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.
Highlights
Improved medical care and lifestyle continue to increase life span and with it age-related brain disorders [1]
The study included 17 clinically healthy individuals with self-reported cognitive decline (Subjective Cognitive Decline group, subjective cognitive decline (SCD), no objective finding of cognitive decline), 12 individuals diagnosed with amnestic MCI (aMCI), 11 individuals diagnosed with Dementia, and 15 healthy subjects; no significant differences were noted between groups ages and the rest motor threshold (RMT) (Table 1)
All subjects underwent a thorough evaluation of brain functional performance and health including MRI scans, a computerized cognitive evaluation including four main cognitive domains: memory, executive function (EF), attention, information processing speed (IPS), and DELPHI (TMS-EEG) neurophysiological brain network evaluation
Summary
Improved medical care and lifestyle continue to increase life span and with it age-related brain disorders [1]. The American Academy of Neurology has recently recommended an annual cognitive health assessment for patients 65 years and older [2]. The rationale behind this recommendation asserts that brain diseases may be delayed or prevented if detected at early stages and that certain risks associated with compromised brain health are modifiable [3]. The lack of effective evaluation tools for brain health leaves most clinical assessments to be based on the patient’s clinical history and simple cognitive screening, and the American Academy of Neurology (AAN) has recommended routine assessment of cognitive health in high-risk patients. Specific physiological changes in brain network connectivity and plasticity are known to occur at the early stages of the disease and it is estimated that a large proportion of cerebrovascular diseases and dementias may be prevented or at least delayed if detected during early pathophysiology stages [5]
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