Brain Network Integrity Changes in Subjective Cognitive Decline: A Possible Physiological Biomarker of Dementia

Hilla Fogel; Ofri Levy-Lamdan; Noa Zifman; Tal Hiller; Shai Efrati; Gil Suzin; Dallas C Hack; Iftach Dolev; David Tanne

doi:10.3389/fneur.2021.699014

Brain Network Integrity Changes in Subjective Cognitive Decline: A Possible Physiological Biomarker of Dementia

Front Neurol. 2021 Aug 30:12:699014. doi: 10.3389/fneur.2021.699014. eCollection 2021.

Authors

Hilla Fogel¹, Ofri Levy-Lamdan¹, Noa Zifman¹, Tal Hiller¹, Shai Efrati^{2

3}, Gil Suzin², Dallas C Hack⁴, Iftach Dolev¹, David Tanne^{3

5}

Affiliations

¹ QuantalX Neuroscience, Beer-Yaacov, Israel.
² Sagol Center for Hyperbaric Medicine and Research, Shamir Medical Center, Zerifin, Israel.
³ Sackler School of Medicine and Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel.
⁴ Department of Physical Medicine and Rehabilitation, Virginia Commonwealth University, Richmond, VA, United States.
⁵ Stroke and Cognition Institute, Rambam Healthcare Campus, Haifa, Israel.

Abstract

Objective: The current study seeks to illustrate potential early and objective neurophysiological biomarkers of neurodegenerative cognitive decline by evaluating features of brain network physiological performance and structure utilizing different modalities. Methods: This study included 17 clinically healthy individuals with self-reported cognitive decline (Subjective Cognitive Decline group, SCD, no objective finding of cognitive decline), 12 individuals diagnosed with amnestic Mild Cognitive Impairment (aMCI), 11 individuals diagnosed with Dementia, and 15 healthy subjects. All subjects underwent computerized cognitive performance testing, MRI scans including T1 for gray matter (GM) volume quantification, DTI for quantification of white matter (WM) microstructure fractional anisotropy (FA) and mean diffusivity (MD), and brain network function evaluation using DELPHI (TMS-EEG) measures of connectivity, excitability, and plasticity. Results: Both DELPHI analysis of network function and DTI analysis detected a significant decrease in connectivity, excitability, and WM integrity in the SCD group compared to healthy control (HC) subjects; a significant decrease was also noted for aMCI and Dementia groups compared to HC. In contrast, no significant decrease was observed in GM volume in the SCD group compared to healthy norms, a significant GM volume decrease was observed only in objectively cognitively impaired aMCI subjects and in dementia subjects. Conclusions: This study results suggest that objective direct measures of brain network physiology and WM integrity may provide early-stage biomarkers of neurodegenerative-related changes in subjects that have not yet displayed any other objective measurable cognitive or GM volume deficits which may facilitate early preventive care for neurodegenerative decline and dementia.

Keywords: DELPHI; Dementia-Alzheimer's disease; brain network; gray matter; mild cognitive impairment; plasticity; subjective cognitive decline; white matter.