tDCS). A similar protocol was used for bvFTD patients (n1⁄420), but with inverted polarity: cathodal stimulation of the DMN or anodal stimulation of the SN. DMN stimulation was centered over the right inferior parietal lobe, SN stimulation over the right dorsolateral prefrontal cortex. The stimulation protocol included ten daily 25-minutes tDCS sessions at 1.5 mA. Clinical and resting-state fMRI data were collected before and after the tDCS sessions. Outcome measures were changes from baseline in clinical (evaluated by Wilcoxon signed-rank test) and DMN and SN functional connectivity (expressed as mean Z-score values from independent component analysis) variables. Results: Anodal stimulation was followed by beneficial effects on cognition in AD (memory, language, visuospatial abilities; p<0.05) and bvFTD (language; p<0.05). Cathodal stimulation of the anti-correlated network had positive effects on behavioral symptoms in both AD and bvFTD (neuropsychiatric inventory; p<0.05) and on memory in AD only (p<0.05). On imaging outcomes, a significant network*arm*timepoint interaction was observed in AD (p1⁄40.017), due to an opposite pattern of network changes between anodal (augmented DMN and decreased SN connectivity) and cathodal (decreased DMN and increased SN connectivity) arms. In bvFTD, this interaction was not significant (p1⁄40.85) due to similar network changes between arms (augmented SN and decreased DMN connectivity), while the network*timepoint term was significant (p1⁄40.023). Conclusions: These results suggest that in AD anodal stimulation of the target network may be more effective than cathodal stimulation of the anti-correlated network in modulating cognition and functional connectivity. In bvFTD, both protocols resulted in similar connectivity modulation but with different cognitive/behavioral effects, indicating that distinct network dynamics may influence the clinical response.