AUTHOR=Eyjolfsdottir Helga , Koenig Thomas , Karami Azadeh , Almqvist Per , Lind Göran , Linderoth Bengt , Wahlberg Lars , Seiger Åke , Darreh-Shori Taher , Eriksdotter Maria , Jelic Vesna 

TITLE=Fast Alpha Activity in EEG of Patients With Alzheimer’s Disease Is Paralleled by Changes in Cognition and Cholinergic Markers During Encapsulated Cell Biodelivery of Nerve Growth Factor

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=Volume 14 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2022.756687

DOI=10.3389/fnagi.2022.756687

ISSN=1663-4365

ABSTRACT=Background: Basal forebrain cholinergic neurons are dependent on nerve growth factor (NGF) for growth and survival and these cells are among the first to degenerate in Alzheimer’s disease (AD). Targeted delivery of NGF has been suggested as a potential therapy for AD.  This hypothesis was tested in a clinical trial with encapsulated cell biodelivery of NGF (NGF-ECB) in AD patients. Three of six patients showed improved biomarkers for cognition by the end of the study. Here, we report on the effects of targeted delivery of NGF on human resting EEG.
Materials and methods: NGF-ECB implants were implanted bilaterally in the basal forebrain of six AD patients for 12 months. Quantitative EEG recordings were made at baseline, three- and twelve months of NGF delivery,  and analyzed for correlation with changes in Mini-mental state examination (MMSE) and levels of the cholinergic marker choline acetyltransferase (ChAT) in cerebrospinal fluid (CSF). 
Results: We found significant correlations between the three study points (baseline, 3 and 12 months) and the topographic variance of EEG spectral power correlated both with changes in MMSE and CSF ChAT. This possible effect of NGF was identified in a narrow window of alpha frequency 10-11.5 Hz, where a stabilization in MMSE score during treatment was related to an increase in EEG alpha power. A similar relation was observed between the alpha power and ChAT. More theta power at 6.5 Hz was on the contrary associated with a decrease in CSF ChAT during the trial period.  
Conclusion: In this exploratory study, there was a positive correlative pattern between physiological high frequency alpha activity and stabilization in MMSE and increase in CSF ChAT in AD patients receiving targeted delivery of NGF to the cholinergic basal forebrain.