Review Article

A Systematic Review of Intervention Studies Examining Nutritional and Herbal Therapies for Mild Cognitive Impairment and Dementia Using Neuroimaging Methods: Study Characteristics and Intervention Efficacy

Table 1

Neuroimaging technique, description, example quantification methods (by no means exhaustive), advantages, limitations, and relevance in CM studies on people with dementia.

Neuroimaging techniqueDescriptionQuantificationAdvantagesLimitationsRelevance in CM dementia research

EEGQuantifies the electrical activity of the brain generated by electrical field potentials from excitatory and inhibitory neuronal activity.Resting state EEG spectral activity (delta, theta, alpha, beta, gamma): power analyses and scalp-based functional connectivity measures (coherence, phase-lag).
Event-related measures: ERPs, EPs, SST, and ERSP including ERS and ERD.
Very high temporal resolution, relatively inexpensive, noninvasive, portable options available.Poor spatial resolution due to volume conduction
Not as well-suited to investigations of subcortical dementia.
Captures subtle changes in cognitive and/or sensory function.
Allows for the mechanisms of action of CM therapies to be explored.
Noninvasive and portable options increase its usability in groups with more significant impairments.
Suitable for acute and chronic studies.

fMRIMeasures changes in brain blood flow caused by neuronal activity.Resting state: Region of interest functional connectivity approach.
Event-related: BOLD response.
Good spatial resolution, particularly with high resolution scanners (e.g., 7 T).Poor temporal resolution: the BOLD response lags by 1-2 s behind the actual neuronal activity. Claustrophobia and high-pitched noises can make scanning uncomfortable for participants.Captures changes in cognitive and/or sensory function that can have their source localised in the brain.

SPECTQuantifies changes in brain blood flow and metabolism. Nuclear gamma camera captures a gamma-emitting tracer being absorbed by brain tissue at the same rate as blood flow.Regional CBF.Relatively cheap compared to other functional imaging methods (e.g., PET, fMRI).Administration of radioactive isotope (usually injection) and exposure to gamma radiation.
Low spatial resolution (1 cm).
Useful in assessing interventions for dementia as SPECT can differentiate dementia pathologies (e.g., vascular dementia versus Alzheimer’s disease).
Allows for the mechanisms of action of CM therapies to be explored.

PETTypically assesses regional brain glucose metabolism by detecting gamma rays emitted by a positron-emitting tracer.Regional CBF.Different novel isotopes allow distinction between Alzheimer’s pathology and other dementias (PiB-PET).Administration of radioactive isotope.Different isotopes allow for tagging of different biochemical processes (e.g., FDG-PET for glucose uptake, or PiB-PET for amyloid imaging).
Allows for the mechanisms of action of CM therapies to be explored.

MEGMeasures magnetic fields generated by the electrical activity of the brain.Similar to EEG, resting state measures (delta, theta, alpha, beta, gamma band power) and event-related measures are available.Very high temporal resolution, and better spatial resolution (i.e., more accurate) compared to EEG.Detects only tangential components of current source, so primarily sensitive to activity within sulci.Captures subtle changes in cognitive and/or sensory function.
Allows for the mechanisms of action of CM therapies to be explored.
Suitable for acute and chronic studies.

fNIRSfNIRS captures changes in blood flow by detecting haemoglobin concentrations through the transmission and absorption of NIR light.A range of measures are used, DOT or NIRI being popular forms of fNIR.Noninvasive and portable.Limitations when trying to measure activity in subcortical tissue.CM intervention-associated changes in CBF can be ascertained.
Mechanism of action can be explored due to the modulation of haemoglobin.

MRIStructural MRI images the anatomy of the brain using magnetic fields, radio waves, and field gradients.Most frequently used measures are voxel-based morphometry and ROI analyses.Good spatial resolution, particularly with high resolution scanners (e.g., 7 T).No functional information available.Volumetric changes in brain regions (or whole brain) can be investigated.
Any changes are best explored in chronic studies.

DTIMeasures diffusion of water in order to provide information on tissue microstructures so that white matter pathways within and between brain regions can be explored.Tractography and tensor estimation.Exploration of brain networks is becoming increasingly popular within the field.
Better resolution with more angles (e.g., 61 direction scan).
No functional information available.White matter integrity and structural network connectivity can be explored.
Any changes are best explored in chronic studies.

Note. BOLD = blood oxygenation level dependent; CBF = cerebral blood flow; CM = complementary therapies; DOT = diffuse optical tomography; DTI = diffusion tensor imaging; EEG = electroencephalograph; EPs = evoked potentials; ERD = event-related de-synchronisation; ERPs = event-related potentials; ERSP = event-related spectral perturbation; ERS = event-related synchronisation; FDG-PET = fluorodeoxyglucose-positron emission tomography; MRI = magnetic resonance imaging; MEG = magnetoencephalograph; NIRI = near-infrared imaging; NIRS = near-infrared spectroscopy; PET = positron emission tomography; PiB-PET = Pittsburgh compound B-positron emission tomography; ROI = region of interest; SPECT = single photon emission computed tomography; SST = steady-state topography.
Can be addressed to a certain extent in connectivity analyses which partial out instantaneous zero-phase contributions.